Description
Intent
Policy
BlackBoxWarning
Guidelines
References
  
  
  
  
  
CrossReferences
ApplicableDrugs
  
  
235
  
4/1/2023Rx.01.272CommercialOyenusi, Oluwadamilola

Vulvovaginal candidiasis (VVC) is one of the most common causes of vulvovaginal itching and discharge. The disorder is characterized by inflammation in the setting of Candida species. Treatment is indicated for the relief of symptoms. Recurrent vulvovaginal candidiasis (RVVC) is defined as three or more episodes of symptomatic infection within one year.

Oteseconazole is an antifungal drug. It is an azole metalloenzyme inhibitor that inhibits the enzyme CYP51 (also known as 14α demethylase). It demethylates the 14-α position of lanosterol to yield ergosterol, a compound that plays a key role in maintaining the integrity of cell membranes in yeast and fungi, thereby inhibiting fungal growth.

Vivjoa™ is indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in females with a history of RVVC who are NOT of reproductive potential.



​The intent of this policy is to communicate the medical necessity criteria for oteseconazole (Vivjoa™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Oteseconazole (Vivjoa™) is approved when ALL of the following are met:

  1. Diagnosis of recurrent vulvovaginal candidiasis (RVVC); and
  2. Member is not of reproductive potential; and
  3. Diagnosis of RVVC is confirmed by ONE of the following:
    1. Positive potassium hydroxide (KOH) preparation; or
    2. Vaginal fungal culture; and
  4. Member has experienced 3 or more symptomatic episodes of vulvovaginal candidiasis (VVC) within the past 12 months; and
  5. Inadequate response or inability to tolerate BOTH of the following:
    1. One intravaginal product (e.g., clotrimazole, miconazole, terconazole); and
    2. Oral fluconazole

Authorization duration: 4 months 


n/a

Sobel J. Candida vulvovaginitis: Treatment. UpToDate. Revised December 2022. Available from: uptodate.com. Accessed February 24, 2023.

VivjoaTM (oteseconazole) [package insert]. Durham, NC: Mycovia Pharmaceuticals, Inc; April 2022. Available at https://vivjoa.com/pi/VIVJOA-Full-Prescribing-Information.pdf. Accessed February 24, 2023.


112/8/202212/8/20236/29/2023 5:59 AMNo presence informationsrv_ppsgw_NP

Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​


Brand NameGeneric Name
Vivjoa™oteseconazole


241
  
10/1/2023Rx.01.33CommercialOyenusi, Oluwadamilola

The US Food and Drug Administration (FDA) approves labeling that details uses for which a pharmaceutical agent can be marketed.  The approved uses identify the specific disease states that the agent has been shown to be safe, efficacious and meet all clinical requirements set forth by the FDA. An off-label or unlabeled use of a prescription drug or biologic is a use that has not been approved by the US Food and Drug Administration (FDA) and which is not identified in package labeling. Use of a drug for any indication, dose or dose frequency, treatment duration, patient population, or route of administration other than those approved by the FDA and listed on the label or packaging insert is considered an off-label or unlabeled use.Off-label use of prescription drugs and biologics not meeting the medical necessity criteria is considered experimental/investigational and may not be a covered by the prescription drug benefit.
 
In determining whether there is clinical evidence to support a medical necessity determination, the pharmacy benefits manager ​ will consider the quality of the published evidence as well as an assessment of the following information as submitted by the requesting physician. Off-label uses are medically accepted if they are supported in either of the following:

(1) one or more authoritative compendia, and none list it as not indicated, unsupported, not recommended, or equivalent terms; or

(2) in peer-reviewed medical literature.

Reliable evidence must demonstrate that the proposed off-label use for the specified medical condition is safe and effective and that the treatment's beneficial effects outweigh its risks.

Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications in which original manuscripts are published only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication. In order for a use to be supported by clinical research, it must have been studied in at least two clinical trials conducted at different centers, and the results must have been published in national or international peer-reviewed journals with an editorial committee composed of physicians. Peer-reviewed medical literature does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).

According to the National Cancer Institute, clinical trials are usually conducted in a series of steps called phases. These are outlined as follows:

Phase 0 trials are the first step in testing a new agent in people. Phase 0 trials will evaluate how the new agent is processed in the body and how it exerts its clinical effects in the body. Phase 0 trials enroll a small number of individuals (10-15 individuals) who are administered a very small amount of the new agent.

Phase I trials evaluate what dose is safe, how a new agent should be given (by mouth, injected into a vein, or injected into the muscle), and how often. Researchers watch closely for any harmful side effects. Phase I trials usually enroll a small number of individuals (20 or more individuals) and take place at only a few locations. The dose of the new therapy or technique is increased a little at a time. The highest dose with an acceptable level of side effects is determined to be appropriate for further testing.

Phase II trials study the safety and effectiveness of an agent or intervention and evaluate how it affects the human body. Phase II studies usually focus on a particular aspect of a disease and include fewer than 100 patients.

Phase III trials compare a new agent or intervention (or new use of a standard one) with the current standard therapy. Participants are randomly assigned to the standard group or the new group, usually by computer. This method, called randomization, helps to avoid bias and ensures that human choices or other factors do not affect the study's results. In most cases, studies move into Phase III testing only after they have shown promise in Phases I and II. Phase III trials often include large numbers of individuals across the country.

Phase IV trials are conducted to further evaluate the long-term safety and effectiveness of a treatment. They usually take place after the treatment has been approved for standard use. Several hundred to several thousand people may take part in a Phase IV study. These studies are less common than Phase I, II, or III trials.

Prescription pharmaceutical agents available in the United States have FDA approved labeling. The label specifies which disease states a drug can be used to treat. However, use of a pharmaceutical agent may expand past the approved labeling and into what is known as off-label use. Coverage for off-label or experimental use will require Prior Authorization.  

Off-label uses are medically accepted and thus approved when ONE of the following is met:

  1. The narrative text in American Hospital Formulary Service--Drug Information (AHFS-DI®) is supportive of the use; OR
  2. The use is classified as Category 1 or 2A by National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium™; OR
  3. The use is classified as Class I or Class IIa in Micromedex®; OR
  4. Adequate published clinical research (supplied by the provider) as defined below:

Authorization duration: 2 years

PUBLISHED CLINICAL RESEARCH

In order for an off-label use to be supported by published clinical research, all of the following criteria must be met:

A. The prescription drug or biologic must have been studied in at least two clinical trials conducted at different centers and the results must have been published in a national or international peer-reviewed journals with an editorial committee composed of physicians.  Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications.  It does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).

B. A use is considered supported by clinical research when it appears in at least two Phase III clinical trials that have definitively demonstrated its safety and effectiveness as an appropriate medical treatment for the condition.  If no Phase III trial evidence is available, at least two Phase II clinical trials with reasonably large patient samples showing consistent results of safety and efficacy may be considered in certain instances (e.g. rare diseases in which a Phase III study might be difficult to complete in a reasonable period of time after completion of the Phase II studies. Or when overwhelmingly good evidence of safety and effectiveness is noted in Phase II studies

Reliable evidence must demonstrate that the proposed off label use for the specified medical condition is safe and effective and that the beneficial effects of the treatment outweigh its risks.
In determining whether there is supportive clinical evidence for a particular use of a prescription drug or biologic, the Company considers the quality of the evidence in published, peer-reviewed medical literature.  Among other things, such consideration involves the assessment of the following:

1.     The prevalence and life history of the disease when evaluating the adequacy of the number of subjects and the response rate

2.     The effect on the individual's well-being and other responses to therapy that indicate effectiveness (e.g. reduction in mortality, morbidity, and signs and symptoms)

3.     Whether the clinical characteristics of the beneficiary and the indication are adequately represented in the published evidence

4.     Whether the study is appropriate to address the clinical question, such as:

  1. If the study design is appropriate to address investigative questions (e.g. in some clinical studies, it may be unnecessary or not feasible to use randomized, double-blind trial, placebos, or crossover)
  2. If non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs
  3. Generally, case reports are considered uncontrolled, are based on anecdotal information, and do not provide adequate supportive clinical evidence for determining accepted uses of drugs.

5.     The off-label use is supported by published clinical research and the results have been published in major, peer-reviewed medical journals such as, but not limited to:

 

American Journal of MedicineGynecologic Oncology
American Journal of PsychiatryInternational Journal of Radiation, Oncology, Biology and Physics
Annals of Internal MedicineJournal of Clinical Oncology
Annals of OncologyJournal of Obstetrics and Gynecology
Annals of Surgical OncologyJournal of Pediatrics
Archives of Pediatric and Adolescent MedicineJournal of the National Cancer Institute
Biology of Blood and Marrow TransplantationJournal of the National Comprehensive Cancer Network (NCCN)
British Journal of CancerJournal of Urology
British Journal of HematologyLancet
British Journal of MedicineLancet Oncology
CancerLeukemia
Clinical Cancer ResearchPediatrics
DrugsRadiation Oncology
European Journal of CancerThe Journal of the American Medical Association

 

EXPERIMENTAL/INVESTIGATIONAL

Prescription drugs that are considered experimental/investigational are not covered because the safety and/or efficacy of the drug for those purposes cannot be established by a review of the available published peer reviewed literature.  Prescription drugs and biologics are considered experimental/investigational for any of the following:

  1. The prescription drug or biologic has not received FDA approval for any indication
  2. The off-label use of the prescription drug or biologic does not meet the medical necessity criteria listed in this policy (i.e. the off-label use is not recognized by the appropriate compendia or published clinical research)
  3. The FDA determined the prescription drug or biologic to be contraindicated for specific condition(s) or specific off-labels use(s)
  4. The off-label use is not medically accepted or not indicated by a compendium for specific conditions (i.e. the indication is Category # in NCCN, Class III in Micromedex®) or when the narrative text in AHFS-DI® or Clinical Pharmacology® is not supportive

 

a. The absence of narrative text for an off-label use is considered neither supportive nor non-supportive

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided.  These medical records may include, but are not limited to records from the professional provider's office, hospital, nursing home, home health agency, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider.  All documentation is to be available to the Company upon request.  Failure to produce the requested information may result in a denial for the service.

N/A
N/A
156/8/20236/8/202410/1/2023 1:23 AMNo presence informationsrv_ppsgw_P
N/A
 

This policy applies to all drugs that have clinical management policies addressing them.

245
  
10/1/2023Rx.01.6CommercialOyenusi, Oluwadamilola

Aztreonam (Cayston®) is a monobactam antibiotic, which is part of the beta-lactam class, that binds to penicillin binding proteins of susceptible bacteria and leads to inhibition of bacterial cell wall synthesis and death of the cell.

Aztreonam (Cayston®) is indicated to improve respiratory symptoms in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infections. Safety and effectiveness has not been established in pediatric patients below the age of 7 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia.


 

The intent of this policy is to communicate the medical necessity criteria for aztreonam (Cayston®) as provided under the member’s prescription drug benefit.


 

INITIAL CRITERIA: Aztreonam (Cayston®) is approved when ALL of the following are met:

  1. Member is 7 years of age or older; AND
  2. Diagnosis of cystic fibrosis; AND
  3. Evidence of Pseudomonas aeruginosa in the lungs confirmed by culture; AND
  4. Susceptibility results indicating that the Pseudomonas aeruginosa is sensitive to aztreonam; AND
  5. FEV1 that is 25% to 75% of predicted

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Aztreonam (Cayston®) is re-approved when ALL of the following are met:

  1. Diagnosis of cystic fibrosis; AND
  2. Evidence of Pseudomonas aeruginosa in the lungs confirmed by culture; AND
  3. Documentation of positive clinical response to therapy (e.g. improvement in lung function demonstrated by improved FEV1)

Reauthorization duration: 2 years


N/A

Cayston® [package insert]. Foster City CA. Gilead Sciences. November 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=67300ca3-8c53-4ce4-8e86-2c03be1f9b8a&type=display.  Accessed June 22, 2023.  

McCoy K, Quittner A, Oermann C, et al. Inhaled Aztreonam Lysine for chronic airway pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care 2008; 178(9): 921-928. Accessed June 22, 2023. 

Oermann C, Retsch-Bogart G, Quittner A, et al. An 18 month study of the safety and efficacy of repeated courses of inhaled Aztreonam Lysine in Cystic Fibosis. Pediatric Pulmonology2010; 45(11): 1121-1134. Accessed June 22, 2023.

Retsch-Bogart G, Quittner A, Gibson R, et al. Efficacy and Safety of inhaled Aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135(5): 1223-1232.  Accessed June 22, 2023.​



 


 


 

156/8/20236/8/202410/1/2023 1:23 AMNo presence informationsrv_ppsgw_P
Rx.01.33 Off-Label Use
 


Brand Name Generic Name
Cayston® Aztreonam

246
  
10/1/2023Rx.01.100CommercialOyenusi, Oluwadamilola

In the United States, it is estimated that 2.7 to 3.9 million people are chronically infected with HCV. Chronic HCV infection occurs after acute infection with the virus. It is estimated that approximately 75%-85% of acute infections become chronic. The remaining 15%-25% clear the virus without treatment and do not develop chronic HCV. Genotype (GT) 1 is the most prevalent, with the breakdown as follows: GT 1a: 46.2%, GT1b: 26.3%, GT2: 10.7%, GT3: 8.9%, GT4: 6.3%, GT6: 1.1%, mixed GT/ other: 0.5%. 

The goal of treating chronic HCV is to "reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR)." SVR is defined as the "continued absence of detectable HCV RNA at least 12 weeks after completion of therapy" and is considered a marker for cure of HCV. Several benefits are associated with HCV cure, including decreases in liver inflammation, progression to liver fibrosis, hepatocellular carcinoma, liver-related mortality and liver transplantation. 

This policy follows the AASLD/IDSA guidelines.  Current treatment regimens consist of at least 2 agents.  Monotherapy is not recommended. 

Elbasvir/ grazeprevir (Zepatier®) is a product containing an HCV NS5A inhibitor (elbasvir) and an HCV NS3/4A protease inhibitor in a fixed dose combination.

Glecaprevir/pibrentasvir (Mavyret™) is a fixed-dose combination of glecaprevir, an HCV NS2/4A inhibitor, and pibrentasvir, an HCV NS5A inhibitor.  

Ledipasvir/ sofosbuvir (Harvoni®) is a combination product that contains an HCV NS5A replication inhibitor (ledipasvir) and an HCV NS5B RNA-dependent polymerase inhibitor (sofosbuvir) in a fixed dose combination. 

Ombitasvir/ paritaprevir/ ritonavir and dasabuvir (Viekira Pak®) is a combination product that contains an HCV NS5A replication inhibitor (ombitasivir), an HCV NS3/4A protease inhibitor (parataprevir) and a booster (ritonavir) as a fixed dose tablet along with an HCV NS5B RNA-dependent RNA polymerase inhibitor (dasabuvir) as a separate tablet.   

Sofosbuvir (Sovaldi®) inhibits HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. 

Sofosbuvir/velpatasvir/voxilaprevir (Vosevi®) is a fixed-dose combination of sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor; velpatasvir, an HCV NS5A inhibitor; and voxilaprevir, an HCV NS3/4A protease inhibitor. 

Velpatisvir/ sofosbuvir (Epclusa®) is a combination product that contains an HCV NS5A replication inhibitor (velpatisvir) and an HCV NS5B RNA-dependent polymerase inhibitor (sofosbuvir) in a fixed dose combination.



The intent of this policy is to communicate the medical necessity criteria for elbasvir/ grazeprevir (Zepatier®), ledipasvir/ sofosbuvir (Harvoni®), ombitasvir/ paritaprevir/ ritonavir and dasabuvir (Viekira Pak®), sofosbuvir (Sovaldi®), velpatasvir/ sofosbuvir (Epclusa®), glecaprevir/pibrentasvir (Mavyret™), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi®) as provided under the member’s prescription drug benefit.


TREATMENT NAIVE

A. Genotype 1

MavyretTM is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 56 days (8 weeks)


Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 1; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 84 days (12 weeks)*; and
  5. Inadequate response or inability to tolerate brand Epclusa® (applies to valpatasvir/sofosbuvir only), details of intolerability must be provided

 Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 84 days (12 weeks)*; and
  5. Inadequate response or inability to tolerate brand Harvoni® (applies to lepipasvir/sofosbuvir only), details of intolerability must be provided

 Zepatier® is approved when ALL of the following are met:

  1. Age 12 years or older or weighing at least 30kg; and
  2. Diagnosis of HCV genotype 1; and
  3. Results of testing for baseline high fold-change NS5A resistance-associated variant are provided (for genotype 1a); and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (MavyretTM), brand Harvoni® or brand Epclusa®, details of intolerability must be provided; and
  6. Used concurrently with ribavirin for genotype 1a when baseline high fold-change NS5A resistance-associated variant are detected; and
  7. Approved length of therapy:
    1. Genotype 1a without baseline high fold-change NS5A resistance-associated variant or genotype 1b: 84 days (12 weeks)*
    2. Genotype 1a with baseline high fold-change NS5A resistance-associated variant: 112 days (16 weeks)*


Viekira Pak® is approved when ALL of the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 1; and
  3. ONE of the following:
      1. Genotype 1a without cirrhosis; or
      2. Genotype 1b with absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (MavyretTM), brand Harvoni® or brand Epclusa®, details of intolerability must be provided; and​
  5. Used concurrently with ribavirin for genotype 1a; and
  6. Approved length of therapy: 84 days (12 weeks) *


B. Genotype 2

MavyretTM is approved when all of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 2; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 56 days (8 weeks)*


Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met: 

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 2; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided.; and
  5. Approved length of therapy: 84 days (12 weeks)*


C. Genotype 3


MayvretTM is approved when ALL of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 3; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: : 56 days (8 weeks)*

 Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 3; and
  3. Absence of decompensated cirrhosis (i.e. compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided.; and
  5. Concurrent use of ribavirin if compensated cirrhosis and Y93H substitution present; and
  6. Approved length of therapy: 84 days (12 weeks)

Vosevi® is approved when ALL of the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 3; and
  3. Compensated cirrhosis; and
  4. Presence of Y93H; and​
  5. Approved length of therapy: 84 days (12 weeks)*


D. Genotype 4 

MavyretTM is approved when ALL of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 4; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 56 days (8 weeks)
     

Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

  1. Age 3 years or older; and 
  2. Diagnosis of chronic HCV genotype 4; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
  5. Approved length of therapy: 84 days (12 weeks)*


Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 4; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
  5. Approved length of therapy: 84 days (12 weeks)*

 
Zepatier® is approved when ALL of the following are met:

  1. Age 12 years or older or weighing at least 30kg; and
  2. Diagnosis of chronic HCV genotype 4; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (MavyretTM), brand Harvoni® or  brand Epclusa®, details of intolerability must be provided; and​
  5. Approved length of therapy: 84 days (12 weeks)*


E. Genotype 5 or 6


MavyretTM is approved when ALL of the following are met:

  1. Age 3 years or older ; and
  2. Diagnosis of chronic HCV genotype 5 or 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Approved length of therapy: 56 days (8 weeks)


Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL of the following are met:

  1. Age 3 years or older ; and
  2. Diagnosis of chronic HCV genotype 5 or 6; and​
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
  5. Approved length of therapy: 84 days (12 weeks)*


Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 5 or 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  4. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
  5. Approved length of therapy: 84 days (12 weeks)*


RETREATMENT (note: Retreatment for interferon or interferon plus first generation protease inhibitor failures should be treated as treatment naïve)

Sofosbuvir-Based and Elbasvir/Grazoprevir Treatment Failures

A. Genotype 1, 2, 4, 5 and 6

Mavyret™ is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
  5. Approved length of therapy: 112 days (16 weeks)

Vosevi® is approved when ALL the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
  5. Approved length of therapy: 84 days (12 weeks)*

B. Genotype 3

Vosevi® is approved when ALL the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 3 and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Sofosbuvir-Based therapy or Zepatier (Elbasvir/Grazoprevir); and
  5. Approved length of therapy: 84 days (12 weeks)*


Glecaprevir/Pibrentasvir Treatment Failures

A. Genotype 1, 2, 3, 4, 5, 6

Mavyret™ and Sovaldi® is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir); and
  5. Concurrent use of ribavirin; and
  6. Approved length of therapy: 112 days (16 weeks)

Vosevi® is approved when ALL the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir); and

Approved length of therapy: 84 days (12 weeks)


Multiple DAA Treatment Failures (All Genotypes), Including Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir) or Sofosbuvir Plus Mavyret™ (Glecaprevir/Pibrentasvir)

A. Genotypes 1, 2, 4, 5, 6

Mavyret™ and Sovaldi is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
  5. Concurrent use of ribavirin; and
  6. Approved length of therapy: 112 days (16 weeks)

Vosevi® is approved when ALL the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 4, 5, 6; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir; and
  5. Concurrent use of ribavirin (for members with compensated cirrhosis); and
  6. Approved length of therapy: 168 days (24 weeks)​

B. Genotype 3

Mavyret™ and Sovaldi is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 3; and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
  5. Concurrent use of ribavirin; and
  6. Approved length of therapy:
    1. NO cirrhosis - 112 days (16 weeks)
    2. Compensated cirrhosis up to 168 days (24 weeks)

Vosevi® is approved when ALL the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of chronic HCV genotype 3 and
  3. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  4. Member failed Mavyret (Glecaprevir/Pibrentasvir) and Sovaldi (sofosbuvir) or Vosevi® (Sofosbuvir/Velpatasvir/Voxilaprevir); and
  5. Concurrent use of ribavirin (for members with compensated cirrhosis); and
  6. Approved length of therapy: 168 days (24 weeks)



DECOMPENSATED CIRRHOSIS (moderate to severe hepatic impairment; Child Turcotte Pugh B or C)

A. Treatment Naive

Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 4, 5, or 6; and
  3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
  4. One of the following:
    1. Concurrent use of ribavirin; or
    2. Member is unable to tolerate ribavirin; and
  5. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
  6. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details or intolerability must be provided; and
  7. Approved length of therapy:
    1. Without ribavirin: 168 days (24 weeks)*; or
    2. With ribavirin: 84 days (12 weeks)*


Velpatasvir/sofosbuvir (Epclusa®) is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, or 6; and
  3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
  4. One of the following:
    1. Concurrent use of ribavirin; or
    2. Member is unable to tolerate ribavirin; and
  5. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
  6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
  7. Approved length of therapy:
    1. With ribavirin: 168 days (24 weeks)*; or
    2. Without ribavirin: 168 days (24 weeks)*


B. Retreatment with Prior Sofosbuvir or NS5A inhibitor-base treatment

Ledipasvir/ sofosbuvir (Harvoni®) is approved when ALL of the following are met:

  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 4, 5, or 6; and
  3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
  4. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
  5. Concurrent use of ribavirin; and
  6. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details or intolerability must be provided; and
  7. Approved length of therapy: 168 days (24 weeks)*
Velpatasvir/sofosbuvir (Epclusa®) is approved when ALL of the following are met:
  1. Age 3 years or older; and
  2. Diagnosis of chronic HCV genotype 1, 2, 3, 4, 5, or 6; and
  3. Documentation of decompensated cirrhosis (defined as Child Turcotte Pugh class B or C) or hepatocellular carcinoma; and
  4. Prescribed by a hepatitis C expert (i.e., hepatologist, liver transplant surgeon) ; and
  5. Concurrent use of ribavirin; and
  6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only) details of intolerability must be provided; and
  7. Approved length of therapy: 168 days (24 weeks)*



RECURRENT HCV POST LIVER TRANSPLANT

Genotype 1

MavyretTM is approved when there is documentation of ALL of the following:

  1. Age 3 years or older; and 
  2. Diagnosis of HCV genotype 1; and
  3. Documentation of liver transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Approved length of therapy: 84 days (12 weeks)*


Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:

  1. Age 3 years or older; and
  2. Diagnosis of HCV genotype 1; and
  3. Documentation of liver transplant; and
  4. Used with ribavirin; and
  5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
  6. Approved length of therapy: 84 days (12 weeks)*​

Viekira Pak® is approved when ALL of the following are met:

  1. Age 18 years or older; and
  2. Diagnosis of HCV genotype 1; and
  3. Documentation of liver transplant; and
  4. Documentation of normal hepatic function; and
  5. Documentation of mild fibrosis; and
  6. Used with ribavirin; and
  7. Documentation of a dispensed prescription for and inability to tolerate glecaprevir/ pibrentasvir (Mavyret™) or brand Harvoni®, details of intolerability must be provided; and
  8. Approval length: 24 weeks


B. Genotype 2 or 3
MavyretTM is approved when ALL of the following are met:

  1. Age 3 years or older ; and
  2. Diagnosis of HCV genotype 2 or 3; and
  3. Documentation of liver transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Approved length of therapy: 84 days (12 weeks)*


Velpatasvir/ sofosbuvir (Epclusa®) is approved when ALL the following are met:

  1. Age 3 years or older ; and
  2. Diagnosis of HCV genotype 2 or 3; and
  3. Documentation of liver transplant; and
  4. Used with ribavirin; and
  5. Presence of cirrhosis; and
  6. Inadequate response or inability to tolerate brand Epclusa® (applies to velpatasvir/sofosbuvir only), details of intolerability must be provided; and
  7. Approved length of therapy: 84 days (12 weeks)*

C. Genotype 4, 5 or 6

Mavyret™ is approved when there is documentation of ALL of the following:

  1. Age 3 years or older; and
  2. Diagnosis of HCV genotype 4, 5, or 6; and
  3. Documentation of liver transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis) ; and
  5. Approved length of therapy: 84 days (12 weeks)*

Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:
  1. Age 3 years or older; and
  2. Diagnosis of HCV genotype 4, 5, or 6; and
  3. Documentation of liver transplant; and
  4. Used with ribavirin; and
  5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
  6. Approved length of therapy: 84 days (12 weeks)*



KIDNEY TRANSPLANT RECIPIENT

A.    Genotype 1 or 4

MavyretTM  is approved when there is documentation of ALL of the following:

  1. Age 3 years or older ; and
  2. Diagnosis of HCV genotype 1 or 4; and
  3. Documentation of kidney transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Approved length of therapy: 84 days (12 weeks)*  

Ledipasvir/ sofosbuvir (Harvoni®) is approved when there is documentation of ALL of the following:

  1. Age 3 years or older; and
  2. Diagnosis of HCV genotype 1 or 4; and
  3. Documentation of kidney transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Inadequate response or inability to tolerate brand Harvoni® (applies to ledipasvir/sofosbuvir only), details of intolerability must be provided; and
  6. Approved length of therapy: 84 days (12 weeks)*


B. Genotype 2,3,5, or 6


MavyretTM is approved when there is documentation of ALL of the following:

  1. Age 3 years or older; and
  2. Diagnosis of HCV genotype 2,3,5, or 6; and
  3. Documentation of kidney transplant; and
  4. Absence of decompensated cirrhosis (i.e., compensated cirrhosis or no cirrhosis); and
  5. Approved length of therapy: 84 days (12 weeks)*



*Approved length of therapy: if therapy was initiated prior to coverage with the plan, authorization will only be granted to allow completion of the specified therapy.  Authorizations will end 180 days after receipt of request.

Maximum doses per day apply

 

DrugMaximum dose per day (tablets)
velpatasvir/ sofosbuvir (Epclusa®)1
velpatasvir/ sofosbuvir (Epclusa®) pack 200-50mg2
velpatasvir/ sofosbuvir (Epclusa®) pack 150-37.5mg1
MavyretTM3
Mavyret™ pak 50-20mg5
Ledipasvir/sofosbuvir (Harvoni®)1

Sovaldi® 1
Viekira Pak®6
Zepatier®1
Vosevi®1


HCV Treatment Regimens that are not recommended and considered not medically necessary

  1. Sofosbuvir with ribavirin x 24 weeks (except in genotype 2 post liver transplant)
  2. Peg-interferon and ribavirin with or without sofosbuvir, simeprevir, telaprevir, or boceprevir)
  3. Monotherapy with peg-interferon, ribavirin, or a direct-acting antiviral
  4. Simeprevir, paritaprevir, or elbasvir/grazopevir based regimens in those decompensated cirrhosis

Epclusa® (velpatasvir/sofosbuvir), Sovaldi® (sofosbuvir), Viekira Pak® (ombitasvir/paritaprevir/ritonavir/dasabuvir), Harvoni® (ledipasvir/sofosbuvir),  Zepatier® (elbasvir/grazoprevir), Mavyret™ (glecaprevir and pivrentasvir) & Vosevi® (sofosbuvir/velpatasvir/voxilaprevir):
RISK OF HEPATITIS B REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV:
Hepatitis B virus (HBV) reactivation has been reported, in some cases resulting in fulminant hepatitis, hepatic failure, and death. 

 

 

American Association for the Study of Liver Disease, Infectious Diseases Society or America, International Antiviral Society-USA. Recommendations for testing, managing and treating Hepatitis C. Available from https://www.hcvguidelines.org/.  Accessed August 03, 2023

Epclusa® (velpatasvir/sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; May, 2022. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf. Accessed August 03, 2023

Harvoni® (ledipasvir/sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; March 2020. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf. Accessed August 03, 2023

Hepatitis C Information for Health Professionals. Centers for Disease Control and Prevention. July 2019. Available from: http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed August 03, 2023

Mavyret™ (glecaprevir/pibrentasvir) [package insert]. North Chicago, IL: AbbVie, Inc.; June 2021. Available from https://www.rxabbvie.com/pdf/mavyret_pi.pdf. Accessed August 03, 2023

Sovaldi® (sofosbuvir) [package insert]. Forest City, CA: Gilead Sciences, Inc; April 2021. Available from: https://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf?evo_source=SOVALDI. Accessed August 03, 2023

Viekira Pak® (ombitasvir/ paritaprevir/ ritonavir and dasabuvir) [package insert]. North Chicago, IL: AbbVie, Inc; Nov 2020. Available from: https://www.rxabbvie.com/pdf/viekirapak_pi.pdf. Accessed August 03, 2023

Vosevi™ (sofosbuvir/velpatasvir/voxilaprevir) [package insert]. Foster City, CA: Gilead Sciences, Inc.; November 2019. Available from: http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/vosevi/vosevi_pi.pdf. Accessed August 03, 2023

Zepatier® (elbasvir/ grazeprovir) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; May 2022. Available from: https://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf. Accessed August 03, 2023






286/8/20236/8/202410/1/2023 1:24 AMNo presence informationsrv_ppsgw_P
Off-label Drug Use Rx.01.33​
 


Brand NameGeneric Name
Epclusa®velpatasvir/ sofosbuvir
Harvoni®ledipasvir/ sofosbuvir
Viekira Pak®
ombitasvir/ paritaprevir/ ritonavir and dasabuvir
Sovaldi®
sofosbuvir
Zepatier®
elbasvir/grazoprevir
​MavyretTM

​glecaprevir/pibrentasvir 
​Vosevi®
​sofosbuvir/velpatasvir/voxilaprevir 
   
248
  
10/1/2023Rx.01.131CommercialOyenusi, Oluwadamilola

Lomitapide a synthetic lipid-lowering agent, directly binds and inhibits microsomal triglyceride transfer protein, which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B-containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and very low-density lipoprotein (VLDL). The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.

Lomitapide (Juxtapid®) is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).

Proprotein convertase subtilisin/ kexin type 9 (PCSK9) is a serine protease synthesized primarily by the liver and intestines.  PCSK9 promotes the degradation of low density lipoprotein (LDL) receptors, thus preventing them from being recycled back to the plasma membrane where they can bind more LDL. Inhibitors of PCSK9 increase recycling of LDL receptors which in turn increases the capacity to remove LDL cholesterol (LDL-C) from the blood. These agents are monoclonal antibodies administered subcutaneously.

Alirocumab (Praluent®) and evolocumab (Repatha®) are indicated:

  • in adults with established cardiovascular disease (CVD) to reduce the risk of myocardial infarction, stroke, and coronary revascularization ​
  • as an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C 
  • as an adjunct to other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C 

According to current guidelines, HMG-CoA reductase inhibitors (statins) are the mainstay of pharmacologic therapy for treating elevated LDL-C for both primary and secondary prevention of atherosclerotic cardiovascular disease.  Lifestyle modifications are a critical component of treating elevated LDL-C and should be used in conjunction with pharmacologic therapy.  

Clinical trials of PCSK9 inhibitors demonstrated reductions in LDL-C approximately 50-60%.  Reauthorization criteria will include a reduction from baseline of 25% or greater, which will assess adherence with the medication.

Bempedoic acid (Nexletol™) is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver.  ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway.  Bempedoic ​acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively.  ACSVL1 is expressed primarily in the liver.  Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors.

Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine.  The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.  Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.  This causes a reduction of hepatic cholesterol stores and an increase in LDL receptors, resulting in clearance of cholesterol from the blood.

Bempedoic acid (Nexletol™) and bempedoic acid/ezetimibe (Nexlizet™) is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.



 


The intent of this policy is to communicate the medical necessity criteria for lomitapide (Juxtapid®), alirocumab (Praluent®), evolocumab (Repatha®), bempedoic acid (Nexletol™), and bempedoic acid/ezetimibe (Nexlizet™) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Lomitapide (Juxtapid®) is approved when  ALL of the following are met:

  1. Diagnosis of Homozygous Familial Hypercholesterolemia; and
  2. Used as an adjunct to lipid lowering treatments and a low-fat diet with ONE of the following:
    1. Genetic confirmation of 2 mutant alleles at the LDL receptor, Apo B, PCSK9, or LDL receptor adaptor protein 1 (i.e. LDLRAP1 or ARH); or
    2. Untreated LDL-C > 500mg/dL or treated LDL cholesterol ≥ 300mg/dL with either of the following:
      1. Cutaneous or tendinous xanthoma prior to 10 years of age, or
      2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; AND
  3. ONE of the following:
    1. Inadequate response to one of the following medications in combination with ezetimibe:
      1. Simvastatin (daily doses ≥ 40mg); or
      2. Atorvastatin (daily doses ≥ 20mg); or
      3. Rosuvastatin (daily doses ≥ 10mg); or
    2. Member has experience ONE of the following:
      1. Rhabdomyolysis or muscle symptoms with creatine kinase (CK) elevations > 10 times upper limit of normal (ULN) on any statin; or
      2. Myalgia (muscle symptoms without CK elevations) or myositis (muscle symptoms with CK elevations < 10 times ULN) with TWO statins; AND
  4. Inadequate response or inability to tolerate evolocumab (Repatha®) or alirocumab (Praluent®); and
  5. Prescribed by or in consultation with one of the following:
    1. Cardiologist; or
    2. Endocrinologist; or
    3. Lipid specialist
​Initial authorization duration: 6 months

Reauthorization criteria: Lomitapide (Juxtapid®) is re-approved when there is a reduction in LDL level of at least 25% since initiation of therapy.

Reauthorization duration: 12 months

 

INITIAL CRITERIA: Alirocumab (Praluent®) is approved when ALL of the following are met:

  1. Diagnosis of ONE of the following:
    1. Hyperlipidemia; or
    2. Homozygous familial hypercholesterolemia and one of the following:
      1. Diagnosis confirmed by genetic test; or
      2. Untreated LDL-C >500mg/dL with either of the following:
        1. Cutaneous or tendinous xanthoma prior to 10 years of age; or 
        2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; or
    3. Atherosclerotic cardiovascular disease as diagnosed by either stress test, angiography, atherosclerotic event (e.g., MI, angina, stroke, claudication, carotid stenosis) or arterial intervention for atherosclerotic diseases (e.g., coronary, peripheral, carotid); and
  2. ONE of the following:
    1. LDL-C 70 mg/dL or greater after a minimum 8-week trial of at least moderate-intensity statin therapy; or
    2. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member has rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN); or
        3. Hepatotoxicity from statin use (increase AST/ALT exceeding 3 times ULN); OR
      3. Liver disease documented by Child Pugh A or worse or AST/ALT exceeding 3 times ULN for at least 6 weeks; and
  3. Inadequate response or inability to tolerate evolocumab (Repatha®)
Initial authorization duration: 6 months.


REAUTHORIZATION CRITERIA Alirocumab (Praluent®) is re-approved when there is a sustained reduction in LDL-C of at least 25% since initiation of therapy.

Reauthorization duration: 12 months

 

INITIAL CRITERIA: Evolocumab (Repatha®) is approved when ALL of the following are met:

  1. Diagnosis of ONE of the following:
    1. Hyperlipidemia; or
    2. Homozygous familial hypercholesterolemia and one of the following:
      1. Diagnosis confirmed by genetic test; or
      2. Untreated LDL-C >500mg/dL with either of the following:
        1. Cutaneous or tendinous xanthoma prior to 10 years of age; or
        2. Elevated LDL cholesterol prior to lipid-lowering therapy consistent with HeFH in both parents; or
    3. Atherosclerotic cardiovascular disease as diagnosed by either stress test, angiography, atherosclerotic event (e.g., MI, angina, stroke, claudication, carotid stenosis) or arterial intervention for atherosclerotic disease (e.g., coronary, peripheral, carotid); AND
  2. ONE of the following:
    1. LDL-C 70 mg/dL or greater after a minimum 8-week trial of at least moderate-intensity statin therapy; or
    2. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member had rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN; or
        3. Hepatotoxicity from statin use (increased AST/ALT exceeding 3 times ULN); OR
      3. Liver disease documented by Child Pugh A or worse OR AST/ALT exceeding 3 times ULN for at least 6 weeks​


Initial Authorization duration: 6 months

Reauthorization criteria:  Evolocumab (Repatha®) is re-approved when there is a sustained reduction in LDL-C of at least 25% since initiation of therapy

Reauthorization duration: 12 months

 

INITIAL CRITERIA: Bempedoic acid (Nexletol™), bempedoic acid/ezetimibe (Nexlizet™) is approved when ALL of the following are met:

  1. One of the following diagnoses:
    1. Heterozygous familial hypercholesterolemia (HeFH); or
    2. Atherosclerotic cardiovascular disease (ASCVD) as diagnosed by either stress test, angiography, atherosclerotic event (e.g., MI, angina, stroke, claudication, carotid stenosis) or arterial intervention for atherosclerotic diseases (e.g., coronary, peripheral, carotid); and
  2. One of the following:
    1. LDL-C 70 mg/dL or greater after at least 8 consecutive weeks of statin therapy and member will continue to receive statin therapy at maximally tolerated dose; or
    2. Inability to tolerate statin therapy as documented by ONE of the following:
      1. Member has rhabdomyolysis or symptoms with creatine kinase (CK) exceeding 10 times the upper limit of normal (ULN) on any statin; or
      2. ONE of the following with TWO statins:
        1. Myalgia (no CK elevation); or
        2. Myositis (CK less than 10 times ULN); or
        3. Hepatotoxicity from statin use (increase AST/ALT exceeding 3 times ULN); or
      3. Liver disease documented by Child Pugh A or worse or AST/ALT exceeding 3 times ULN for at least 6 weeks; and
  3. ONE of the following:
    1. Member has been receiving at least 8 consecutive weeks of ezetimibe (Zetia®) therapy as adjunct to maximally tolerated statin therapy; or
    2. Member has contraindication or intolerance to ezetimibe (Zetia®)

      Initial Authorization duration: 6 months

REAUTHORIZATION CRITERIA: Bempedoic acid (Nexletol™), Bempedoic acid/ezetimibe (Nexlizet™) is approved when ALL of the following are met:

  1. Documentation of sustained reduction of LDL-C by at least 17% from the time therapy began or sustained below 70mg/dL; and
  2. ONE of the following:
    1. Member continues to receive other lipid-lowering therapy (e.g., statins, ezetimibe) at the maximally tolerated dose; or
    2. Member has inability to tolerate other lipid-lowering therapy (e.g., statins, ezetimibe)

Reauthorization duration: 12 months

 

Risk of hepatotoxicity:

Lomitapide (Juxtapid®) can cause elevations in transaminases. In clinical trials, of patients treated with lomitapide had at least 1 elevation in ALT or AST at least 3 times the upper limit of normal (ULN) or higher. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), alkaline phosphatase or partial thromboplastin time (PTT).

Lomitapide also increase hepatic fat (hepatic steatosis), with or without concomitant increase in transaminases. In the trials of patients with heterozygous familial hypercholesterolemia and hyperlipidemia, the median absolute increase in hepatic fat was 6% (lomitapide) after 26 weeks of treatment from 0% at baseline, measured by magnetic resonance imaging (MRI) and 1% at baseline, measured by magnetic resonance spectroscopy (MRS) respectively. Hepatic steatosis is a risk factor for advanced liver disease, including steatohepatitis and cirrhosis.

 

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of lomitapide if the ALT or AST are at least 3 times the ULN. Discontinue lomitapide for clinically significant liver toxicity.

 

Because of the risk of hepatotoxicity, lomitapide are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).​

Farnier M, Bruckert E. Severe familial hypercholesterolemia: Current and future management. Arch Cardiovasc Dis. 2012 Dec; 105(12):656-65. Accessed June 23, 2023.


Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis, and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidology. 2011;5:S1-S8. Accessed June 23, 2023.


Grundy SM, Cleeman JI, Merz NB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004; 110:227-39. Accessed June 23, 2023.


Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for the patient-centered management of dyslipidemia: Part 1- full report. J Clin Lipidology. 2015;9:129-69. Accessed June 23, 2023.


Juxtapid® (lomitapide) [prescribing information.] Cambridge, MA. Aegerion Pharmaceuticals. December 2019. Available at: http://juxtapidpro.com/prescribing-information. Accessed June 23, 2023.


Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012 Aug; 223(2):262-8. Accessed June 23, 2023.


Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines. Circulation. 2013. Available from: http://circ.ahajournals.org/cgi/content/short/129/25_suppl_2/S1?rss=1&ssource=mfr. Accessed June 23, 2023.


Visser ME, Witztum JL, Stroes ES, et al. Antisense oligonucleotides for the treatment of dyslipidaemia. Eur Heart J. 2012 Jun; 33(12):1451-8. doi: 10.1093/eurheartj/ehs084. Epub 2012 May 24.


Lambert G, Sjouke B, Choque B, Kastelein JJP, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012; 53(12): 2515-24. DOI: 10.1194/jlr.R026658. Accessed June 23, 2023.


Farnier M. PCSK9: From discovery to therapeutic applications. Arch Cardiovascular Dis. 2014; 107: 58-66. DOI: 10.1016/j.acvd.2013.10.007. Accessed June 23, 2023.


Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis, and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidology. 2011;5:S1-S8. Accessed June 23, 2023


Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for the patient-centered management of dyslipidemia: Part 1- full report. J Clin Lipidology. 2015;9:129-69. Accessed June 23, 2023.


Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly Jr DD, DePalma SM, Minissian, MB, Orringer CE, Smith Jr SC, 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Exper Decision Consensus Pathways. Journal of the American College of Cardiology (2017), doi: 10.1016/j.jacc.2017.07.745. Accessed June 23, 2023.


Nexletol™ (bempedoic acid) [prescribing information]. Ann Arbor, MI: Esperion Therapeutics, Inc.; February 2020. Available from: https://pi.esperion.com/nexletol/nexletol-pi.pdf. Accessed June 23, 2023.


Nexlizet™ (bempedoic acid and ezetimibe) [prescribing information]. Ann Arbor, MI: Esperion Therapeutics, Inc.; February 2020. Available from: https://pi.esperion.com/nexlizet/nexlizet-pi.pdf. Accessed June 23, 2023.


Praluent® (alirocumab) [package insert]. Bridgewater, NJ. Sanofi-Aventis US LLC. April 2021.  Available from: http://products.sanofi.us/praluent/praluent.pdf. Accessed June 23, 2023.


Repatha® (evolocumab) [package insert]. Thousand Oaks, CA. Amgen Inc. February 2021. Available from: https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/repatha/repatha_pi_hcp_english.pdf. Accessed June 23, 2023.


Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines. Circulation. 2013. https://doi.org/10.1161/01.cir.0000437738.63853.7a. Accessed June 23, 2023.


Varghese MJ. Familial hypercholesterolemia: a review. Ann Pediatr Cardiol. 2014;7:107-17. Accessed June 23, 2023.


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Off-Label Use Rx.01.33


Brand nameGeneric name
Juxtapid®Lomitapide
Praluent®alirocumab
Repatha®evolocumab
Nexletol™Bempedoic acid
Nexlizet™Bempedoic acid/ezetimibe

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10/1/2023Rx.01.134CommercialOyenusi, Oluwadamilola

The Food and Drug Administration (FDA) defines pharmacy compounding as the practice in which pharmacists combine, mix, or alter ingredients to create unique medications that meet the specific needs of an individual patient. Generally, drugs are compounded for patients that have allergic reactions to inactive ingredients in FDA approved products or for those patients who require a different formulation of a medication that is not commercially available.  

Compounding pharmacies are regulated by State Boards of Pharmacy and the FDA (if they are outsourcing facilities). For non-outsourcing facilities, drugs can be compounded only if certain conditions are met, such as, valid prescription requirement for an identified individual patient; or in limited quantities before obtaining the actual prescription by the pharmacy. Moreover, FDA restricts the production of essential copies of approved and unapproved non-prescription drugs.

A compounded product is not considered medically necessary when it replicates a commercially available product (unless the commercially available product is temporarily unavailable), contains a drug product or component that has been removed from the market because it is unsafe or not effective or contains a drug product or component that is excluded from the member's benefit. 


 

The intent of this policy is to communicate the medical necessity criteria for compounded products, consistent with Pharmacy Compounding of Human Drug Products Under Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, where at least one ingredient is a prescription drug, as provided under the member's prescription drug benefit.

This policy will also be used to review requests for ingredients which are not considered standard coverage under the prescription drug benefit that are used in compounded products.  This includes requests for injectable medications that are used as part of a compound for a route of administration other than injectable. 


 

A compounded product, including a commercially available compounding kit, is considered medically necessary when ALL of the following are met:

  1. The active prescription ingredient(s) of the compound is FDA approved or supported by accepted compendium as stated in the Off-Label Use policy for the indication and route of administration; AND

  2. The product as compounded is not commercially available. This may include a current short supply* of the commercially available product or the member has a medical need for a dosage form, strength or formulation other than what can be accomplished with a commercially available product; AND

  3. Member had an inadequate response or inability to tolerate all commercially available therapeutic alternatives to treat the condition for which the compound has been requested; AND

  4. The compound does not contain any product(s) that were withdrawn or removed from the market due to safety reasons; AND

  5. The compound is not used for, nor does it contain, a product that is indicated for an excluded benefit (e.g., cosmetic)

Additionally, authorization may be placed to allow access to the prescription benefit for products that are not considered standard coverage (e.g. drugs administered intravenously) when all the following are met:

  1. All of the above criteria are for medically necessary are met for the compounded product; AND

  2. The product is being used in a compound that will be administered through a route that is considered standard coverage for the prescription benefit (e.g., oral, topical, inhalation, etc.). Bladder installation may be considered if the above criteria are met.

Authorization length for short supply of the commercially available product will be six months.All other authorizations: 2 years

http://www.accessdata.fda.gov/scripts/drugshortages/default.cfm

* http://www.ashp.org/Drug-Shortages/Current-Shortages


 


See labeling for specific ingredients used in a compound.


American Pharmacists Association. Frequently Asked Questions About Pharmaceutical Compounding. Available from: http://www.pharmacist.com/frequently-asked-questions-about-pharmaceutical-compounding. Accessed June 22, 2023.

ASHP Guidelines on Outsourcing Sterile Compounding Services. January 2014. Available from:  http://www.ajhp.org/content/71/2/145?sso-checked=true.  June 22, 2023.

International Academy of Compounding Pharmacist. Available from: http://www.iacprx.org/. Accessed June 22, 2023.

Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug and Cosmetic Act. December 2016. Available from:  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacy-compounding-human-drug-products-under-section-503a-federal-food-drug-and-cosmetic-act . Accessed  June 22, 2023.

Pharmacy Compounding of Human Drug Products Under Section 503B of the Federal Food, Drug and Cosmetic Act. January 2018. Available from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM510153.pdf. Accessed  June 22, 2023.

Report: Limited FDA Survey of Compounded Drug Products. June 2018. Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm155725.htm, Accessed  June 22, 2023.

USP Compounding Standards and Resources.  Available from: http://www.usp.org/usp-healthcare-professionals/compounding?gclid=CJfWt97qmsECFedzMgodCzgA_w. Accessed June 22, 2023.


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Off Label Use Policy (Rx.01.33)

Note: All routes of administration listed may not be covered under the pharmacy benefit, e.g. intravenous, intramuscular.

 

P​roduct

Description

Compound claims greater than $75

compound where the submitted claim cost is greater than or equal to $75

Various

Compounding kit

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10/1/2023Rx.01.149CommercialOyenusi, Oluwadamilola
Hemophilia is a bleeding disorder caused by clotting factor deficiencies.  Hemophilia is a rare X-linked, congenitally acquired disease that leads to a deficiency in coagulation factor, VIII (hemophilia A) or IX (hemophilia B).  Hemophilia A or B occurs in approximately 1 out of  10,000 births.  Hemophilia A is more common than hemophilia B, representing approximately 80-85% of hemophilia cases. The disorder is further characterized by the percentage of serum clotting factor activity as compared to the normal range:


  • Severe hemophilia: clotting factor levels are less than 1% of normal
  • Moderate hemophilia: clotting factor levels are 1-5% of normal
  • Mild hemophilia: clotting factors are 5-40% of normal

Treatment of hemophilia generally involves an infusion of the deficient factors to allow for more normalized clotting response and decreased incidence of uncontrolled bleeding events.

Treatment regimens are individualized based on disease severity and may include prophylactic infusions of clotting factors, on demand infusions of clotting factors, or a combination of both.  Perioperative infusions are also part of the treatment regimen.

While Hemophilia A and hemophilia B are the most common types of hemophilia, 1 in every 500,000 to 2 million people have coagulation disorders caused by deficiencies in clotting factors other than factor VIII or IX. The products listed below include those with indications to treat these rare forms of coagulation disorders.

 
DrugFactorHemophilia AHemophilia BAcquired hemophiliaVon Willebrand diseaseCongenital fibrinogen deficiencyHereditary factor X deficiencyCongenital factor XIII deficiencyControl of bleeding episodes, on demandPerioperative managementRoutine prophylaxis
Advate®Recombinant factor VIIIXXXX
Adynovate®Recombinant factor VIII, PEGylatedXXXX
Afstyla®Recombinant Factor VIIIXXXX
Alphanate®Factor VIII/ von Willebrand factor complex, humanXX (in certain circumstances)XXX
Alphanine SD®Factor IX, humanXXXX
Alprolix®Recombinant factor IX, Fc fusion proteinXXXX
Altuviiio™

Recombinant Fc-VWF-XTEN fusion

protein-ehtl

X      XXX
Benefix®Factor IX, recombinantXXXX
Coagadex®Factor X, humanXXX
Corifact®Factor XIII concentrate, humanXXX
Eloctate®Recombinant factor VIII, Fc fusion proteinXXXX
Esperoct®Recombinant, glycopegylated-exeiX      XXX
Feiba [NF] ®Anti-inhibitor coagulant complexX (with inhibitors)X (with inhibitors)XXX
Hemlibra®Factor IXa/ factor X, directed antibodyX        X
Hemofil M®Factor VIII, humanX XXX
Humate P®Factor VIII/ von Willebrand factor complex, humanXX (in certain circumstances)XXX
Idelvion®Factor IX, recombinant albumin fusion proteinXXXX
Ixinity®Factor IX, recombinantXXXX
Jivi®Recombinant, PEGylated, Factor VIIIX      XXX
Koate DVI®Factor VIII, humanXXXX
Kogenate FS®Recombinant factor VIIIXXXX
Kovaltry®Recombinant factor VIIIXXXX
Mononine®Factor IX, humanXXXX
Novoeight®Recombinant factor VIIIXXXX
Novoseven RT®Recombinant factor VIIaXXXXX
Nuwiq®Recombinant factor VIIIXXXX
Obizur®Recombinant factor VIII, porcine sequenceXX
Profilnine®Factor IX, humanXXX
Rebinyn®Recombinant Factor IX X     XX 
Recombinate®Recombinant factor VIIIXXXX
Riastap®Fibrinogen concentrate, humanXX
Rixubis®Factor IX, recombinantXXXX
Sevenfact®Factor VIIa, recombinantXX        
Tretten®Factor XIII A subunit, recombinantX (A subunit)X
Vonvendi®Von Willebrand Factor RecombinantXX
Wilate® von Willebrand/ factor VIII complex, humanXX
Xyntha® [Solufuse]Recombinant factor VIIIXXXX

The intent of this policy is to communicate the medical necessity criteria for Advate®, Adynovate®, Afstyla®, Alphanate®, Alphanine SD®, Alprolix®, Altuviiio™, Benefix®, Coagadex®, Corifact®, Eloctate®, Esperoct®, Feiba NF®, Hemlibra®, Hemofil M®, Humate P®, Idelvion®, Ixinity®, Jivi®, Koate DVI®, Kogenate FS®, Kovaltry®, Mononine®, Novoeight®, Novoseven RT®, Nuwiq®, Obizur®, Profilnine®, Rebinyn®, Recombinate®, Riastap®, Rixubis®, Sevenfact®, Tretten®, Vonvendi®, Wilate®, and Xyntha®/Xyntha® SolofuseTM as provided under the member's prescription drug benefit.

Advate®, Adynovate®, Afstyla®, Alphanate®, Alphanine SD®, Alprolix®, Altuviiio™, Bebulin®, Benefix®, Coagadex®, Corifact®, Eloctate®, Esperoct®, Feiba NF®, Helixate FS®, Hemlibra®, Hemofil M®, Humate P®, Idelvion®, Ixinity®, Jivi®, Koate DVI®, Kogenate FS®, Kovaltry®, Monoclate P®, Mononine®, Novoeight®, Novoseven RT®,Nuwiq®, Obizur®, Profilnine®, Rebinyn®, Recombinate®, Riastap®, Rixubis®, Sevenfact®, Tretten®, Vonvendi®, Wilate®, Xyntha®/Xyntha® Solofuse are approved when there is a diagnosis of an FDA approved indication​

Approval duration: 2 years 




Feiba® NF
Thrombotic/Thromboembolic events: Thrombotic and thromboembolic events have been reported during postmarketing surveillance following infusion of anti-inhibitor coagulant complex, particularly following the administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving anti-inhibitor coagulant complex for signs and symptoms of thromboembolic events.
 

Hemlibra®
Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur.
 
Novoseven®, Sevenfact®
Serious arterial and venous thrombotic events following administration of Novoseven and Sevenfact RT have been reported.  Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive Novoseven and Sevenfact RT.  Monitor patients for signs and symptoms of activation of the coagulation system and for thrombosis.

Advate® (antihemophilic factor, human recombinant) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation; March 2023.  Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=80fa03d2-cd4c-4155-9b57-1396c4fa42da&type=display#section-9. Accessed June 23, 2023.

Adynovate® (antihemophilic factor, recombinant, PEGylated) [package insert]. Westlake Village, CA. Baxalta US Inc. March 2023.  Available from: https://www.shirecontent.com/PI/PDFs/ADYNOVATE_USA_ENG.pdf. Accessed June 23, 2023.

Afstyla® (antihemophilic factor, recombinant, single chain) [package insert]. Kankakee, IL. CSL Berhing, LLC. April 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=51f19873-a63f-4229-9477-5da4ecf31cde&type=display. Accessed June 23, 2023.

Alphanate® (antihemophilic factor/ von willebrand factor complex, human) [package insert]. Los Angeles, CA. Grifols Biologicals Inc. March 2021.  Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5a7aea94-654c-4113-9014-c3137de0a931&type=display. Accessed June 23, 2023.

Alphanine SD® (coagulation factor IX, human) [package insert]. Los Angeles, CA. Grifols Biologicals Inc. March 2021.  Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3e99052d-4442-4283-8915-c9a796c77008&type=display. Accessed June 23, 2023.

Alprolix® (coagulation factor IX, recombinant, Fc fusion protein) [package insert]. Cambridge, MA. Biogen Idec Inc. May 2023. Available from: http://products.sanofi.us/Alprolix/alprolix.html. Accessed June 23, 2023.

Altuviiio™ (antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl) [package insert]. Waltham, MA. Bioverativ Therapeutics Inc. March 2023. Available from: https://products.sanofi.us/altuviiio/altuviiio.pdf. Accessed June 23, 2023.

BeneFIX® (coagulation factor IX, recombinant) [package insert]. Philadelphia, PA. Wyeth Pharmaceuticals Inc. June 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=85faa5bc-cee5-4ef1-8d80-bdbcb7eba1e4&type=display. Accessed June 23, 2023.

Bolton-Maggs PHB. Rare coagulation disorders. Available from: http://www1.wfh.org/publication/files/pdf-1188.pdf. Accessed June 23, 2023.

Coagadex® (coagulation factor X, human) [package insert]. Durham, NC. Bio Products Laboratory USA, Inc. September 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ad20e6ff-98bc-47e6-aa00-7fb441edd2b0&type=display. Accessed June 23, 2023.

Corifact® (coagulation factor XIII, human) [package insert]. Kankakee, IL. CSL Behring LLC. December 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=96f1b658-01b0-43a7-9aba-693271389a78&type=display. Accessed June 23, 2023.

Eloctate® (antihemophilic factor, recombinant, Fc fusion protein) [package insert]. Cambridge, MA. December 2020. Biogen, Inc. Available from: http://products.sanofi.us/Eloctate/Eloctate.pdf. Accessed June 23, 2023.

Esperoct® (antihemophilic factor, recombinant, glycopegylated-exei) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc.; October 2019. Available from: https://www.novo-pi.com/esperoct.pdf. Accessed June 23, 2023.

Feiba® (antiinhibitor coagulant complex) [package insert].  Westlake Village, CA. Baxter Healthcare Corporation. February 2020. Available from: http://www.baxalta.com/assets/documents/feiba_us_pi.pdf. Accessed June 23, 2023.

Feiba NF® (antiinhibitor coagulant complex) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation. February 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=752604e5-4ea2-44f4-83ed-1569373f6412&type=display. Accessed June 23, 2023.

Hemlibra® (antihemophilic factor, humanized) [package insert]. South San Francisco, CA. Genentech, Inc. June 2020. Available from:  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2483adba-fab6-4d1b-96c5-c195577ed071. Accessed June 23, 2023.

Hemofil M® (antihemophilic factor, human) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b8953ff7-3bba-4a0b-a486-f26fb81f05d9&type=display. Accessed June 23, 2023.

Humate-P® (antihemophilic factor/ von Willebrand factor complex, human) Kankakee, IL. CSL Behring LLC. June 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c5f4b63b-8d8b-45b3-b530-2f1c32a1b852&type=display. Accessed June 23, 2023.

Idelvion® (coagulation factor IX, recombinant, albumin fusion protein) [package insert]. Kankakee, IL. CSL Behring. July 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f74301bf-95e2-44ab-a8b6-98aa07b04683&type=display. Accessed June 23, 2023..

Ixinity® (coagulation factor IX, recombinant) [package insert]. Baltimore, MD. Cangene Corporation. September 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1cae46d1-f463-488a-9e8b-3431ef1de1e4&type=display. Accessed June 23, 2023.

Jivi® [antihemophilic factor (recombinant), PEGylated-aucl] [prescribing information]. Whippany, NJ. Bayer Healthcare LLC. August 2018. Available from: https://labeling.bayerhealthcare.com/html/products/pi/Jivi_PI.pdf. Accessed June 23, 2023.

Koate-DVI® (antihemophilic factor, human) [package insert]. Reasearch Triangle Park. NC. Grifols Therapeutics, Inc. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2f77d685-e382-b2e7-2414-0d3a3448688a&type=display. Accessed June 23, 2023.

Kogenate FS® (antihemophilic factor, recombinant) [package insert] Whippany, NJ. Bayer HealthCare LLC. December 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=01c6292d-b670-415b-9d8e-7df92c0adc0f&type=display, Accessed June 23, 2023.

Kovaltry® (antihemophilic factor recombinant) [package insert]. Whippany, NJ. Bayer HealthCare LLC. January 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=89ba5048-469c-4f08-a173-81b0c6f3004d&type=display. Accessed June 23, 2023.

Mononine® (coagulation factor IX, human) [package insert].   Kankakee, IL. CSL Behring LLC. February 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=16f35cdb-7a3b-481b-a25b-0a065aea2c9b&type=display. Accessed June 23, 2023.

Novoeight® (antihemophilic factor, recombinant) [package insert]. Plainsboro, NJ. Novo Nordisk, Inc, July 2020. Available from: https://www.novo-pi.com/novoeight.pdf. Accessed June 23, 2023.

Novoseven RT® (coagulation factor VIIa, recombinant) [package insert]. Plainsboro, NJ. Novo Nordisk, Inc, July 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ea65c32f-8518-4383-b621-17056c0eebc0&type=display. Accessed June 23, 2023.

Nuwiq® (antihemophilic factor, recombinant) [package insert]. Hoboken, NJ. Octapharma USA, Inc. September 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d6cb51f8-3acd-412c-93ec-41a8017dff3e&type=display. Accessed June 23, 2023.

Obizur® (antihemophilic factor, recombinant, porcine sequence) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation. July 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a69ccbb3-7648-4978-8c6d-7ca6b95a9b01&type=display. Accessed June 23, 2023.

Profilnine SD® (factor IX complex) [package insert]. Los Angeles, CA. Grisfols Biologicals Inc. June 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=79821042-86a5-4a64-b621-76de0a0bbab2&type=display. Accessed June 23, 2023.

Rebinyn® (factor IX, recombinant) [package insert[. Plainsboro, NJ. Novo Nordisk Inc. June 2020.  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0ea37235-35fd-410d-b8c4-40ba15fe1294  Available from: Accessed June 23, 2023.

Recombinate® (antihemophilic factor, recombinant) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation. June 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2a569ec5-08d7-44ab-b649-384a496e173c&type=display. Accessed June 23, 2023.

Riastap® (fibrinogen injection) [package insert]. Kankakee, IL. CSL Behring LLC. July 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=903dc8d0-39da-462c-9dac-004e0c7a26cc&type=display. Accessed June 23, 2023.

Rixubis® (coagulation factor IX, recombinant) [package insert]. Westlake Village, CA. Baxter Healthcare Corporation. June 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f5070a92-96b8-476a-a2dc-18b22d95e5e0&type=display. Accessed June 23, 2023.

Sevenfact® (coagulation factor VIIa (recombinant)-jncw]) [package insert]. Louisville, KY. HEMA Biologics. April 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b23ad666-8ce0-4e0b-9eff-c6983ac5f7e6. Accessed June 23, 2023.

Srivastava A, et al. Guidelines for the management of hemophilia. Available form: https://www1.wfh.org/publication/files/pdf-1472.pdf. Accessed June 23, 2023.

Tretten® (coagulation factor XIII a-subunit, recombinant) [package insert]. Plainsboro, NJ. Novo Nordisk, Inc, June 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8664978e-1814-4930-aca5-97a24455f6df&type=display. Accessed June 23, 2023.

Vonvendi® (von Willebrand factor, recombinant) [package insert]. Westlake Village, CA. Baxalta US, Inc. February 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=53b6d198-6175-4a26-8606-dc0d2a0f12d6&type=display. Accessed June 23, 2023.

Wilate® (Factor VII/VWF) [package insert]. Hoboken, NJ. Octapharma USA, Inc. September 2019. Available from: https://www.wilateusa.com/wp-content/uploads/2019/10/20190923_pil_18x_USA_26.pdf. Accessed June 23, 2023.

Xyntha® (antihemophilic factor, recombinant) [package insert]. Philadelphia, PA. Wyeth Pharmaceuticals Inc. August 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=52e97c7f-8240-4cd6-afd2-c452ab2f6e32&type=display. Accessed June 23, 2023.​




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Off-Label Use Rx.01.33
 

Drug Names

Advate®

Adynovate®

Afstyla®

Alphanate®

Alphanine SD®

Alprolix®

Altuviiio™

BeneFIX®

Coagadex®

Corifact®

Eloctate®

Esperoct®

Feiba NF®

Hemlibra®

Hemofil M®

Humate-P®

Idelvion®

Ixinity®

Jivi®

Koate-DVI®

Kogenate FS®

Kovaltry®

Mononine®

Novoeight®

Novoseven RT®

Nuwiq®

Obizur®

Profilnine SD®

Rebinyn®

Recombinate®

Riastap®

Rixubis®

Sevenfact®

Tretten®

Vonvendi®

Wilate®

Xyntha®


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10/1/2023Rx.01.166CommercialOyenusi, Oluwadamilola

Droxidopa (Northera®) is indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy.  Effectiveness beyond two weeks of treatment has not been demonstrated. The continued effectiveness of droxidopa should be assessed periodically.

The exact mechanism of action of droxidopa in the treatment of neurogenic orthostatic hypotension is unknown.  Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which is extensively distributed throughout the body. Droxidopa is believed to exert its pharmacological effects through norepinephrine and not through the parent molecule or other metabolites.  Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction. Droxidopa in humans induces small and transient rises in plasma norepinephrine. Droxidopa is also known as L-dihydroxyphenylserine, or L-DOPS.​


 

The intent of this policy is to communicate the medical necessity criteria for droxidopa (Northera®) as provided under the member’s prescription drug benefit.

INITIAL CRITERIA: Droxidopa (Northera®) is approved when ALL of the following are met:

  1. Diagnosis of symptomatic neurogenic orthostatic hypotension; and
  2. Prescribed by, or in consultation with, ONE of the following:
    1. Cardiologist; or
    2. Neurologist; or
    3. Nephrologist; and
  3. Member is 18 years of age or older; and
  4. Attempt has been made to manage neurogenic orthostatic hypotension through at least one non-pharmacologic intervention (e.g. use of compression stockings/abdominal binder, increasing salt/fluid intake, participation in regular exercise, discontinue or reduce hypotensive or antihypertensive medications); and 
  5. Inadequate response or inability to tolerate midodrine or fludrocortisone; and
  6. For the Brand Northera only, inadequate response or inability to tolerate generic droxidopa

Initial authorization duration: 1 month
 

REAUTHORIZATION CRITERIA: Droxidopa (Northera®) is re-approved when ALL of the following are met:

  1. Diagnosis of symptomatic neurogenic orthostatic hypotension; and
  2. For the Brand Northera only, inadequate response or inability to tolerate generic droxidopa
  3. Prescribed by, or in consultation with, ONE of the following:
    1. Cardiologist; or
    2. Neurologist; or
    3. Nephrologist; and
  4. Documentation of positive clinical response to therapy (e.g. improvement in symptoms such as orthostatic dizziness, lightheadedness, etc.)

Reauthorization duration: 12 months


Supine hypertension: Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Elevating the head of the bed lessens the risk of supine hypertension, and blood pressure should be measured in this position. If supine hypertension cannot be managed by elevation of the head of the bed, reduce or discontinue Northera.​

Northera (droxidopa) [package insert]. Deerfield IL. Lundbeck Pharmaceutical LLC. July 2019. Available at:https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2179f02c-48d7-48eb-8007-5ae43d8d16bc&type=display . Accessed June 22, 2023.

Droxidopa. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed June 22, 2023. 

Freeman R.  Current pharmacologic treatment for orthostatic hypotension. Clinical Autonomic Research 2008; 18(1):14-18. Accessed June 22, 2023.

Freeman R. Neurogenic orthostatic hypotension. New England Journal of Medicine 2008; 358:615-624. Accessed June 22, 2023.



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Off-Label Use Rx.01.33


Generic

Brand

Droxidopa

Northera®

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10/1/2023Rx.01.174CommercialOyenusi, Oluwadamilola

Heart failure affects approximately 5.1 million Americans.  While survival after a diagnosis of heart failure has improved, it is still about 50% at 5 years after diagnosis.  In patients with symptomatic heart failure and left ventricular ejection fraction (LVEF) < 40%, current guidelines recommend angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), beta blockers, diuretics and aldosterone antagonists as standard of care.  With the exception of diuretics, these classes of medications decrease mortality from heart failure with reduced EF.  Diuretics provide symptomatic relief, however the effects of diuretics on morbidity and mortality are not known.

 
Ivabradine reduces spontaneous pacemaker activity at the cardiac sinus node by blocking the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel to selectively inhibit If-current, thus reducing the heart rate. Ventricular repolarization and myocardial contractility are not affected.  Increased heart rate is an ineffective compensatory mechanism and is recognized as an independent risk factor in heart failure. 
 
Corlanor® (ivabridine) is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure  with reduced left ventricular ejection fraction and for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients ages 6 months and older.
 
Ivabradine is also indicated for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients who are in sinus rhythm with an elevated heart rate.

 
Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.

 

Verquvo® (vericiguat) is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

The intent of this policy is to communicate the medical necessity criteria for Corlanor® (ivabradine) and Verquvo™ (vericiguat) as provided under the member's prescription drug benefit.

Chronic heart failure

INITAL CRITERIA: Corlanor® (ivabradine) is approved when ALL of the following are met:

  1. Diagnosis of stable, symptomatic chronic heart failure; and
  2. Member is 18 years of age or older; and
  3. Left ventricular ejection fraction (LVEF) ≤ 35%; and
  4. Sinus rhythm with resting heart rate ≥ 70 beats per minute; and
  5. Member is clinically stable for at least 4 weeks on an optimized and stable clinical regimen which includes:
    1. Maximally tolerated doses of beta blockers (i.e., bisoprolol, carvedilol, metoprolol succinate ER) or inability to tolerate these beta blockers; and
    2. ACE inhibitors or ARBs or inability to tolerate ACE inhibitor or ARB; and
  6. Prescribed by or in consultation with a cardiologist

INITIAL CRITERIA: Vericiguat (Verquvo™) is approved when ALL of the following are met:

  1. Diagnosis of chronic heart failure; and
  2. Member is age 18 or older; and
  3. Member has an ejection fraction of less than 45 percent; and
  4. Member has New York Heart Association (NYHA) Class II, III or IV symptoms; and
  5. One of the following:
    1. Member was hospitalized for heart failure within the last 6 months; or
    2. Member used outpatient intravenous diuretics (e.g., bumetanide, furosemide) for heart failure within the last 3 months; and
  6. Inadequate response or inability to tolerate both of the following at a maximally tolerated dose:
    1. One of the following:
      1. Angiotensin converting enzyme (ACE) inhibitor (e.g., captopril, enalapril); or
      2. Angiotensin II receptor blocker (ARB) (e.g., candesartan, valsartan); or
      3. Angiotensin receptor-neprilysin inhibitor (ARNI) [e.g., Entresto (sacubitril and valsartan)]; and
    2. Beta blocker (i.e.., bisoprolol, carvedilol, metoprolol succinate ER); and
  7. Prescribed by or in consultation with a cardiologist 

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Vericiguat (Verquvo™) or ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy

Reauthorization duration: 2 years


Inappropriate sinus tachycardia 

INITIAL CRITERIA: Ivabradine (Corlanor®) is approved when ALL of the following are met: 
  1. Diagnosis of inappropriate sinus tachycardia; and 
  2. Member is 18 years of age or older; and 
  3. Inadequate response or inability to tolerate one beta-blocker; and 
  4. Prescribed by or in consultation with a cardiologist 

Initial authorization duration: 2 years 

REAUTHORIZATION CRITERIA: Ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy. 

Reauthorization duration: 2 years 

Heart failure due to dilated cardiomyopathy 

INITIAL CRITERIA: Ivabradine (Corlanor®) is approved when ALL of the following are met: 
  1. Diagnosis of stable, symptomatic heart failure due to dilated cardiomyopathy; and 
  2. Member is 6 months of age to 18 years of age; and 
  3. Member is in sinus rhythm; and 
  4. Member has elevated heart rate; and 
  5. Prescribed by or in consultation with a cardiologist 

Initial authorization duration: 2 years 

REAUTHORIZATION CRITERIA: Ivabradine (Corlanor®) is re-approved when there is documentation of positive clinical response to therapy. 

Reauthorization duration: 2 years 



Vericiguat (Verquvo™)

  • Do not administer VERQUVO to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.

Borer JS, Bohm M, Ford I, et al. Efficacy and safety of ivabradine in patients with severe chronic systolic heart failure (from the SHIFT study). Am J Cardiol. 2014;113:497-503. Accessed June 26, 2023.

Corlanor (ivabradine) [package insert]. Thousand Oaks, CA: Amgen, Inc. August 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d&type=display. Accessed July 22, 2021.

Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation. 2013. Doi: 10.1161/CIR.0b013e31828124ad. Available from: http://circ.ahajournals.org/content/127/1/e6.full.pdf+html. Accessed June 26, 2023.

Ivabradine. Micromedex. Available from: http://www.micromedexsolutions.com/. Accessed June 26, 2023.

Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376 (9744):875-85. Accessed June 26, 2023.

Yancy CW, Jessup M, Bozkurk B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013. Doi: 10.1016/j.jacc.2013.05.020. Available from: http://circ.ahajournals.org/content/128/16/e240.full.pdf+html. Accessed June 26, 2023.

Yancy CW, Jessup M, Bozkurk B, et al.ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update to the 2013 ACC/AHA Guidelines for the Management of Heart Failure. Circulation. 2016. DOI: 10.1161/CIR.0000000000000435. Available from: http://circ.ahajournals.org/content/circulationaha/early/2016/05/18/CIR.0000000000000435.full.pdf. Accessed June 26, 2023.

Cappato R, Castelvecchio S, Ricci C, et. Al. Clinical Efficacy of Ivabradine in Patients with Inappropriate Sinus Tachycardia. Journal of the American College of Cardiology. Vol. 60, No 15, 2012. October 9, 2012: 1323-9. Accessed June 26, 2023.

Olshansky B, Sullivan R. Inappropriate Sinus Tachycardia. Journal of the American College of Cardiology. Vol. 61, No 8, 2013. February 26, 2013:793-801. Accessed June 26, 2023.

Sheldon RS, Grubb BP, Olshansky B, et. Al. 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope. Available at: https://www.hrsonline.org/Policy-Payment/Clinical-Guidelines-Documents/2015-HRS-Document-on-POTS-IST-VVS. Accessed June 26, 2023.

Verquvo™ (vericiguat) [prescribing information]. Whitehouse Station (NJ); Merck & Co. Inc.; February 2023. Available at: https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_pi.pdf. Accessed June 26, 2023.
 


 



 

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Rx.01.33 Off-Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

Brand NameGeneric Name
Corlanor®ivabradine
Verquvo™vericiguat
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10/1/2023Rx.04.2Claim Payment PolicyOyenusi, Oluwadamilola

Presently, the FDA requires prescription drugs to demonstrate safety and efficacy prior to marketing, however, this was not always mandatory.  In 1906, the Pure Food and Drug Act prohibited adulterated, misbranded, poisonous or deleterious drugs from being manufactured, sold or transported.  The Pure Food and Drug Act was repealed and replaced with the Federal Food, Drug, and Cosmetic Act of 1938, which required evidence of safety for new drugs.  The law was amended further in 1962 to strengthen the requirements for safety and add an additional requirement for a manufacturer to demonstrate efficacy of the drug.

The Orange Book identifies FDA approved drugs that have undergone the required safety and efficacy requirements of the Federal Food, Drug, and Cosmetic Act.  If a medication is not included in the orange book, it has not demonstrated safety and efficacy in accordance with the Federal Food, Drug, and Cosmetic Act requirements.  Drugs that entered the market based solely on safety and drugs that were on the market prior to 1938 are not included in the Orange Book. 

Some drugs, mostly older products, are available on the market despite lacking FDA approval for a variety of historical reasons.  Examples include, but are not limited to, a manufacturer combining two approved products into a combination product without obtaining approval and a manufacturer marketing a currently approved product without obtaining FDA approval. 

 

Prescription Drugs are defined by the plan as:

A Legend Drug or Controlled Substance, which:

  • Has been approved by the Food and Drug Administration(FDA) for a specific use; and
  • Can, under federal or state law, be dispensed only pursuant to a Prescription Order

 

A non-FDA approved drug will be considered for formulary inclusion if all the following criteria are met:

  • The drug entered the market prior to 1938; and
  • The drug is not commercially available in an FDA approved form of the same route of administration; and
  • The drug meets the criteria outlined in the Experimental/Investigational Use Policy

The prescription drug benefit covers certain prescription drugs approved by the FDA pursuant to a prescription order.  Details of covered drugs may be found in the member’s benefit booklet.

 

The intent of this policy is to communicate the prescription drug benefit coverage based on medical necessity of drugs that are not approved by the Food and Drug Administration (FDA).

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Prescription drugs that are commercially available but not approved by the FDA are not considered a covered benefit.

Some prescription drugs that are not FDA approved, and not otherwise excluded, will be covered under the pharmacy benefit for certain plans as required by the Patient Protection and Affordable Care Act (PPACA) or as defined in the member's benefit booklet . These items include but may not be limited to the following products as listed:

  • Prenatal vitamins, oral
  • Preventative vitamins and minerals as required by the PPACA
  • Cholecalciferol (vitamin D3) 50,000 units*
  • Sulfuric acid/ phenosulfonic acid solution*

Some prescription drugs that came to market prior to 1938, prior to the current FDA approval process, and not otherwise excluded, will be covered under the prescription drug benefit if they are deemed medically accepted as defined in the Off-Label Use policy.  These items include but may not be limited to the following products as listed: 

  • Aluminum chloride topical 
  • Hydrocortisone suppositories
  • Hyoscyamine 
  • Phenobarbital 
  • Opium tincture 
  • Morphine suppositories 
  • Sodium chloride for inhalation 
  • Homatropine ophthalmic
  • Thyroid products (e.g., Armour Thyroid, Nature-Thyroid, NP Thyroid, WP Thyroid) 
  • Phenazopyridine HCL (Pyridium) 100mg and 200mg tablets 
  • Nitro-time CPCR 
  • Salsalate tablet 

*Exceptions will be made for these products to meet essential health benefit requirements



 

 

Academy of Managed Care Pharmacy. Practice Advisory on Unapproved Medications. Available from: https://www.amcp.org/sites/default/files/2019-03/Practice%20Advisory%20on%20Unapproved%20Meds%20_memohead_.pdf. Accessed June 22, 2023.

US Food and Drug Administration. Federal Food and Drugs Act of 1906. Available from: https://www.fda.gov/about-fda/changes-science-law-and-regulatory-authorities/part-i-1906-food-and-drugs-act-and-its-enforcement. Accessed June 22, 2023.

US Food and Drug Administration. Laws Enforced by FDA. Available from https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/default.htm . Accessed June 22, 2023.

US Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Available from: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed June 22, 2023.

US Food and Drug Administration. Orange Book Preface. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079068.htm. Accessed June 22, 2023.

US Food and Drug Administration. Unapproved Prescription Drugs: Drugs Marketed in the United States That Do Not Have Required FDA Approval. Available from: https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/enforcementactivitiesbyfda/selectedenforcementactionsonunapproveddrugs/default.htm . Accessed June 22, 2023.

Preventive Health Services. Available from: https://www.healthcare.gov/coverage/preventive-care-benefits/. Accessed June 22, 2023.

Barowsky H, Schwartz SA. Method for Evaluating Diphenoxylate Hydrochloride: Comparison of Its Antidiarrheal Effect with that of Camphorated Tincture of Opium. JAMA. 1962;180(12):1058-1060.

Beckwith MC. Diarrhea in Palliative Care Patients. Journal of Pharmaceutical Care in Pain & Symptom Control. 2010;7(4):91-108.​


 



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​Cost Share Exception Policy for Preventive Medications and Women's Preventive Services under the PPACA Rx.01.178

Prescription Vitamins, Dietary Supplements, and Medical Foods Rx.04.5

Off-Label Use  Rx.01.33                   

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10/1/2023Rx.04.3Claim Payment PolicyOyenusi, Oluwadamilola

​Convenience packs combine two or more individual drug products into a single package.  Products included in a convenience pack may include prescription products, over the counter products, and/or products not approved by the Food and Drug Administration (FDA).   

​The intent of this policy is to communicate the coverage position of convenience packs.

 

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Convenience packs as described above are not covered under the pharmacy benefit because each product is available independently.

A prescriber may issue a prescription or prescriptions for the individual components of the convenience pack.  The individual components will be covered pursuant to the terms of member's benefit.

Examples of convenience packs include, but are not limited to:

  • DermacinRx Clorhexacin, which contains the following:
    • Mupirocin 2% ointment – covered as a pharmacy benefit
    • Chlorhexidine gluconate 4% solution, dimethicone 5% cream not covered (not an FDA approved product)
  • Diclovix DM PAK 1.5-8% which contains the following:
    • Diclofenac sodium solution 1.5% - covered as a pharmacy benefit
    • Menthol gel 8% therapy pack – not covered (not FDA approved product)​​



​N/A

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​Non-FDA approved Products Rx.04.2

Off-Label Use Rx.01.33

 
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10/1/2023Rx.01.176CommercialOyenusi, Oluwadamilola

Periodic paralyses are a group of rare, inherited neuromuscular disorders, resulting from mutations in the genes that regulate muscle ion channels.  These disorders are characterized by episodes of painless muscle weakness where the affected muscles become weak and unable to contract.

The two most common types of periodic paralyses are hypo- and hyper-kalemic.  Hypokalemic periodic paralysis is characterized by a fall in potassium levels in the blood. In individuals with this mutation attacks often begin in adolescence and are triggered by strenuous exercise, high carbohydrate meals, or by injection of insulin, glucose, or epinephrine. Weakness may be mild and limited to certain muscle groups, or more severe and affect the arms and legs. Attacks may last for a few hours or persist for several days. Some patients may develop chronic muscle weakness later in life. Hyperkalemic periodic paralysis is characterized by a rise in potassium levels in the blood. Attacks often begin in infancy or early childhood and are precipitated by rest after exercise, fasting, cold exposure, or ingestion of small amounts of potassium. Attacks are usually shorter, more frequent, and less severe than the hypokalemic form. Muscle spasms are common. Weakness in an attack can be focal, affecting only one limb, but generalized weakness with hypotonia is more common.

Dichlorphenamide is an oral carbonic anhydrase inhibitor indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. The precise mechanism by which dichlorphenamide exerts its therapeutic effects in patients with periodic paralysis is unknown. 



The intent of this policy is to communicate the medical necessity criteria for dichlorphenamide (Keveyis®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Dichlorphenamide (Keveyis®) is approved when of ALL of the following are met:

  1. Treatment of primary hyperkalemic periodic paralysis, primary hypokalemic paralysis, and related variants; and

  2. Prescribed by or in consultation with a neurologist; and

  3. No documentation of ANY of the following:

    1. Concomitant use of high dose aspirin; or

    2. Severe pulmonary disease; or

    3. Hepatic insufficiency; and

  4. Member is 18 years of age or older

 Initial authorization duration: 3 months

 

CONTINUAITON CRITERIA: Dichlorphenamide (Keveyis®) is reapproved when there is documentation of positive clinical response to therapy as evidenced by a decrease in weekly attack frequency from baseline​.

Continuation authorization duration: 2 years

​N/A

Dichlorphenamide. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com/. Accessed June 23, 2023.

Gutmann L, Conwit R. Hyperkalemic periodic paralysis. UpToDate. November 2021.  Available at: https://www.uptodate.com/contents/hyperkalemic-periodic-paralysis. Accessed June 23, 2023.

Keveyis® (dichlorphenamide) [package insert]. Hawthorne NY. Taro Pharmaceuticals USA, Inc. November 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/011366s030lbl.pdf. Accessed June 23, 2023.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Familial Periodic Paralyses Information Page. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Familial-Periodic-Paralyses-Information-page. Last updated January 2023. Accessed June 23, 2023.

 



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Off-Label Use Rx.01.33


Brand Name

Generic Name

Keveyis®

Dichlorphenamide

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10/1/2023Rx.04.5Claim Payment PolicyOyenusi, Oluwadamilola

 

A dietary supplement is defined by the Food and Drug Administration as "a product intended for ingestion that contains a 'dietary ingredient' intended to add further nutritional value to (supplement) the diet. A 'dietary ingredient' may be one, or any combination, of the following substances:

  • a vitamin
  • a mineral
  • an herb or other botanical
  • an amino acid
  • a dietary substance for use by people to supplement the diet by increasing the total dietary intake
  • a concentrate, metabolite, constituent, or extract"

The US Food and Drug Administration (FDA) defines a medical food as a "food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation." FDA section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)). The FDA further defines medical foods as "foods that are specially formulated and processed (as opposed to a naturally occurring foodstuff used in a natural state) for a patient who is seriously ill or who requires use of the product as a major component of a disease or condition's specific dietary management." Medical foods are "intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone." They also "provide nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation."

Current benefit language states the plan will not cover:

  • Dietary supplements
  • Amino acid supplements
  • Medical foods (exceptions may apply; refer to benefit language for details)
  • Prescription vitamins except for pre-natal and pediatric vitamins

The intent of this policy is to communicate the coverage of prescription vitamins, dietary supplements, and medical foods under the member’s prescription drug benefit.

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Prescription vitamins, dietary supplements, and medical foods are not covered under the pharmacy benefit.

An exception to allow coverage under the member's plan will be in place for prescription medication that are either mandated when used as a preventive medication as described in the Patient Protection and Affordable Care Act (PPACA) or medically necessary for the treatment of a specific illness as determined by the plan.

The following prescription products are covered under the member's prescription benefit:

ProductsClinical Use
Calcitriol oralManagement of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (creatinine clearance 15 to 55 mL/min) not yet on dialysis.
Cholecalciferol (vitamin D3) 50,000 unitsTreatment of hypoparathyroidism, refractory rickets, also known as vitamin D resistant rickets, and familial hypophosphatemia. This is an over the counter preparation included to meet essential health benefit requirements.
Cyanocobalamin inhaledMaintenance of normal hematologic status in pernicious anemia patients who are in remission following intramuscular (IM) vitamin B12 therapy and who have no nervous system involvement
Dialysis vitamins oral as identified by indication in product labelWasting syndrome in chronic renal failure, uremia, and impaired metabolic function of the kidney
Doxercalciferol oralSecondary hyperparathyroidism (dialysis patients): Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Secondary hyperparathyroidism (predialysis patients): Treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease.
Ergocalciferol oralTreatment of hypoparathyroidism, refractory rickets, also known as vitamin D resistant rickets, and familial hypophosphatemia.
Paracalcitol oralHyperparathyroidism: For the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease stage 3 and 4, and chronic kidney disease stage 5 in patients on hemodialysis or peritoneal dialysis.
Pediatric vitaminsNutritional supplement for children
Phytonadione oralAnticoagulant-induced prothrombin deficiency caused by coumarin or indandione derivatives.
Coagulation disorders: Phytonadione is indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity.
Potassium aminobenzoate oral The treatment of scleroderma, dermatomyositis, morphea, linear scleroderma, pemphigus, and Peyronie's disease.
Prenatal vitaminsNutritional supplement used prior to conception, during pregnancy, and in the postnatal period
Prescription electrolytesElectrolyte repleters (i.e., potassium) and electrolyte depleters (ie calcium acetate)

Medical food guidance documents & regulatory information. Available from: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/MedicalFoods/. Accessed June 22, 2023.

Preventive Health Services. Available from: https://www.healthcare.gov/coverage/preventive-care-benefits/. Accessed June 22, 2023.

Dietary supplements. Available from: https://www.fda.gov/food/dietarysupplements/. Accessed June 22, 2023.​




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Formulary Exception policy Rx.06.61
 

Medical Foods (ie, Enteral Nutrition and Nutritional Formulas) and Low-Protein Modified Food Products 08.00.18j

Non-FDA Approved Products Rx.04.2 

Off-Label Use Rx. 01.33

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10/1/2023Rx.01.182CommercialOyenusi, Oluwadamilola

Irritable bowel syndrome (IBS), a common, functional gastrointestinal disorder, is defined as abdominal discomfort associated with altered bowel habits.  Three subtypes of IBS exist: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed type (IBS-M).  Diagnosis of IBS is based solely on clinical criteria as there are no radiologic or endoscopic abnormalities in IBS and no biomarker has proven reliable for diagnosis.  Approximately 10-15% of the general adult population is affected by IBS.

Hepatic encephalopathy (HE) is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting.  It manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma.

Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO) is a condition in which the small bowel is colonized by excessive aerobic and anaerobic microbes. Therapy is typically begun after confirming SBBO/SIBO by breath test. Patients with SBBO/SIBO could present with bloating, flatulence, abdominal discomfort, or chronic watery diarrhea.

Rifaximin (Xifaxan®), a semisynthetic antibiotic, is derived from rifampin.  It inhibits bacterial protein synthesis and growth by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking one of the steps in transcription.  Rifaximin is indicated for reduction in risk of overt HE recurrence in adults, treatment of IBS-D in adults, and Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO).  When treating IBS-D, the course of therapy is 14 days.  The regimen may be repeated up to 2 times.   



The intent of this policy is to communicate the medical necessity criteria for rifaximin (Xifaxan®) as provided under the member’s prescription drug benefit.


Hepatic disease with risk of hepatic encephalopathy

INITIAL CRITERIA: Rifaximin (Xifaxan®) 550 mg is approved when BOTH of the following are met:

  1. Diagnosis of hepatic disease with risk for hepatic encephalopathy (i.e., previous episode of hepatic encephalopathy, advanced liver disease, hepatocellular carcinoma); and
  2. Inadequate response or inability to tolerate lactulose

Initial authorization duration: 2 years (Maximum daily dose 2/day)

REAUTHORIZATION CRITERIA Rifaximin (Xifaxan®) 550mg is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years (Maximum daily dose 2/day)


Irritable Bowel Syndrome with Diarrhea

INITIAL CRITERIA: Rifaximin (Xifaxan®) 550mg is approved when All of the following are met:

  1. Diagnosis of irritable bowel syndrome- diarrhea; and
  2. Inadequate response or inability to tolerate an antispasmodic; and
  3. Member does not exceed 3 courses (42 days) of therapy

Initial authorization duration: 3 months (max of 14 days/84 days; Maximum daily dose 3/day)

REAUTHORIZATION CRITERIA: Rifaximin (Xifaxan®) 550mg is re-approved when ALL of the following are met:
  1. Diagnosis of irritable bowel syndrome – diarrhea; and
  2. BOTH of the following:
    1. Member does not exceed 3 courses (42 days) of therapy; and
    2. No documentation of rifaximin (Xifaxan®) treatment within the last 10 weeks.

Reauthorization duration: 3 months (max of 14 days/84 days; Maximum daily dose 3/day)


Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO)

INITIAL CRITERIA: Rifaximin (Xifaxan®) 550mg is approved when ALL of the following are met:

  1. Diagnosis of Small Bowel Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO); and
  2. Inadequate response or inability to tolerate two of the following antibiotics:
    1. Neomycin; or
    2. Amoxicillin/clavulanic acid (Augmentin); or
    3. Ciprofloxacin (Cipro); or
    4. Trimethoprim-sulfamethoxazole (Bactrim); or
    5. Doxycycline (Vibramycin) or minocycline (Minocin) or tetracycline; or
    6. Metronidazole (Flagyl); or
    7. Cephalexin (Keflex)

Initial authorization duration: 3 months (Maximum daily dose 3/day)

​​REAUTHORIZATION CRITERIA: Rifaximin (Xifaxan®) 550mg is re-approved when there is documentation of Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO) recurrence following successful initial treatment


Reauthorization duration: 3 months (Maximum daily dose 3/day)




​None

American Association for the Study of Liver Diseases and European Association for the Study of the Liver. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. Journal of Hepatology. Available from: http://www.easl.eu/medias/cpg/Hepatic-Encephalopathy-Chronic-Liver-Disease/English-report.pdf. Accessed June 23, 2023.

Ford AC, Moayyedi P, Lacy, BE, et al. American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation. Am J Gastroenterol. 2014: 109:S2-S26; doi: 1001038/ajg.2014.187

Weinberg DS, Smalley W, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome. Gastroenterology. 2014; 147(5):1146-48.

Xifaxan® (rifaximin) [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; September 2022. Available from: https://shared.salix.com/shared/pi/xifaxan550-pi.pdf. Accessed June 23, 2023.

Pimentel M. Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, February 2022. Accessed June 23, 2023.



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Off-Label Use Rx.01.33

 

Brand Name
Generic Name
Xifaxan®
Rifaximin


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10/1/2023Rx.04.6Claim Payment PolicyOyenusi, Oluwadamilola

​Injectable drugs indicated for administration by a healthcare professional are covered under the medical benefit.  There are times when an exception is requested to cover such drugs under the member's prescription drug benefit where they are otherwise excluded.

The intent of this policy is to describe circumstances when injectable medications typically covered under the medical benefit may be covered under the member’s prescription drug benefit.

Coverage is subject to the terms, conditions, and limitations of the member's contract.

The following medications are covered under the medical benefit:

  1. Cyanocobalamin (vitamin B12) injection

  2. Heparin injection

  3. Hydrocortisone injection

  4. Methotrexate injection (vial)

  5. Testosterone injection

  6. Estrogen vials

  7. Non-insulin syringes/needles

A benefit exception will be made to cover cyanocobalamin injection, heparin injection, hydrocortisone injection, methotrexate vials under the prescription drug benefit when ALL of the following are met:

  1. The requested drug is being used for a Food and Drug Administration approved indication or compendium supported indication as outlined in Off-label Use policy; and

  2. The prescriber assumes responsibility for teaching the member proper preparation, administration and disposal; and

  3. The prescriber provides a statement indicating the reason prescription drug benefit products are not an option, and

  4. ONE of the following:

    1. Provider does not stock the requested medication; or

    2. Access at the provider's office is not feasible due to frequency of administration

A benefit exception will be made to cover testosterone vials and estrogen vials under the prescription drug benefit when ALL of the following are met:

  1. One of the following is met:

    1. The requested drug is being used for a Food and Drug Administration approved indication or compendium supported indication as outlined in the Off-Label Use policy; or

    2. The requested drug is being used as hormone therapy in children, adolescents, and adults with persistent, well-documented gender dysphoria diagnosed in accordance with the criteria established in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition [DSM-5] or is gender diverse as defined in The World Professional Association for Transgender Health (WPATH): Standards of Care, 8th Version (SOC-8) as outlined in medical policy Gender Affirming Interventions (11.09.02); and 

  2. The prescriber assumes responsibility for teaching the member proper preparation, administration and disposal; and

  3. The prescriber provides a statement indicating the reason prescription drug benefit products are not an option, and

  4. ONE of the following:

    1. Provider does not stock the requested medication; or

    2. Access at the provider's office is not feasible due to frequency of administration

A benefit exception will be made to cover non-insulin syringes/needles under the prescription drug benefit when required to administer an injectable medication and not supplied with the product.

Coverage is subject to the terms of the member's prescription drug benefit, including but not limited to cost-share.

Authorization duration: 2 years

​N/A

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Off-Label Use Rx.01.33

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10/1/2023Rx.01.184CommercialOyenusi, Oluwadamilola

An interim clinical policy is the written description of the plan’s utilization management position concerning the use or application of a new or recently introduced product that is covered under the pharmacy benefit. These policies are implemented prior to review by the Pharmacy and Therapeutics Committee. Criteria are based on an initial clinical review performed by Clinical Pharmacy Services. The intent of the interim policy is to provide a means to manage newly approved products while allowing sufficient time for a thorough clinical review and evaluation by the Pharmacy and Therapeutics Committee. The product to which an interim clinical policy applies is considered medically necessary when requested for an indication approved by the Food and Drug Administration and, when available, there is inadequate response or inability to tolerate one generic alternative and one preferred brand with the same indication. The policy is effective as of the date of market entry.  A clinical policy, if issued, will be available when approved by the Pharmacy and Therapeutics Committee within 180 days of the drug market entry, designated by the Medispan release date. If a clinical policy is not approved within 180 days, the interim clinical policy will be retired. Interim clinical policy will remain in effect until the clinical policy effective date.

​The intent of this policy is to communicate the medical necessity criteria for new or recently introduced products as provided under the member’s prescription drug benefit.

A new or recently introduced product will be considered medically necessary when both of the following are met:

  1. Diagnosis of an FDA approved indications; and
  2. Inadequate response or inability to tolerate BOTH of the following (when available):
    1. One generic alternative with the same indication; and
    2. One preferred brand with the same indication

Authorization duration: 2 years

​N/A

​None

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​Off-Label Use Rx. 01.33

Applicable drugs will vary as new products are released to market.

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10/1/2023Rx.01.208CommercialOyenusi, Oluwadamilola

Idiopathic thrombocytopenia purpura (ITP): ITP is an immune disorder in which the blood doesn't clot normally. ITP can cause excessive bruising and bleeding and can be characterized as an unusually low level of platelets, or thrombocytes, in the blood results in ITP.

Thrombocytopenia in patients with hepatitis C: Thrombocytopenia can occur in patients with chronic hepatitis C virus (HCV) infection. The pathophysiology is multifactorial and includes direct bone marrow suppression, an overactive spleen, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia.

Aplastic Anemia: A blood disorder caused by failure of the bone marrow to make enough new blood cells. Bone marrow is a sponge-like tissue inside the bones that makes stem cells that differentiate into red blood cells, white blood cells, and platelets.

Thrombocytopenia in patients with chronic liver disease: Individuals with chronic liver disease have varying degree of thrombocytopenia which may be caused by impaired platelet production from decreased hepatic synthesis of thrombopoietin. In addition, individuals with advanced liver disease may have reduced platelet function due to coexisting uremia, infection, and/or endothelial abnormalities. These factors combined put the individuals with chronic liver disease at an increased risk for bleeding especially during procedures.

Mechanism of Action:

Eltrombopag olamine (Promacta®) tablets contain a thrombopoietin (TPO) receptor agonist for oral administration. Eltrombopag interacts with the transmembrane domain of the TPO receptor which initiates signaling cascades that induce proliferation and differentiation from bone marrow progenitor cells ultimately increasing platelet production. 

Eltrombopag olamine (Promacta®) is a thrombopoietin receptor agonist indicated for the treatment of:

  1. Thrombocytopenia in adult and pediatric patients 1 year and older with chronic idiopathic thrombocytopenia purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. 
  2. Thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. PROMACTA should only be used in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. 
  3. In combination with standard immunosuppressive therapy for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia.
  4. Patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

Fostamatinib disodium (Tavalisse) is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK). The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-activating receptors and B-cell receptor. The fostamatinib metabolite R406 reduces antibody-mediated destruction of platelets.

Fostamatinib disodium (Tavalisse) is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Avatrombopag (Doptelet®) and lusutrombopag (Mupleta®) tablets contain a thrombopoietin (TPO) receptor agonist for oral administration. They stimulate proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production. Lusutrombopag induces megakaryocyte maturation by interacting with the transmembrane domain of human TPO receptor expressed on megakaryocytes.

Avatrombopag (Doptelet®) and Lusutrombopag (Mupleta®)are indicated for the treatment of thrombocytopenia in adult patients  with chronic liver disease who are scheduled to undergo a procedure. ​

Doptelet® (avatrombopag) is also indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.

​The intent of this policy is to communicate the medical necessity criteria for eltrombopag olamine (Promacta®), fostamatinib disodium (Tavalisse™), avatrombopag (Doptelet®), lusutrombopag (Mulpleta®) as provided under the member's prescription drug benefit.

Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

INITIAL CRITERIA: Eltrombopag olamine (Promacta®) is approved when ALL of the following are met:

  1. Diagnosis of relapsed/refractory chronic immune (idiopathic) thrombocytopenic purpura (ITP) for greater than 6 months; and
  2. Member is 1 year of age or older; and
  3. Baseline platelet count is less than 30,000/mcL; and
  4. Insufficient response to corticosteroids, immunoglobulins, or splenectomy; and
  5. Prescribed by or in consultation with a hematologist/oncologist​

Initial authorization duration: 2 years

INITIAL CRITERIA: Fostamatinib (Tavalisse™) is approved when all of the following are met:

  1. Diagnosis of chronic immune (idiopathic) thrombocytopenic purpura; and
  2. Baseline platelet count is less than 30,000/mcL; and
  3. Member's degree of thrombocytopenia and clinical condition increase the risk of bleeding; and
  4. Documentation of an inadequate response or inability to tolerate ONE of the following:
    1. Corticosteroids; or 
    2. Immunoglobulins; or
    3. Splenectomy; or
    4. Thrombopoietin receptor agonists (e.g., Nplate®, Promacta®); or
    5. Rituximab; and
  5. Prescribed by or in consultation with a hematologist/oncologist; and
  6. Member is 18 years of age or older

Initial authorization duration: 2 years

INITIAL CRITERIA: Avatrombopag (Doptelet®) is approved when ALL of the following are met:

  1. Diagnosis of Chronic Immune Thrombocytopenia (ITP) or relapsed/refractory ITP; and
  2. Baseline platelet count is less than 30,000mcL; and
  3. Inadequate response or inability to tolerate ONE of the following: 
    1. corticosteroids; or
    2. imunoglobulins; or
    3. splenectomy; or
    4. Rituxan (rituximab); and
  4. Member's degree of thrombocytopenia and clinical condition increase the risk of bleeding; and
  5.  Prescribed by or in consultation with a hematologist/oncologist; and
  6. Member is 18 years of age or older
Initial authorization duration: 2 years

CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®), Fostamitinib (Tavalisse™), Avatrombopag (Doptelet®) is re-approved when ALL of the following are met:

  1. Diagnosis of chronic immune (idiopathic) thrombocytopenic purpura; and
  2. Documentation of a positive clinical response to Promacta®, Tavalisse™, Doptelet® therapy as evidence by an increase in platelet count to a level sufficient to avoid clinically important bleeding; and
  3. Prescribed by or in consultation with a hematologist/oncologist

Continuation authorization duration: 2 years.

Aplastic anemia

INITIAL CRITERIA: Eltrombopag olamine (Promacta®) is approved when ALL of the following are met:

  1. Diagnosis of severe aplastic anemia; and
  2. Member is 2 years of age or older; and
  3. One of the following:
    1. Inadequate response or inability to tolerate immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine; or
    2. Documentation that the requested drug will be used in combination with antithymocyte globulin (ATG) and cyclosporin and
  4. Member has thrombocytopenia defined as platelet count less than 30,000/mcL; and
  5. Prescribed by or in consultation with a hematologist/oncologist

Initial authorization duration: 2 years

CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®) is re-approved when ALL of the following are met:

  1. Diagnosis of relapsed/refractory chronic immune (idiopathic) thrombocytopenic purpura (ITP) or severe aplastic anemia; and
  2. Documentation of a positive clinical response to Promacta therapy; and
  3. Prescribed by or in consultation with a hematologist/oncologist

Continuation authorization duration: 2 years

Thrombocytopenia associated with hepatitis C

INITIAL CRITERIA: Eltrombopag olamine (Promacta®) is approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia associated with hepatitis C; and
  2. Member is 18 years of age or older; and
  3. ONE of the following:
    1. Member has thrombocytopenia defined as platelets less than 90,000/mcL for initiation (pre-treatment) of interferon-based therapy; or
    2. Member has thrombocytopenia defined as platelets less than 75,000/mcL for maintenance of optimal interferon-based therapy; and
  4. Prescribed by or in consultation with one of the following:
    1. Hematologist/ oncologist
    2. Gastroenterologist
    3. Hepatologist
    4. Infectious disease specialist
    5. HIV specialist

Initial authorization duration: 48 weeks

CONTINUATION CRITERIA: Eltrombopag olamine (Promacta®) is re-approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia associated with hepatitis C; and
  2. ONE of the following:
    1. For members that started treatment with Promacta prior to initiation of treatment with interferon, BOTH of the following:
      1. Member is currently on antiviral interferon therapy for treatment of chronic hepatitis C, and
      2. Member reached a threshold platelet count that allows initiation of antiviral interferon therapy with Promacta treatment by week 9; or
    2. For members that started treatment with Promacta while on concomitant treatment with interferon, member is currently on antiviral interferon therapy for treatment of chronic hepatitis C; and
  3. Prescribed by or in consultation with one of the following:
    1. Hematologist/ oncologist
    2. Gastroenterologist
    3. Hepatologist
    4. Infectious disease specialist
    5. HIV specialist

Continuation authorization duration: 48 weeks

Thrombocytopenia in Chronic Liver Disease Prior to Planned Procedure

Lusutrombopag (Mulpleta®) or Avatrombopag (Doptelet®) is approved when ALL of the following are met:

  1. Diagnosis of thrombocytopenia; and
  2. Member has chronic liver disease; and
  3. Member is scheduled to undergo a procedure; and
  4. Baseline platelet count is less than 50,000/mcL; and
  5. Member is 18 years of age or older

Approval duration: 1 month

Eltrombopag olamine (Promacta®):

1.     Risk For Hepatic Decompensation In Patients With Chronic Hepatitis C

  • In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation. 

2.     Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended.

“Aplastic Anemia." Genetic and Rare Diseases Information Center, National Institute of Health, 5 July 2017, rarediseases.info.nih.gov/diseases/5836/aplastic-anemia. Accessed June 22, 2023.

Dahal, Sumit, et al. “Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection." Advances in Pediatrics., U.S. National Library of Medicine, 1 Mar. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5333732/. Accessed June 22, 2023.

Doptelet® (avatrombopag) [package insert]. Durham, NC. AkaRx, Inc. July 2021. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e2d5960d-6c18-46cc-86bd-089222b09852&type=display. Accessed June 22, 2023.

Eltrombopag olamine (Promacta®) [package insert]. Basel, Switzerland. Novartis Pharmaceuticals Co. Ltd. March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2&type=display. Accessed June 22, 2023.

Mulpleta® (lusutrombopag) [package insert]. Florham Park, NJ. Shionogi Inc., April 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f9fd0cfd-717d-4a87-99bc-de7b38807e55&type=display. Accessed June 22, 2023.

Shah, N. MD, Intagliata, N, MD. December 2021. Hemostatic abnormalities in patients with liver disease. UpToDate. Access June 22, 2023.

“Idiopathic Thrombocytopenic Purpura (ITP)." Mayo Clinic, Mayo Foundation for Medical Education and Research, 9 Aug. 2017, www.mayoclinic.org/diseases-conditions/idiopathic-thrombocytopenic-purpura/diagnosis-treatment/drc-20352330. Accessed June 22, 2023.

Tavalisse™ (fostamatinib) [package insert]. San Francisco, CA. Rigel Pharmaceutical, Inc. November 2020. Available from: https://tavalisse.com/downloads/pdf/Tavalisse-Full-Prescribing-Information.pdf. Accessed June 22, 2023.


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Rx.01.33 Off Label Use

Brand NameGeneric Name
Promacta®Eltrombopag olamine
Tavalisse™fostamatinib
Doptelet®avatrombopag
Mulpleta®lusutrombopag
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10/1/2023Rx.01.213CommercialOyenusi, Oluwadamilola

Mycobacterium avium complex (MAC) is the most common pulmonary nontuberculous mycobacterial (NTM) infections of the lung in almost all regions of the world. Antimycobacterial treatment is prolonged and potentially difficult to tolerate and should only be considered in individuals who meet the clinical, radiographic, and microbiologic criteria for the diagnosis of nontuberculous mycobacterial infection. Three-drug combination regimen is recommended for those treated for MAC pulmonary disease and treatment is continued until sputum cultures are consecutively negative for at least 12 months.

Amikacin liposome inhalation suspension (Arikayce®) is an aminoglycoside antibacterial indicated in adults who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.  

​The intent of this policy is to communicate the medical necessity criteria for amikacin liposome inhalation suspension (Arikayce®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: ​Arikayce® (amikacin liposome inhalation suspension) is approved when ALL of the following are met:

1. Diagnosis of refractory Mycobacterium avium complex (MAC) lung disease; and

2. Member has not achieved negative sputum cultures after a minimum of 6 consecutive months of multidrug background regimen therapy; and

3. Documentation that the medication will be used as part of a combination antibacterial regimen; and

4. Member is 18 years of age or older; and

5. Prescribed by or in consultation with a pulmonologist or infectious diseases specialist

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Arikayce® (amikacin liposome inhalation suspension) is re-approved when both of the following are met:

  1. Documentation of positive clinical response to therapy; and
  2. Documentation that the medication will be used as part of a combination antibacterial regimen

Reauthorization duration: 12 months


​WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS

ARIKAYCE has been associated with a risk of increased respiratory adverse reactions, including, hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.

Arikayce® (amikacin liposome inhalation suspension) [prescribing information]. Bridgewater, NJ. Insmed®. February 2023. Available at: https://www.arikayce.com/pdf/full-prescribing-information.pdf. Accessed June 22, 2023.

Kasperbauer, S. Treatment of Mycobacterium avium complex pulmonary infections in adults. UpToDate Web site. September 2021. www.uptodate.com. Accessed June 22, 2023. ​



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Rx.01.33 Off-Label Use

Brand NameGeneric Name
Arikayce®Amikacin liposome inhalation suspension
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10/1/2023Rx.01.215CommercialOyenusi, Oluwadamilola

​Hereditary transthyretin amyloidosis (hATTR) is a rare autosomal dominant, progressively debilitating, and often fatal genetic disease characterized by the accumulation of abnormal amyloid protein in tissues. Transthyretin (TTR) is produced primarily by the liver and is responsible for the transport of thyroxine and retinol binding protein-vitamin A complex. The hATTR genetic mutations lead to mutated TTR protein which results in destabilization from the TTR tetramer into monomers and oligomers, protein misfolding, and aggregation resulting in formation of TTR amyloid fibrils.   hATTR can present with peripheral and/or autonomic neuropathy, infiltrative cardiomyopathy, vitreous amyloid, or leptomenigeal disease.

Inotersen (Tegsedi™) is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Inotersen (Tegsedi™) is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.  

Transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) occurs when amyloidosis occurs in the cardiac tissue.  Wild type ATTR-CM typically presents in men aged 65 years and older, but it can occur in women and in younger patients. Amyloid accumulates in the cardiac tissue leading to atrial and ventricular wall thickening and diastolic dysfunction, arrhythmias, and preserved ejection fraction heart failure.  For wild type ATTR-CM, the median survival is reported to be 3.6 years.

 

Patients with wild type ATTR may also present with bilateral carpal tunnel syndrome as an initial symptom years before the onset of cardiac symptoms (Sekijima 2015).

Due to the lack of effective therapy, testing for ATTR-CM has been underutilized. Testing may include echocardiogram, cardiac magnetic resonance imaging (MRI), and nuclear scintigraphy. Tissue biopsy, either endomyocardial tissue or other locations such as abdominal fat pad, is the gold standard for diagnosis of amyloidosis. A non-invasive test to identify those with ATTR-CM is radiotracer 99mtechnetium pyrophosphate scan (99mTc-PYP). The FDA-has not yet approved 99mTc-PYP test for the diagnosis of ATTR-CM, but it is being used in clinical practice (Vyndaqel Dossier 2019).

Tafamidis meglumine (Vyndaqel®, Vyndamax ®) is a selective transthyretin (TTR) stabilizer, limiting the dissociation of the native TTR tetramer into monomers, which reduces TTR amyloid fibril formation.

Tafamidis meglumine (Vyndaqel®, Vyndamax ®) is indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. 


 

​The intent of this policy is to communicate the medical necessity criteria for inotersen (TegsediTM) ), tafamidis meglumine (Vyndamax®, Vyndaqel®) as provided under the member's prescription drug benefit.

​INITIAL CRITERIA Tegsedi™ (inotersen) is approved when ALL of the following are met:

  1. Diagnosis of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis with transthyretin mutation (e.g., V30M) confirmed by molecular genetic testing; and
  2. Documentation of ONE of the following baseline ambulation parameters in either the Familial Amyloid Polyneuropathy (FAP) Stage or Polyneuropathy Disability (PND) Score
    1. Stage 1 (unimpaired ambulation) or 2 (assisted ambulation) on the Familial Amyloid Polyneuropathy (FAP) staging tool; or
    2. Score I, II, IIIa, or IIIb on the Polyneuropathy Disability (PND) scoring tool; AND
  3. Documented presence of cardiac or renal manifestations, or motor, sensory, or autonomic neuropathy related to the hATTR amyloidosis with polyneuropathy (e.g., neuropathic pain, muscle weakness that affects daily living, orthostatic hypotension, diarrhea, nausea, vomiting, heart failure, arrhythmias, proteinuria, renal failure; vision disorders, such as vitreous opacity, dry eyes, glaucoma, or pupils with an irregular or scalloped appearance; and
  4. Documentation confirming the member has not had a liver transplant; and
  5. Prescribed by or in consultation with a neurologist, geneticist, or professional provider specializing in the treatment of amyloidosis; and
  6. Member is 18 years of age or older; and
  7. No concurrent use with patisiran (Onpattro), vutrisiran (Amvuttra), or any other RNA interference agents
​Initial authorization duration: 16 months


CONTINUATION CRITERIA Tegsedi™ (inotersen) is re-approved when  BOTH of the following are met:

  1. Documentation of one of the following
    1. Stage 1 (unimpaired ambulation) or 2 (assisted ambulation) on the Familial Amyloid Polyneuropathy (FAP) staging tool; or
    2. Score I, II, IIIa, or IIIb on the Polyneuropathy Disability (PND) scoring tool; and
  2. Documented improvement or stability in the signs and symptoms hATTR amyloidosis with polyneuropathy (e.g., neuropathic pain, muscle weakness that affects daily living, orthostatic hypotension, diarrhea, nausea, vomiting, heart failure, arrhythmias, proteinuria, renal failure; vision disorders, such as vitreous opacity, dry eyes, glaucoma, or pupils with an irregular or scalloped appearance), based on objective or standard evaluation scales.
Continuation authorization duration: 2 years​

 

INITIAL CRITERIA Tafamidis meglumine (Vyndamax®, Vyndaqel®) is approved when ALL of the following are met:

  1. Member is 18 years of age or older; AND
  2. Diagnosis of transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) confirmed by ONE of the following:
    1. Member has a transthyretin (TTR) mutation (e.g., V122I), or
    2. Cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of TTR amyloid deposits, or
    3. All of the following: echocardiogram or cardiac magnetic resonance image suggestive of amyloidosis, scintigraphy scan suggestive of cardiac TTR amyloidosis, and absence of light-chain amyloidosis; AND
  3.  Prescribed by or in consultation with a cardiologist; and
  4. One of the following:
    1. History of heart failure (HF), with at least one prior hospitalization for HF, or
    2. Presence of clinical signs and symptoms of HF (e.g., dyspnea, edema); or
  5. Member has New York Heart Association (NYHA) Functional Class I, II, or III heart failure.

Initial authorization duration: 12 months



REAUTHORIZATION CRITERIA: Tafamidis meglumine (Vyndamax®, Vyndaqel®) is re-approved when ALL of the following are met:
  1. Positive clinical response to therapy; and
  2. Member continues to have NYHA Functional Class I, II, or III heart failure; and
  3. Prescribed by or in consultation with a cardiologist.

 Reauthorization duration: 12 months

 

​WARNING: THROMBOCYTOPENIA AND GLOMERULONEPHRITIS

Thrombocytopenia

  • TEGSEDI causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can be life-threatening.
  • Testing prior to treatment and monitoring during treatment is required

Glomerulonephritis
  • TEGSEDI can cause glomerulonephritis that may require immunosuppressive treatment and may result in dialysis-dependent renal failure.
  • Testing prior to treatment and monitoring during treatment is required

 

Gorevic PD. Genetic factors in the amyloid diseases. UpToDate Web site. Updated December 18, 2018. Available from: http://www.uptodate.com/. Accessed June 29, 2023.

Grogan M, Scott CG, Kyle RA, et al. Natural history of wild type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014-1020.

Hawkins PN, Ando Y, Dispenzeri A, et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47:625-638.

Klaassen SHC, Tromp J, Nienhuis HLA, et al. Involvement at presentation in hereditary transthyretin-derived amyloidosis and the value of N-terminal pro-B-type natriuretic peptide. Am J Cardiol. 2018;121:107-112.

Maurer MS, Grogan DR, Judge DP, et al. Tafamidis in transthyretin amyloid cardiomyopathy. Effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail. 2015;8:519-526.

Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.

Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016.

Fontana M. Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis. UpToDate Web site. Updated August 2022. Available from: https://www.uptodate.com/contents/cardiac-amyloidosis-clinical-manifestations-and-diagnosis?search=clinical-manifestations-and-diagnosis-of-amyloid-cardiomyopathy&source=search_result&selectedTitle=1~80&usage_type=default&display_rank=1. Accessed June 29, 2023.

Merlini G, Planté-Bordeneuve V, Judge DP, et al. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Trans Res. 2013;6:1011-1020.

Mundayat R, Steward M, Alvir J, et al. Positive effectiveness of tafamidis in delaying disease progression in transthyretin familial amyloid polyneuropathy up to 2 years: an analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS) Neurol Ther. 2018;7:87-101.

Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in diagnosis and treatment of the most common types. Curr Opin Cardiol. 2018;33(5):571-579.

Pfizer Press Release. FDA issues complete response letter for Pfizer's tafamidis meglumine new drug application. https://investors.pfizer.com/investor-news/press-release-details/2012/FDA-Issues-Complete-Response-Letter-For-Pfizers-Tafamidis-Meglumine-New-Drug-Application/default.aspx. June 18, 2012. Accessed June 29, 2023.

Plante-Bordeneuve V. Update in the diagnosis and management of transthyretin familial amyloid polyneuropathy. J Neurol. 2014;261:1227-1233.

Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-2200.

Seferović PM, Polovina M, Bauersachs J, et al. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;21:553-576.

Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86:1036-1043.

Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28:10-21.

Tegsedi™ (inotersen) [prescribing information]. Boston MA. Akcea Therapeutics, Inc. June 2022. Available at: https://tegsedi.com/wp-content/uploads/2018/10/prescribing-information.pdf. Accessed June 29, 2023.

Vyndaqel and Vyndamax (tafamidis, tafamidis meglumine )[prescribing information]. New York, NY: Pfizer Pharmaceuticals, Inc. April 2023. Available from: labeling.pfizer.com/ShowLabeling.aspx?id=11685. Accessed June 29, 2023.



 



 


 

 

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Off-Label Use Rx.01.33

Brand NameGeneric Name
Tegsedi™Inotersen
Vyndamax®, Vyndaqel®Tafamidis meglumine



265
  
10/1/2023Rx.01.217CommercialOyenusi, Oluwadamilola

 

Neurotrophic keratitis (NK) is a rare degenerative corneal disease caused by impairment in the first branch of the trigeminal nerve which leads to a decrease in or absence of corneal sensitivity. Loss of sensitivity impairs wound healing, leading to corneal epithelial breakdown, development of ulcerations, melting of the stroma, and corneal perforation. Diagnosis, prognosis, and treatment are based on disease severity, which is classified into 3 stages. Stage 1 (mild) NK is characterized by ocular surface irregularity and reduced vision; stage 2 (moderate) is characterized by a non-healing persistent epithelial defect (PED); and stage 3 (severe) exhibits corneal ulceration involving subepithelial (stromal) tissue, which may progress to corneal melting and perforation.  

Therapy for stage 1 disease aims to prevent epithelial breakdown, generally by administering preservative-free artificial tears and discontinuing all topical and systemic medications associated with ocular surface toxicity. The use of punctal plugs may also help increase tear volume. The goal of treatment for stage 2 NK is to promote healing of the epithelial defect and to avoid the development of a corneal ulcer. In addition to the therapies in the previous stage, topical antibiotics are recommended to prevent infections. Therapeutic corneal or scleral contact lenses may be used to promote healing; however, there may be an increased risk of secondary infections. Autologous serum eye drops, which contain components of natural tears, have increasingly been used to treat ocular surface disorders including NK. The main goal of treatment at stage 3 is to prevent corneal thinning and perforation. Various surgeries and procedures are available to treat ulcers not responding to medical treatment. Tarsorrhaphy is the most commonly used procedure to promote corneal healing. Alternative treatments include botulinum-induced ptosis, amniotic membrane transplantation, eyelid closure with tape, patching, and use of the conjunctival flap to cover the corneal surface.

Cenegermin-bkbj (Oxervate™) is a novel recombinant human nerve growth factor (rhNGF) produced in Escherichia coli that is structurally identical to human NGF. NGF is an endogenous protein involved in the differentiation and maintenance of neurons, which acts through specific high-affinity and low affinity NGF receptors in the anterior segment of the eye to support corneal innervation and integrity. Cengermin-bkbj (Oxervate™) is the first FDA-approved pharmacologic therapy indicated for the treatment of neurotropic keratitis (NK). Oxervate™ is an 8-week treatment cycle per affected eye(s).




 

​The intent of this policy is to communicate the medical necessity criteria for cenegermin-bkbj (Oxervate™) as provided under the member’s prescription drug benefit.

INITIAL CRITERIA Cenegermin-bkbj (Oxervate™) is approved when ALL of the following are met:

  1. Diagnosis of Stage 2 or 3 neurotrophic keratitis; and
  2. Documentation of an inadequate response or inability to tolerate at least one over-the-counter ocular lubricant used at an optimal dose and frequency for at least two weeks (e.g., artificial tears, lubricating gels/ointments, etc.); and
  3. Prescribed by or in consultation with an ophthalmologist; and
  4. Submission of chart documentation indicating treatment of left eye, right eye, or both; and
  5. Member will not exceed 8 weeks of Oxervate therapy per affected eye(s)

Initial authorization duration: 3 months

REAUTHORIZATION CRITERIA Cenegermin-bkbj (Oxervate™) is re-approved when ALL of the following are met:
  1. Submission of chart documentation indicating treatment of left eye, right eye, or both; and
  2. One of the following:
    1. Member has received less than or equal to 8 weeks of therapy (one course of therapy) per affected eye(s); and
    2. Documentation of clinical rationale for treatment greater than 8 weeks (e.g., member has a recurrence of neurotropic keratitis in the same eye, or treatment of a different eye); and
  3. Documentation of clinical response to prior Oxervate™ therapy; and
  4. Member will not exceed a total of 16 weeks of Oxervate™ therapy per affected eye(s); and
  5. Prescribed by or in consultation with an ophthalmologist

Reauthorization duration: 3 months

Lifetime limit: 16 weeks of therapy per affected eye



 

None

 

Bonini S, Lambiase A, Rama P, et al.; REPARO Study Group. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125(9):1332-1343. Accessed June 22, 2023.

Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2019; 66:107-131. Accessed June 22, 2023.

Oxervate® (cenegermin-bkbj) [prescribing information]. Boston, MA: Dompe U.S. Inc. October 2019. Available at:  https://oxervate.com/pdf/PrescribingInformation.pdf. Accessed June 22, 2023.

Pflugfelder SC, Massaro-Giordano M, Perez VL, Hamrah P, Deng SX, Espandar L, Foster CS, Affeldt J, Seedor JA, Afshari NA, Chao W, Allegretti M, Mantelli F, Dana R. Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial. Ophthalmology. 2020 Jan;127(1):14-26. Accessed June 22, 2023.

Pocobelli A, Komaiha C, De Carlo L, Pocobelli G, Boni N, Colabelli Gisoldi RAM. Role of Topical Cenegermin in Management of a Cornea Transplant in a Functionally Monocular Patient with Neurotrophic Keratitis and Facial Nerve Palsy: A Case Report. Int Med Case Rep J. 2020 Nov 11;13:617-621. Acccessed June 22, 2023.

Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratisis. Clin Ophthalmol. 2014; 8:571-579. Accessed June 22, 2023.

Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Opthalmologica. 2014;231(4):191-197. Accessed June 22, 2023.

Versura P, Giannaccare G, Pellegrini M, Sebastiani S, Campos EC. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018; 10:37-45. Accessed June 22, 2023.


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​Rx.01.33 Off-Label Use
Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

Brand Name
Generic Name
Oxervate™cenegermin-bkbj
266
  
10/1/2023Rx.01.221CommercialOyenusi, Oluwadamilola

Commercial payers, including managed care organizations and self-funded groups, must ensure appropriate use of drugs in healthcare setting. One way to accomplish this goal is to review claims that exceed a defined threshold.

Prescription claims with a total cost exceeding $10,000 per claim reject for preliminary review at the point-of-sale with message “claim dollar amount exceeded", requiring the dispensing pharmacist to contact the pharmacy benefit manager. This will apply to any claim that exceeds $10,000, allowing them to be reviewed for clinical appropriateness prior to dispensing. For drugs not meeting approval criteria per Off-Label Use policy, the use for which the drug was prescribed would be deemed experimental/investigational.  


 

​The intent of this policy is to communicate the medical necessity criteria for claims exceeding $10,000 as provided under the member's prescription benefit.

Claims that exceed $10,000 are approved when the use, including indication, dose, quantity, and duration, for the requested drug is approved by the FDA or considered medically accepted per Off-Label Use policy.


Authorization duration: 2 years, or for the duration of applicable medical necessity approval (for submitted cost plus $3000) 


 

​N/A

Academy of Managed Care Pharmacy® (AMCP). Where We Stand - Fraud, Waste and Abuse in Prescription Drug Benefits. Revised April 2015. Available at: https://www.amcp.org/policy-advocacy/policy-advocacy-focus-areas/where-we-stand-position-statements/fraud-waste-and-abuse-prescription-drug-benefits. Accessed July 21, 2021.

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​Off Label Use Policy Rx.01.33
Compounded Products Rx.01.134
Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76


 

​Drug claims where total drug cost exceeds $10,000



 

267
  
10/1/2023Rx.01.228CommercialOyenusi, Oluwadamilola

Elevated triglyceride levels are associated with and appear to be implicated in the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Atherosclerosis is the most common underlying pathology in patients with CVD. Fasting plasma triglyceride concentrations may be categorized according to the National Cholesterol Education Program (NCEP) as normal (<150 mg/dL), borderline (150–199 mg/dL), high triglyceride (HTG; 200–499 mg/dL), and severe HTG (HTG; ≥500 mg/dL). Patients with triglycerides above 500 mg/dL are also at risk of pancreatitis. Elevated plasma triglyceride concentrations contribute to increased risk of cardiovascular disease, both directly and because such elevations are associated with risk factors such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Diet and lifestyle changes along with treatment or elimination of secondary causes are recommended before direct pharmacotherapy. If these changes are not possible or not effective, initiating triglyceride-lowering pharmacotherapy may be required.

Vascepa® (icosapent ethyl) is indicated:

  1. As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
    1. Established cardiovascular disease or
    2. Diabetes mellitus and 2 or more additional risk factors for cardiovascular disease.
  2. As an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

 

The mechanisms of action contributing to reduction of cardiovascular events with Vascepa® (icosapent ethyl) are not completely understood but are likely multi-factorial. Increased omega-3 fatty acid eicosapentaenoic acid (EPA) lipid composition from carotid plaque specimens and increased circulating EPA/arachidonic acid ratio have been observed following EPA treatment. EPA inhibits platelet aggregation under some ex vivo conditions. However, the direct clinical meaning of individual findings is not clear.

​The intent of this policy is to communicate the medical necessity criteria for icosapent ethyl (Vascepa®) as provided under the member's prescription drug benefit.


 

Severe Hypertriglyceridemia

INITIAL CRITERIA: Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

  1. Diagnosis of severe hypertriglyceridemia defined as pre-treatment triglyceride level greater than or equal to 500 mg/dl; and
  2. Member is 18 years of age or older; and  
  3. Medication will be used adjunct to an appropriate lipid-lowering diet; and
  4. Member has an inadequate response or inability to tolerate omega-3-acid ethyl esters (generic Lovaza®); and
  5. For Brand Vascepa® only, inadequate response or inability to tolerate generic Icosapent ethyl capsules

Initial authorization duration: 6 Months

REAUTHORIZATION CRITERIA: Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

  1. Documentation of positive clinical response to therapy; and
  2. Member continues to use the medication adjunct to an appropriate lipid-lowering diet

Reauthorization duration: 2 years

Hypertriglyceridemia—Reduction of risk of cardiovascular events

INITIAL CRITERIA Icosapent ethyl (Vascepa®) is approved when ALL of the following are met:

  1. Diagnosis of hypertriglyceridemia; and
  2. Member is 18 years of age or older; and  
  3. Member has pre-treatment triglyceride level between 150 mg/dL to 499 mg/dL; and
  4. ONE of the following: 
    1. Member has established cardiovascular disease; OR
    2. Both of the following:
      1. Diagnosis of diabetes mellitus; and
      2. Member has 2 or more additional risk factors for cardiovascular disease (e.g., cigarette smoking, hypertension, creatinine clearance less than 60 ml/min, etc.); and
  5. One of the following:
    1. Member has been receiving 12 consecutive weeks of statin therapy at maximally tolerated dose and will continue to receive statin therapy at maximally tolerated dose; or
    2. ​​Inability to tolerate statin therapy; and
  6. For Brand Vascepa® only, inadequate response or inability to tolerate generic Icosapent ethyl capsules

​Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA Icosapent ethyl (Vascepa®) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy; and
  2. One of the following:
    1. Member continues to receive statin therapy at maximally tolerated dose; or
    2. Inability to tolerate statin therapy

 

 

Reauthorization duration: 2 years


 


​N/A

Skulas-Ray AC, Wilson PWF, Harris WS et al on behalf of the American Heart Association. Omega-3 fatty acids for the management of hypertriglyceridemia. Circulation. 2019;140. Accessed June 23, 2023.

Vascepa® (icosapent ethyl) [prescribing information]. Bridgewater, NJ: Amarin Pharma, Inc.; September 2021. Available from: https://amarincorp.com/docs/Vascepa-PI.pdf. Accessed June 23, 2023.

Yuan, G, Al-Shali, KZ, Hegele, RA. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ. 2007;176:1113–1120. doi: 10.1503/cmaj.060963. Accessed June 23, 2023.


 

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​Off-Label Use Rx.01.33​


 

Brand nameGeneric name
Vascepa®Icosapent ethyl


 

268
  
10/1/2023Rx.01.229CommercialOyenusi, Oluwadamilola

The life cycle of HIV can be broken down into 6 steps: (1) entry (binding and fusion), (2) reverse transcription, (3) integration, (4) replication (transcription and translation), (5) assembly, and (6) budding and maturation. The identification and understanding of these processes have provided the basis for antiretroviral agents used to treat HIV.

Antiretroviral agents are the standard of care for treating HIV infections. Antiretroviral therapies with different mechanism of action are usually taken in combination to suppress viral load, improve CD4 cell count, prolong survival, and reduce risk of transmitting HIV to others. Viral failure is defined as patients who had viral loads greater than 400 copies/mL and no viable antiretroviral combination therapy available due to failing at least four of six antiretroviral classes.

Fostemsavir is a prodrug without significant biochemical or antiviral activity that is hydrolyzed to the active moiety, temsavir, which is an HIV-1 attachment inhibitor. Temsavir binds directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160 and selectively inhibits the interaction between the virus and cellular CD4 receptors, thereby preventing attachment. Additionally, temsavir can inhibit gp120-dependent post-attachment steps required for viral entry into host cells

Rukobia (fostemsavir), in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

Enfuvirtide is an antiretroviral drug that interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes.

Fuzeon (enfuvirtide) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy



​The intent of this policy is to communicate the medical necessity criteria for Rukobia® (fostemsavir) and Fuzeon® (enfuvirtide) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Fostemsavir (Rukobia®) is approved when ALL of the following are met:
  1. Diagnosis of HIV-1; and 
  2. Member is 18 years of age or older; and 
  3. Will be used in combination with other antiretroviral(s); and 
  4. Member is treatment-experienced with multi-drug resistant HIV-1 infection; and
  5. Member is failing their current antiretroviral regimen due to resistance, intolerance, or safety concerns.

Initial Authorization duration: 12 months

CONTINUATION CRITERIA: Fostemsavir (Rukobia®) is re-approved when there is documentation of positive clinical response to therapy (e.g., decrease in viral load from baseline; HIV-1 RNA <200 copies/mL was achieved; increase in CD4+ cell count over time)

Continuation authorization duration: 2 years

INITIAL CRITERIA: Enfuvirtide (Fuzeon®) is approved when ALL of the following are met: 
  1. Diagnosis of HIV-1; and
  2. Member weighs at least 11kg; and
  3. Will be used in combination with other antiretroviral(s); and
  4. Member is treatment experienced; and
  5. Member is experiencing HIV-1 replication despite ongoing antiretroviral therapy

Initial authorization duration: 12 months

CONTINUATION CRITERIA: Enfuvirtide (Fuzeon®) is re-approved when there is documentation of positive clinical response to therapy (e.g., decrease in viral load from baseline; HIV-1 RNA <200 copies/mL was achieved; increase in CD4+ cell count over time)

Continuation authorization duration: 2 years



​N/A

Rubkobia® (fostemsavir) [package insert]. Research Triangle Park, NC: ViiV Healthcare; January 2022. Available from: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/RUKOBIA/pdf/RUKOBIA-PI-PIL.PDF. Accessed June 22, 2023.

Henrich TJ, Kuritzkes DR. HIV-1 entry inhibitors: recent development and clinical use. Curr Opin Virol. 2013;3(1):51-57. doi:10.1016/j.coviro.2012.12.002. Accessed June 22, 2023.

Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2010–2015. HIV Surveillance Supplemental Report 2018;23(No. 1). http://www.cdc.gov/ hiv/library/reports/hiv-surveillance.html. Published March 2018. Accessed June 22, 2023.

Kozal M, Aberg J, Pialoux G, et al. Rostemsavir in Adults with Multidrug-Resistant HIV-1 infection, N Eng J Med. 2020 26 March; 382:1232-1243. Accessed June 22, 2023.

Rukobia (fostemsavir), Micromedex. Accessed June 22, 2023.

Fuzeon (enfuvirtide) prescribing information. South San Francisco (CA): Genentech, Inc.; December 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6935e846-d5a1-49e5-89a2-f8ebe4d5590d#S12.4. Accessed June 22, 2023.


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​Rx.01.33 Off Label Use


Brand NameGeneric Name
Rukobia®Fostemsavir
Fuzeon®Enfuvirtide
269
  
10/1/2023Rx.01.240CommercialOyenusi, Oluwadamilola

Blepharoptosis, or ptosis of the eyelid, refers to drooping of the upper eyelid that usually results from a congenital or acquired abnormality of the muscles that elevate the eyelid. Ptosis may be the presenting sign or symptom of serious neurologic disease. Depending on the degree of ptosis, presenting symptoms may range from an asymptomatic subtle cosmetic defect to significant visual deficits. Standard of care is surgery. While effective in improving visual function and quality-of-life measures, there are risks associated with surgical intervention. The Müller muscle, an accessory smooth muscle, maintains upper eyelid elevation and is innervated by the sympathetic nervous system. Therefore, the Müller muscle is a common surgical and pharmacological target. 

Oxymetazoline is an alpha adrenoceptor agonist targeting a subset of adrenoreceptors in Mueller's muscle of the eyelid. Oxymetazoline (Upneeq™) is indicated for the treatment of acquired blepharoptosis in adults.

Oxymetazoline (Upneeq™), when used solely to change the appearance of any portion of the face, without improving the physiologic functioning of that portion of the body, is considered cosmetic use. 


​The intent of this policy is to communicate the medical necessity criteria for Oxymetazoline (Upneeq™) as provided under the member's prescription drug benefit. 


INITAL CRITERIA: Oxymetazoline (Upneeq™) is approved when ALL of the following are met:

  1. Diagnosis of acquired blepharoptosis; and
  2. Request is not for an excluded benefit (i.e. cosmetic - solely for lifting the eyelid to improve appearance); and
  3. Member has obstructed visual field in primary gaze or down gaze due to blepharoptosis; and
  4. One of the following:
    1. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in primary gaze; or
    2. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in down gaze; or
    3. Superior visual field loss of at least 12 degrees or 24 percent; and
  5. Other treatable causes of blepharoptosis have been ruled out (e.g., recent botulinum toxin injection, myasthenia gravis); and
  6. Prescribed by or in consultation with an ophthalmologist or optometrist
Initial authorization duration: 3 months​


REAUTHORIZATION CRITERIA: Oxymetazoline (Upneeq™) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., improvement in superior visual field, increase in Marginal reflex distance-1 [MRD-1]); and
  2. One of the following:
    1. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in primary gaze; or
    2. Marginal reflex distance-1 (MRD-1) is less than or equal to 2mm in down gaze; or
    3. Superior visual field loss of at least 12 degrees or 24 percent

Reauthorization duration: 12 months



​N/A

Upneeq™ (oxymetazoline hydrochloride ophthalmic solution) [prescribing information]. Bridgewater, NJ: RVL Pharmaceuticals, Inc; May 2023. Available from: https://www.upneeq.com/Upneeq-PI.pdf. Accessed June 23, 2023.

Slonim CB, Foster S, Jaros M, et al. Association of Oxymetazoline Hydrochloride, 0.1%, Solution Administration With Visual Field in Acquired Ptosis: A Pooled Analysis of 2 Randomized Clinical Trials [published online ahead of print, 2020 Oct 1]. JAMA Ophthalmol. 2020;138(11):1168-1175. doi:10.1001/jamaophthalmol.2020.3812

Lee, MS. Overview of ptosis. UpToDate Web site. March 2023. www.uptodate.com. Accessed June 23, 2023.






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​Rx.01.33 Off Label Use

Brand NameGeneric Name
Upneeq™Oxymetazoline hydrochloride


270
  
10/1/2023Rx.01.255CommercialOyenusi, Oluwadamilola

Chronic kidney disease exacerbates the cardiovascular risk associated with type 2 diabetes.

Mineralocorticoid receptor overactivation is associated with kidney and cardiovascular diseases, through inflammation and fibrosis that lead to progressive kidney and cardiovascular dysfunction.

Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.

Kerendia® (finerenone) is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease associated with type 2 diabetes.



​The intent of this policy is to communicate the medical necessity criteria for finerenone (Kerendia®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Finerenone (Kerendia®) is approved when ALL of the following are met:

  1. Diagnosis of chronic kidney disease (CKD) associated with type 2 diabetes (T2D); and
  2. Member is 18 years of age or older; and
  3. One of the following:
    1. Minimum 30-day supply trial of a maximally tolerated dose and will continue therapy with ONE of the following:
      1. Generic angiotensin-converting enzyme (ACE) inhibitor (e.g., benazepril, lisinopril); or
      2. Generic angiotensin II receptor blocker (ARB) (e.g., losartan, valsartan); or
    2. Member has contraindication or intolerance to ACE inhibitors or ARBs

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Finerenone (Kerendia®) is re-approved with documentation of positive clinical response to therapy (e.g., reduced incidence of a sustained declined in eGFR, kidney failure, or renal death)

Reauthorization duration: 2 years

​N/A

Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi: 10.1056/NEJMoa2110956. Accessed June 22, 2023.

Kerendia® (finerenone) [package insert]. Whippany, NJ: Bayer HealthCare Pharma, Inc.; September 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf. Accessed June 22, 2023.

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​Rx.01.33 Off Label Use

Brand Name

Generic Name

​Kerendia®

​finerenone

272
  
10/1/2023Rx.01.261CommercialOyenusi, Oluwadamilola

​The normal eye creates a clear image by bending (refracting) light in order to focus it onto the retina. Refractive errors occur when a component of the eye's optical system fails to focus the optical image. Presbyopia ("aging sight") is a non-refractive error that also affects visual acuity. Presbyopia occurs when the lens loses its normal accommodating power and can no longer focus on objects viewed at arm's length or closer. Approximately 128 million adults in the United States are living with presbyopia. Presbyopia has traditionally been treated with corrective lenses or surgery.

Pilocarpine (Vuity™) is indicated for the treatment of presbyopia in adults.

Pilocarpine hydrochloride is a cholinergic muscarinic agonist which activates muscarinic receptors located at smooth muscles such as the iris sphincter muscle and ciliary muscle. Vuity contracts the iris sphincter muscle, constricting the pupil to improve near and intermediate visual acuity while maintaining some pupillary response to light. Vuity also contracts the ciliary muscle and may shift the eye to a more myopic state.

​The intent of this policy is to communicate the medical necessity criteria for Pilocarpine (Vuity™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Pilocarpine (Vuity™) is approved when ALL of the following are met:

  1. Diagnosis of presbyopia; and
  2. Prescribed by or in consultation with ONE of the following:
    1. Ophthalmologist; or
    2. Optometrist; and
  3. Member is unable to use corrective lenses (e.g., eyeglasses or contact lenses)

Initial authorization duration: 1 month 

REAUTHORIZATION CRITERIA: Pilocarpine (Vuity™) is re-approved when BOTH of the following are met:
  1. Documentation of positive clinical response to therapy (e.g., improvement in near vision in low light conditions without loss of distance vision); and
  2. Prescribed by or in consultation with one of the following:
    1. Ophthalmologist; or
    2. Optometrist

Reauthorization duration: 6 months 

​N/A

Mian, SI. Visual impairment in adults: Refractive disorders and presbyopia. UpToDate. September 2022. Available at: https://www.uptodate.com/contents/visual-impairment-in-adults-refractive-disorders-and-presbyopia?search=presbyopia&source=search_result&selectedTitle=1~17&usage_type=default&display_rank=1. Accessed June 22, 2023.

Vuity (pilocarpine hydrochloride) [prescribing information]. North Chicago, IL: AbbVie Inc; March 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d806897-8a2a-4518-8c68-0ec3b778de50 . Accessed June 22, 2023.​


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​Rx.01.33 Off Label Use

Brand NameGeneric Name
​Vuity™​Pilocarpine
273
  
10/1/2023Rx.01.263CommercialOyenusi, Oluwadamilola

Vernal keratoconjunctivitis (VKC) is an allergic inflammation of conjunctiva that is bilateral and usually seasonally recurrent. There are three types of vernal conjunctivitis: palpebral (papillae primarily involving upper tarsal conjunctiva), limbal (papillae located at limbus), and mixed (components of both palpebral and limbal types). Histopathologic exam of affected conjunctiva shows small lymphoid follicles composed of increased mast cells, eosinophils, and lymphocytes, mononuclear cells and macrophages, CD4 T lymphocytes and B lymphocytes, fibroblasts, and newly secreted collagen (extracellular matrix components). As disease progresses, cellular infiltration and new collagen deposition form giant papillae (squamous epithelial hyperplasia and dense fibrous tissue containing inflammatory cells). Inflammation of limbal palisades and tarsal conjunctiva produces nodules, due to firm attachments of conjunctiva.

Cyclosporine is a calcineurin inhibitor immunosuppressant agent when administered systemically. Following ocular administration, cyclosporine is thought to act by blocking the release of pro-inflammatory cytokines such as IL-2. The exact mechanism of action in the treatment of VKC is not known.

Verkazia® ophthalmic emulsion is a calcineurin inhibitor immunosuppressant indicated for the treatment of vernal keratoconjunctivitis in children and adults.


​The intent of this policy is to communicate the medical necessity criteria for Cyclosporine (Verkazia®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA Cyclosporine (Verkazia®) is approved when ALL of the following are met:

  1. Diagnosis of moderate to severe vernal keratoconjunctivitis confirmed by the presence of clinical signs and symptoms (e.g., itching, photophobia, giant papillae at the upper tarsal conjunctiva or at the limbus, thick mucus discharge, conjunctival hyperaemia); and
  2. Member is 4 years of age or older; and
  3. Inadequate response or inability to tolerate one of the following:
    1. Topical ophthalmic “dual-acting” mast cell stabilizer and antihistamine (e.g., olopatadine, azelastine); or
    2. Topical ophthalmic mast cell stabilizers (e.g., cromolyn); and
  4. Inadequate response or inability to tolerate short term use (up to 2 to 3 weeks), of topical ophthalmic corticosteroids (e.g., dexamethasone, prednisolone, fluoromethalone); and
  5. Prescribed by or in consultation with one of the following:
    1. Ophthalmologist or
    2. Optometrist

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA Cyclosporine (Verkazia®) is re-approved when there is documentation of positive clinical response to therapy as evidenced by an improvement in clinical signs and symptoms (e.g., itching, photophobia, papillary hypertrophy, mucus discharge, conjunctival hyperaemia).

Reauthorization duration: 2 years



​N/A

DynaMed. Vernal Keratoconjunctivitis. EBSCO Information Services. https://www.dynamed.com/condition/vernal-keratoconjunctivitis. Accessed June 23, 2023.

 

Verkazia® (cyclosporine) [package insert]. Emeryville, CA: Santen Incorporated; June 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214965s000lbl.pdf. Accessed June 23, 2023.​




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Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit



Brand NameGeneric Name
Verkazia®Cyclosporine


274
  
10/1/2023Rx.01.265CommercialOyenusi, Oluwadamilola

​Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease characterized by hypertrophy of a nondilated left ventricle in the absence of any other cardiac or systemic disease (such as hypertension) that could account for observed hypertrophy, microvascular dysfunction and myocardial fibrosis. Histopathological features include myofiber disarray and myocardial fibrosis resulting from microvascular ischemia and cell death. HCM is caused largely by mutations in genes encoding thick and thin contractile myofilament proteins of the cardiac sarcomere. Phenotypically, HCM can be obstructive (70% of patients), with presence of left ventricular outflow tract obstruction, or nonobstructive (30% of patients). Complications include syncope, heart failure, and sudden death.


Mavacamten is an allosteric and reversible inhibitor selective for cardiac myosin. Mavacamten modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. Mavacamten shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.

Mavacamten is indicated for treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.



​The intent of this policy is to communicate the medical necessity criteria for Mavacamten (Camzyos™) as provided under the member's prescription drug benefit.

​INITIAL CRITERIA: Mavacamten (Camzyos™) is approved when ALL of the following are met:


  1. Submission of medical records (e.g., chart notes, lab values) confirming a diagnosis of symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM); and 
  2. Members is 18 years of age or older; and 
  3. Member’s baseline left ventricular ejection fraction (LVEF) is greater than or equal to 55%; and 
  4. Member has Valsalva left ventricular outflow tract (LVOT) peak gradient greater than or equal to 50 mmHg at rest or with provocation; and
  5. Inadequate response or inability to tolerate BOTH of the following at a maximally tolerated dose:
    1. Non-vasodilatingOne beta blocker (e.g., bisoprolol, propranolol); orand
    2. Calcium channel blocker (e.g., verapamil, diltiazem); and
  6. Prescribed by or in consultation with a cardiologist

Initial authorization duration: 6 months


REAUTHORIZATION CRITERIA: Mavacamten (Camzyos™) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., improved symptom relief); and
  2. Member's left ventricular ejection fraction (LVEF) is greater than or equal to 50%; and
  3. Prescribed by or in consultation with a cardiologist.
Reauthorization duration: 12 months​


​Risk of Heart Failure

  • CAMZYOS can cause heart failure due to systolic dysfunction.
  • Echocardiogram assessments of left ventricular ejection fraction (LVEF) required before and during CAMZYOS use.
  • Initiation in patients with LVEF <55% not recommended. Interrupt if LVEF <50% or if worsening clinical status.
  • Certain CYP450 inhibitors and inducers are contraindicated in patients taking CAMZYOS because of an increased risk of heart failure.

CAMZYOS is available only through a restricted program called the CAMZYOS REMS Program.


DynaMed. Hypertrophic Cardiomyopathy. EBSCO Information Services. https://www.dynamed.com/condition/hypertrophic-cardiomyopathy. Accessed June 26, 2023.

 

Camzyos™ (mavacamten) [prescribing information]. Brisbane, CA: MyoKardia, Inc.; June 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214998s000lbl.pdf. Accessed June 26, 2023.


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​Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit




Brand NameGeneric Name
CamzyosTMMavacamten


275
  
10/1/2023Rx.01.266CommercialOyenusi, Oluwadamilola

Hemolytic anemia is a disease that results in the premature death (hemolysis) of red blood cells (RBC) at a faster rate than the body can produce. Hemolytic anemia can be categorized as intrinsic and extrinsic. Intrinsic hemolytic anemia is genetically inherited and results in abnormalities in the cell membrane and overall blood cell production. Extrinsic hemolytic anemia is acquired as a secondary effect resulting from certain immunologic diseases, infections and medications. The glycolytic pathway is a metabolic pathway that breaks down glucose into pyruvate via the Pyruvate kinase (PK) enzyme, which leads to the production of ATP and NADH. A deficiency in the pyruvate kinase enzyme in homozygous patients causes a defect in the glycolytic pathway that is known to cause hemolytic anemia. The exact mechanism of hemolysis is unknown.

Mitapivat is a Pyruvate Kinase activator that targets defective PK enzymes in RBC’s. 

Mitapivat (Pyrukynd®) is indicated for the treatment hemolytic anemia in adults with a PK enzyme deficiency.



​The intent of this policy is to communicate the medical necessity criteria for Mitapivat (Pyrukynd®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Mitapivat (Pyrukynd®) is approved when ALL of the following are met: 

  1. Diagnosis of hemolytic anemia confirmed by the presence of chronic hemolysis (e.g., increased indirect bilirubin, elevated lactated dehydrogenase [LDH], decreased haptoglobin, increased reticulocyte count); and
  2. Diagnosis of pyruvate kinase deficiency confirmed by molecular testing of ALL of the following mutations on the PLKR gene:
    1. Presence of at least 2 variant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene, of which at least 1 was a missense variant; and
    2. Member is not homozygous for the c.1436G>A (p.R479H) variant; and 
    3. Member does not have 2 non-missense variants (without the presence of another missense variant) in the PKLR gene; and 
  3. Hemoglobin is less than or equal to 10g/dL; and 
  4. Member has symptomatic anemia or is transfusion dependent; and 
  5. Other causes of hemolytic anemias (e.g., infections, toxins, drugs) were ruled out; and 
  6. Member is 18 years of age and older; and 
  7. Prescribed by or in consultation with a hematologist 

Initial authorization duration: 6 months 

REAUTHORIZATION CRITERIA: Mitapivat (Pyrukynd®) re-approved when ALL of the following are met: 
  1. Documentation of positive clinical response to therapy (e.g., hemoglobin greater than or equal to 1.5g/dL from baseline sustained on 2 or more follow ups (weeks 16, 20 and 24) during the fixed dose period without transfusions; reduction in transfusions of greater than or equal to 33% in the number of red blood cell units transfused during the fixed dose period compared with the member’s historical transfusion burden; improvement in markers of hemolysis from baseline (e.g., bilirubin, lactated dehydrogenase [LDH], haptoglobin, reticulocyte count)); and 
  2. Prescribed by or in consultation with a hematologist 

Reauthorization duration: 12 months 




​N/A

Pyrukynd® (mitapivat) [prescribing information]. Agios Pharmaceuticals, Inc.; February 2022. https://www.pyrukynd.com/hcp/. Accessed June 22, 2023.

 

Braunstein EM. Glycolytic Pathway Defects. Merck & Co., Inc., Rahway, NJ.; June 2022. https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/glycolytic-pathway-defects. Accessed June 22, 2023.




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​Rx.01.33 Off Label Use​

Brand NameGeneric Name
Pyrukynd®Mitapivat


286
  
1/1/2024Rx.01.89CommercialOyenusi, Oluwadamilola

Hyponatremia is defined as a relative excess of water in relation to sodium.  Treatment approaches depend on the duration, severity, and cause of hyponatremia.

Tolvaptan (Samsca®) is a selective vasopressin V2 receptor antagonist. Tolvaptan antagonizes the effect of vasopressin and causes an increase in urine water excretion that results in an increase in free water clearance, a decrease in urine osmolality and a resulting increase in serum sodium concentrations.

Tolvaptan (Samsca®) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium < 125meq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) including patients with heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the growth of numerous fluid filled cysts in the kidneys which progressively decreases kidney function and lead to permanent kidney damage. It is the most common inherited disorder of the kidneys. Symptoms usually develop between the ages of 30 and 40, but they can begin earlier, even in childhood.

Tolvaptan (Jynarque®) is a selective vasopressin (V2) receptor antagonist.  Patients with autosomal dominant polycystic kidney disease have elevated levels of vasopressin. Tolvaptan works by preventing vasopressin from binding to its receptor which then decreases the rate of cell proliferation and fluid secretion into the cystic lumen, ultimately inhibiting the growth of the fluid filled cysts in the kidneys and slows the worsening of kidney function.

Tolvaptan (Jynarque®) is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

The intent of this policy is to communicate the medical necessity criteria for tolvaptan (Samsca®, Jynarque®) as provided under the member's prescription drug benefit.


Hyponatremia

INITIAL CRITERIA Tolvaptan (Samsca®) is approved when ALL of the following are met:

  1. Member is 18 years of age or older; and
  2. Clinically significant hypervolemic or euvolemic hyponatremia  and ONE of the following:
    1. Serum sodium less than 125meq/L; or
    2. Serum sodium 125-134meq/L with symptoms (ie nausea, vomiting, headache, lethargy, confusion, etc);

      and
  3. Inadequate response or inability to tolerate therapies to control hyponatremia (ie fluid restriction, diuretics, demeclocycline,  etc); and
  4. Prescribed by or in consultation with a cardiologist, nephrologist, or endocrinologist; and
  5. Brand Samsca only, inadequate response or inability to tolerate generic tolvaptan​

Initial authorization duration: 30 days

REAUTHORIZATION CRITERIA Tolvaptan (Samsca®) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response; and
  2. Liver function is monitored and there are no signs or symptoms of liver injury; and
  3. Prescriber is aware of the risk of liver injury with use beyond 30 days
Reauthorization duration: 12 months


Autosomal dominant polycystic kidney disease

INITIAL CRITERIA Tolvaptan (Jynarque®) is approved when ALL of the following are met:

  1. Member is 18 years of age or older; and
  2. Diagnosis of autosomal dominant polycystic kidney disease with risk of rapidly progressing kidney disease; and
  3. Baseline serum transaminases and bilirubin obtained prior to initiation of therapy; and
  4. Prescribed by or in consultation with nephrologist or kidney transplant specialist

Initial authorization duration: 3 months
 
REAUTHORIZATION CRITERIA Tolvaptan (Jynarque®) is re-approved when ALL of the following are met:

  1. ONE of the following
    1. Decline in kidney function has slowed; or
    2. Kidney pain has improved; and
  2. Serum transaminase less than 3 times the upper limit of normal; AND
  3. Bilirubin less than 2 times upper limit of normal

Reauthorization duration: 12 months


Tolvaptan (Samsca®)
INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM
Tolvaptan (Samsca®) should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely.
Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.


Tolvaptan (Jynarque®) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported.
Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity.
Because of the risks of serious liver injury, Jynarque® is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the JYNARQUE REMS Program

Jynarque® (tolvaptan) [package insert] Tokyo, Japan. Otsuka Pharmaceutical Co, Ltd. -October 2020. Available at: https://www.otsuka-us.com/media/static/JYNARQUE-PI.pdf. Accessed - November 17, 2023..

 

Samsca® (tolvaptan) [package insert]. Tokyo, Japan. Otsuka Pharmaceutical Co, Ltd. -April 2021. Available at:https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566&type=display.  Accessed November 17, 2023.

 

Sterns RH. Overview of the treatment of hyponatremia in adults. UpToDate. June 2021. Available at: https://www.uptodate.com/contents/overview-of-the-treatment-of-hyponatremia-in-adults?source=search_result&search=hyponatremia&selectedTitle=2~150#H25. Accessed November 17, 2023.

 

Tolvaptan (Kidney Disease): MedlinePlus Drug Information." MedlinePlus, U.S. National Library of Medicine, 15 July 2018, medlineplus.gov/druginfo/meds/a609033.html.​



149/14/20239/14/20241/1/2024 1:22 AMNo presence informationsrv_ppsgw_P
Off-Label Use Policy Rx.01.33
 

Brand NameGeneric Name
Samsca®Tolvaptan
Jynarque®Tolvaptan
289
  
1/1/2024Rx.01.61CommercialOyenusi, Oluwadamilola
 
The Company utilizes a tiered cost-sharing structure for medications covered under the pharmacy benefit.  Members should refer to their benefit booklet for more information.
 

Formulary Tier Exceptions

The following tier exceptions requests will be considered:

 

Select Drug Formulary

  1. Non-preferred drug to be covered at the:
    1. Preferred brand tier if the product is a brand medication; or
    2. Generic tier if the product is generic medication
  2. All other tiers are restricted to the benefit design and thus are not eligible for a tier exception

Value Formulary

  1. Non-formulary medication to be covered at the highest level of cost share.  These exceptions are not eligible for tier reduction.
  2. Non-preferred drug to be covered at the:
    1. Preferred brand tier if the product is a brand medication; or
    2. Generic tier if the product is generic medication
  3. All other tiers are restricted to the benefit design and thus are not eligible for a tier exception.

CHIP

  1. Non-preferred drug medication to be covered at the:
    1. Preferred brand tier if the product is a brand; or
    2. Generic tier if the product is generic
  2. Brand medication to be covered at the generic benefit level

The following tiers are defined by the benefit and are not eligible for a tier exception:

  1. Specialty tier
  2. Preferred brand tier
  3. Generic tier

Cost Share Exceptions for Preventive Care Services and Women's Preventive Services

The services listed in this policy are considered preventive care services when the criteria in this policy are met, when they are identified as preventive services in the Company's benefit contracts and when they are mandated by state or federal law.  This policy supports the preventative care services listed in the US Preventive Services Task Force (USPSTF) as A or B Recommendations and the Women's Preventive Services (WPS) provision of Patient Protection and Affordable Care Act (PPACA). These products are available without cost-sharing with a prescription when provided by a participating retail or mail-order pharmacy.

Based on the USPSTF recommendation the following products are available at zero-dollar cost-share.  All medications refer to generic, single ingredient products unless otherwise noted.

 
 
CategoryRecommendationMedication
​ASPIRIN

Pregnant Women Who Are At High Risk for Preeclampsia :

The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication after 12 weeks of gestation in pregnant females who are at high risk for preeclampsia.

aspirin 81mg or less
TOBACCO CESSATION MEDICATIONTobacco cessation medication is covered as a preventive service for all adults who use tobacco products.Chantix ®, bupropion, Nicotrol®, generic nicotine gums and patches
FOLIC ACIDThe USPSTF recommends that all females planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid.folic acid 400 mcg to 800 mcg (including generic prenatal vitamins with the above listed folic acid dose)
FLUORIDEIn accordance with the preventive exam age schedule set forth by American Academy of Pediatrics (AAP)/Bright Futures, oral fluoride, up to 0.5mg, is covered as a preventive service for children ages 6 months to 16 years whose water supply is deficient in fluoride.fluoride up to 0.5mg for children 6 months to 16 years of age
BREAST CANCER CHEMO-PREVENTIONThe USPSTF recommends that clinicians engage in shared, informed decision making with individuals who are at increased risk for breast cancer about medications to reduce their risk. For asymptomatic females 35 years or older without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ, who are at increased risk for breast cancer and at low risk for adverse medication effects from breast cancer chemoprevention, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen.tamoxifen 20mg
CONTRACEPTIVESThe contraceptive methods for women currently identified by the FDA include: (1) sterilization surgery for women; (2) surgical sterilization implant for women; (3) implantable rod; (4) IUD copper; (5) IUD with progestin; (6) shot/injection; (7) oral contraceptives (combined pill); (8) oral contraceptives (progestin only); (9) oral contraceptives extended/continuous use; (10) patch; (11) vaginal contraceptive ring; (12) diaphragm; (13) sponge; (14) cervical cap; (15) condom; (16) spermicide; (17) emergency contraception; and (18) emergency contraception (Ella)injection/shot, oral contraceptives, etonogestrel-ethinyl estradiol vaginal ring, diaphragms, sponge, cervical cap, condom, spermicide, emergency contraceptive, Ella®, Phexxi®.  [Note: IUDs and implantable products are covered under the medical benefit. See referenced policy]
BOWEL PREP FOR COLONOSCOPYThe USPSTF recommends screening for colorectal cancer starting at age 45 years and continuing until age 75 years.PEG 3350- electrolyte, Gavilyte-C, Gavilyte-G, Gavilyte-N, Trilyte with flavor packets, Gavilyte-H with bisacodyl, PEG-prep,PEG 3350 powder for solution
STATIN PREVENTIVE MEDICATION

The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (i.e. dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year risk of a cardiovascular event of 10% or greater.

lovastatin 10, 20, 40 mg
HIV PrEPPreexposure prophylaxis (PrEP) with effective antiretroviral therapy for persons who are at high risk of HIV acquisition

emtricitabine/tenofovir disoproxil

fumarate 200mg-300mg,

tenofovir 300mg



Certain medications have additional indications that are not addressed by the preventative care measure, such as raloxifene, or have generic alternatives, such as branded contraceptives.  Thus, the plan employs medical management to administer the requirements. The policy below outlines the process by which an exception can be obtained for medications that may apply to the USPSTF recommendation or the WPS provision of the PPACA but are not coded as $0 at the point-of-sale.

 

*This policy does not apply to the Premium Formulary
The intent of this policy is to communicate the medical necessity criteria for formulary exception requests as provided under the member's prescription drug benefit.
Tier Exceptions:

A non-preferred drug will be covered at the preferred tier for brand medications as listed below when there is documentation of inadequate response or inability to tolerate at least three preferred or generic tier alternatives in the same pharmacological class*. Reasonably equivalent therapeutic class alternatives will be considered when there are limited pharmacological class alternatives available.

  1. Brand medication to preferred brand tier or
  2. Generic medication to generic tier

Non-formulary Exceptions:

A medication that is non-formulary, will be covered at the appropriate level of cost share when the following is met:

There is documentation of inadequate response or inability to tolerate at least three formulary alternatives in the same pharmacological class*. Reasonably equivalent therapeutic class alternatives will be considered when there are limited pharmacological class alternatives available. Safety edits (age and quantity limits) will apply to non-formulary requests



CHIP (IN Focus ID 10093453)

A brand medication may be covered at the generic benefit level when there is documentation of an inadequate response or inability to tolerate at least three generic alternatives in the same pharmacological class*. Reasonably equivalent therapeutic class alternatives will be considered when there are limited pharmacological class alternatives available.


Compounded Products:

A non-preferred compounded product may be covered at the preferred (formulary) tier when there is an inadequate response or inability to tolerate/use all other formulary alternatives.

Note: Compounded products are specially made products to meet the needs of an individual member and are not considered generics and thus not eligible for an exception to the generic tier.

$0 Cost-Share Override

An exception to allow no-cost share is approved when:

  1. The drug is described as either a preventative medication identified by the US Preventive Services Task Force (USPSTF) or Women's Preventive Services provision of the Patient Protection and Affordable Care Act (PPACA); and if applicable
  2. For branded products, ALL of the following:
    1. Inadequate response or inability to tolerate the generic equivalent, if available
    2. Inadequate response or inability to tolerate a generic alternative
    3. The prescriber has provided documentation indicating the requested product is medically necessary

*If there are fewer than three alternatives, all alternatives in the pharmacological class must be considered.

Premium Formulary: This policy does not apply to the premium formulary.

Authorization duration: 2 years

Truvada® (emtricitabine and tenofovir disoproxil fumarate), tenofovir

  1. Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued Truvada® and tenofovir. Hepatic function should be monitored closely in HBV-infected patients who discontinue Truvada® and tenofovir. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Truvada® (emtricitabine and tenofovir disoproxil fumarate)

  1. Truvada® used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug resistant HIV-1 variants have been identified with the use of Truvada® for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate Truvada® for HIV-1 PrEP if signs or symptoms of acute HIV infection are present unless negative infection status is confirmed.
 
 
 

 

Bright Futures Period Schedule. Available at:  https://downloads.aap.org/AAP/PDF/periodicity_schedule.pdf. Accessed November 21, 2023.

USPSTF A and B Recommendations by Date. US Preventive Services Task Force Web Site. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations?SORT=D&DESC=1.  Updated September 2022. Accessed November 21, 2023.

Truvada® (emtricitabine and tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; June 2020. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/hiv/truvada/truvada_pi.pdf. Accessed November 21, 2023.

Viread® (tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; April 2019. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf. Accessed November 21, 2023.



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Rx.01.33 Off Label Use

Rx.01.2 Applicable Age Edits

Rx.01.134 Compounded Product

Rx.01.76 Quantity Level Limits for Pharmaceutical Covered under the Pharmacy Benefit

Rx.01.197 Opioid Policy

00.06.02 Preventive Care Services Medical Policy ​


 


N/A

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1/1/2024Rx.01.10CommercialOyenusi, Oluwadamilola

Hyperammonemia is a urea cycle disorder due to a deficiency of an enzyme in the pathway that can cause life-threatening metabolic decompensations in infancy. Survivors frequently have severe neurologic injury. Frequent vomiting and poor appetite with food refusal and protein aversion are common in patients with UCD. In newborns, central hyperventilation leading to respiratory alkalosis is an early sign of hyperammonemia. Infants become symptomatic after feeding in which initial signs include somnolence, inability to maintain normal body temperature, poor feeding followed by vomiting lethargy and coma.


 

N-acetylglutamate synthetase (NAGS) deficiency is a rare, autosomal, recessive genetic disorder in which lack of NAGS enzyme leads to hyperammonemia (excess ammonia).  NAGS deficiency is one of several urea cycle disorders.


Carglumic acid (Carbaglu®) is a synthetic structural analogue of N-acetylglutamate (NAG), which is produced from glutamate and acetyl-CoA in a reaction catalyzed by N-acetylglutamate synthase (NAGS), a mitochondrial liver enzyme. NAG acts as an essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS 1) in liver mitochondria. CPS 1  catalyzes the first reaction  of the urea cycle, . NAG is the product of NAGS, a mitochondrial liver enzyme. Carglumic acid acts as a CPS 1 activator   in NAGS deficiency patients , thereby facilitating ammonia detoxification and urea production by removing the block in the urea cycle

Carglumic Acid (Carbaglu®) is indicated for adjunctive therapy in the treatment of acute hyperammonemia due to NAGS deficiency, propionic acidemia (PA) or methylmalonic acidemia (MMA), and maintenance therapy of chronic hyperammonemia due to the deficiency of the hepatic enzyme NAGS.

The intent of this policy is to communicate the medical necessity criteria for carglumic acid (Carbaglu®) as provided under the member's prescription drug benefit.

Acute Hyperammonemia due to N-acetylglutamate Synthase (NAGS) Deficiency

APPROVAL CRITERIA: Carglumic Acid (Carbaglu®) is approved when all of the following are met:

  1. Diagnosis of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency; and 
  2. Medication will be used as adjunctive therapy to other ammonia lowering therapies (e.g., protein restriction, ammonia scavengers, dialysis) 
  3. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders

Authorization duration: 3 months

Acute Hyperammonemia due to Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA)

APPROVAL CRITERIA: Carglumic Acid (Carbaglu®) is approved when all of the following:

  1. Diagnosis of acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA); and
  2. Medication will be used as adjunctive therapy to other ammonia lowering therapies (e.g., intravenous glucose, insulin, protein restriction, dialysis); and
  3. Patient's plasma ammonia level is greater than or equal to 50 micromol/L; and
  4. Medication will be used for a maximum duration of 7 days; and
  5. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders


​Authorization duration: 3 months

Chronic Hyperammonemia due to N-acetylglutamate Synthase (NAGS) Deficiency

INITIAL CRITERIA: Carglumic Acid (Carbaglu®) is approved when all of the following:

  1. Diagnosis of chronic hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency; and
  2. NAGS deficiency has been confirmed by genetic/mutational analysis; and
  3. Medication will be used as maintenance therapy; and
  4. Prescribed by or in consultation with a provider who specializes in the treatment of metabolic disorders

Initial authorization duration: 2 years

​REAUTHORIZATION CRITERIA: Carglumic acid (Carbaglu®) is re-approved when there is documentation of positive clinical response to therapy (e.g., plasma ammonia level within the normal range).


Reauthorization duration: 2 years​




N/A

Carbaglu® [package insert]. Lebanon NJ. Recordati Rare Diseases, Inc.  September 2021. Available at: https://www.carbaglu.com/wp-content/uploads/2020/01/carbaglu-prescribing-information.pdf. Accessed NOVEMBER 21, 2023.

N-acetylglutamate synthetase deficiency. National organization for rare disorders. Available at: http://rarediseases.org/rare-diseases/n-acetylglutamate-synthetase-deficiency/. Accessed NOVEMBER 21, 2023.

Lee B. Urea cycle disorders: clinical features and diagnosis. UpToDate website. June 2021. Available at http://www.uptodate.com/. Accessed Accessed NOVEMBER 21, 2023.


 


 

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Off-Labe Use Rx01.33
 

Brand Name Generic Name
Carbaglu® Carglumic Acid
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Male hypogonadism is characterized by low testosterone levels.  Primary hypogonadism is characterized by low testosterone levels in the setting of elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations.  Examples of primary hypogonadism include, but are not limited to, Klinefelter syndrome, castration (physical or chemical), and trauma.  Secondary hypogonadism, also referred to as hypogonadotropic hypogonadism, is characterized by low testosterone levels in the setting of normal or low LH and FSH.  In this type of hypogonadism, dysfunction of the hypothalamus or pituitary is the underlying etiology.  Examples of hypogonadotopic hypogonadism include, but are not limited to, idiopathic hypogonadotropic hypogonadism, Kallman syndrome, and pituitary tumors, surgery, or destruction.


Gender dysphoria, according to the World Professional Association for Transgender Health (WPATH), is defined as the discomfort arising from incongruence between an individual's gender identity and their external sexual anatomy. The standard of care for individuals affected by gender dysphoria include extensive counseling, hormonal therapy and surgery. Androgen hormone therapy is used to induce physical changes to match gender identify in transgender men (female-to-male, FTM). The goal of therapy is to maintain hormone levels in the normal physiological range for the targeted gender, to stop menses and induce virilization, including a male pattern of sexual and facial hair, change in voice, and male physical contours. Both topical and injectable testosterone products are effective for the management of gender dysphoria.

The active ingredient in all products listed is testosterone. Exogenous testosterone serves to replace testosterone in individuals who are deficient.  Testosterone therapy is indicated for replacement therapy in patients with low testosterone levels due to primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). Testosterone enanthate intramuscular injection and methyltestosterone can also be used to stimulate puberty in carefully selected males with clearly delayed puberty. Methyltestosterone is also indicated for the treatment of metastasis from malignant tumor of breast in women 1 to 5 years postmenopausal with inoperable metastatic skeletal disease.

The intent of this policy is to communicate the medical necessity criteria for Androgel®, Androderm®, Fortesta®, Jatenzo®, Tlando®, Natesto®,  Testim®, Vogelxo®, Xyosted™, Kyzatrex®, methyltestosterone (Methitest®), and generic testosterone products as provided under the member’s prescription drug benefit.

Primary or secondary hypogonadism

INITIAL CRITERIA: Androgel®, generic transdermal testosterone products, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), or methyltestosterone (Methitest®) is approved when ALL of the following are met:

    1. Diagnosis of primary or secondary hypogonadism; and
    2. Member is 18 years of age or older; and
    3. ONE of the following:
      1. Negative history of prostate and breast cancer; OR
      2. History of prostate cancer status post prostatectomy and documentation that the risk versus benefit has been assessed; and
    1. For Androgel®, Androderm®,  Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), methyltestosterone(Methitest®) only, inadequate response or inability to tolerate generic transdermal testosterone ; and
    2. New users only, low (morning) testosterone level

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Androgel®, generic transdermal testosterone products, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), methyltestosterone (Methitest®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years​

Gender dysphoria

INITIAL CRITERIA Androgel®, generic transdermal testosterone products, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), or methyltestosterone (Methitest®) is approved for use as hormone therapy in children, adolescents, and adults with gender dysphoria when there is documentation of persistent, well-documented gender dysphoria diagnosed in accordance with criteria established in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Androgel®, generic transdermal testosterone products, Androderm®, Fortesta®, Natesto®, Testim®, Vogelxo®, Xyosted™, testosterone undecanoate (Jatenzo®, Tlando®, Kyzatrex®), methyltestosterone (Methitest®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years
 


 

Transdermal testosterone (Androgel®, Fortesta®, Testim®, Vogelxo®)

Secondary exposure: Virilization has been reported in children who were secondarily exposed to transdermal testosterone. Ensure that children avoid contact with unwashed or unclothed application sites in men using transdermal testosterone.  Advise patients to strictly adhere to recommended instructions for use.

Testosterone enanthate (Xyosted™) and testosterone undecanoate capsule (Jatenzo®, Tlando®, Kyzatrex®)

Blood pressure increase:

  • Xyosted™, Kyzatrex® and Jatenzo® can cause blood pressure (BP) increases that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke and cardiovascular death.
  • Before initiating Xyosted™, Kyzatrex® and Jatenzo®, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled.
  • Periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension and re-evaluate whether the benefits of Xyosted™, Kyzatrex® and Jatenzo®  outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease on treatment.
  • Due to this risk, use Xyosted™, Kyzatrex® and Jatenzo®  only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies.

Androderm® (testosterone) [package insert]. Irvine, CA. Allergan USA, Inc. May 2020. Available from: https://www.allergan.com/assets/pdf/androderm_pi. Accessed NOVEMBER 20, 2023.

AndroGel® (testosterone) [package insert]. North Chicago, IL. AbbVie. May 2019. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8677ba5b-8374-46cb-854c-403972e9ddf3&type=displayAccessed NOVEMBER 20, 2023.

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.

Fortesta® (testosterone) [package insert]. Malvern, PA. Endo Pharmaceuticals, Inc. June 2020. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=053a7300-0bce-11e0-9d16-0002a5d5c51b&type=display. Accessed NOVEMBER 20, 2023.

Gooren L . Hormone treatment of the adult transsexual patient. Horm Res. 2005;64(Suppl 2):31–36

Gooren LJG , Giltay EJ  . Review of studies of androgen treatment of female-to-male transsexuals: effects and risks of administration of androgens to females. J Sex Med . 2008;5(4):765–776.

Jatenzo® (testosterone undecanoate) capsules [prescribing information]. Northbrook, IL. Clarus Therapeutics, Inc. March 2019. Available from: https://www.jatenzo.com/assets/pdfs/jatenzo-pi.pdf. Accessed NOVEMBER 20, 2023.

Kaplan AL, Trinh QD, Sun M, Carter SC, Nguyen PL, Shih YC, Marks LS, Hu JC. Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends. J Sex Med. 2014 Apr;11(4):1063-70.

Kaufman J, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol. 2004;172(3):920-922.

Kyzatrex® (testosterone undecanoate) [prescribing information]. Raleigh, NC: Marius Pharmaceuticals LLC. September 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f7167a7-2a25-47e2-acf5-33f499fce971. Accessed NOVEMBER 20, 2023.

Matsumoto AM. Diagnosis and evaluation of male hypogonadism. Medscape CME. 2008. Available from: http://www.medscape.org/viewarticle/575491. Accessed NOVEMBER 20, 2023.

Meriggiola MC , Gava G  . Endocrine care of transpeople part I. A review of cross-sex hormonal treatments, outcomes and adverse effects in transmen. Clin Endocrinol (Oxf) . 2015;83(5):597–606.

Methitest® (methyltestosterone) [prescribing information]. Bridgewater, NJ: Amneal Pharmaceuticals LLC.; October 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=77bb4ef4-c10e-4acc-8225-651d003f4561. Accessed NOVEMBER 20, 2023.

Meza J, Weaver K, Martin S. FPIN's clinical inquiries. Testosterone therapy and risk recurrence after treatment of prostate cancer. Am Fam Physician. 2013 Oct 15;88(8):Online. Available from: http://www.aafp.org/afp/2013/1015/od5.pdf

Moore E , Wisniewski A , Dobs A  . Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab . 2003;88(8):3467–3473.

Natesto® (testosterone) [package insert]. Malvern, PA. Endo Pharmaceuticals, Inc. December 2017. Available from: http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b0343bcc-7320-4bf2-bcb3-d95b6f4ba5fe&type=display. Accessed NOVEMBER 20, 2023.

Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshults LI, Khera M. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol. 2013 Aug;190(2):639-44. Accessed NOVEMBER 20, 2023.

Seftel AD, Mack RJ, Secrest AR, et, al. Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning. J Androl. 2004; 25(6):963-972.

Steidle C, Schwartz S, Jacoby K, et, al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab. 2003; 88(6):2673-2681.

Testim® (testosterone) [package insert]. Malvern, PA. Auxilium Pharmaceuticals. April 2018. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9f2aae1f-898d-4955-be31-678e0cf85395&type=display. Accessed NOVEMBER 20, 2023.

Testosterone. Micromedex. Available from: http://www.micromedexsolutions.com. Accessed NOVEMBER 20, 2023.

Tlando® (testosterone undecanoate) [package insert]. Ewing, NJ. Antares Pharma Inc. March 2022. Available from: https://www.tlando.com/application/files/9416/5366/3764/TLANDO_PI__Medication_Guide__FINAL__032822.pdf#hcpisi. Accessed NOVEMBER 20, 2023.

Vogelxo® (testosterone) [package insert]. Maple Grove, MN.  Upsher-Smith Laboraories, Inc. April 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2dd150f6-cdfd-4d51-8888-12b288f26262&type=display. Accessed NOVEMBER 20, 2023.

Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FCW. Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008 Nov;159(5):507-514.

Xyosted™ (testosterone enanthate) injection [package insert]. Ewing, NJ. Antares Pharma, Inc. November 2019. Available at: https://www.xyosted.com/PI.pdf. Accessed NOVEMBER 20, 2023.

The World Professional Association for Transgender Health. Standards of Care for the Heath of Transsexual, Transgender, and Gender Nonconforming People. 7th version. 2019. Available at: https://www.wpath.org/publications/soc. Accessed NOVEMBER 20, 2023.




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Rx.01.33 Off-Label Use
 


Brand NameGeneric Name
Androgel®Testosterone
Androderm®Testosterone
Fortesta®Testosterone
Natesto®Testosterone
Striant®Testosterone
Testim®Testosterone
Vogelxo®Testosterone
Jatenzo®, Tlando®, Kyzatrex®Testosterone undecanoate
Testred®, Android®, Methitest®Methyltestosterone
Xyosted™Testosterone enanthate

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Parathyroid hormone (PTH) and calcitriol are the two major hormones that regulate calcium and phosphate homeostasis.  PTH maintains serum ionized calcium concentrations in a narrow range by stimulating renal tubular calcium reabsorption and bone resorption.  Chronic exposure to high PTH results in bone resorption, however intermittent administration of recombinant human PTH stimulates bone formation to a greater extent than resorption, at least over the first 12 months of therapy.  While PTH is an effective treatment for osteoporosis, it is generally not a first line drug due to route of administration (subcutaneous), long-term safety concerns, and availability of other agents.

Teriparatide is recombinant human PTH. Abaloparatide is a human parathyroid hormone related peptide (PTHrP(1-34)).

 Teriparatide (Forteo®) is indicated:

  • For the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. These include women with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant of previous osteoporosis therapy, based upon physician assessment.
  • To increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. These include men with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant to previous osteoporosis therapy, based upon physician assessment.
  • For treatment of osteoporosis associated with sustained systemic glucocorticoid therapy at high risk fracture.

 

Abaloparatide (Tymlos™) is indicated: 
  • For the treatment of postmenopausal women with osteoporosis at high risk of fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
  • For the treatment to increase bone density in men with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.


The intent of this policy is to communicate the medical necessity criteria for abaloparatide (Tymlos™) and teriparatide (Forteo®) as provided under the member's prescription drug benefit. 


 

 

Primary or hypogonadal osteoporosis in men and Glucocorticoid-induced osteoporosis in men or women

INITIAL CRITERIA: Teriparatide (Forteo®) is approved when ALL of the following are met:

  1. The member is 18 years of age or older; and
  2. ONE of the following:
    1. Primary or hypogonadal osteoporosis in men; or
    2. Glucocorticoid-induced osteoporosis in men or women (daily dose greater than or equal to 5mg prednisone or equivalent for at least 3 months); and
  3. ONE of the following:
    1. Member is high risk for fracture defined by ONE of the following:
      1. History of osteoporotic fractures; or
      2. At least two risk factors for a fracture (e.g., endocrine disorders, gastrointestinal disorders, use of medications associated with low bone mass or bone loss such as corticosteroids); or
      3. Member has a T score of at least -2.5 standard deviations below the young adult mean (T-score ≤ -2.5); or
    2. Inadequate response or inability to tolerate ONE of the following osteoporosis therapies:
      1. Bisphosphonates; or
      2. Hormone replacement therapy; or
      3. Selective estrogen receptor modulators (SERMs); or
      4. Calcitonin salmon (Miacalcin); or
      5. Denosumab (Prolia); and
  4. For Forteo® only, inadequate response or inability to tolerate Teriparatide® manufactured by Alvogen

Initial Authorization duration: 12 months


REAUTHORIZATION CRITERIA: Teriparatide (Forteo®) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response; and
  2. ONE of the following:
    1. Cumulative lifetime therapy does not exceed 2 years; or
    2. For Forteo® only, member remains at or has returned to having a high risk for fracture despite a total of 24 months of use for parathyroid hormones

Reauthorization duration: 12 months

​​

Postmenopausal osteoporosis

INITIAL CRITERIA: Abaloparatide (Tymlos™) or teriparatide (Forteo®) is approved when ALL of the following are met:

  1. The member is 18 years of age or older; and
  2. Diagnosis of postmenopausal osteoporosis; and
  3. ONE of the following:
    1. Member is high risk for fracture defined by ONE of the following:
      1. Member has a T score of at least -2.5 standard deviation below the young adult mean (T-score ≤ -2.5); or
      2. History of osteoporotic fractures; or
      3. At least two risk factors for a fracture (e.g., endocrine disorders, gastrointestinal disorders, use of medications associated with low bone mass or bone loss such as corticosteroids); or
    2. Inadequate response or inability to tolerate ONE of the following osteoporosis therapies:
      1. Bisphosphonates; or
      2. Hormone replacement therapy; or
      3. Selective-estrogen receptor modulators (SERMs); or
      4. Calcitonin-salmon (Miacalcin®); or
      5. Denosumab (Prolia®); and
  4. For Forteo® only, inadequate response or inability to tolerate Teriparatide® manufactured by Alvogen​

Initial Authorization duration: 12 months  

REAUTHORIZATION CRITERIA: Abaloparatide (Tymlos™) or teriparatide (Forteo®) is re-approved when BOTH of the following are met:

  1. Documentation of positive clinical response; and
  2. ONE of the following:
    1. Cumulative lifetime therapy does not exceed 2 years; or
    2. For Forteo® only, member remains at or has returned to having a high risk for fracture despite a total of 24 months of use for parathyroid hormones 

Reauthorization duration: 12 months

Increase bone density in men with osteoporosis at high risk for fracture

INITIAL CRITERIA: Abaloparatide (Tymlos®) is approved when ALL of the following are met:

  1. Diagnosis of primary or hypogonadal osteoporosis; and
  2. The member is 18 years of age or older; and
  3. Both of the following:
    1. Bone mineral density (BMD) T-score of -2.5 or lower in the lumbar spine, femoral neck, total hip, or radius (one-third radius site); and
    2. One of the following:
      1. History of low-trauma fracture of the hip, spine, proximal humerus, pelvis, or distal forearm; or
      2. Inadequate response or inability to tolerate at least one osteoporosis treatment (e.g., alendronate, zoledronic acid, Prolia [denosumab])

​​​Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Abaloparatide (Tymlos®) is re-approved when BOTH of the following are met:
  1. Documentation of positive clinical response; and
  2. Cumulative lifetime therapy does not exceed 2 years

​Reauthorization duration: 12 months​

* Coverage duration of Teriparatide and Tymlos™ is limited to 730-day supply max per lifetime. All other treatment durations are considered Experimental/Investigational.

**Osteoporosis defined as T score of the individual's bone mineral density (BMD) is at least -2.5 standard deviations below the young adult mean OR history of osteoporotic fracture (i.e. hip, spine, etc.)


 


N/A

Forteo® (teriparatide) [package insert]. Indianapolis, IN. Lilly USA, LLC. April 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0&type=display. Accessed October 02, 2023.

Prolia® (denosumab) [package insert]. Thousand Oaks, CA. Amgen Inc. January 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=49e5afe9-a0c7-40c4-af9f-f287a80c5c88&type=display. Accessed October 02, 2023.

Rosen CJ. Parathyroid hormone/parathyroid hormone-related protein analog for osteoporosis. UpToDate. January 2023. Available at: https://www.uptodate.com/contents/parathyroid-hormone-therapy-for-osteoporosis?source=search_result&search=teriparatide&selectedTitle=4~150. Accessed October 02, 2023.

Tymlos™ (abaloparatide) [package insert]. Waltham, MA: Radius Health, Inc. December 2022. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=712143d9-e21e-4013-bb3b-3426a21060a8&type=display. Accessed October 02, 2023.


 


 

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Rx.01.33 Off-Label Use
 

Brand Name

Generic Name

Tymlos™

abaloparatide

Forteo®

teriparatide


296
  
1/1/2024Rx.01.22CommercialOyenusi, Oluwadamilola

Individuals, who are transfusion-dependent, receive excess iron with each transfusion.  In non-transfusion-dependent thalassemia (NTDT), elevated iron levels are related to suppression of hepcidin levels, increased intestinal iron absorption, and increased release of recycled iron from the reticuloendothelial system.  The excess iron accumulates in various tissues, including cardiac, liver, pulmonary, and endocrine glands, due to lack of an active mechanism to excrete iron.  The goal of iron chelation therapy in iron overload is to reduce iron levels, prevent complications, and reduce morbidity.

Deferasirox (Exjade®/ Jadenu®) is indicated for the treatment of transfusional hemosiderosis (chronic iron overload due to blood transfusions) in individuals who are 2 years of age or older and for the treatment of chronic iron overload in patients 10 years of age and older with NTDT syndromes and with a liver iron concentration (LIC) of at least 5 mg Fe per gram of dry weight (Fe/ g dw) and a serum ferritin greater than 300 mcg/L.

Deferiprone (Ferriprox®) is an iron chelator indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Deferasirox (Exjade®/Jadenu®) is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper, there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.


Deferiprone (Ferriprox®) is a chelating agent with an affinity for ferric ion (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable over a wide range of pH values.

The intent of this policy is to communicate the medical necessity criteria for deferasirox (Exjade®/ Jadenu®) and deferiprone (Ferriprox®) as provided under the member's prescription drug benefit.​

Chronic iron overload in blood transfusions dependent anemia

INITIAL CRITERIA: Deferasirox (Exjade®/Jadenu®) is approved when ALL of the following are met:

  1. Diagnosis of chronic iron overload due to blood transfusions; and
  2. Member is 2 years of age or older; and
  3. Serum ferritin levels are consistently greater than 1000 mcg/L (as demonstrated with at least two lab values within two months prior to treatment)
  4. For Brand Exjade and Brand Jadenu only, inadequate response or inability to tolerate generic deferasirox

Initial authorization duration: 12 months

 
​​CONTINUATION CRITERIA: Deferasirox (Exjade®/Jadenu®) is re-approved there is documentation of a decreased serum ferritin level compared with baseline level for transfusion dependent anemia.

Continuation duration: 2 years​


INITIAL CRITERIA: Deferiprone (Ferriprox®) is approved when all of the following are met:

  1. Diagnosis of transfusional iron overload due to Sickle Cell disease or other transfusion-dependent anemia; and
  2. Member is 3 years of age or older; and
  3. Inadequate response or inability to tolerate one of the following chelation therapy:
    1. Generic deferoxamine; or
    2. generic deferasirox; and
  4. For Brand Ferriprox tablets only, Inadequate response or inability to tolerate generic deferiprone tablets; and
  5. Current chelation therapy is inadequate

Initial authorization duration: 12 months


​​CONTINUATION CRITERIA: Deferiprone (Ferriprox®) is re-approved when there is documentation of positive clinical response to therapy (e.g., decline in serum ferritin levels from baseline).

Continuation duration: 2 years​


Chronic iron overload in non-transfusion-dependent Thalassemia Syndrome

INITIAL CRITERIA: Deferasirox (Exjade®/Jadenu®) is approved when ALL of the following are met:

  1. Diagnosis of chronic iron overload in Non-Transfusion-Dependent Thalassemia Syndromes; and
  2. Member is 10 years of age or older; and
  3. Serum ferritin levels are consistently greater than 300 mcg/L and liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) (as demonstrated with at least two lab values within 2 months prior to treatment)

Initial authorization duration: 12 months

 
CONTINUATION CRITERIA: Deferasirox (Exjade®/Jadenu®) is re-approved when there is documentation of a decreased serum ferritin level compared with the baseline level or reduction in LIC (liver iron concentration) for non-transfusion dependent Thalassemia Syndrome

Continuation duration: 2 years


INITIAL CRITERIA: Deferiprone (Ferriprox®) is approved when ALL of the following are met:

  1. Diagnosis of transfusional iron overload due to Thalassemia Syndrome; and
  2. Member is 3 years of age or older; and
  3. Inadequate response or inability to tolerate one of the following chelation therapy:
    1. Generic deferoxamine; or
    2. Generic deferasirox; and
  4. For Brand Ferriprox tablets only, Inadequate response or inability to tolerate generic deferiprone tablets; and
  5. Current chelation therapy is inadequate

Initial authorization: 12 months
 
​​CONTINUATION CRITERIA: Deferiprone (Ferriprox®) is re-approved when there is documentation of positive clinical response to therapy (e.g., greater than or equal to 20% decline in serum ferritin levels from baseline).

Continuation duration: 2 years​


 

 

Deferasirox (Exjade/ Jadenu)

Renal failure: Deferasirox can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Deferasirox is contraindicated in adults and pediatric patients with eGFR less than 40 ml/min/1.73m2. Use caution in pediatric patients with eGFR between 40 and 60 ml/min/1.3m2. For patients with renal impairment (eGFR 40-60 ml/min/1.73m2) reduce starting dose by 50%. Measure serum creatinine and determine creatinine clearance (CrCl)prior to initiation of therapy and monitor renal function at least monthly thereafter. For patients with baseline renal impairment or increased risk of acute renal failure, monitor creatinine weekly for the first month, then at least monthly thereafter. Monitor serum ferritin monthly to evaluate for overchelation. Use the minimum dose to establish and maintain a low iron burden. Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine. Interrupt deferasirox therapy when acute kidney injury is suspected and during volume depletion.

Hepatic failure: Deferasirox can cause hepatic injury including hepatic failure and death. Measure serum transaminases and bilirubin in all patients prior to initiating treatment, every 2 weeks during the first month, and at least monthly thereafter. Avoid use of deferasirox in patients with severe (Child-Pugh class C) hepatic impairment and reduce the dose in patients with moderate (Child-Pugh class B) hepatic impairment. Interrupt deferasirox therapy when acute liver injury is suspected and during volume depletion.

GI hemorrhage: Deferasirox can cause GI hemorrhages, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts. Monitor patients and discontinue deferasirox for suspected GI ulceration or hemorrhage.

Deferiprone (Ferriprox)

Agranulocytosis/Neutropenia: Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor the ANC weekly during therapy. Interrupt deferiprone therapy if neutropenia develops. If infection develops, interrupt deferiprone and monitor the ANC more frequently. Advise patients taking deferiprone to report immediately any symptoms indicative of infection. For neutropenia, instruct the patient to immediately discontinue deferiprone and all other medications with potential to cause neutropenia. Obtain a complete blood count (CBC), white blood count (WBC corrected for the presence of nucleated red blood cells, ANC and a platelet count daily until recovery. For agranulocytosis, consider hospitalization and other clinically appropriate management.


 



Biyani CS. Cystinuria. Available at http://emedicine.medscape.com/article/435678-overview. Accessed November 15, 2023.

 Exjade (deferasirox) [package insert]. East Hanover NJ. Novartis Pharmaceuticals Corporation.  Revised July 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3495a70c-870c-4968-940e-8baea152cf85&type=display. Accessed November 15, 2023.

Ferriprox (deferiprone) [package insert]. Rockville MD. ApoPharma USA, Inc.  Revised  May 2020.  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=97f7bfcb-8666-464c-87b6-9621ceca5ee2&type=display. Accessed November 15, 2023.

 Gilroy RK. Wilson Disease. Available at: http://emedicine.medscape.com/article/183456-overview#a1. Accessed November 15, 2023.

Jadenu (deferasirox) [package insert]. East Hanover NJ. Novartis Pharmaceuticals Corporation. Revised July 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee89140-fff1-4443-9f42-24ac004fcda1. Accessed November 15, 2023.

 Mir M. Transfusion induced iron overload. Available at: http://emedicine.medscape.com/article/1389732-overview. Accessed November 15, 2023.

Musallam KM, Rivella S, Vichinsky E, Rachmilewitz. Non-transfusion-dependent thalassemias. Haematologica. June 2013;98:833-844. DOI: 10.3324/haematol.2012.066845


 

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Off-Label Use policy Rx.01.33


Brand NameGeneric Name
ExjadeDeferasirox
JadenuDeferasirox
Ferriprox
Deferiprone


 

298
  
1/1/2024Rx.01.54CommercialOyenusi, Oluwadamilola

Mecasermin (Increlex®) is indicated for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Mecasermin is a recombinant form of human insulin-like growth factor I (rhIGF-I) that mediates anabolic and growth-promoting effects of growth hormone. Endogenous Insulin Growth Factor1 (IGF-1) is required for normal growth and brain development. IGF-1 is in part directed towards stimulating the uptake of glucose, fatty acids, and amino acids so that metabolism supports growing tissues. Mecasermin increases in insulin sensitivity by mimicking some actions of insulin.

The intent of this policy is to communicate the medical necessity criteria for mescasermin (Increlex®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Mecasermin (Increlex®) is approved when all of the following are met: 

  1. Diagnosis of growth failure in children with ONE of the following:
    1. All of the following:
      1. Severe primary insulin-like growth factor-1 deficiency (IGF-D); and
      2. Height standard deviation (SD) score of less than or equal to 3.0 SD scores below normal (growing at below the third percentile for age and sex); and
      3. Baseline IGF-1 (SD) score of less than or equal to 3.0 SD scores below normal (based on age- and sex-related reference ranges); and
      4. Normal or elevated GH level (based on GH stimulation testing); or
    2. Both of the following:
      1. Growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH;  and
      2. Measured titers of GH-neutralizing antibodies; and
  2. Member is 2 years of age or older; and
  3. Open epiphyses (bone growth plates) (bone age less than 14 years for girls and less than 16 years for boys); and
  4. Prescribed by or in consultation with an endocrinologist

 

Initial Authorization duration: 12 months

CONTINUATION CRITERIA: Continuation of mecasermin (Increlex®) is reapproved when all of the following are met:

  1. Growth velocity greater than or equal to 2 cm/year; and
  2. Yearly evaluation by an endocrinologist; and
  3. BOTH of the following
    1. Expected adult height is not obtained; and
    2. Documentation of expected adult height goal

 Continuation duration: 12 months

None

Increlex® (mecasermin) [prescribing information]. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc. December 2019. Available online at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a8b27a1b-a611-4f91-ad22-76d4b390c3ae&type=display#section-10.1.  Accessed on November 30, 2023

 

Mecasermin. Micromedex Solutions [Internet database]. Available at: www.micromedexsolutions.com. Accessed November 30, 2023

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Off-Label Use Rx.01.33

Brand NameGeneric Name
Increlex®mecasermin

299
  
1/1/2024Rx.01.109CommercialOyenusi, Oluwadamilola

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of angioedema. The most frequently implicated areas during an attack of HAE include areas of the skin, gastrointestinal tract, and upper respiratory tract, including the larynx. Involvement of the larynx may lead to fatality by asphyxiation. During episodes of HAE, individuals experience severe edema of the affected areas, characterized by gradual worsening over 24 hours and resolution within 2-5 days without treatment. Importantly, symptoms of HAE exclude urticaria and pruritis.

Several forms of hereditary angioedema exist, with type I and II being most common. In most cases, individuals with HAE demonstrate a deficiency in C1 inhibitor caused by mutation in the C1 inhibitor gene. .

Neither anabolic steroids nor antifibrinolytic drugs, used for prophylaxis of HAE attacks, are reliably effective in treating acute HAE attacks.  Epinephrine, corticosteroids, and antihistamines are also not effective for treating HAE attacks and are not recommended by current guidelines.  Guidelines recommend that patients with HAE have access to an "effective, on-demand, HAE-specific agent" to manage acute attacks. 

Mechanism of Action

Vasodilation results from excessive bradykinin production, a downstream effect from a deficiency in C1 (a subset of Complement protein) inhibitor protein. C1-inhibitor protein inhibits kallikrein, which is a protease that activates the potent vasodilator, bradykinin.  Modulation of the C1 cascade is a target for the prophylaxis and treatment of acute attacks of HAE.   Patients with HAE have low levels of endogenous or functional C1 esterase inhibitor (C1INH). Although the events that induce attacks of angioedema in HAE patients are not well understood, it is thought that contact system activation occurs. Contact system activation results in increased levels of bradykinin which causes increases in vascular permeability which results in the clinical manifestations of HAE.

Sajazir™/Firazyr® (icatibant) inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of hereditary angioedema.  Icatibant is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.   

Haegarda® (C1 esterase inhibitor subcutaneous [human]) is a plasma-derived concentrate of C1 esterase inhibitor (human) that is indicated for routine prophylaxis to prevent HAE attacks in patients 6 years of age and older. 

Cinryze® (C1 esterase inhibitor [human]) is C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in pediatric (6 years old and above), adolescent and adult patients with HAE.

Berinert® (C1 esterase inhibitor [human] is a plasma-derived C1 esterase inhibitor (human) indicated for the treatment of acute abdominal, facial, or laryngeal HAE attacks in adult and pediatric patients.

Orladeyo™ (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

Ruconest® is a C1 esterase inhibitor [recombinant] indicated for the treatment of acute attacks in adults and adolescent patients with HAE.

Takhzyro® (lanadelumab-flyo) is a human monoclonal antibody that acts to inhibit plasma kallikrein, and is indicated for prevention of HAE in patients 2 years of age and older. Kallikrein is a protease that activates bradykinin, a potent vasodilator implicated in the pathogenesis of angioedema attacks in patients with HAE. Inhibition of kallikrein results in downstream inhibition of bradykinin production.

The intent of this policy is to communicate the medical necessity criteria for Takhzyro® (lanadelumab-flyo), Haegarda® (C1 esterase inhibitor subcutaneous [human]), Cinryze® (C1 esterase inhibitor [human]), Berinert® (C1 esterase inhibitor [human]), Ruconest® (C1 inhibitor recombinant), Sajazir™/Firazyr® (icatibant), and Orladeyo™ (berotralstat) as provided under the member's pharmacy benefit. 

Prophylaxis against angioedema attacks

INITIAL CRITERIA: C1 esterase inhibitor (human) (Cinryze® or Haegarda®) is approved when ALL of the following are met:

  1. Diagnosis of hereditary angioedema (HAE) is confirmed by decreased serum levels of C4 and absence or marked decrease (less than 50 percent of normal) of the level or function of C1-INH; and
  2. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist; and
  3. Member is 6 years of age or greater; and
  4. For Cinryze only, inadequate response or inability to tolerate ONE of the following:
    1. Haegarda; or
    2. Takhzyro; or
    3. Orladeyo
​Initial authorization duration: 2 years
 
REAUTHORIZATION CRITERIA CI esterase inhibitors (human) (Cinryze® or Haegarda®) is re-approved with documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Lanadelumab-flyo (Takhzyro®) injection or berotralstat (Orladeyo®is approved when all of the following are met:
  1. Diagnosis of hereditary angioedema (HAE); and
  2. One of the following:
    1. For Takhzyro, member is 2 years of age or older; or
    2. For Orladeyo, member is 12 years of age or older; and
  3. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: Lanadelumab-flyo (Takhzyro®), or berotralstat (Orladeyo®) is re-approved with documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

_______________________________________________________________________________________________

Treatment of angioedema attacks

INITIAL CRITERIA: C1 esterase inhibitor (human) (Berinert®) is approved when ALL of the following are met:
  1. Diagnosis of treatment of acute abdominal, facial, or laryngeal attacks of HAE in adults and pediatric patients; and
  2. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist; and
  3. One of the following:
    1. Inadequate response or inability to tolerate C1 esterase inhibitor recombinant (Ruconest®); or
    2. One of the following:
      1. Member is 12 years of age or younger; or
      2. Documentation that member has history of laryngeal attacks

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: C1 esterase inhibitors (human) (Berinert®) is re-approved with documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: C1 esterase inhibitor recombinant (Ruconest®) is approved when ALL of the following are met:

  1. Diagnosis of treatment of acute attacks of HAE in adults and adolescents over the age of 12 years; and
  2. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist.

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA: C1 esterase inhibitor recombinant (Ruconest®) is re-approved with documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Icatibant (Firazyr® /Sajazir™) is approved when ALL of the following criteria are met:

  1. Member is 18 years of age or older; and
  2. Diagnosis of hereditary angioedema; and
  3. Prescribed by or in consultation with an immunologist, allergist, or pulmonologist

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Icatibant (Firazyr®/Sajazir™) is re-approved with documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

None


Firazyr® (icatibant) [package insert]. Lexinton MA. Shire Orphan Therapeutics. Oct, 2021  Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ed6657ca-ab68-477a-9968-e12dc928b540&type=display. Accessed December 5, 2023

 

Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema.  J Allergy Clin Immunol. 2013; Volume 131, issue 6, pages 1491-1493.e25. Accessed December 5, 2023.

 

Haegarda® (C1 esterase inhibitor subcutaneous [human]). [package insert]. Kanakee, IL: CSL Behring. January 2022. Available at: http://labeling.cslbehring.com/PI/US/HAEGARDA/EN/HAEGARDA-Prescribing-Information.pdf. Accessed December 5, 2023.

 

Cinryze® (C1 esterase inhibitor [human]). [package insert]. Lexington, MA: Shire ViroPharma Inc. January 2021. Available at: http://pi.shirecontent.com/PI/PDFs/Cinryze_USA_ENG.pdf. Accessed December 5, 2023.

 

Berinert® (C1 esterase inhibitor [human]). [package insert]. Kanakee, IL: CSL Behring. September 2021. Available at: http://labeling.cslbehring.com/PI/US/Berinert/EN/Berinert-Prescribing-Information.pdf. Accessed December 5, 2023

 

Orladeyo™ (berotralstat). [prescribing information]. Durham, NC: BioCryst Pharmaceuticals, Inc. March 2022. Available at: https://orladeyohcp.com/wp-content/uploads/ORLADEYO_PI_V1_2020.pdf. Accessed December 5, 2023.  

 

Ruconest® (C1 esterase inhibitor [recombinant]). [package insert]. Raleigh, NC: Santarus, Inc. April 2020. Available at: https://www.ruconest.com/PDF/ruconest-pi.pdf. Accessed December 5, 2023

 

Sajazir™ (icatibant) [package insert]. Cambridge, United Kingdom. Cycle Pharmaceuticals Ltd. June 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1756aca0-21a1-4898-8d6c-9666738db45c. Accessed December 5, 2023

 

Takhzyro®. [package insert]. Lexington, MA: Dyax Corp., wholly-owned subsidiary of Shire US Inc. February 2023. Available at: https://www.shirecontent.com/PI/PDFs/TAKHZYRO_USA_ENG.pdf. Accessed December 5, 2023.

 

Zuraw B MD, Farkas H MD. Hereditary angioedema (due to C1 inhibitor deficiency): Pathogenesis and diagnosi. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. Accessed on December 5, 2023


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Rx.01.33 Off Label Use

​Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit

Brand NameGeneric Name
Firazyr®/Sajazir™icatibant
Haegarda®C1 esterase inhibitor subcutaneous [human]
Cinryze®
C1 esterase inhibitor [human]
Berinert®C1 esterase inhibitor [human]
Orladeyo™

berotralstat

 

Ruconest®C1 esterase inhibitor [recombinant]
Takhzyro®lanadelumab-flyo

302
  
1/1/2024Rx.01.132CommercialOyenusi, Oluwadamilola

Cushing's disease is caused by an adrenocorticotropic hormone (ACTH) secreting pituitary tumor.  Surgical intervention is required for optimal treatment of Cushing's disease.  When surgery is delayed, contraindicated, or unsuccessful, medical therapy may be required.  Cabergoline and pasireotide are medications that target the tumor and may help normalize urinary free cortisol.

Pasireotide (Signifor®) exerts its pharmacological activity via binding to somatostation receptors (SSTRs). Pasireotide binds and activates the SSTRs, resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion. 

Osilodrostat (Isturisa®) is a cortisol synthesis inhibitor. It inhibits 11beta-hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland.

Mifepristone (Korlym®) is a selective antagonist of the progesterone receptor at low doses and blocks the glucocorticoid receptor (GR-II) at higher doses. Mifepristone has high affinity for the GR-II receptor but little affinity for the GR-I (MR, mineralocorticoid) receptor. In addition, mifepristone appears to have little or no affinity for estrogen, muscarinic, histaminic, or monoamine receptors.

Levoketoconazole (Recorlev®) inhibits key steps in the synthesis of cortisol and testosterone, principally those mediated by CYP11B1 (11β hydroxylase), CYP11A1 (the cholesterol side-chain cleavage enzyme, the first step in the conversion of cholesterol to pregnenolone), and CYP17A1 (17α-hydroxylase).

Pasireotide (Signifor®) is indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative. 

Osilodrostat (Isturisa®) is indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.

Mifepristone (Korlym®) indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.

Levoketoconazole (Recorlev®) is indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative

The intent of this policy is to communicate the medical necessity criteria for pasireotide (Signifor®), osilodrostat (Isturisa®), mifepristone (Korlym®), and levoketoconazole (Recorlev®) as provided under the member's prescription drug benefit.

Cushing's Disease

INITIAL CRITERIA Pasireotide (Signifor®) or osilodrostat (Isturisa®) is approved when ALL of the following are met:

  1. Diagnosis of Cushing's disease; and
  2. Member has failed surgery or is not a candidate for surgery; and
  3. Member is 18 years of age or older; and
  4. Prescribed by or in consultation with an endocrinologist; and
  5. For Osilodrostat (Isturisa®) only, inadequate response or inability to tolerate pasireotide (Signifor® [LAR])

Initial Authorization duration: 6 months

REAUTHORIZATION CRITERIA Pasireotide (Signifor®) or osilodrostat (Isturisa®) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response to therapy (i.e., reduction in cortisol levels, improvement in signs or symptoms of the disease); and
  2. Prescribed by or in consultation with an endocrinologist

Reauthorization duration: 2 years

INITIAL CRITERIA Levoketoconazole (Recorlev®) is approved when ALL of the following are met: 
  1. Diagnosis of Cushing’s syndrome; and 
  2. Member is 18 years of age or older; and 
  3. Member is being treated for endogenous hypercortisolemia (e.g., pituitary adenoma, ectopic tumor, adrenal adenoma); and
  4. One of the following:
    1. Member is not a candidate for surgery; or
    2. Surgery has not been curative; and
  5. Inadequate response or inability to tolerate oral ketoconazole; and
  6. Prescribed by or in consultation with an endocrinologist

Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA Levoketoconazole (Recorlev®) is re-approved when there is documentation of positive clinical response to therapy as demonstrated by one of the following:
  1. Normalization of urinary free cortisol (UFC); or
  2. At least a 50% decrease in UFC levels
Reauthorization duration: 2 years

Hyperglycemia secondary to Cushing's Syndrome

INITIAL CRITERIA Mifepristone (Korlym®) is approved when ALL of the following are met:

  1. Hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance; and
  2. Member has failed surgery or is not a candidate for surgery; and
  3. Prescribed by or in consultation with an endocrinologist; and
  4. Member is not pregnant; and
  5. Member is 18 years of age or older

Initial Authorization duration: 6 months

REAUTHORIZATION CRITERIA Mifepristone (Korlym®) is re-approved when ALL of the following are met:

  1. Documentation of positive clinical response to therapy (e.g., improved, or stable glucose tolerance while on therapy); and
  2. Prescribed by or in consultation with an endocrinologist

Reauthorization duration: 2 years
 

Mifepristone (Korlym®)

TERMINATION OF PREGNANCY

Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively.  The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with KORLYM and prevented during treatment and for one month after stopping treatment by the use of a non-hormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential.

Levoketoconazole (Recorlev®)

HEPATOTOXICITY AND QT PROLONGATION

Cases of hepatotoxicity with fatal outcome or requiring liver transplantation have been reported with oral ketoconazole. Some patients had no obvious risk factors for liver disease.RECORLEV is associated with serious hepatotoxicity. Evaluate liver enzymes prior to and during treatment.

RECORLEV is associated with dose-related QT interval prolongation. QT interval prolongation may result in life threatening ventricular dysrhythmias such as torsades de pointes. Perform ECG prior to and during treatment.

Nieman LK. Medical therapy of hypercortisolism (Cushing's syndrome). UpToDate. August 2022. Available at: https://www.uptodate.com/contents/medical-therapy-of-hypercortisolism-cushings-syndrome?source=search_result&search=cushings%20disease&selectedTitle=8~100#H1. Accessed December 05, 2023.

 

Nieman LK. Overview of the treatment if Cushing's syndrome. UpToDate. November 2021. Available at: https://www.uptodate.com/contents/overview-of-the-treatment-of-cushings-syndrome?source=search_result&search=cushings%20disease%20management&selectedTitle=1~100#H4. Accessed December 05, 2023.

 

Isturisa® (osilodrostat) [prescribing information]. Lebanon, NJ: Recordati Rare Disease, Inc.; March 2020. Available from: https://www.isturisa.com/pdf/isturisa-prescribing-information.pdf. Accessed December 05, 2023.

 

Korlym® (mifepristone) [prescribing information]. Menlo Park, CA: Corcept Therapeutics Inc.; November 2019. Available from: https://www.korlym.com/wp-content/uploads/2018/01/K-00017-NOV-2019_electronic-PI_r8_FINAL.pdf. Accessed December 05, 2023.

 

Recorlev® (levoketoconazole) [prescribing information]. Chicago, IL: Xeris Pharmaceuticals, Inc.; December 2021. Available from: https://www.recorlev.com/full-prescribing-information.pdf. Accessed December 05, 2023.

 

Signifor® (pasireotide) [package insert]. East Hanocer, NJ. Novartis Pharmaceuticals Corporation. June 2020. Available at: https://www.signiforlar.com/pdf/signifor-lar-pi.pdf. Accessed December 05, 2023.​

 



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 Off-Label Use policy Rx.01.33
 

​Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76


 

Brand nameGeneric name
Signifor®Pasireotide
Isturisa®Osilodrostat
Korlym®
Mifepristone
Recorlev®Levoketoconazole

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Actinic keratoses (AKs or solar keratoses) are keratotic macules, papules, or plaques resulting from the intraepidermal proliferation of atypical keratinocytes in response to prolonged exposure to ultraviolet radiation. AKs are a concern because the majority of cutaneous squamous cell carcinoma (SCCs) arise from pre-existing AKs, and AKs that will progress to SCC cannot be distinguished from AKs that will spontaneously resolve or persist.

Cutaneous T cell lymphoma (CTCL) describes a heterogeneous group of neoplasms of skin-homing T cells. CTCL represent approximately 75 to 80 percent of all primary cutaneous lymphomas. Mycosis fungoides (MF) and primary cutaneous CD30+ lymphoproliferative disorders (LPD) account for approximately 90 percent of CTCL.

Ingenol mebutate (Picato®) is indicated for the topical treatment of actinic keratosis (AK).

Ingenol mebutate (Picato®) is an inducer of cell death. The mechanism of action by which ingenol mebutate gel induces cell death in treating AK lesions is unknown.

Diclofenac 3% gel (Solaraze®) is indicated for the topical treatment of AK.

The mechanism of action of diclofenac 3% gel (Solaraze®) in the treatment of AK is unknown.

Tirbanibulin (Klisyri™) is indicated for the topical treatment of actinic keratosis on the face or scalp.

Tirbanibulin is a microtubule inhibitor. The mechanism of action of KLISYRI for the topical treatment of actinic keratosis is unknown. 

 

Imiquimod (Zyclara™) is indicated for the topical treatment of clinically typical visible or palpable, actinic keratoses (AK) of the full face or baling scalp in immunocompetent adults and the treatment of external genital and perianal warts (EGW)/condyloma acuminata in patients 12 years or older.

 

Imiquimod is a Toll-like receptor 7 agonist. The mechanism of action of Zyclarain treating AK and EGW lesions is unknown.



 

The intent of this policy is to communicate the medical necessity criteria for  ingenol mebutate (Picato®) diclofenac 3% (Solaraze®) tirbanibulin (Klisyri®), and imiquimod (Zyclara™) as provided under the member's prescription drug benefit.

Actinic Keratosis
 
INITIAL CRITERIA Ingenol mebutate (Picato®), diclofenac 3% (Solaraze®) gel, imiquimod (Zyclara®) 3.75%, 2.5%,
or tirbanibulin (Klisyri®) is approved when BOTH of the following are met:

  1. Diagnosis of actinic keratosis; and
  2. Member is 18 years of age or older; and 
  3. ONE of the following:
    1. For imiquimod (Zyclara®) 3.75%, 2.5% only, inadequate response or inability to tolerate imiquimod 5%; or
    2. For Tirbanibulin (Klisyri®) only, inadequate response or inability to tolerate BOTH of the following generics:
      1. Fluorouracil; and
      2. Imiquimod ​​

Initial authorization duration:

  • 30 days for tirbanibulin (Klisyri®), ingenol mebutate (Picato®) imiquimod (Zyclara®) 3.75%, 2.5%.
  • 3 months for diclofenac 3% (Solaraze®)

 REAUTHORIZATION CRITERIA Ingenol mebutate (Picato®), diclofenac 3% (Solaraze®) gel, imiquimod (Zyclara®)

3.75%, 2.5%, or tirbanibulin (Klisyri®) is re-approved when there is documentation of a diagnosis of actinic keratosis at a different site.

Reauthorization duration:

  • 30 days for tirbanibulin (Klisyri®), ingenol mebutate (Picato®) imiquimod (Zyclara®) 3.75%, 2.5%.
  • 3 months for diclofenac 3% (Solaraze®) ​


Genital warts

INITIAL CRITERIA Imiquimod (Zyclara®) 3.75% is approved when BOTH of the following are met:

  1. Diagnosis of genital warts; and
  2. Member is 12 years of age or older; and
  3. Inadequate response or inability to tolerate imiquimod 5%
Initial authorization duration: 30 days

 
REAUTHORIZATION CRITERIA Imiquimod (Zyclara®) 3.75% is re-approved when there is documentation of positive clinical response to therapy.

 

Reauthorization duration: 30 days



Solaraze® (diclofenac 3%):

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial and stroke, which can be fatal. This risk may occur in treatment and may increase with duration of use.

Solaraze® is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Jorizzo J. Treatment of actinic keratosis. UpToDate. July 2021. Available at: https://www.uptodate.com/contents/treatment-of-actinic-keratosis?source=search_result&search=actinic%20keratosis&selectedTitle=1~46. Accessed October 02, 2023.

Picato® (ingenol mebutate) [package insert]. Parsippany, NJ.  Leo Pharma Inc. March 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5accc7a5-8209-4680-b0ae-2a6963500419&type=display.  Accessed October 02, 2023.

Solaraze® (diclofenac 3%) [package insert]. Melville, NY. PharmaDerm. April 2016. Available at:  https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=89a7bfbd-051f-4d87-a642-96b0df81b8e2&type=display. Accessed October 02, 2023.

Willemze R. Classification of primary cutaneous lymphomas. UpToDate. March 2020. Available at: https://www.uptodate.com/contents/classification-of-primary-cutaneous-lymphomas?source=machineLearning&search=CTCL&selectedTitle=7~106&sectionRank=1&anchor=H474649238#H474649238. Accessed October 02, 2023.

Klisyri™ (tirbanibulin) [package insert]. Exton, PA: Almirall; August 2021. Available from: https://klisyrihcp.com/assets/klisyri-prescribing-information.pdf. Accessed October 02, 2023.

Zyclara™ (imiquimod) [package insert]. Bridgewater, NJ: Bausch Health US, LLC; June 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=28cd9b5b-680b-480f-b33d-9c5b52bbf03d. Accessed October 02, 2023.​


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Off-Label Use policy Rx.01.33

Brand NameGeneric Name
Picato®ingenol mebutate

Solaraze®

Klisyri

diclofenac 3%

Tirbanibulin

ZyclaraImiquimod




305
  
1/1/2024Rx.01.157CommercialOyenusi, Oluwadamilola

Generalized lipodystrophy is a disorder characterized by the absence or diffuse deficiency of adipose tissue, resulting in deficiency of the hormone, leptin. Leptin is important for appetite suppression, and deficiency results in uncontrolled intake of calories and subsequent deposit in areas such as the liver or muscle. Patients with generalized lipodystrophy often develop metabolic disorders such as insulin resistance and/or elevation in serum triglycerides.

Metreleptin is a recombinant human leptin analog that binds to and activates the human leptin receptor (ObR), which belongs to the class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.  Activation of the leptin receptor by metreleptin mimics native leptin, which is responsible for signaling the CNS with the status of energy stores in the body.

Metreleptin (Myalept®) is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency  in patients with congenital or acquired generalized lipodystrophy.



 

The intent of this policy is to communicate the medical necessity criteria for metreleptin (Myalept®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Metreleptin (Myalept®) is approved when ALL of the following are met:

  1. Diagnosis of congenital or acquired generalized lipodystrophy (excluding other forms of lipodystrophy); and
  2. Prescribed as adjunct to diet as replacement therapy; and
  3. Member is refractory to current standards of care for lipid and diabetic management; and
  4. Prescribed by or in consultation with an endocrinologist; and
  5. Documentation demonstrates that member has at least one of the following metabolic abnormalities:
    1. Insulin resistance (defined as requiring more than 200 units per day)
    2. Hypertriglyceridemia
    3. Diabetes

Initial Authorization duration: 12 months


CONTINUATION CRITERIA: Continuation of metreleptin (Myalept®) is reapproved when there is documentation of positive clinical response to metreleptin (Myalept®) therapy (e.g., sustained reduction in Hemoglobin A1c or triglycerides from baseline)

Continuation authorization duration:  2 years

 

 

 

WARNING: RISK OF ANTI-METRELEPTIN ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA

Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with metreleptin. The consequences of these neutralizing antibodies are not well characterized but could include inhibition of endogenous leptin action and/or loss of metreleptin efficacy. Severe infection and/or worsening metabolic control have been reported. Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of metreleptin efficacy during treatment.

T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with metreleptin. Carefully consider the benefits and risks of treatment with metreleptin in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy.

Because of these risks associated with the development of anti-metreleptin antibodies that neutralize endogenous leptin and/or metreleptin and the risk for lymphoma, metreleptin is available only through a restricted risk evaluation and mitigation strategy (REMS) program.


Metreleptin.  Micromedex Solutions [database on the Internet]. Available at: www.micromedexsolutions.com.   Accessed November 30, 2023.

 

Myalept® (metreleptin) [prescribing information]. Cambridge, MA. Aegerion Pharmaceuticlas, Inc. May 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c986f93b-855d-4ef0-b620-5d41a0513e48&type=display. Accessed November 30, 2023

 

Mantzoros, MD. Lipodystrophic syndromes Post TW, ed. November 30 ,2023​

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Off-Label Use Rx. 01.33


Brand Name

Generic Name

Myalept®

metreleptin

306
  
1/1/2024Rx.01.169CommercialOyenusi, Oluwadamilola

Insulin stimulates peripheral glucose uptake by inhibiting hepatic glucose production and glucose uptake by skeletal muscle and fat.

Afrezza® is a rapid-acting insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

The intent of this policy is to communicate the medical necessity criteria for insulin human, inhalation (Afrezza®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Afrezza® is approved when ALL of the following are met:

  1. Member is 18 years of age or older; and
  2. One of the following:
    1. Both of the following:
      1. Diagnosis of type I diabetes mellitus; and
      2. Used in combination with a long-acting insulin (e.g., Lantus)
    2. Diagnosis of type II diabetes mellitus; and
  3. Spirometry (FEV1) completed prior to initiation of therapy to identify potential lung disease (must provide the result); and
  4. Member is a non-smoker for a minimum of 6 months; and
  5. Absence of chronic lung disease such as asthma or chronic obstructive pulmonary disease; and
  6. Prescribed by or in consultation with an endocrinologist  

Initial authorization duration: 6 months

REAUTHORIZATION CRITERA: Afrezza® is re-approved when the following are met:

  1. There is documentation of spirometry value (FEV1) has not declined ≥ 20% from baseline; and
  2. There is documentation of positive clinical response to therapy

Reauthorization duration:  2 years

 

 

 

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

Acute bronchospasm has been observed in patients with asthma and COPD using Afrezza®.

Afrezza® is contraindicated in patients with chronic lung disease such as asthma or COPD.

Before initiating Afrezza®, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

 

Afrezza® (insulin human, inhalation) [package insert].Bridgewater, NJ: Sanofi-aventis US LLC. February 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=29f4637b-e204-425b-b89c-7238008d8c10&type=display. Accessed NOVEMBER 21, 2023.

 

Insulin human inhalation. Micromedex. Available from: http://www.micromedexsolutions.com. Accessed NOVEMBER 21, 2023​



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Off-Label Use Rx.01.33

Inclusion of a drug in this table does not imply coverage. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

Brand NameGeneric Name
Afrezza®Insulin human, inhalation
307
  
1/1/2024Rx.01.172CommercialOyenusi, Oluwadamilola

 

Hypoparathyroidism is a disorder characterized by hypocalcemia and deficiency of parathyroid hormone (PTH).  Hyperphosphatmeia, hypercalciuria and reduced concentrations of 1,25-dihydroxyvitamin D are additional characteristics of hypoparathyroidism.  Calcium and vitamin D supplementation is the standard therapy for hypoparathyroidism, with the goal of achieving serum calcium levels in the low-normal range and avoiding hypercalciuria.  Thiazide diuretics may be used as adjunctive therapy to increase distal tubule calcium reabsorption. 

Natpara® is recombinant human PTH (rhPTH), identical to endogenous human PTH.  PTH increases serum calcium by increasing renal tubular calcium reabsorption, increasing intestinal calcium absorption, and by increasing bone turnover which releases calcium into the circulation.  PTH maintains calcium and phosphate homeostasis.  PTH increases in serum calcium occur in a dose dependent manner. 

Natpara® is indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. It has not been studied in hypoparathyroidism due to calcium-sensing receptor mutation or post-surgical hypoparathyroidism.

The intent of this policy is to communicate the medical necessity criteria for Natpara ® (parathyroid hormone) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Natpara® (parathyroid hormone) is approved when ALL of the following are met:  

  1. Member is 18 years of age or older; and
  2. Diagnosis of hypocalcemia for patients with hypoparathyroidism NOT caused by either of the following:
    1. Calcium-sensing receptor mutations; or
    2. Acute post-surgical hypoparathyroidism; and
  3. Member is not well controlled on calcium supplements and active forms of vitamin D; and
  4. Used as an adjunct to calcium and vitamin D; and
  5. Member has normal thyroid-stimulating hormone concentrations if not on thyroid hormone replacement therapy (or if on therapy, the dose had to have been stable for greater than or equal to 3 months); and
  6. Member has normal magnesium and serum 25-hydroxyvitamin D concentrations; and
  7. Prescribed by or in consultation with an endocrinologist

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Natpara® (parathyroid hormone) is re-approved when there is documentation of positive clinical response to therapy (i.e., member has achieved and maintained serum calcium levels in the ideal range; member has achieved reduction in oral calcium and vitamin D intake).

Reauthorization duration: 2 years

 


 

Potential risk of osteosarcoma

  • In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. A risk to humans could not be excluded
  • Because of the potential risk of osteosarcoma, prescribe  Natpara® only to patients who cannot be well-controlled on calcium and active forms of vitamin D and for whom the potential benefits are considered to outweigh the potential risk 
  • Avoid use of Natpara® in patients who are at increased baseline risk for osteosarcoma (including those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma or patients with a history of prior external beam or implant radiation therapy involving the skeleton)

Natpara® is available only through a restricted program called the Natpara REMS Program



 


Cusano NE, Rubin MR, Sliney J, Bilezikian JP. Mini-review:   new therapeutic options for hypoparathyroidism. Endocrine. 2012;41:410-14.

 

Natpara® (parathyroid hormone) [package insert]. Lexington, MA. Shire-NPS Pharmaceuticals, Inc. July 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d11fba31-0a6c-11e3-8ffd-0800200c9a66&type=display. Accessed November 17, 2023.

 

Parathyroid hormone. Micromedex. Available from: http://www.micromedexsolutions.com. Accessed November 17, 2023. ​


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Off-Label Use Rx.01.33

Brand NameGeneric Name
Natpara®parathyroid hormone
308
  
1/1/2024Rx.01.181CommercialOyenusi, Oluwadamilola

Cells that rapidly divide such as bone marrow and myeloid cells require vitamin B12 to mature and proliferate. Vitamin B12 is necessary for hematopoiesis, nucleoprotein synthesis, and myelin synthesis.  Additionally, it is required for fat and carbohydrate breakdown and protein synthesis. Vitamin B12 is bound to protein rich foods and comes from the diet. Hydrochloric acid and gastric protease break it down into its free form. The free form of vitamin B12 must be combined with intrinsic factor, which is produced by gastric parietal cells, in order to be absorbed in the distal ileum. Pernicious anemia is an autoimmune disease that is associated with the destruction of the parietal cells that secrete intrinsic factor.  The inability to absorb vitamin B12 results in a severe deficiency which, if left untreated, can lead to megaloblastic anemia, GI lesions, or neurologic defects.

Cyanocobalamin is the most widely used form of vitamin B12 to treat and maintain normal hematologic status in patients with pernicious anemia. It has identical hematopoietic activity to the anti-anemic factor that is present in the liver. Cyancobalamin is also indicated as a supplement for other vitamin B12 deficiencies, such as dietary deficiency and malabsorption of vitamin B12,

Cyanocobalamin is available in oral, sublingual, and injection dosage forms. Cyanocobalamin nasal spray, a new route of administration, provides an alternative route of administration for vitamin B12 deficiency.

Cyanocobalamin inhalation (Nascobal®) is indicated for:

  1. Vitamin B12 maintenance therapy in adult patients with pernicious anemia who are in remission following intramuscular vitamin B12 therapy and who have no nervous system involvement.
  2. Treatment of adult patients with dietary, drug-induced, or malabsorption-related vitamin B12 deficiency not due to pernicious anemia.
  3. Prevention of vitamin B12 deficiency in adult patients with vitamin B12 requirements in excess of normal.


 

The intent of this policy is to communicate the medical necessity criteria for cyanocobalamin inhalation (Nascobal®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Cyanocobalamin inhalation (Nascobal®) is approved when ALL of the following are met:

  1. Diagnosis of ONE of the following:
    1. Pernicious anemia in members requiring maintenance therapy who are in remission following intramuscular vitamin B12 therapy and who have no nervous system involvement; or
    2. Dietary deficiency of vitamin B12 due to strict vegetarian diet; or
    3. Malabsorption of vitamin B12 due to a structural or functional damage to the stomach or ileum; or
    4. Inadequate secretion of intrinsic factor; or
    5. Competition for vitamin B12 by intestinal parasites or bacteria (e.g., tapeworm, blind loop syndrome); or
    6. Inadequate utilization of vitamin B12 (e.g., antimetabolites are employed in treatment of neoplasia); and
  2. Member is 18 years of age or older; and
  3. Inadequate response or inability to tolerate oral and sublingual cyanocobalamin
     

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA Cyanocobalamin inhalation (Nascobal®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

​N/A

 

Nascobal (cyanocobalamin inhalation) prescribing information. Spring Valley (NY). Par Pharmaceutical Companies, Inc. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021642Orig1s015lbl.pdf. Revised November 2018. Accessed November 15, 2023.

National Institutes of Health: Vitamin B12 Dietary Supplement Fact Sheet [Internet]. Bethesda (MD):National Institutes of Health; [updated 2020 March 30]. Available from: https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. Accessed November 15, 2023.

Schrier SL. Clinical manifestations and diagnosis of vitamin B12 and folate deficiency. UpToDate website. Last updated September 29, 2022. Available at: http://www.uptodate.com/. Accessed November 15, 2023.

Schrier SL. Causes and pathophysiology of vitamin B12 and folate deficiencies. UpToDate website. Last updated June 16, 2021. Available at http://www.uptodate.com/ Accessed November 15, 2023.​




 

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Off-Label Use Rx.01.33


Brand Name

Generic Name

Nascobal

Cyanocobalamin


309
  
1/1/2024Rx.01.190CommercialOyenusi, Oluwadamilola

​Pheochromocytomas are rare catecholamine secreting tumors, usually located within the adrenal glands, which may result in life-threatening hypertension or arrhythmias.  Pheochromocytomas reportedly occur in 0.05-0.2% of hypertensive individuals.  This is likely an underestimate, since some patients are asymptomatic.  Approximately 10% of pheochromocytomas are discovered incidentally and 50% had diagnosis made on autopsy.  

Unlike catecholamine release from healthy adrenal tissue, catecholamine release from pheochromocytomas is not regulated and the triggers for their release are unclear.  Additionally, most pheochromocytomas predominantly release norepinephrine compared to predominantly epinephrine release from healthy adrenal tissue.

Surgical resection is the treatment of choice, usually resulting in cure of the hypertension.  Medical therapy is used preoperatively, for hypertensive crises, and as primary therapy for individuals with metastatic pheochromacytomas.  Alpha adrenergic blockade is the cornerstone of pharmacologic therapy for pheochromocytomas.  In the perioperative setting, phenoxybenzamine is initiated 10-14 days prior to surgery, in conjunction with volume expansion.  Beta blockade is initiated only after adequate alpha blockade has been achieved.  Selective alpha 1 blocking agents (doxazosin, terazosin, prazosin) may be used when long term therapy is required, but are not recommended for the preoperative management.

Phenoxybenzamine is a long acting alpha adrenergic receptor antagonist, which produces and maintains a "chemical sympathectomy" when orally administered.  Phenoxybenzamine (Dibenzyline®) is indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. 

The intent of this policy is to communicate the medical necessity criteria for phenoxybenzamine (Dibenzyline®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Phenoxybenzamine (Dibenzyline®) is approved when ALL of the following are met:

  1. Diagnosis of pheochromocytoma; and
  2. Member is 18 years of age or older; and
  3. Prescribed by or in consultation with a nephrologist, endocrinologist or endocrine surgeon; and 
  4. For brand Dibenzyline only, inadequate response or inability to tolerate generic phenoxybenzamine 


Initial Authorization duration: 6 months


REAUTHORIZATION CRITERIA: Phenoxybenzamine (Dibenzyline®) is re-approved when both of the following are met:


1. Documentation of positive clinical response; and
2. Yearly evaluation by prescriber for long-term use


Reauthorization duration: 12 months

​N/A

Blake MA. Pheochromocytoma. Available from:http://emedicine.medscape.com/article/124059-overview. Accessed November 17, 2023.​

Dibenzyline® (phenoxybenzamine) [package insert]. St. Michael, Barbados. Concordia Pharmaceuticals. Dec 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8852dd44-098c-4d99-88e0-a092a8e08e11&type=display. Accessed November 17, 2023.


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Off-Label Use Rx. 01.33

Brand nameGeneric name
Dibenzyline®phenoxybenzamine
310
  
1/1/2024Rx.01.193CommercialOyenusi, Oluwadamilola

The Company utilizes a tiered cost-sharing structure for medications covered under the pharmacy benefit.  Members should refer to their benefit booklet for more information.
Formulary Tier Exceptions

The following tier exceptions requests will be considered:

A. Select Drug Formulary

  1. Non-preferred drug to be covered at the: 
    1. Preferred brand tier if the product is a brand medication; or
    2. Generic tier if the product is generic medication
  2. All other tiers are restricted to the benefit design and thus are not eligible for a tier exception

B.  Value Formulary

  1. Non-formulary medication to be covered at the highest level of cost share.  These exceptions are not eligible for tier reduction.
  2. Non-preferred drug to be covered at the:
    1. Preferred brand tier if the product is a brand medication; or
    2. Generic tier if the product is generic medication
  3. All other tiers are restricted to the benefit design and thus are not eligible for a tier exception.

The following tiers are defined by the benefit and are not eligible for a tier exception:

  1. Specialty tier
  2. Preferred brand tier
  3. Generic tier 

Cost Share Exceptions for Preventive Care Services and Women's Preventive Services

The services listed in this policy are considered preventive care services when the criteria in this policy are met, when they are identified as preventive services in the Company's benefit contracts and when they are mandated by state or federal law.  This policy supports the preventative care services listed in the US Preventive Services Task Force (USPSTF) as A or B Recommendations and the Women's Preventive Services (WPS) provision of Patient Protection and Affordable Care Act (PPACA). These products are available without cost-sharing with a  prescription when provided by a participating retail or mail-order pharmacy.

Based on the USPSTF recommendation the following products are available at zero-dollar cost-share.  All medications refer to generic, single ingredient products unless otherwise noted.​

 

CategoryRecommendationMedication
​ASPIRIN

Pregnant Women Who Are At High Risk for Preeclampsia :

The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication after 12 weeks of gestation in pregnant females who are at high risk for preeclampsia.

aspirin 81mg or less
TOBACCO CESSATION MEDICATIONTobacco cessation medication is covered as a preventive service for all adults who use tobacco products.Chantix ®, bupropion, Nicotrol®, generic nicotine gums and patches
FOLIC ACIDThe USPSTF recommends that all females planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid.folic acid 400 mcg to 800 mcg (including generic prenatal vitamins with the above listed folic acid dose)
FLUORIDEIn accordance with the preventive exam age schedule set forth by American Academy of Pediatrics (AAP)/Bright Futures, oral fluoride, up to 0.5mg, is covered as a preventive service for children ages 6 months to 16 years whose water supply is deficient in fluoride.fluoride up to 0.5mg for children 6 months to 16 years of age
BREAST CANCER CHEMO-PREVENTIONThe USPSTF recommends that clinicians engage in shared, informed decision making with individuals who are at increased risk for breast cancer about medications to reduce their risk. For asymptomatic females 35 years or older without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ, who are at increased risk for breast cancer and at low risk for adverse medication effects from breast cancer chemoprevention, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen.tamoxifen 20mg
CONTRACEPTIVESThe contraceptive methods for women currently identified by the FDA include: (1) sterilization surgery for women; (2) surgical sterilization implant for women; (3) implantable rod; (4) IUD copper; (5) IUD with progestin; (6) shot/injection; (7) oral contraceptives (combined pill); (8) oral contraceptives (progestin only); (9) oral contraceptives extended/continuous use; (10) patch; (11) vaginal contraceptive ring; (12) diaphragm; (13) sponge; (14) cervical cap; (15) condom; (16) spermicide; (17) emergency contraception; and (18) emergency contraception (Ella)injection/shot, oral contraceptives, etonogestrel-ethinyl estradiol vaginal ring, diaphragms, sponge, cervical cap, condom, spermicide, emergency contraceptive, Ella®, Phexxi®  [Note: IUDs and implantable products are covered under the medical benefit. See referenced policy]
BOWEL PREP FOR COLONOSCOPYThe USPSTF recommends screening for colorectal cancer starting at age 45 years and continuing until age 75 years.PEG 3350- electrolyte, Gavilyte-C, Gavilyte-G, Gavilyte-N, Trilyte with flavor packets, Gavilyte-H with bisacodyl, PEG-prep,PEG 3350 powder for solution
STATIN PREVENTIVE MEDICATION

The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (i.e., dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year risk of a cardiovascular event of 10% or greater.

lovastatin 10, 20, 40 mg
HIV PrEPPreexposure prophylaxis (PrEP) with effective antiretroviral therapy for persons who are at high risk of HIV acquisition

emtricitabine/tenofovir disoproxil

fumarate 200mg-300mg,

tenofovir 300mg


Certain medications have additional indications that are not addressed by the preventative care measure, such as raloxifene, or have generic alternatives, such as branded contraceptives.  Thus, the plan employs medical management to administer the requirements. The policy below outlines the process by which an exception can be obtained for medications that may apply to the USPSTF recommendation or the WPS provision of the PPACA but are not coded as $0 at the point-of-sale.



 

The intent of this policy is to communicate the medical necessity criteria for formulary exception requests as provided under the member's prescription drug benefit.

 

Tier Exceptions

A non-preferred drug will be covered at the preferred tier for brand medications as listed below when there is documentation of inadequate response or inability to tolerate at least three preferred or generic tier alternatives in the same pharmacological class*. Reasonably equivalent therapeutic class alternatives will be considered when there are limited pharmacological class alternatives available.

  1. Brand medication to preferred brand tier or
  2. Generic medication to generic tier

 

Non-formulary Exceptions:

A medication that is non-formulary, will be covered at the appropriate level of cost share when there is documentation of inadequate response or inability to tolerate at least three formulary alternatives in the same pharmacological  class*. Reasonably equivalent therapeutic class alternatives will be considered when there are limited pharmacological class alternatives available. Safety edits (age and quantity limits) will apply to non-formulary requests.

Compounded Products

A non-preferred compounded product may be covered at the preferred (formulary) tier when there is an inadequate response or inability to tolerate/use all other formulary alternatives.

Note: Compounded products are specially made products to meet the needs of an individual member and are not considered generics and thus not eligible for an exception to the generic tier.

 

$0 Cost-Share Override

An exception to allow no-cost share is approved when:

  1. The drug is described as either a preventative medication identified by the US Preventive Services Task Force (USPSTF) or Women's Preventive Services provision of the Patient Protection and Affordable Care Act (PPACA); and if applicable
  2. For branded products, ALL of the following:
    1. Inadequate response or inability to tolerate the generic equivalent, if available
    2. Inadequate response or inability to tolerate a generic alternative
    3. The prescriber has provided documentation indicating the requested product is medically necessary
       

 

*If there are fewer than three alternatives, all alternatives in the pharmacological class must be considered.

Authorization duration: 2 years

Truvada® (emtricitabine and tenofovir disoproxil fumarate), tenofovir

  1. Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued Truvada® and tenofovir. Hepatic function should be monitored closely in HBV-infected patients who discontinue Truvada® and tenofovir. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Truvada® (emtricitabine and tenofovir disoproxil fumarate)

  1. Truvada® used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug resistant HIV-1 variants have been identified with the use of Truvada® for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate Truvada® for HIV-1 PrEP if signs or symptoms of acute HIV infection are present unless negative infection status is confirmed.



 


Bright Futures Period Schedule. Available at: periodicity_schedule.pdf (aap.org). Accessed November 30, 2023

 

USPSTF A and B Recommendations by Date. US Preventive Services Task Force Web Site. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations Updated September 2022. Accessed November 30, 2023

 

Truvada® (emtricitabine and tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; June 2020. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/hiv/truvada/truvada_pi.pdf. Accessed November 30, 2023

 

Viread® (tenofovir disoproxil fumarate) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; April 2019. Available from: https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf. Accessed November 30, 2023


169/14/20239/14/20241/1/2024 1:26 AMNo presence informationsrv_ppsgw_P

Rx.01.33 Off Label Use

Rx.01.2 Applicable Age Edits

Rx.01.134 Compounded Product

Rx.01.76 Quantity Level Limits for Pharmaceutical Covered under the Pharmacy Benefit

Rx.01.197 Opioid Policy

00.06.02 Preventive Care Services Medical Policy ​


Inclusion of a drug in this table does not imply coverage. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

311
  
1/1/2024Rx.01.197CommercialOyenusi, Oluwadamilola

Opioid analgesics are classified as full agonists, mixed agonist-antagonists, or partial agonists by their activity at opioid receptors. There are three major classes of opioid receptors in the central nervous system (CNS): mu, kappa, and delta. Mu-receptor activation causes analgesia, respiratory depression, miosis, reduced GI motility, and euphoria.  Kappa-receptor activation also causes analgesia, but may also produce effects such as dysphoria and hallucinations, which limit use.  Delta-receptor activation produces some analgesia but may also cause seizures at high doses and has some antidepressant effects.  Morphine-like opioid agonists have activity at the mu, kappa, and delta receptors, but have the highest affinity for the mu receptors1. Opioid agonists include natural opium alkaloids (e.g., codeine, morphine), semisynthetic analogs (e.g., hydrocodone, hydromorphone, oxycodone, oxymorphone), and synthetic compounds (e.g., fentanyl, levorphanol, methadone, sufentanil, tapentadol, tramadol). There is no defined maximum dose for most opioids. The ceiling to analgesic effectiveness is imposed only by adverse reactions. Adverse effects of opioids include constipation, nausea and vomiting, dizziness, sedation, respiratory depression2. Long-term use of high dose narcotics may also have significant adverse effects including but not limited to endocrinological effects, such as, hypogonadism, impotence in males, menstrual irregularities, and galactorrhea in women; and opioid induced hyperanalgesia caused by damage to the nociceptors thus increasing pain sensitivity3

Opioid analgesics are commonly prescribed in pain management.  Pain is classified into non-cancer and cancer related pain. Non-cancer related pain may be acute or chronic while cancer-related pain may be a mixture of both2. When using opioid agents to manage pain, the choice should be made based on patient acceptance, pain intensity, analgesic effectiveness, pharmacodynamic, pharmacokinetic and side effect profiles. Like the treatment of many disease states, pain treatment should be initiated with the most effective agent with minimal side effects. Prior to starting patient on opioid pain management, pain severity and intensity should be thoroughly assessed using patient medical history, physical examination and different pain assessment tools4. In the management of mild non-cancer pain, the American Pain Society recommends the use of non-opioid analgesics such as acetaminophen and NSAIDs as first line agents. If pain relief is not adequate, opioid analgesics could be considered as the next line of treatment. Combination treatments of opioid with acetaminophen or NSAIDs are recommended when treating moderate to severe non-cancer pain. Common opioid analgesics like oxycodone and hydrocodone are often co-formulated with acetaminophen or NSAIDs and have a maximum dose to limit the amount of acetaminophen and NSAIDs exposure. It is recommended not to exceed 4000 mg of acetaminophen per day, 3200 mg of ibuprofen or 4000 mg (3900mg for controlled-, extended-, and delayed-release products) of aspirin daily.

Pain that is associated with cancer or a malignant condition is known as cancer related pain. Cancer related pain may be acute and/or chronic. Pain related to cancer is usually the result of damage to parts of the body from cancer metastasis or therapies such as chemotherapy, radiation and surgical procedures. Opioid analgesics play an important role in pain management for oncology patients. The World Health Organization (WHO) developed a pain relief regimen known as the WHO's Pain Relief Ladder which provides guidelines for pain management in cancer patients5. Like non-cancer related pain, opioid analgesics are reserved for moderate to severe cancer pain. Patients with mild pain should try non-opioid analgesics such as acetaminophen, ibuprofen, or naproxen first. Opioid agents or opioid combination are reserved for moderate to severe cancer pain or when inadequate pain relief is not achieved with non-opioid analgesics.

The potency of opioids is not consistent across all medications.  Morphine milligram equivalents (MME) is a conversion factor used to standardize the dose of an opioid into the equivalent dose of morphine to easily compare doses of different opioid agents and assess the risk of the doses.  Conversion factors are included in the table below. 

Several utilization tools are in place to prevent abuse and overuse of opioids.  These include MME limits, days' supply limits, and quantity limits.

  1. MME limits: MME Limits are in place to limit the total dosage of opioids a patient can receive in a day. Regimens, whether single drug or multiple drugs, that exceed 90 MME are subject to MME limit.  Higher doses of opioids, along with other factors, are associated with increased risk of opioid overdose.  The threshold of 90 MME is based on the recommendations from the Centers for Disease Control and Prevention: “When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day."   
  2. Days' Supply Limits: Day supply limits are in place to limit the total days a patient can receive opioids. “The probability of long-term opioid use increases most sharply in the first days of therapy, particularly after 5 days or 1 month of opioids have been prescribed," according to the Centers for Disease Control and Prevention (CDC).  Long-term opioid use often begins with treatment of acute pain. To address these statistics, all opioids individual opioids with a dose less than or equal to 90 morphine milligram equivalents (MME) are subject to 5 days' supply limit.  Continuation beyond five days requires review.
  3. Quantity Limits: Quantity limits are in place to optimize doses and achieve the prescribed dose using the least number of tablets, capsules, patches, films, liquids, suppositories, etc. that a patient can receive in a day. Opioids are subject to limits on the quantity per day. While opioid doses are variable and may have no true maximum, quantity limits are in place to address safety concerns, including abuse, addiction, and diversion. The limits in this policy restrict quantities to either the daily MME of 90 mg of a single agent or the FDA limit of additional product components such as 4 grams of acetaminophen, 3.2 grams of ibuprofen or 4 grams of aspirin

Morphine Milligram Equivalent (MME) Conversion Factors for Commonly Prescribed Opioid Analgesics

Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors12
Type of Opioid (strength units)MME Conversion Factor
Buprenorphine film/tablet (mg) 30
Buprenorphine patch (mcg/hr) 12.6
Buprenorphine film* (mcg) 0.03 
Butorphanol (mg)
Codeine (mg) 0.15 
Dihydrocodeine (mg) 0.25 
Fentanyl buccal or SL tablets, or lozenge/troche (mcg) 0.13 
Fentanyl film or oral spray (mcg) 0.18 
Fentanyl nasal spray (mcg) 0.16 
Fentanyl patch** (mcg) 7.2
Hydrocodone (mg)
Hydromorphone (mg) 5
Levorphanol tartrate (mg) 11 
Meperidine hydrochloride (mg) 0.1 
Methadone (mg) 4.7
Morphine (mg)
Opium (mg)
Oxycodone (mg) 1.5 
Oxymorphone (mg)
Pentazocine (mg) 0.37 
Tapentadol (mg) 0.4 
Tramadol (mg) 0.2 


These conversion factors will be used to determine the MME/day of all opioids being prescribed.  Calculate the total daily dose of the opioid in the left column and multiply by the conversion factor to determine to MME/ day.  If multiple agents are being used, add the MME of the individual agents to get the total MME of the regimen.    These values do not constitute clinical guidance or recommendations for converting patients from one form of opioid analgesic to another.  Extra caution applies to methadone (conversion factor depends on dose) and fentanyl (patches are dosed in mcg/hour rather than mg/day).  Please consult the manufacturer's full prescribing information for such guidance. 

12 These conversion factors are based on CMS “Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors" found here: https://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/Opioid-Morphine-EQ-Conversion-Factors-Aug-2017.pdf

*The MME conversion factor for buprenorphine patches is based on the assumption that one milligram of parenteral buprenorphine is equivalent to 75 milligrams of oral morphine and that one patch delivers the dispensed micrograms per hour over a 24 hour day. Example: 5 ug/hr buprenorphine patch X 24 hrs = 120 ug/day buprenorphine = 0.12 mg/day = 9 mg/day oral MME. In other words, the conversion factor not accounting for days of use would be 9/5 or 1.8. However, since the buprenorphine patch remains in place for 7 days, we have multiplied the conversion factor by 7 (1.8 X 7 = 12.6). In this example, MME/day for four 5 µg/hr buprenorphine patches dispensed for use over 28 days would work out as follows: Example: 5 ug/hr buprenorphine patch X (4 patches/28 days) X 12.6 = 9 MME/day. Please note that because this allowance has been made based on the typical dosage of one buprenorphine patch per 7 days, you should first change all Days Supply in your prescription data to follow this standard, i.e., Days Supply for buprenorphine patches= # of patches x 7

**The MME conversion factor for fentanyl patches is based on the assumption that one milligram of parenteral fentanyl is equivalent to 100 milligrams of oral morphine and that one patch delivers the dispensed micrograms per hour over a 24 hour day. Example: 25 ug/hr fentanyl patch X 24 hrs = 600 ug/day fentanyl = 60 mg/day oral morphine milligram equivalent. In other words, the conversion factor not accounting for days of use would be 60/25 or 2.4. However, since the fentanyl patch remains in place for 3 days, we have multiplied the conversion factor by 3 (2.4 X 3 = 7.2). In this example, MME/day for ten 25 µg/hr fentanyl patches dispensed for use over 30 days would work out as follows: Example: 25 ug/hr fentanyl patch X (10 patches/30 days) X 7.2 = 60 MME/day. Please note that because this allowance has been made based on the typical dosage of one fentanyl patch per 3 days, you should first change all Days Supply in your prescription data to follow this standard, i.e., Days Supply for fentanyl patches= # of patches X 3.

Butalbital containing products in tension-type headache

Butalbital is a barbiturate that is commonly prescribed in combination with acetaminophen and caffeine to treat different types of headaches such as tension-type and migraines. It works by decreasing motor activity and depress the sensory cortex causing CNS depression ranging from sedation to general anesthesia6. The analgesia effect of barbiturate is unknown. However, there are limited studies that show the efficacy of butalbital in the treatment of tension type headache and migraine7. In addition, overuse of barbiturate products could lead to dependency, withdrawal, and drug-induced headache. Therefore, when selecting a treatment for tension-type headache as well as other types of headaches, butalbital containing products should only be used if first line analgesics like acetaminophen or NSAIDs provide insufficient relief. In acute management, butalbital products should not be used more than 3 days7

Opioid Containing Cough and cold products

Opioid containing cough and cold products are thought to suppress cough via action on the central cough center. While the products are widely used, data are limited regarding efficacy.  Like opioids used to treat pain, cough and cold products containing an opioid are subject to days' supply limits, quantity limits, and morphine milligram equivalent (MME) limits.

 

Days' Supply and Quantity limits

Quantity limits are designed to allow a sufficient supply of medication based upon FDA-approved or medically accepted maximum daily doses and length of therapy of a particular drug. Quantity limits may be expressed as quantity over time or maximum daily dose.  Additionally, there are some medications to which a limit on the days' supply is applied.

  1. Quantity over time: This quantity limit is based on dosing guidelines over a rolling time period, usually 30 days.
  2. Maximum daily dose (maximum quantity per day): This quantity limit is based on maximum number of units of the drug allowed per day.
  3. Days' supply limit: This limits the numbers of days of therapy within a defined period of time. Maximum daily dose applies to days' supply limits.

Summary Of Utilization Managment

Summary Table of Criteria on Opioid Medications
CriteriaShort Acting OpioidsLong Acting Opioids (including opioid patches)Transmucosal Immediate Release Fentanyl (TIRF)
MME Limit YesYesYes
Day Supply LimitYes*NoNo
Quantity LimitYesYesYes
Opioid Prior AuthorizationNo*YesYes

*Note: short-acting opioids are available without prior authorization for two 5-day supplies within 60 days or less. Greater than a total of a 10 day supply within 60 days requires prior authroization.

 

The intent of this policy is to communicate the medical necessity criteria including prior authorization, quantity limits, and days’ supply for opioid analgesics, buprenorphine containing medication assistant treatments, and butalbital containing headache medications as provided under the member's prescription drug benefit.

​PRIOR AUTHORIZATION

I. Transmucosal Immediate Release Fentanyl (TIRF) Product fentanyl citrate is considered medically necessary when:

A. INITIAL CRITERIA [Authorization duration: 1 year]: Transmucosal Immediate Release Fentanyl (TIRF) Products are considered medically necessary when there is documentation of ALL of the following:
    1. Use for breakthrough pain associated with active cancer treatment or cancer not in remission in members who are receiving long-acting opioid therapy; and
    2. Member is 18 years of age or older (16 years of age and older for fentanyl citrate); and
    3. Member is tolerant to current opioid therapy (i.e., adherence to one of the following regimens for one week or longer: 25mcg of transdermal fentanyl hourly, 30mg of oxycodone daily, 60mg of oral morphine daily, 8mg of oral hydromorphone daily, 25mg of oral oxymorphone daily; or an equianalgesic dose of another opioid)
B. REAUTHORIZATION CRITERIA [Authorization duration: 1 year]:  Transmucosal Immediate Release Fentanyl (TIRF) product is re-approved when there is documentation of continued use for breakthrough pain associated with active cancer treatment or cancer not in remission in members who are currently receiving long-acting opioid therapy

 
II. Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting opioids for continuation beyond 30 days [Authorization duration: 1 year] - are considered medically necessary as follows:

A. INITIAL CRITERIA: The requested product or regimen is considered medically necessary when there is ONE of the following  
1. Pain associated with active cancer treatment, cancer not in remission, or sickle cell anemia (regardless of age); OR
2. Severe, persistent chronic pain with documentation of diagnosis associated with pain and ALL of the following:
 
      1. Documentation of a current patient-prescriber opioid treatment agreement (signed within one year of request); and
      2. ONE of the following
        1. Regimen prescribed by or in consultation with a pain management specialist within last 6 months. Must provide name of physician and date of last visit. Physician must be Board Certified by one of the following:
          1. American Board of Anesthesiology- Pain Management; or
          2. American Board of Psychiatry & Neurology- Pain Management; or
          3. American Board of Physical Medicine & Rehabilitation; or
          4. American Osteopathic Association- Pain Management

          ​or

        2. The member has been evauated for at least TWO of the following therapies:
            1. Physical therapy; or
            2. Psychotherapy; or
            3. Adjuvant medications specific to causative condition including but not limited to any of the following: antidepressants, anticonvulsants, muscle relaxants, anti-inflammatory agents.

B. REAUTHORIZATION CRITERIA [Authorization duration: 1 year]:  Re-authorization of the requested opioid product or regimen containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting opioids for continuation beyond 30 days is considered medically necessary when there is documentation of ONE of the following:

  1. Pain associated with active cancer treatment, cancer not in remission, or sickle cell anemia (regardless of age) AND documentation that a urine drug screen (UDS) will performed by prescriber within 1 year of request.

OR

      2. Severe, persistent chronic pain with documentation of diagnosis associated with pain and ALL of the following:

    1. Documentation of a current patient-prescriber opioid treatment agreement (signed within one year of request); and
    2. documentation that a urine drug screen (UDS) will be performed by prescriber within 1 year of request.
III. Appropriate Utilization with Medication Assistant Treatments (MAT) for opioid use disorder - [Authorization duration: 2 months] - Opioid analgesics will require prior authorization for medical necessity when filled within two months of a paid claim for either buprenorphine/naloxone (Bunavail®/Suboxone®/Zubsolv®) or buprenorphine sublingual tablet. Opioid analgesic products are approved in patients that have received buprenorphine/naloxone or buprenorphine in the previous two months when there is documentation of a treatment plan showing discontinuation of buprenorphine containing MAT.

 
DAYS' SUPPLY AND QUANTITY LIMITS

 
Day supply limit Criteria
A. Short-acting opioids for short term use (greater than two 5-day fills within 60 days for 18 and older, and greater than two 3-day fills within 60 days for age less than 18)  [Authorization duration: 1 month for a 30 days' supply] - an exception is approved when ALL of the following are met:
1. INITIAL CRITERIA
  1. Diagnosis of acute pain; and
  2. Prescriber reviewed member's history in state Prescription Drug Monitoring Program website; and
  3. Prescriber counseled member (or member's representative) on risk of addiction; and
  4. Substance abuse screening done by prescriber
2. REAUTHORIZATION CRITERIA see Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting low dose opioids for continuation beyond additional 30 days Prior Authorization criteria under section under section II.A above​.
 
B. Opioid containing cough and cold products are limited to two five (5) day fills within 60 days for 18 and older and two 3-day fills within 60 days for age less than 18 - an exception is approved when

 
1. INITIAL CRITERIA: there is documentation of inadequate response or inability to tolerate non-opioid therapies for the indication [Authorization duration 1 month]
 
2. REAUTHORIZATION CRITERIA: Documentation the underlying etiology of cough has been identified and treated, if applicable (e.g. allergic rhinitis, asthma, GERD) [Authorization duration 6 months]
 
C. Butalbital containing headache products are limited to one five (5) day fill within 30 days.  Opioid containing headache products are limited to one three (3) day fill within 30 days for less than 18 years of age, an exception is approved as follows: 
 
 
 

1. INITIAL CRITERIA [Authorization duration: 3 months]: All of the following:

a. Diagnosis of one of the following:

i. Tension-type or muscular headache

ii. Migraine headache

b. Member is 12 years of age or older

c. Inadequate response or inability to tolerate TWO of the following:

i. At least two triptans

ii. Non-steroid anti-inflammatory drugs (e.g. ibuprofen, naproxen)

iii. Neuroleptics (e.g. prochlorperazine, metoclopramide)

iv. Dihydroergotamine

 

2. REAUTHORIZATION CRITERIA: [Authorization duration: 1 year]: All of the following:

a. Diagnosis of one of the following:

i. Tension-type or muscular headache

ii. Migraine headache

b. Member is 12 years of age or older

c. Prescribed by or in consultation with a neurologist or a headache specialist, or pain specialist

d. Inadequate response or inability to tolerate NSAIDs

e. Ongoing assessment of medication-overuse headache

 

II. Quantity limit Criteria
A. Opioid pain products [authorization duration = 1 year] An increased quantity of an opioid medication is approved when there is documentation of ALL of the following:

1. Current patient-prescriber opioid treatment agreement (signed within one year of request); and
2. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
3. ONE of the following:
​​​a. The dose cannot be achieved with commercially available clinical dosage forms; or
b. Documentation indicating medical necessity for a quantity that exceeds the plan limit (e.g. GI malabsorption).

B. Cough and cold products [Authorization duration: 1 month for initial; 6 months for reauthorizations] - An increased quantity of an opioid containing cough and cold medication is approved when there is documentation of ALL of the following:
    1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
    2. Documentation of diagnosis requiring long-term therapy with requested cough/ cold medications; and
    3. Inadequate response or inability to tolerate non-opioid therapies for the indication

 
C. Butalbital containing headache products [Authorization duration:1 year] - An increased quantity of a butalbital containing headache medication is approved when there is documentation of ALL of the following:
    1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
    2. Inadequate response or inability to tolerate prophylactic therapy; and
    3. Prescribed by or in consultation with a neurologist, headache specialist or pain specialist.

       
D. Buprenorphine/ naloxone (Bunavail®/Suboxone®/Zubsolv®) and buprenorphine  sublingual tablet [Authorization duration: 6 months]: buprenorphine/ naloxone or buprenorphine for the treatment of opioid use disorder are approved in quantities greater than those specified in the policy when ALL of the following  are met:
    1. The requested dose and frequency do not exceed FDA approved dosing or are supported by compendia; and
    2. The dose cannot be achieved with commercially available dosage forms; and
    3. Inadequate response to lower doses 

1. Respiratory depression: 21, 22, 30, 31, 32, 33, 34, 35, 40, 43  TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER®, Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Zohydro ER(hydrocodone ER), Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorpheniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)


Fatal respiratory depression has occurred in patients treated with the above listed opioid products, including following use in opioid-intolerant patients and improper dosing. Be sure to monitor for sign and symptoms of respiratory depression, especially during initiation of the drugs. The substitution of fentanyl sublingual/buccal for any other fentanyl product may result in fatal overdose. Because of the risk of respiratory depression, fentanyl products are contraindicated for use as an as-needed analgesic, or in the management of acute or postoperative pain, including headache/migraine and in opioid-intolerant patients. In addition, the concomitant use of fentanyl sublingual with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations and may cause potentially fatal respiratory depression.

For hydromorphone and ER products like morphine ER, oxycodone ER, hydrocodone ER, tapentadol ER, and oxymorphone ER products, instruct patients to swallow a whole tablet. Crushing, chewing, snorting, or dissolving tablets can cause rapid release and absorption that could lead to fatal overdose and even death. Note: Avinza® capsule contents may be sprinkled on applesauce and swallowed without chewing19. Hydromorphone is a potent Schedule II controlled opioid agonist. Schedule II opioid agonists have the highest potential for abuse and risk of producing respiratory depression. Alcohol, other opioids, and CNS depressants (sedative-hypnotics) potentiate the respiratory depressant effects of hydromorphone, increasing the risk of respiratory depression that might result in death.
 
2. Medication errors: 32, 33 TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), Qdolo® (tramadol)

Substantial differences exist in the pharmacokinetic profile of fentanyl sublingual/buccal compared with other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose. When prescribing, do not convert patients on a mcg-per-mcg basis from any other fentanyl products to fentanyl sublingual/buccal. When dispensing, do not substitute a fentanyl sublingual/buccal prescription for other fentanyl products.

3. Addiction and Abuse potential: 21, 22, 30, 31, 32, 33, 34, 42, 43 TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER®​, Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Zohydro ER(hydrocodone ER), Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)

 All opioid analgesics regardless of formulation are classified as Schedule II controlled substance, with high abuse liability. They expose patients and drug users to the risk of opioid addiction, abuse, and misuse, which can lead to overdose and death. Diversion, addiction, and abuse potential should be considered when prescribing or dispensing opioid analgesics. Providers must monitor all patients regularly for the development of these behaviors or conditions. Due to the risk for misuse, abuse, addiction, and overdose, some products such as fentanyl sublingual/buccal is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program, outpatients, health care providers who prescribe to outpatients, pharmacies, and distributors must enroll in the program. Further information is available at http://www.TIRFREMSaccess.com or by calling 1-866-822-1483
 
4. Cytochrome P450 3A4 interaction: 30, 31  TIRFs (Actiq®, Fentora®, Subsys®), Lazanda®, Duragesic®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM ,Roxybond®), Zohydro ER™ (hydrocodone ER), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorpheniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)

The concomitant use of fentanyl, oxycodone ER and hydrocodone ER with all cytochrome P450 3A4 (CYP3A4) inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone ER and any CYP3A4 inhibitor or inducer.
 
5. Accidental exposure 21, 22, 30, 31, 32, 33, 34, 42, 43: Duragesic®, Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER® , Nucynta ER®/ Opana ER®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM Roxybond®), Zohydro ER™, Buprenorphine (Belbuca and Butrans), benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorphniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib)

Deaths due to a fatal overdose of the above listed opioid analgesics have occurred when children and adults were accidentally exposed to the drugs. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure. Accidental ingestion of even 1 dose, especially in children, can result in a fatal overdose and death.

6. Neonatal opioid withdrawal syndrome: 21, 22, 30, 31, 32, 33, 34, 44, 43 
Prolonged use of opioid analgesics especially Duragesic®,  Hydromorphone (Dilaudid, Exalgo®), Methadone, Morphine Sulfate: ArymoTM ER, Avinza®, Kadian®, and MS Contin®, Morphabond ER® , Nucynta ER®/ Opana ER® (tapentadol ER, and oxymorphone ER), Zohydro ER™, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Buprenorphine (Belbuca and Butran), benzhydrocodone/acetaminophen (Apadaz®), codeine phosphate and chlorpheniramine maleate (Tuxarin®), codeine polistirex and chlorpheniramine (Tuzistra XR), Qdolo® (tramadol), levorphanol , Seglentis® (tramadol/celecoxib)can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
 
7. Exposure to heat: Duragesic® (31)
Exposure of the fentanyl application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase fentanyl absorption and has resulted in fatal overdose of fentanyl and death. Patients wearing fentanyl systems who develop fever or increased core body temperature due to strenuous exertion are also at risk for increased fentanyl exposure and may require an adjustment in the dose of fentanyl to avoid overdose and death.

8. Life-threatening QT prolongation: Methadone 29

QT interval prolongation and serious arrhythmia like torsades de pointes have occurred during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients for changes in cardiac rhythm during initiation and titration of methadone.
 
9. Treatment of opioid addiction: Methadone29

For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.
 
10. Interaction with alcohol 21, 22, 30, 31, 32, 33, 34, 35, 40: Morphine Sulfate: Avinza®, Kadian®, and MS Contin®, Nucynta ER®/ Opana ER®, Zohydro ER™, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®), Buprenorphine (Belbuca and Butran), benzhydrocodone/acetaminophen (Apadaz®)

 When using with alcohol, all opioid analgesic products have the potential to cause excessive sedation and may increase blood concentration of certain opioids like tapentadol, oxymorphone, and morphine. This could lead to fatal overdose and death. Instruct patients to avoid alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking opioid analgesics. 

11. Information about oral morphine and oxycodone solution23, 29  : Morphine Sulfate: Avinza®, Kadian®, and MS Contin®, Oxycodone (Oxycontin®, oxycodone concentrate, OxaydoTM, Roxybond®)

 Morphine oral solution is available in 10 mg per 5 mL, 20 mg per 5 mL, and 100 mg per 5 mL (20 mg/mL) concentrations. The 100 mg per 5 mL (20 mg/mL) concentration is indicated for use in opioid-tolerant patients only. Take care when prescribing and administering morphine oral solution to avoid dosing errors due to confusion between different concentrations and between milligrams and milliliters, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Keep morphine oral solution out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately.

Oxycodone concentrated oral solution is available as a 20 mg/mL concentration and is indicated for use in opioid-tolerant patients only. Take care when prescribing and administering oxycodone concentrated oral solution to avoid dosing errors due to confusion between milligram and milliliter, and other oxycodone solutions with different concentrations, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Keep oxycodone out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately.
 
12. Abuse Deterrent Technology: Oxaydo™ (37)

 This formulation incorporates Acura's patented AVERSION® (abuse-deterrent) Technology which Acura states is a patented mixture of gelling ingredients and nasal irritants designed to address common forms of opioid abuse. OXAYDO can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing in situations where there is concern about an increased risk of misuse or abuse. OXAYDO may be abused by crushing, chewing, snorting or injecting the product and these practices pose a significant risk to the abuser that could result in overdose and death.

 A Risk Evaluation and Mitigation Strategy (REMS) is included in the label of the several medications.  A REMS is a safety strategy to manage known or potential serious risks associated with a medication and to enable patients to have continued access to such medicines by managing their safe use.  Refer to the individual product labels for details on the REMS programs.
 

13. Risks from Concomitant Use with Benzodiazepines or other CNS Depressants: ArymoTM ER 42, Morphabond ER® 43, benzhydrocodone/acetaminophen (Apadaz®), codeine polistirex and chlorphniramine (Tuzistra XR), codeine phosphate and chlorpheniramine maleate (Tuxarin®), levorphanol, Qdolo® (tramadol), Seglentis® (tramadol/celecoxib) 

Concomitant use of opioid with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depressions, coma, and death.

14. Life threatening respiratory depression and death have occurred in children who received codeine; most cases followed tonsillectomy and/or adenoidectomy and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. TUXARIN ER, TUZISTRA XR are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of TUXARIN ER, TUZISTRA XR for adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

Life-threatening respiratory depression and death have occurred in children who received Qdolo® (tramadol). Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism. Qdolo® is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of Qdolo® in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.

15. Hepatotoxicity: benzhydrocodone/acetaminophen (Apadaz®)

APADAZ contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed

4000 milligrams per day, and often involve more than one acetaminophen-containing product.


16. Cardiovascular thrombotic events (Seglentis®)


Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use. SEGLENTIS is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

17. Gastrointestinal bleeding, ulceration, and perforation (Seglentis®)

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms.
Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious (GI) events.

18. Ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children (Seglentis®)

Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism. SEGLENTIS is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of SEGLENTIS in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.



 


 

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Tuxarin® (codeine phosphate and chlorpheniramine maleate) [package insert]. Irvine, CA: Nexgen Pharma, Inc. June 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206323s006lbl.pdf. Accessed December 5, 2023.

Apadaz® (benzhydrocodone and acetaminophen) [prescribing information]. Coralville, IA: KemPharm, Inc. October 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208653s005lbl.pdf. Accessed December 5, 2023.

Tuzistra® XR (codeine polistirex and chlorpheniramine polistirex). Tris Pharmac, Inc. October 2018. Available at: https://www.tuzistraxr.com/wp-content/uploads/2018/11/Tuzistra-PI.pdf. Accessed December 5, 2023.

Qdolo® (tramadol). Athena Bioscience, Inc. September 2020. Available at: https://qdolo.com/wp-content/uploads/2020/10/QDOLO-Prescribing-Information.pdf. Accessed December 5, 2023.

Seglentis® (tramadol/celecoxib) [package insert]. Montgomery, AL: Kowa Pharmaceuticals America, Inc.; October 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213426s000lbl.pdf. Accessed December 5, 2023.​




229/14/202312/8/20231/1/2024 1:26 AMNo presence informationsrv_ppsgw_P

Prior Authorization Requirements for Select Drugs Rx.01.202

Off-Label Use Rx.01.33

All products containing the active ingredients in the chart below are subject to the following:

II. Opioid regimens containing greater than 90 morphine milligram equivalents per day

III. Appropriate Utilization with Medication Assistant Treatments (MAT) for opioid use disorder

Active ingredient
Benzhydrocodone
Codeine

Dihydrocodeine
Fentanyl
Hydrocodone
Hydromorphone
Levorphanol                                    
Meperidine                                                
Methadone                                                      
Morphine
Opium
Oxycodone                                                     
Oxymorphone                         
Tapentadol
Tramadol                                               

 

The table below identifies medications that are found in the following sections of this policy:

  • I. Transmucosal Immediate Release Fentanyl (TIRF) Products (¥ identifies impacted medications)
  • II. Opioid regimens containing greater than 90 morphine milligram equivalents per day, long acting opioids, and short acting low dose opioids for continuation beyond 30days (*identifies impacted long acting opioids)
  • Days' Supply and Quantity Limits
Drug NameDays' Supply Limit  Maximum Quantity per DayQuantity limit per rolling 30 days, unless otherwise specified (tablet, capsule)
Acetaminophen/codeine #2 300/15mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Acetaminophen/codeine #3 300/30mg tab two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Acetaminophen/codeine #4 300/60mg tab two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Acetaminophen/codeine liquid two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
Aspirin/codeine two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Benzhydrocodone/acetaminophen (Apadaz®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Buprenorphine film* (Belbuca®) No2
Buprenorphine patch* (Butrans®) No4 patches
Buprenorphine sublingual tablet 2mgNo4 
Buprenorphine sublingual tablet 8mgNo3
Buprenorphine/naloxone (Suboxone® 2/0.5mg, 4/1mg) No4
Buprenorphine/ naloxone (Suboxone® 8/2mg) No3
Buprenorphine/ naloxone (Suboxone® 12/3mg) No2
Buprenorphine/naloxone (Zubsolv® 1.4/0.36mg, 2.9-0.71mg)No4
Buprenorphine/naloxone (Zubsolv® 5.7/1.4mg, 0.7/0.18mg)No3
Buprenorphine/naloxone (Zubsolv® 8.6/2.1mg)No2
Buprenorphine/naloxone (Zubsolv® 11.4-2.9mg)No1
Buprenorphine/naloxone (Bunavail® 2.1/0.3mg)No4
Buprenorphine/naloxone (Bunavail® 4.2/0.7mg)No3
Buprenorphine/naloxone (Bunavail® 6.3/1mg)No1
Butalbital/apap (Allzital®, Marten®)one 5-day fill per 30 days6 
Butalbital/apap/caffeine  without codeine (Esgic®, Fioricet®)one 5-day fill per 30 days6 
Butalbital/apap/caffeine with codeine (Esgic®, Fioricet®/codeine)one 5-day fill per 30 days for 18 and over; one 3-day fill per 30 days for less than 186 
Butalbital/asa/caffeine  without codeine (Fiorinal®) one 5-day fill per 30 days6 
Butalbital/asa/caffeine with codeine (Fiorinal®/Codeine)one 5-day fill per 30 days for 18 and over; one 3-day fill per 30 days for less than 186 
Carisoprodol/ aspirin/ codeine (Soma® compound with codeine)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
Codeine sulfate tablets 15mg, 30mgtwo 5-day fills per 60 for 18 and older; two 3-day fills per 60 days for less than 1812 
Codeine sulfate tablets 60mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Codeine sulfate solution two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Codeine/chlorpheniramine (Tuxarin® ER)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 182 
Codeine/chlorpheniramine tablets (Tuzistra® XR)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1820mL 
Codeine/ chlorpheniramine solution (Z-Tuss® AC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Dihydrocodeine/ acetaminophen/ caffeine (Trezix®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1810 
Fentanyl IR¥ (Actiq®, Fentora®, Subsys®) No4
Fentanyl nasal solution¥  (Lazanda®) No1
Fentanyl patch* (Duragesic®) No15 patches
Guaifenesin/ codeine (GG/codeine,  Coditussin® AC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Guaifenesin/ codeine (MAR-COF® CG, Trymine® CG)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1845mL 
Guaifenesin/ codeine (M-Clear® WC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
Hydrocodone bitartrate ER* (Hysingla® ER) No1 
Hydrocodone bitartrate ER* (Zohydro® ER) No2
Hydrocodone/acetaminophen 2.5/325mg, 5/300mg,7.5/300mg, 5/325mg, 7.5/325mg tab (Vicodin®, Norco®, Lortab®, Xodol®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812
Hydrocodone/apap 10/325mg, 10/300mg tab (Vicodin®, Norco®, Lortab®, Xodol®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Hydrocodone/apap liquid (10mg/325mg/15ml, 2.5mg/167mg/5ml, 5mg/333mg/10ml, 7.5mg/325mg/15ml, 10mg/300mg/15ml) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
Hydrocodone/chlorpheniramine two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1810mL 
Hydrocodone/chlorpheniramine (TussiCaps®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 182 
Hydrocodone/ homatropine (Hydromet®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830mL 
Hydrocodone/ homatropine two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Hydrocodone/ibuprofen  two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 185 
Hydromorphone (Dilaudid®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Hydromorphone 1mg/1ml liquid (Dilaudid®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812mL 
Hydromorphone extended release* (Exalgo®) No2 
Levorphanol tartrate 2mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Levorphanol tartrate 3mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 184 
Meperidine 50mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1867mL 
Meperidine HCL (Demerol®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Methadone* tabs 5mg, 10mgNo6 
Methadone solution* 5mg/5mlNo60mL 
Methadone solution* 10mg/5mlNo30mL 
Methadone solution* (Methadose concentrate,
Methadose sugar-free concentrate) 10mg/1ml
No6mL 
Morphine 10mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1845 mL 
Morphine 20mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1823 mL 
Morphine concentrate 20mg/1ml, 10mg/0.5ml, 5mg/0.25ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186mL 
Morphine sulfate IR (MSIR®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186
Morphine sulfate ER capsules* (Avinza®) No1
Morphine sulfate ER capsules* (Kadian®) No2 
Morphine sulfate SR* (Morphabond®) No3
Morphine sulfate SR* (MS Contin® Arymo® ER) No3
Morphine sulfate/naltrexone* (Embeda®) No2
Morphine suppositories 5mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1818 
Morphine suppositories 10mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Morphine suppositories 20mg, 30mg two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Opium tincturetwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 18N/A 
Oxycodone 7.5mg tab (Oxaydo®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
Oxycodone HCL (Oxy® IR/Roxicodone®/Oxaydo®, Roxybond®) 5mg caps/tabstwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Oxycodone HCL (Oxy® IR/Roxicodone®, Roxybond®), 10mg, 15 mg, 30mg caps/tabstwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Oxycodone 5mg/5ml liquidtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860 mL 
Oxycodone highly concentrated liquid 20mg/1ml liquid (Eth-Oxydose®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186mL 
Oxycodone HCL ER* (Oxycontin®) No3
Oxycodone ER* (Xtampza® ER) No2 
Oxycodone/Acetaminophen, Endocet® (Percocet®,Primlev®, Nalocet®, Prolate®) 2.5/325mg tab, 2.5/300mg tab, 5/300mg, 5/325mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Oxycodone/Acetaminophen (Primlev®, Prolate®)
7.5/300mg tab, 10/300mg tab
two 5-day fills
per 60 days for
18 and older;
two 3-day fills
per 60 days for
less than 18
6 
Oxycodone/acetaminophen 7.5/325mg tab (Endocet®/Percocet®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 188 
Oxycodone/acetaminophen 10/325mg tab (Endocet®/Percocet®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Oxycodone/acetaminophen 5mg/325mg/5ml liquid two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860 
Oxycodone/aspirin 4.8355/325mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1812 
Oxycodone/Acetaminophen (Prolate®) 10-300mg/5ml solnTwo 5-days fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830 ml 
Oxycodone/ibuprofen tablets 5/400mg tabtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 184 
Oxymorphone HCL (Opana®) two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Oxymorphone HCL ER* (Opana® ER) No3 
Phenylephrine/ brompheniramine/ codeine (M-End® PE)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1890mL 
Phenylephrine/ chlorpheniramine/ codeine (Capcof®)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Phenylephrine/ dexchlorpheniramine/ codeine (Pro-red® AC)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Promethazine/codeine 6.25-10mg/5mL syruptwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830mL 
Promethazine/ phenylephrine/ codeine 6.25-5-10mg/5mLtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1830mL 
Pseudoephedrine/ brompheniramine/ codeine (MAR-COF® BP)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Pseudoephedrine/codeine/ guaifenesin (Virtussin
DAC) solution 30-10-100 MG/5ML
two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1840mL 
Pseudoephedrine/ dexbrompheniramine/ codeine (M-End® Max D)two 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 1860mL 
Tapentadol (Nucynta®) 50mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 184 
Tapentadol (Nucynta®) 75mg, 100mgtwo 5-day fills per 60 days for 18 and older; two 3-day fills per 60 days for less than 186 
Tapentadol ER* (Nucynta® ER) No2 
Tramadol (Ultram®) 8 
Tramadol (Ultram® ER and Conzip®) 1 
Tramadol/acetaminophen (Ultracet®) 8
Tramadol/celecoxib (Seglentis®)No4 
Tramadol 100 mg 4 
Tramadol (Qdolo®) 80ml 

313
  
1/1/2024Rx.01.206CommercialOyenusi, Oluwadamilola

Sickle cell disease (SCD) is caused by a point mutation in the beta-globin gene, resulting in defective hemoglobin, which is less soluble than normal fetal or adult hemoglobin. The red blood cells become sickled in shape causing hemolytic anemia and vaso-occlusion, which can lead to acute and chronic pain, and tissue ischemia. SCD refers to any of the syndromes in which the sickle mutation is co-inherited with a mutation at the other beta globin allele that reduces normal beta globin production. It includes sickle cell anemia, sickle beta thalassemia, and hemoglobin sickle cell disease.

Endari® is an amino acid indicated to reduce the acute complications of sickle cell disease in adults and pediatric patients 5 years of age and older.

The mechanism of action of the amino acid L-glutamine in treating sickle cell disease (SCD) is not fully understood. Oxidative stress phenomena are involved in the pathophysiology of SCD. Sickle red blood cells (RBCs) are more susceptible to oxidative damage than normal RBCs, which may contribute to the chronic hemolysis and vaso-occlusive events associated with SCD. The pyridine nucleotides, NAD+ and its reduced form NADH, play roles in regulating and preventing oxidative damage in RBCs. L-glutamine may improve the NAD redox potential in sickle RBCs through increasing the availability of reduced glutathione.

Voxelotor (Oxbryta®) is a hemoglobin S polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs). By increasing the affinity of Hb for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization. Nonclinical studies suggest that voxelotor may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity. Oxbryta® is indicated for the treatment of sickle cell disease in adults and pediatric patients 4 years of age and older. 

The intent of this policy is to communicate the medical necessity criteria for L-glutamine (Endari®) and voxelotor (Oxbryta®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA L-glutamine (Endari®) is approved when ALL of the following are met:

  1. Diagnosis of sickle cell disease; and
  2. Member is 5 years of age or older; and
  3. Member has had 2 or more painful sickle cell crises within the past 12 months; and
  4. Prescribed by or in consultation with a hematologist/oncologist or specialist with expertise in the diagnosis and management of sickle cell disease, and
  5. Documentation of ONE of the following:
    a. Concurrent hydroxyurea therapy; or
    b. Inadequate response or inability to tolerate hydroxyurea
     

Initial authorization duration: 12 months

CONTINUATION CRITERIA L-glutamine (Endari®) is re-approved when there is documentation of positive clinical response to therapy from baseline (e.g., reduction in the number of sickle cell crises, fewer hospitalizations due to sickle cell pain, etc.).


Continuation authorization duration: 2 years

INITIAL CRITERIA Voxelotor (Oxbryta®) is approved when ALL of the following are met:

  1. Diagnosis of sickle cell disease; and
  2. No concurrent therapy with crizanlizumab-tmca (Adakveo®); and
  3. Member is 4 years of age or older; and
  4. Member had at least one vaso-occlusive crisis (VOC) event within the past 12 months (e.g., acute painful crisis, acute chest syndrome); and
  5. Hemoglobin level that is between 5.5g/dL and 10.5g/dL prior to therapy initiation; and
  6. Inadequate response or inability to tolerate hydroxyurea (i.e. Siklos, Droxia); and
  7. Prescribed by or in consultation with a hematologist/oncologist or specialist with expertise in the diagnosis and management of sickle cell disease.

Initial authorization duration: 12 months

CONTINUATION CRITERIA Voxelotor (Oxbryta®) is re-approved when there is documentation of positive clinical response to Oxbryta® therapy (e.g., an increase in hemoglobin level of greater than or equal to 1 g/dL from baseline, decreased annualized incidence rate of VOCs)

Continuation authorization duration: 2 years

​N/A


Endari® (L-glutamine oral powder) [prescribing information]. Torrance, CA: Emmaus Medical, Inc.; October 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208587s000lbl.pdf. Accessed October 02, 2023.

Oxbryta® (voxelotor) [prescribing information]. South San Francisco, CA: Global Blood Therapeutics, Inc., August 2023. Available at: https://hcp.oxbryta.com/pdf/prescribing-information.pdf. Accessed October 02, 2023.

Vichinsky Elliott P. Overview of the clinical manifestations of sickle cell disease. UpToDate. Accessed October 02, 2023.​



89/14/20239/14/20241/1/2024 1:26 AMNo presence informationsrv_ppsgw_P

Off-Label Use Rx.01.33

Brand NameGeneric Name

Endari®

Oxbryta®

L-glutamine

Voxelotor

314
  
1/1/2024Rx.01.211CommercialOyenusi, Oluwadamilola

​Endometriosis is defined as endometrial glands and stroma that occur outside the uterine cavity. Lesions are typically in the pelvis; however, they can occur at multiple sites. It affects many women throughout their lifetime and although it is considered nonmalignant, the pain and discomfort associated with the condition can be severe and debilitating.

Elagolix (Orilissa™) is a gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of ORILISSA results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.

Elagolix (Orilissa™) is indicated for the management of moderate to severe pain associated with endometriosis.

​The intent of this policy is to communicate the medical necessity criteria for elagolix (Orilissa™) as provided under the member's prescription drug benefit.

Elagolix (Orilissa™) is approved when all of the following are met:

  1. Diagnosis of moderate to severe pain associated with endometriosis; and
  2. Member is 18 years of age or older; and
  3. ONE of the following:
    1. Inadequate response or inability to tolerate BOTH of the following:
      1. One non-steroidal anti-inflammatory drug; and
      2. Contraceptives; or
    2. Member has had surgical ablation to prevent recurrence

Authorization duration: 2 years

Coverage duration is limited to:

  1. 24 months/ lifetime for 150mg tablet
  2. 6 months/ lifetime for 200mg tablet


All other treatment durations are considered Experimental/ Investigational. ​​

​N/A

Elagolix (Orilissa™) [package insert]. North Chicago, IL. AbbVie, Inc. June 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210450s000lbl.pdf. Accessed NOVEMBER 21, 2023

Schenken, R. MD. Endometriosis: Pathogenesis, clinical features, and diagnosis. UpToDate. Accessed NOVEMBER 21, 2023.​



69/14/20239/14/20241/1/2024 1:26 AMNo presence informationsrv_ppsgw_P

Off Label Use Rx.01.33

Inclusion of a drug in this table does not imply coverage. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

Brand NameGeneric Name
Orilissa™Elagolix
315
  
1/1/2024Rx.01.210CommercialOyenusi, Oluwadamilola

​Phenylketonuria is a disorder affecting the aromatic amino acid, phenylalanine. It results from a deficiency of phenylalanine hydroxylase (PAH) and if untreated is characterized by intellectual disability.


Pegvaliase-pqpz (Palynziq™) is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations.


Pegvaliase-pqpz (Palynziq™) is indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.

​The intent of this policy is to communicate the medical necessity criteria for Pegvaliase-pqpz (Palynziq™) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Pegvaliase-pqpz (Palynziq™) is approved when ALL of the following are met:

  1. Member is 18 years of age or older, and
  2. Member has diagnosis of phenylketonuria with uncontrolled blood phenylalanine concentration of greater than 600 micromol/L on existing management (e.g., medical foods, Kuvan®); and
  3. Member will continue to have phenylalanine blood levels measured periodically during therapy

Initial Authorization duration: 6 months

CONTINUATION CRITERIA: Pegvaliase-pqpz (Palynziq™) is re-approved when there is documentation of a positive clinical response to Pegvaliase-pqpz (Palynziq™) therapy (i.e., reduction in blood phenylalanine concentrations).

Continuation Authorization duration: 2 years

​WARNING: RISK OF ANAPHYLAXIS
See full prescribing information for complete boxed warning.

  • Anaphylaxis has been reported after administration of Palynziq and may occur at any time during treatment.
  • Administer the initial dose of Palynziq under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed.
  • Prescribe auto-injectable epinephrine. Prior to first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during Palynziq treatment.
  • Palynziq is available only through a restricted program called the Palynziq REMS.

Pegvaliase-pqpz (Palynziq™) [package insert]. Novato, CA. BioMarin Pharmaceutical, Inc. November 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761079s000lbl.pdf. Accessed October 02, 2023.

Bodamer, O. Overview of Phenylketonuria. UpToDate. Access October 02, 2023. 



 
69/14/20239/14/20241/1/2024 1:26 AMNo presence informationsrv_ppsgw_P

Off-Label Use Rx. 01.33

Brand NameGeneric Name
Palynziq™Pegvaliase-pqpz
317
  
1/1/2024Rx.01.230CommercialOyenusi, Oluwadamilola

Chronic Granulomatous Disease (CGD) is a disorder that causes the immune system to malfunction, resulting in immunodeficiency in patients. CGD is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. These defects result in the inability of phagocytes (neutrophils, monocytes, and macrophages) to destroy certain microbes. Patients with CGD are susceptible to infections from foreign invaders such as bacteria and fungi. Severe Malignant osteopetrosis is a disease where osteoclasts do not function the right way, and abnormal bone development occurs. This abnormal bone development can cause anemia, bleeding, and immunodeficiency.

Interferons bind to specific cell surface receptors and initiate a sequence of intracellular events that lead to the transcription of interferon-stimulated genes. The three major groups of interferons (alpha, beta, gamma) have partially overlapping biological activities that include immunoregulation such as increased resistance to microbial pathogens and inhibition of cell proliferation. Type 1 interferons (alpha and beta) bind to the alpha/ beta receptor. Interferon gamma binds to a different cell surface receptor and is classified as Type 2 interferon. Specific effects of interferon gamma include the enhancement of the oxidative metabolism of macrophages, antibody dependent cellular cytotoxicity (ADCC), activation of natural killer (NK) cells, and the expression of Fc receptors and major histocompatibility antigens.

Actimmune® is an interferon gamma indicated for reducing the frequency and severity of infections associated with Chronic Granulomatous Disease (CGD) and delaying the time to disease progression in patients with severe, malignant osteopetrosis. 

The intent of this policy is to communicate the medical necessity criteria for Interferon gamma-1b (Actimmune®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA: Interferon gamma-1b (Actimmune®) is approved when ONE of the following is met:

  1. Diagnosis of chronic granulomatous disease (CGD); or
  2. Diagnosis of severe, malignant osteopetrosis (SMO)

Initial authorization duration: 2 years

 

REAUTHORIZATION CRITERIA: Interferon gamma-1b (Actimmune®) is reapproved when there is documentation of positive clinical response to therapy (i.e., delay of malignant osteopetrosis disease progression; reduction in the frequency and severity of serious infections associated with Chronic Granulomatous Disease)

Reauthorization duration: 2 years


 

 

​N/A

Actimmune® (interferon gamma) [package insert]. Rosewell, GA; HZNP Inc.: December 2019. Available from: https://www.hzndocs.com/ACTIMMUNE-Prescribing-Information.pdf. Accessed December 05, 2023.

 

Chronic granulomatous disease. US National Library of Medicine website. Updated August 18, 2020. Accessed December 05, 2023. Medlineplus.gov/genetics/condition/chronic-granulomatous-disease/#:~:text=Chroninc%20granulomatous%20disease%20is%20a,such%20bacteria%20and%20fungi.

 

What is severe malignant osteopetrosis (SMO)? Actimmune website. Accessed December 05, 2023 . Actimmune.com/severe-malignant-osteopetrosis/​


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Rx.01.33 Off Label Use

Rx.01.221 Drugs Exceeding Claim Dollar Limit Threshold

Inclusion of a drug in this table does not imply coverage. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

Brand NameGeneric Name
Actimmune®Interferon gamma-1b
318
  
1/1/2024Rx.01.231CommercialOyenusi, Oluwadamilola

Acromegaly is a disease usually caused by a benign tumor on the pituitary gland, causing increased release of growth hormone. Increased release of growth hormone causes an increase in release of insulin-like growth factor I (IGF-I), causing the signs and symptoms of acromegaly. 

Cutaneous flushing and diarrhea are commonly associated with carcinoid syndrome. Most flushing episodes primarily involves the face, neck, upper chest, which become red to violaceous or purple, and is associated with a mild burning sensation. Secretory diarrhea is often debilitating where stools may vary from few to more than 30 per day, are typically watery and non-bloody, can be explosive and accompanied by abdominal cramping. Diarrhea is usually unrelated to flushing episodes, though both can be minimized by pretreatment with octreotide.

Vasoactive intestinal peptide tumor (VIPoma) is suspected in patients with unexplained high-volume secretory diarrhea. Treatment of VIPoma starts with replacement of fluid losses and correction of electrolyte abnormalities. Somatostatin analogs inhibit the secretion of vasoactive intestinal polypeptide and are the treatment of choice to control diarrhea in VIPoma. 

Octreotide exerts pharmacologic actions similar to the natural hormone somatostatin. It is a potent inhibitor of growth hormone, insulin like growth factor-1 (IGF-I), glucagon, and insulin. It suppresses luteinizing hormone response to gonadotropin releasing hormone. Since it releases growth hormone and IGF-I levels, it is beneficial in patients with acromegaly.

Octreotide acetate pen is indicated for:

  • Reduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) [somatomedin C] in adult patients with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.
  • Treatment of severe diarrhea/flushing episodes associated with metastatic carcinoid tumors in adult patients.
  • Treatment of profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) in adult patients.

Mycapssa™ (octreotide) is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide.



 

​The intent of this policy is to communicate the medical necessity criteria for octreotide acetate, and octreotide (Mycapssa®) as provided under the member's prescription drug benefit.

ACROMEGALY
INITIAL CRITERIA: Octreotide acetate or octreotide (Mycapssa™) is approved when ALL the following criteria are met:


1. Member is 18 years of age or older; and
2. Diagnosis of acromegaly; and
3. Prescribed by or in conjunction with an endocrinologist; and
4. One of the following:
a. Inadequate response to surgery or pituitary irradiation; or
b. Not a candidate for surgical resection or pituitary irradiation; and
5. Inadequate response or inability to tolerate a dopamine agonist (e.g., bromocriptine or cabergoline) at maximally tolerated doses; and
6. For Mycapssa™ only, member has responded to and tolerated treatment with Octreotide or Lanreotide products (e.g., Somatulline Depot, Sandostatin, Sandostatin LAR depot).


Initial authorization duration: 12 months


REAUTHORIZATION CRITERIA: Octreotide aetate or octreotide (Mycapssa™) is re-approved with documentation of positive clinical response to therapy (e.g., reduction or normalization of IFG-I or Growth Hormone level for same age and sex)


Reauthorization duration: 2 years
________________________________________
CARCINOID TUMORS, FOR SYMPTOMATIC TREATMENT OF DIARRHEA OR FLUSHING
INITIAL CRITERIA: Octreotide acetate is approved when ALL the following are met:


1. Diagnosis of metastatic carcinoid tumor; and
2. Member requires symptomatic treatment of severe diarrhea or flushing episodes; and
3. Member is 18 years of age or older


Initial authorization duration: 12 months

REAUTHORIZATION CRITERIA: Octreotide acetate  is re-approved with documentation of an improvement in the number of  diarrhea or flushing episodes.


Reauthorization duration: 2 years
________________________________________
VASOACTIVE INTESTINAL PEPTIDE TUMORS, FOR SYMPTOMATIC TREATMENT OF DIARRHEA
INITIAL CRITERIA: Octreotide acetate is approved when ALL the following are met:


1. Diagnosis of vasoactive intestinal peptide tumor; and
2. Member requires the treatment of profuse watery diarrhea, and
3. Member is 18 years of age or older


Initial authorization duration: 12 months


REAUTHORIZATION CRITERIA: Octreotide acetate is re-approved with documentation of an improvement in the number of diarrhea episodes.


Reauthorization duration: 2 years

​N/A

Strosberg, J. Clinical features of carcinoid syndrome. November 2021. UpToDate. Available from: https://www.uptodate.com/contents/clinical-features-of-carcinoid-syndrome?search=carcinoid%20tumor&topicRef=2622&source=see_link#H11. Accessed October 02, 2023. 
 
Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.

Mycapssa® (octreotide) [prescribing information]. Scotland, UK: MW Encap Ltd.; March 2022. Available from: https://label.mycapssa.com/wp-content/uploads/sites/4/2020/06/prescribinginformation.pdf. Accessed October 02, 2023. 


 

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Rx.01.33 Off Label Use​


 

Brand NameGeneric Name
MycapssaOctreotide


 

319
  
1/1/2024Rx.01.232CommercialOyenusi, Oluwadamilola

Acromegaly is a disease usually caused by a benign tumor on the pituitary gland, causing increased release of growth hormone (GH). Increased release of growth hormone causes an increase in release of insulin-like growth factor I (IGF-I), causing the signs and symptoms of acromegaly. Excess GH and IGF-1 have both somatic and metabolic effects. The somatic effects include stimulation of growth of many tissues, such as skin, connective tissue, cartilage, bone, viscera, and many epithelial tissues. The metabolic effects include nitrogen retention, insulin antagonism, and lipolysis.

 
Pegvisomant (Somavert®) is an analog of human growth hormone that has been structurally altered to act as a growth hormone antagonist. It blocks the binding of endogenous growth hormone, interfering with growth hormone signal transduction, causing a decreased serum concentration of IGF-I. 

 
Pegvisomant (Somavert®) is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom these therapies are not appropriate. The goal of treatment is to normalize serum insulin-like growth factor-I (IGF-I) levels.


 

The intent of this policy is to communicate the medical necessity criteria for Pegvisomant (Somavert®) as provided under the member's prescription drug benefit.


 

INITIAL CRITERIA: Pegvisomant (Somavert®) is approved when ALL the following are met:

  1. Diagnosis of acromegaly; and
  2. One of the following:
    1. ​Inadequate response to surgery or pituitary irradiation; or
    2. Not a candidate for surgical resection or pituitary irradiation; and
  3. Inadequate response or inability to tolerate a dopamine agonist (e.g., bromocriptine or cabergoline) at maximally tolerated doses; and
  4. Prescribed by or in consultation with an endocrinologist; and
  5. Member is 18 years of age or older
 
Initial authorization duration: 12 months

REAUTHORIZATION CRITERA: Pegvisomant (Somavert®) is re-approved when there is documentation of positive clinical response to Somavert® therapy (i.e., reduction or normalization of IGF-1)

Reauthorization duration: 2 years

​N/A

Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.

 

Melmed, S. Causes and clinical manifestations of acromegaly. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed  November 17, 2023

 

Somavert® (pegvisomant) for injection [prescribing information]. New York, NY: Pfizer Inc.; July 2023. Available from: labeling.pfizer.com/ShowLabeling.aspx?id=3213. Accessed November 17, 2023.​




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Rx.01.33 Off Label Use

 
Rx.01.221 Drugs Exceeding Claim Dollar Limit Threshold​


 

Brand NameGeneric Name
Somavert®Pegvisomant


 

320
  
1/1/2024Rx.01.234CommercialOyenusi, Oluwadamilola

​Phenylketonuria (PKU) is an inherited disorder that causes elevated blood levels of phenylalanine. PKU is caused by mutations of the PAH gene, which encodes for the enzyme phenylalanine hydroxylase. Phenylalanine hydroxylase converts phenylalanine to tyrosine. Patients with PKU cannot appropriately process phenylalanine from the diet, thus building up to potentially toxic levels in the blood. Excessive amounts of phenylalanine can cause brain and nerve damage if left untreated.


 
Kuvan®, Javygtor® (sapropterin dihydrochloride) is a phenylalanine hydroxylase activator indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia due to tetrahydrobiopterin-(BH4-) responsive Phenylketonuria when used in combination with a low phenylalanine diet.


​The intent of this policy is to communicate the medical necessity criteria for Kuvan®, Javygtor® (sapropterin dihydrochloride) as provided under the member's prescription drug benefit. 

 

INITIAL CRITERIA: Sapropterin dihydrochloride (Kuvan®, Javygtor®) is approved when ALL the following are met:

  1. Diagnosis of phenylketonuria (PKU); and
  2. Used in conjunction with phenylalanine (Phe)-restricted diet; and
  3. Prescribed by or in consultation with a specialiset with expertise in diagnosis and management of phenylketonuria; and​
  4. For Brand Kuvan® and Javygtor® only: inadequate response or inability to tolerate generic sapropterin dihydrochloride

Initial authorization duration: 6 months

CONTINUATION CRITERIA: Sapropterin dihydrochloride (Kuvan®, Javygtor®) is re-approved when ALL the following are met:

  1. Member has had a positive clinical response to therapy (i.e. there is a reduction of phenylalanine (Phe) blood levels from baseline); and
  2. Used in conjunction with phenylalanine (Phe)-restricted diet

Reauthorization duration: 2 years


​N/A

Phenylketonuria. US National Library of Medicine website. Updated April 25, 2023. Medlineplus.gov/genetics/condition/phenylketonuria/#causes. Accessed October 02, 2023.

Javygtor® (sapropterin dihydrochloride) [package insert]. Princeton, NJ: Dr. Reddy's Laboratories Inc.; January 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9f3723f-bf7d-9a72-2ef9-41c5508d6ab4. Accessed October 02, 2023.

Kuvan® (sapropterin dihydrochloride) [package insert]. Novato, CA: BioMartin Pharmaceutical Inc.; February 2021. Available from: https://www.kuvan.com/hcp/wp-content/file/KUVAN_Prescribing_Information1.pdf. Accessed October 02, 2023. 



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Rx.01.33 Off Label Use

Rx.01.221 Drugs Exceeding Claim Dollar Limit Threshold​


 

Brand NameGeneric Name
Kuvan, Javygtor® 
Sapropterin dihydrochloride


 

321
  
1/1/2024Rx.01.244CommercialOyenusi, Oluwadamilola

In a very small percentage of individuals, obesity may occur due to changes in a single gene. The most commonly implicated gene encodes melanocortin 4 (MC4) receptors (the MC4R gene).

 

Melanocortins are a family of melanocyte stimulating hormones (MSHs), some of which regulate hunger, caloric intake, energy expenditure, and bodyweight primarily thorough the MC4 receptor. Impairment in the MC4 receptor pathway leads to hyperphagia and early-onset severe obesity.

 

In normal physiology, leptin receptors (LEPRs) are expressed on proopiomelanocortin (POMC) neurons in the brain. The hormone leptin (from adipose tissue in the periphery) activates the LEPRs causing the POMC neurons to release MSH. The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene codes for enzymes that also generate MSH from POMC-producing neurons. MSH binds to and activates MC4 receptors on MC4 receptor-expressing neurons. This binding stimulates a cascade of neurological signaling that ultimately leads to suppression of hunger, decreased food intake, and increased energy expenditure (FDA clinical review 2020, FDA summary review 2020).

 

Obesity due to POMC, PCSK1, or LEPR deficiency is due to variants in the POMC, PCSK1, or LEPR genes. These are very rare causes of obesity, with approximately 150 reported cases in medical literature for all three causes combined. A defect to one or more of these genes affects hunger levels, satiety, and energy output (metabolism). Individuals are usually a normal weight at birth but hyperphagia leads to progressive weight gain and early-onset obesity, which causes early-onset insulin resistance, hyperlipidemia, cardiovascular disease and other obesity-associated comorbidities. Patients with POMC, PCSK1, or LEPR deficiencies have progressive weight gain, which occurs at an average of 7 to 10 kg per year (Clement et al 2020, FDA press release 2020, FDA clinical review 2020).

 

Obesity in individuals can also be caused by Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive disorder characterized by obesity and several other abnormalities, including microorchidism in men, intellectual disability, retinal dystrophy, polydactyly, renal malformations (particularly calyceal abnormalities), and polyuria and polydipsia. Mutations in at least 15 genes have been described in patients with this syndrome.

Setmelanotide (Imcivree™) is a melanocortin 4 (MC4) receptor agonist indicated for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS), and Bardet-Biedl syndrome (BBS).

Guidelines for general obesity have not yet been updated to include setmelanotide or treatment algorithms for genetic causes of obesity. There is no data to support traditional therapies for obesity would work in these patients such as FDA approved medications, bariatric surgery, or standard-of-care diet and exercise, since the cause of their obesity is genetic. 


​The intent of this policy is to communicate the medical necessity criteria for Setmelanotide (Imcivree) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Setmelanotide (Imcivree™) is approved when ALL of the following are met:

  1. One of the following:
    1. Submission of medical records (e.g., chart notes, lab values) confirming a diagnosis of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR) deficiency by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, or of uncertain significance (VUS); or
    2. Diagnosis of Bardet-Biedl syndrome; and
  2. Other causes or types of obesity have been ruled out (e.g., obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign; obesity associated with other genetic syndromes; polygenic obesity; obesity due to Bardet-Biedl syndrome); and
  3. Member is obese as defined by BMI of ≥30kg/m2 in adults or ≥95th percentile in pediatric patients using growth chart assessments; and
  4. Prescribed by or in consultation with ONE of the following:
    1. Endocrinologist; or
    2. Medical geneticist; or
    3. Specialist in the diagnosis and treatment of obesity; and
  5. Member is 6 years of age or older

Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Setmelanotide (Imcivree™) is reapproved with documentation of positive clinical response to therapy (e.g. 5% weight loss based on baseline body weight or BMI)

Reauthorization duration: 12 months

​N/A

Setmelanotide (Imcivree) [prescribing information]. Rhythm Pharmaceuticals, Inc. June 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213793s000lbl.pdf. Accessed November 21, 2023.

 

Food and Drug Administration (FDA). Clinical Review: Imcivree. 2020. Web site. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213793Orig1s000MedR.pdf. Accessed November 21, 2023.

 

Clement K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicenter, phase 3 trials. Lancet Diabetes and Endocrinol. 2020;8(12):960-970.

 

Perreault, L. Obesity: Genetic contribution and pathophysiology. In: UpToDate. Available from: https://www.uptodate.com/contents/obesity-genetic-contribution-and-pathophysiology?search=imcivree&source=search_result&selectedTitle=1~2&usage_type=default&display_rank=1#H2744130704. Accessed November 21, 2023.



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Rx.01.33 Off Label Use​

​​

​Brand Name
​Generic Name
ImcivreeTM
​Setmelanotide




322
  
1/1/2024Rx.01.246CommercialOyenusi, Oluwadamilola

Molybdenum cofactor deficiency (MoCD) is characterized by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. MoCD is an autosomal recessive disorder that results from one of several single gene defects in the biosynthetic pathway of molybdenum cofactor. Approximately two-thirds of patients have MoCD type A, in which pathogenic variants in molybdenum cofactor synthesis gene 1 (MOSC1) result in the inability to synthesize the first intermediate in the pathway, cyclic pyranopterin monophosphate (cPMP), and the toxic accumulation of sulfites in blood and urine. Most patients present during the first few days of life with exaggerated startle, lethargy, intractable seizures, and autonomic dysfunction, a complex of symptoms that may resemble hypoxic-ischemic encephalopathy.

Patients with MoCD Type A have mutations in the MOCS1 gene leading to deficient synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with fosdenopterin provides an exogenous source of cPMP, which is needed for the activation of molybdenum-dependent enzymes, including SOX, an enzyme that reduces levels of neurotoxic sulfites.

Nulibry™ (fosdenopterin) is cyclic pyranopterin monophosphate (cPMP) indicated to reduce the risk of mortality in patients with MoCD Type A.


The intent of this policy is to communicate the medical necessity criteria for Fosdenopterin (Nulibry™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA Fosdenopterin (Nulibry™) is approved when ALL of the following are met: 

  1. One of the following:
    1. Presumed diagnosis of molybdenum cofactor (MoCD) Type A deficiency; or
    2. Diagnosis of molybdenum cofactor (MoCD) Type A deficiency confirmed by genetic test; and
  2. Prescribed by or in consultation with a physician who specializes in the treatment of inherited metabolic disorders
​Initial authorization duration: 6 months ​


REAUTHORIZATION CRITERIA Fosdenopterin (Nulibry™) is re-approved when ALL of the following are met:

  1. Diagnosis of molybdenum cofactor (MoCD) Type A deficiency as confirmed by genetic test [if not previously confirmed]; and
  2. Prescribed by or in consultation with a physician who specializes in the treatment of inherited metabolic disorders; and
  3. Document of positive clinical response to therapy (e.g., reduction in urine concentrations of S-sulfocysteine (SSC))

Reauthorization duration: 2 years


​N/A



Food and Drug Administration (FDA). Nulibry summary review. June 29, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214018Orig1s000IntegratedR.pdf. Accessed NOVEMEBER 21, 2023

 

Nulibry [affordability and distribution resource guide], Boston, MA: Origin Biosciences, Inc; 2021. Accessed NOVEMEBER 21, 2023

 

Nulibry [dossier], Boston, MA: Origin Biosciences, Inc; March 2021. Accessed NOVEMEBER 21, 2023

 

Nulibry™ (fosdenopterin) [package insert], Boston, MA: Origin Biosciences, Inc; February 2021. Available from: https://www.nulibry.com/pdfs/nulibry-prescribing-information-v2.pdf. Accessed NOVEMEBER 21, 2023

 

Shellhaas, R. Treatment of neonatal seizures. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed NOVEMEBER 21, 2023​




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​Rx.01.33 Off Label Use

Brand Name Generic Name
Nulibry®Fosdenopterin


323
  
1/1/2024Rx.01.247CommercialOyenusi, Oluwadamilola

Hutchinson-Gilford Progeria Syndrome is sporadic, very rare, autosomal dominant, deadly childhood disorder. It is one of the progeroid syndromes also known as Hutchinson-Gilford progeria syndrome (HGPS). Aging is a developmental process that begins with fertilization and ends up with death involving a lot of environmental and genetic factors. The disease firstly involves premature aging and then death from complications of atherosclerosis such as myocardial infarction, stroke, atherosclerosis, or heart failure.

Progeroid laminopathies are characterized by the premature appearance of certain signs of physiological aging in a subset of tissues. They are caused by mutations in genes coding for A-type lamins or lamin-binding proteins.

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

Zokinvy is indicated in patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above:

  • To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS)
  • For the treatment of processing-deficient Progeroid Laminopathies with either:
    • Heterozygous LMNA mutation with progerin-like protein accumulation
    • Homozygous or compound heterozygous ZMPSTE24 mutations


 

​The intent of this policy is to communicate the medical necessity criteria for Lonafarnib (Zokinvy™) as provided under the member's prescription drug benefit. 


INITIAL CRITERIA Lonafarnib (Zokinvy™) is approved when ALL of the following are met:

  1. Submission of medical records (e.g., chart notes, lab values) confirming one of the following:
    1. Diagnosis of Hutchinson-Gilford Progeria Syndrome; or
    2. Genetic testing results confirming a LMNA mutation that results in the production of progerin; or
    3. Processing-deficient Progeroid Laminopathies with one of the following:
      1. Genetic testing results confirming member has a heterozygous LMNA mutation with progerin-like protein accumulation; or
      2. Genetic testing results confirming member has a homozygous or compound heterozygous ZMPSTE24 mutations; and
  2. Member is 12 months of age or older; and
  3. Member has a body surface are of 0.39 m2 and above; and
  4. Prescribed by or in consultation with a specialist with expertise in the diagnosis and management of Progeria

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Lonafarnib (Zokinvy™) is re-approved when all of the following have been met:
  1. Documentation that member has had clinical benefit with the requested drug; and
  2. Prescribed by or in consultation with a specialist with expertise in the diagnosis and management of Progeria

Reauthorization duration: 2 years



 


​N/A

Ahmed MS, Ikram S, Bibi N, Mir A. Hutchinson-Gilford Progeria Syndrome: A Premature Aging Disease. Mol Neurobiol. 2018 May;55(5):4417-4427. doi: 10.1007/s12035-017-0610-7. Epub 2017 Jun 28. PMID: 28660486. Accessed  December 06, 2023.

 

Marcelot A, Worman HJ, Zinn-Justin S. Protein structural and mechanistic basis of progeroid laminopathies. FEBS J. 2021 May;288(9):2757-2772. doi: 10.1111/febs.15526. Epub 2020 Sep 3. PMID: 32799420. Accessed December 06, 2023.

 

Zokinvy™ (lonafarnib) [package insert]. Alto, CA; Eiger BioPharmaceuticals, Inc.; Revised November 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf Accessed December 06, 2023.


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Rx.01.33 Off Label Use​


 

Brand Name Generic Name
Zokinvy™Lonafarnib


 

324
  
1/1/2024Rx.01.250CommercialOyenusi, Oluwadamilola

Tyrosine is an aromatic amino acid important in the synthesis of thyroid hormones, catecholamines, and melanin. Impaired catabolism of tyrosine is a feature of several acquired and genetic disorders that may result in elevated plasma tyrosine concentrations. Tyrosinemia is a genetic disorder characterized by disruptions in the break down of the amino acid tyrosine, a building block of most proteins. If untreated, tyrosine and its byproducts build up in tissues and organs. Hereditary tyrosinemia type 1 (HT1; MIM# 276700), also known as hepatorenal tyrosinemia, is the most severe disorder of tyrosine metabolism.

Nitisinone (Nityr®, Orfadin®) is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1.

 

Nityr® and Orfadin® are indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1

(HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

The intent of this policy is to communicate the medical necessity criteria for Nitisinone (Nityr®, Orfadin®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Nitisinone (Nityr®, Orfadin®) is approved when all of the following are met:

  1. Diagnosis of hereditary tyrosinemia type 1; and
  2. Will be used in combination with dietary restriction of tyrosine and phenylalanine; and
  3. Prescribed by or in consultation with one of the following:
    1. Gastroenterologist
    2. Hepatologist
    3. Other specialist with experience in treating inborn errors of metabolism

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Nitisinone (Nityr®, Orfadin®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years


​N/A


Nityr® (nitisinone) [package insert] Cambridge, UK: Cycle Pharmaceuticals Ltd. October 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209449s000lbl.pdf. Accessed November 21, 2023.

 

Orfadin® (nitsinone) [package insert] Stockholm, Sweden: Swedish Orphan Biovitrum. November 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206356s000lbl.pdf. Accessed November 21, 2023.

 

Tyrosinemia: MedlinePlus Genetics. Medlineplus.gov. Available from: https://medlineplus.gov/genetics/condition/tyrosinemia/. Accessed November 21, 2023.

 

Grompe M. Disorders of tyrosine metabolism. UpToDate. November 2020. Available at: https://www.uptodate.com/contents/disorders-of-tyrosine metabolism?search=orfadin&source=search_result&selectedTitle=2~3&usage_type=default&display_rank=1. Accessed November 21, 2023.​


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Rx.01.33 Off Label Use

 

Brand NameGeneric Name
Nityr®, Orfadin®Nitisinone
328
  
1/1/2024Rx.01.256CommercialOyenusi, Oluwadamilola

Graft-versus-host disease (GVHD) can develop after allogeneic hematopoietic cell transplant (HCT), when immune cells from a non-identical donor (the graft) initiate an immune reaction against a transplant recipient (the host). Chronic GVHD is a syndrome of variable clinical features that resembles autoimmune and other immunologic disorders (eg, scleroderma, Sjögren's syndrome, primary biliary cirrhosis, bronchiolitis obliterans). Clinical manifestations may be widespread, or they may be restricted to a single organ or site. The primary clinical manifestations are skin involvement (resembling lichen planus or cutaneous scleroderma), dry oral mucosa, gastrointestinal tract ulcerations and sclerosis, elevated serum bilirubin, and bronchiolitis obliterans. Chronic GVHD is a major cause of morbidity and mortality after allogeneic HCT, which worsen with increasing disease severity. Patients have impaired physical, social, and psychological well-being and impaired quality of life.

 

Belumosudil is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC50 values of approximately 100 nM and 3 μM, respectively. Belumosudil down- regulated proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.

 

REZUROCK is a kinase inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.

The intent of this policy is to communicate the medical necessity criteria for Belumosudil (Rezurock™) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Belumosudil (Rezurock™) is approved when ALL of the following are met:

  1. Diagnosis of chronic graft-versus-host disease; and
  2. Member is 12 years of age or older; and
  3. Inadequate response or inability to tolerate two or more lines of systemic therapy (e.g., corticosteroids, mycophenolate, etc.); and
  4. Prescribed by or in consultation with one of the following:
    1. Hematologist; or
    2. Oncologist; or
    3. Physician experienced in the management of transplant patients

Initial authorization duration: 2 years

REAUTHORIZATION CRITERIA Belumosudil (Rezurock™) is re-approved if member does not show evidence of progressive disease while on therapy

Reauthorization duration: 2 years

 

​N/A

Rezurock™ [package insert]. Warrendale, PA: Kadmon Pharmaceuticals. April 2023. Available at: https://www.rezurock.com/full-prescribing-information.pdf. Accessed October 02, 2023.

Zeiser R. Clinical manifestations and diagnosis of chronic graft-versus-host disease. UpToDate website. Last updated February 17, 2022. Available at http://www.uptodate.com/. Accessed October 02, 2023.​





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Rx.01.33 Off Label Use

Brand NameGeneric Name
RezurockTMBelumosudil
329
  
1/1/2024Rx.01.267CommercialOyenusi, Oluwadamilola

Testing for genetic mutations in the PIK3CA gene is done at initial MBC diagnosis if tumor is HR+/HER2- following progression on or after an endocrine-based regimen. This gene effects cell growth and development and can contribute to a worse prognosis for patients. Knowledge of the presence of this mutation can inform providers in their treatment selection for these patients.

Alpelisib is a small-molecule phosphatidylinositol-3-kinase (PI3K) inhibitor with selective (and strong) activity against PI3Kα (André 2019). Mutations in the gene encoding the catalytic α-subunit of PI3K (PI3KCA) lead to activation of PI3Kα and Akt-signaling, cellular transformation, and tumor generation. Alpelisib inhibits phosphorylation of PI3K downstream targets (including Akt) and demonstrated activity in cell lines harboring a PIK3CA mutation. When compared with either agent alone, the combination of alpelisib with fulvestrant has synergistic antitumor activity in PIK3CA-mutated, estrogen receptor-positive models.

Activating mutations in PIK3CA may induce a spectrum of overgrowths/malformations comprising clinically recognizable disorders commonly known as PIK3CA-related overgrowth spectrum (PROS). In an animal model PROS phenotype (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome [CLOVES]), alpelisib inhibited the PI3K pathway, resulting in prevention or improvement of organ abnormalities associated with the disease; findings were reversed following alpelisib withdrawal

Breast cancer, advanced or metastatic: Treatment (in combination with fulvestrant) of HR-positive, HER2-negative, PIK3CA-mutated (as detected by an approved test), advanced or metastatic breast cancer in males and postmenopausal females following progression on or after an endocrine-based regimen.

PIK3CA-related overgrowth spectrum: Treatment of severe manifestations of PIK3CA-related overgrowth spectrum in patients ≥2 years of age who require systemic therapy.



​The intent of this policy is to communicate the medical necessity criteria for Alpelisib (Vijoice®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA Alpelisib (Vijoice) is approved when ALL of the following are met:

 

  1. Diagnosis of PIK3CA-Related Overgrowth Spectrum (PROS); and
  2. Documentation of mutation in the PIK3CA gene; and
  3. Member is 2 years of age or older; and
  4. Documentation of severe clinical manifestations (e.g., Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal [CLOVES], Facial Infiltrating Lipomatosis [FIL], Klippel-Trenaunay Syndrome [KTS], Megalencephaly-Capillary Malformation Polymicrogyria [MCAP]); and
  5. Prescribed by or in consultation with a provider who specialized in the treatment of PROS 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA Alpelisib (Vijoice®) is re-approved when ALL of the following are met:

 

  1. Documentation of positive clinical response to therapy (e.g., radiological response defined as a ≥ 20% reduction from baseline in the sum of target lesion volume); and
  2. Prescribed by or in consultation with a provider who specializes in the treatment of PROS

​Reauthorization duration: 12 months 


​N/A

André F, Ciruelos E, Rubovszky G, et al; SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940.[PubMed 31091374]

Venot Q, Blanc T, Rabia SH, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018;558(7711):540-546. doi:10.1038/s41586-018-0217-9[PubMed 29899452]

Vijoice® (alpelisib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2022. Available from: https://www.novartis.com/us-en/sites/novartis_us/files/vijoice.pdf. Accessed October 02, 2023.​



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Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​


Brand NameGeneric Name
Vijoice®Alpelisib


330
  
1/1/2024Rx.01.270CommercialOyenusi, Oluwadamilola

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency due to autoimmune βcell destruction. Insulin is the mainstay of therapy for T1DM. Childhood type 1 diabetes mellitus can present with chronic polydipsia, polyuria, weight loss with hyperglycemia and ketonemia or ketonuria, diabetic ketoacidosis or asymptomatic incidental discovery. 

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and usually relative (rather than absolute) insulin deficiency. Patients with T2DM may have insulin levels that appear normal or elevated. However, the higher blood glucose levels in these patients would be expected to result in even higher insulin values with normally functioning beta cells. Hence, insulin secretion is defective and insufficient to compensate for insulin resistance. Adults with type 2 diabetes are at risk for obesity, hypertension, dyslipidemia, fatty liver disease, sleep apnea, as well as periodontal disease. 

Insulin and its analogs lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis and enhances protein synthesis. Insulin, secreted by the beta cells of the pancreas, is the principal hormone required for proper glucose use in normal metabolic processes.



The intent of this policy is to communicate the medical necessity criteria for Humalog TMPO®, Lyumjev TMPO®, Novolog Relion or Novolin Relion, Insulin aspart, Basaglar TMPO®, Levemir®, Tresiba® (insulin degludec), Insulin glargine, and Semglee® (insulin glargine-YFGN) as provided under the member's prescription drug benefit.




Humalog TMPO®, Lyumjev TMPO®, Novolog Relion, Novolin Relion or Insulin aspart is approved when ALL of the following are met:

  1. Diagnosis of diabetes mellitus; and
  2. Paid claims or submission of medical records (e.g., chart notes) confirming an inadequate response or inability to tolerate TWO of the following:
    1. Novolin®
    2. Novolog®
    3. Humalog®/Insulin lispro
    4. Lyumjev®
    5. Fiasp®
    6. Apidra®
    7. Admelog®
    8. Humulin®

​​Authorization duration: 2 years​


Basaglar TMPO®, Levemir®, Tresiba®, Insulin Degludec, Insulin glargine-YFGN/Semglee®, or insulin Glargine is approved when ALL of the following are met:

  1. Diagnosis of diabetes mellitus; and
  2. Paid claims or submission of medical records (e.g., chart notes) confirming an inadequate response or inability to tolerate THREE of the following:
    1. Lantus®
    2. Toujeo®
    3. Basaglar®
    4. Rezvoglar®

Authorization duration: 2 years 


​N/A


American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2018; 41 (suppl 1): S13-S27. DOI: 10.2337/dc18-S002.

American Diabetes Association. Pharmacologic approaches to glycemic treatment. Diabetes Care. 2018;41 (suppl 1): S73-S85. DOI: 10.2337/dc18-S008.

Levitsky LL, Misra M. Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents. UpToDate website. Last updated September 2020. Available at: http://www.uptodate.com/. Accessed November 20, 2023.

McCulloch DK. Overview of medical care in adults with diabetes mellitus. UpToDate website. Last updated March 21, 2019. Available at: http://www.uptodate.com/. Accessed November 20, 2023.

Basaglar TMPO® [package insert]. Indianapolis, IN 46285. Lilly USA, LLC. July 2021. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/2050692lbl.pdf. Accessed November 20, 2023.

Humalog TMPO® [package insert]. Indianapolis, IN 46285. Lilly USA LLC. November 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020563s115lbl.pdf . Accessed November 20, 2023.

Levemir® [package insert]. Denmark, Bagsvaerd 2880. Novo Nordisk A/S. 2019. Available from: https:///www.accessdata.fda.gov/drugsatfda_docs/label/2019/021536s054lbl.pdf . Accessed November 20, 2023.

Lyumjev TMPO® [package insert]. Indianapolis, IN 46285, USA. Eli Lilly and Company. October 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761109s000lbl.pdf . Accessed November 20, 2023.

Semglee® [package insert]. Morgantown, WV 26505 U.S.A. Mylan Pharmaceutical Inc. July 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761201Orig1s000lbl.pdf . Accessed November 20, 2023.

Tresiba® [package insert]. Denmark, Bagsvaerd 2880. Novo Nordisk A/S. September 2015. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203314lbl.pdf . Accessed November 20, 2023.




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​Off-Label Use Policy Rx.01.33

Quantity level limits for pharmaceuticals covered under the prescription drug benefit Rx.01.76





Brand NameGeneric Name
Basaglar TMPO®Insulin Glargine
Humalog TMPO®Insulin Lispro
Insulin aspart 
Insulin glargine 
Levemir®Insulin Detemir
Lyumjev TMPO®Insulin Lispro-aabc
Novolin® RelionInsulin Regular
Novolog® RelionInsulin aspart
Semglee®Insulin Glargine-yfgn
Tresiba®Insulin Degludec
Insulin Degludec 




333
  
1/1/2024Rx.01.283CommercialOyenusi, Oluwadamilola

​Clostridioides difficile infection (CDI) is one of the most common hospital-acquired (nosocomial) infections and is an increasingly frequent cause of morbidity and mortality among older adult hospitalized patients. C difficile is highly transmissible via the fecal-oral route by ingestion of spores. Recurrent CDI is defined by resolution of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms, usually within two months of discontinuing treatment. Management of a first CDI recurrence consists of antibiotic therapy.

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).  

Limitation of Use: VOWST is not indicated for treatment of CDI.


The intent of this policy is to communicate the medical necessity criteria for Fecal microbiota spores, live-brpk (Vowst™) as provided under the member's prescription drug benefit. 

Fecal microbiota spores, live-brpk (Vowst™) is approved when ALL of the following are met:

  1. Diagnosis of recurrent clostridioides difficile infection (CDI) as defined by both of the following:
    1. Presence of diarrhea defined as a passage of 3 or more loose bowel movements within a 24-hour period for 2 consecutive days; and
    2. A positive stool test for C. difficile toxin or toxigenic C. difficile; and
  2. Member is 18 years of age or older; and
  3. Member has a history of two or more recurrent episodes of CDI within 12 months; and
  4. ALL of the following:
    1. Member has completed at least 10 consecutive days of one of the following antibiotic therapies 2-4 days prior to initiating Vowst:
      1. Oral vancomycin; or
      2. Dificid (fidaxomicin); and
    2. Member has completed the recommended bowel prep (e.g. 296mL of magnesium citrate) the day before and at least 8 hours prior to initiating Vowst; and
    3. Previous episode of CDI is under control (e.g., less than 3 unformed/loose [i.e., Bristol Stool Scale type 6-7] stools/day for 2 consecutive days); and
  5. Prescribed by or in consultation with one of the following:
    1. Gastroenterologist; or
    2. Infectious disease specialist

 

Authorization duration: 14 days


​N/A

VOWST™ (fecal microbiota spores, live-brpk) [package insert]. Brisbane, CA: Aimmune Therapeutics, Inc. April 2023. Available from: https://www.serestherapeutics.com/our-products/VOWST_PI.pdf. Accessed November 20, 2023.


Lamont JT. Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology. In: UpToDate, Post TW (Ed), Wolters Kluwer. Jan 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.


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Rx.01.33 Off Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit Rx.01.76​


Brand NameGeneric Name
Vowst™ fecal microbiota spores, live-brpk


334
  
1/1/2024Rx.01.281CommercialOyenusi, Oluwadamilola

Natural menopause is defined as the permanent cessation of menstrual periods, determined retrospectively after a person with menstrual periods has experienced 12 months of amenorrhea without any other obvious pathologic or physiologic cause. This results in low serum estradiol concentrations and vasomotor symptoms (hot flashes). It occurs at a median age of 51. Hot flashes occur in approximately 75 to 80 percent of menopausal people in the United States. Hormone therapy remains the most effective treatment for hot flashes.

 

Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that blocks neurokinin B (NKB) binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center. Fezolinetant has high affinity for the NK3 receptor (Ki value of 19.9 to 22.1 nmol/L), which is more than 450-fold higher than binding affinity to NK1 or NK2 receptors.

 

VEOZAH (fezolinetant) is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.


The intent of this policy is to communicate the medical necessity criteria for Fezolinetant (Veozah™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Fezolinetant (Veozah™) is approved when all of the following criteria are met:

  1. Diagnosis moderate to severe vasomotor symptoms due to menopause; and
  2. Inadequate response or inability to tolerate a minimum 30-day supply of both of the following:
    1. Menopausal hormone therapy (e.g., generic estradiol vaginal cream, generic estradiol vaginal tablet); and
    2. Non-hormonal therapy (e.g., paroxetine mesylate, venlafaxine hcl, clonidine, etc.)

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Fezolinetant (Veozah™) is re-approved with documentation of positive clinical response to therapy (e.g., decrease in frequency and severity of vasomotor symptoms from baseline, etc.)

 

Reauthorization duration: 12 months


​N/A

VEOZAH (fezolinetant) [package insert]. Northbrook, IL: Astellas Pharma US, Inc. May 2023. Available from: https://www.astellas.com/us/system/files/veozah_uspi.pdf. Accessed November 20, 2023.

 

Santen RJ. Menopausal hot flashes. In: UpToDate, Post TW (Ed), Wolters Kluwer. August 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.


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​Rx.01.33 Off Label Use​

Brand NameGeneric Name
Veozah™Fezolinetant


335
  
1/1/2024Rx.01.282CommercialOyenusi, Oluwadamilola

Activated PI3 kinase delta syndrome (APDS) is a primary immunodeficiency caused by dominant mutations that increase activity of phosphoinositide-3-kinase δ (PI3Kδ). APDS can be caused by mutations in the PIK3CD gene that encodes PI3Kδ catalytic subunit p110δ (APDS1) or mutations in the PIK3R1 gene that encodes regulatory subunit p85α (APDS2). Patients with APDS disease have recurrent sinopulmonary infections with progressive airway damage and bronchiectasis, lymphadenopathy, nodular lymphoid hyperplasia in mucosal tissues, increased incidence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia and EBV-related lymphoma, progressive lymphopenia, elevated serum IgM, and impaired antibody responses.

 

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAkt pathway activity and inhibited proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/Akt pathway, and to the dysregulation of B and T cells.

 

JOENJA® (leniolisib) is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.


The intent of this policy is to communicate the medical necessity criteria for Leniolisib (Joenja®) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Leniolisib (Joenja®) is approved when all of the following are met:

  1. Diagnosis of activated phosphoinositide 3-kinase delta syndrome (APDS); and
  2. Molecular genetic testing confirms mutations in the PIK3CD or PIK3R1 gene; and
  3. Member is 12 years of age or older; and
  4. Member weighs greater than or equal to 45kg; and
  5. Both of the following:
    1. Presence of nodal and/or extranodal proliferation (e.g., lymphadenopathy, splenomegaly, hepatomegaly); and
    2. Presence of other clinical findings and manifestations consistent with APDS (e.g., recurrent sino-pulmonary infections, bronchiectasis, enteropathy); and
  6. Inadequate response or inability to tolerate at least one standard of care treatment for APDS (e.g., Immunoglobulin replacement therapy, antimicrobial prophylaxis [e.g., azithromycin, Bactrim], rituximab, tacrolimus, etc.); and
  7. Prescribed by or in consultation with one of the following:
    1. Hematologist; or
    2. Immunologist

 

Initial authorization duration: 6 months

 

REAUTHORIZATION CRITERIA: Leniolisib (Joenja®) is re-approved with documentation of positive clinical response to therapy (e.g., reduced lymph node size, increased naïve B-cell percentage, decreased severity or frequency of infections/hospitalizations)

 

Reauthorization duration: 12 months

 


​N/A

Michalovich D, Nejentsev S. Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy. Front Immunol. 2018 Feb 27;9:369. doi: 10.3389/fimmu.2018.00369. PMID: 29535736; PMCID: PMC5835040.

 

Notarangelo LD. Hyperimmunoglobulin M syndromes. In: UpToDate, Post TW (Ed), Wolters Kluwer. May 2023. Available from: https://www.uptodate.com. Accessed November 20, 2023.

 

JOENJA® (leniolisib) [package insert]. Saint Quentin Fallavier, France: Pharming Technologies B.V. March 2023. Available from:

https://joenja.com/prescribing-information.pdf. Accessed November 20, 2023.


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​Rx.01.33 Off Label Use​

Brand NameGeneric Name
Joenja®Leniolisib


337
  
4/1/2024Rx.01.2CommercialOyenusi, OluwadamilolaQ4-2023

Age edits are used to ensure appropriate utilization in certain age groups.  An age edit may be placed on a medication when there are concerns for safe use or inappropriate utilization based on indication in a particular age group. Age edits may be based on the FDA approved label, available literature or accepted compendia as listed in the Off-Label Use Policy. When a medication listed below is prescribed to a member outside of the defined age range, the age edit will be applied and prior authorization will be required. 

Retinoids: adapelene (Differin®), tazarotene (Avage®, Tazorac®) and Tretinoin, topical (e.g. Atralin®, Avita®, Retin-A®, Retin A micro®, Altreno™, etc), triafarotene (Aklief®).

Topical retinoids may be used for cosmetic indications, including fine lines and wrinkles, in addition to treating acne.  Coverage of medications intended for cosmetic indications is an excluded benefit.  Studies of topical retinoids for fine lines and wrinkles included patients beginning in their 20s.  An age edit for members over the age of 25 years will be applied to ensure indication is not cosmetic.

Alzheimer medications:Donepezil (Aricept® [ODT]), Rivastigmine (Exelon®), Memantine (Namenda® [XR]), Galantamine (Razadyne® [ER]), Memantine/ donepezil (Namzaric®))

Studies for Alzheimer's disease were primarily conducted in patients over the age of 50 years.  An age edit will be applied to evaluate indication in members under the age of 50 years.

Oral liquids: Age edits may be applied to liquid dosage forms that have a tablet or capsule with the same indication to limit use to those under age 12 years.  Studies show that children as young as 6-11 years of age can be taught how to swallow solid dosage forms. 

Benign Prostate Hypertrophy (BPH); Dutasteride (Avodart®), Finasteride (Proscar®): Studies for BPH indicate this condition is most prevalent in men over the age of 50 years. An age edit will be applied to evaluate indication in members under the age of 50 years.


The intent of this policy is to communicate the medical necessity criteria for medications that have age edits as provided under the member’s prescription drug benefit.

The drugs in the following table are approved in the age ranges listed when there is documentation of all of the following:

  1. FDA or compendia approved indication; and
  2. Not used for an indication that is otherwise excluded (i.e., cosmetic); and
  3. Oral liquid dosage forms that have a tablet or capsule formulation available, one of the following:  
    1. Drug will be administered via nasogastric or gastronomy tube; or
    2. Member is unable to swallow an intact capsule or tablet

 

***Note: Age edits apply to brand and generic products.  Some brand name products have prior authorization in addition to age edit. 
Authorization Duration: 2 years 


Opioids (Butorphanol tartrate NS, Ultram®, Ultram ER®, Ultracet®, Conzip®, codeine containing products, hydrocodone containing cough and cold products)

  • Exposes patients and others to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors and conditions.  
  • Serious, life-threatening, or fatal respiratory depression may occur with use. Monitor for respiratory for respiratory depression, especially during initiation or following a dose increase.
  • Accidental exposure, especially by children, can result in fatal overdose.
  • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatalogy experts.
  • Interactions with drugs affecting cytochrome P450 isoenzymes: the concomitant use of butorphanol tartrate NS with all cytochrome P450 3A4 inhibitors may result in an increase in butorphanol plasma concentrations, which could increase or prolong adverse reactions and potentially fatal respiratory depression. Discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in butorphanol concentration. The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol or codeine are complex and requires careful consideration of the effects on the parent drug and the active metabolite.  
  • Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Treximet® (sumatriptan/naproxen):

  • May cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. Treximet® is contraindicated in the setting of coronary artery bypass graft.
  • NSAID containing products cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

ACE inhibitors (Epaned®, Qbrelis®):

  • Fetal toxicity. When pregnancy is detected discontinue Epaned®/Qbrelis® as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Benzodiazepines (Clobazem, Halcion®, Doral®, Restoril®, Ativan®, Onfi®, Oxazepam®, Tranxene®, Chlordiazepoxide, Estazolam, Flurazepam and Xanax®):

  • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and duration to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.  
  • The use of benzodiazepines exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing benzodiazepine and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction. 
  • Abrupt discontinuation or rapid dosage reduction of benzodiazepines after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue the benzodiazepine or reduce the dosage. 

Non-Steroidal Anti-Inflammatory Drugs (Naprosyn®, Indocin®)

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
  • Naprosyn® and Indocin® are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
  • NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Nortriptyline

  • Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of nortriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Nortriptyline hydrochloride is not approved for use in pediatric patients.

Xatmep™ (methotrexate oral solution):

  • Methotrexate can cause severe or fatal toxicities. Monitor closely and modify dose or discontinue for the following toxicities: bone marrow suppression, infection, renal, gastrointestinal, hepatic, pulmonary, hypersensitivity, and dermatologic. Methotrexate can cause embryo-fetal toxicity and fetal death. Use in polyarticular juvenile idiopathic arthritic arthritis is contraindicated in pregnancy. Consider the benefits and risks of Xatmep™ and risks to the fetus when prescribing Xatmep™ to a pregnant patient with a neoplastic disease. Advise patients to use effective contraception during and after treatment with Xatmep™.

Tegretol® (carbamazepine):

  • Serious and sometimes fatal dermatologic reactions, including Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported during treatment with Tegretol®. Studies in patients of Chinese ancestry have found a strong association between the risk of developing TEN/SJS and the presence of HLA-b*1502, an inherited allelic variant of the HLA-b gene. HLA-b*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-b*1502 prior to initiating treatment with Tegretol®. Patients testing positive for the allele should not be treated with Tegretol® unless the benefit clearly outweighs the risk.
  • Aplastic anemia and agranulocytosis have been reported in association with the use of Tegretol®. Data from a population-based case control study demonstrate that the risk of developing these reactions is 5-8 times greater than in the general population. However, the overall risk of these reactions in the untreated general population is low, approximately six patients per one million population per year for agranulocytosis and two patients per one million population per year for aplastic anemia. Although reports of transient or persistent decreased platelet or white blood cell counts are not uncommon in association with the use of Tegretol®, data are not available to estimate accurately their incidence or outcome. However, the vast majority of the cases of leukopenia have not progressed to the more serious conditions of aplastic anemia or agranulocytosis. Because of the very low incidence of agranulocytosis and aplastic anemia, the vast majority of minor hematologic changes observed in monitoring of patients on Tegretol® are unlikely to signal the occurrence of either abnormality. Nonetheless, complete pretreatment hematological testing should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops.

 

Riomet® [ER] (metformin):

  • Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL.
  • Risk factors include renal impairment, concomitant use of certain drugs, age ≥ 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.
  • If lactic acidosis is suspected, discontinue Riomet institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

 

Proazac® (fluoxetine)

  • Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
  • Monitor for worsening and emergence of suicidal thoughts and behaviors.

Qdolo™ (tramadol)

  • Ensure accuracy when prescribing, dispensing, and administering QDOLO. Dosing errors due to confusion between mg and mL can result in accidental overdose and death
  • QDOLO exposes users to the risks of addiction, abuse and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing QDOLO, and monitor regularly for these behaviors or conditions.
  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products.
  • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially during initiation or following a dose increase.
  • Accidental ingestion of QDOLO, especially by children, can result in a fatal overdose of tramadol.
  • Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism
  • QDOLO is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (4). Avoid the use of QDOLO in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol.
  • Prolonged use of QDOLO, during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
  • The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with QDOLO requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
  • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Thyquidity™ (levothyroxine sodium)

  • Thyroid hormones, including THYQUIDITY, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
Valcyte® (valganciclovir)
 
  • Hematologic Toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with VALCYTE. 
  • Impairment of Fertility: Based on animal data and limited human data, VALCYTE may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females.
  • Fetal Toxicity: Based on animal data, VALCYTE has the potential to cause birth defects in humans.
  • Mutagenesis and Carcinogenesis: Based on animal data, VALCYTE has the potential to cause cancers in humans.​

Accolate® (zafirlukast) [prescribing information]. Wilmington, DE: Par Pharmaceuticals; December 2015. Accessed February 13, 2024
 
Aczone® (dapsone) [prescribing information]. Irvine, CA: Allergan; September 2019. https://www.almirall.us/pdf/aczone_7-5_pi_2019-09.pdf. Accessed February 13, 2024.
 
Adlarity® (donepezil transdermal system) [prescribing information]. Grand Rapids, MI: Corium Inc; March 2022. Available from: https://corium.com/products/ADLARITY/ADLARITY_PI_ENGLISH_US.pdf. Accessed February 13, 2024.
 
Aklief® (trifarotene) [prescribing information]. Fort Worth, TX: Galderma Laboratories, L.P.: October 2019. Available at: https://www.galderma.com/us/sites/g/files/jcdfhc341/files/2019-10/10-2-2019%20Revised%20PI%20NDA%20211527.pdf. Accessed February 13, 2024.
 
Altreno™ (tretinoin) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceutical North America LLC. March 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1412aba5-71aa-4cce-8db4-c189bed1852c&type=display. Accessed February 13, 2024.
 
Atralin™ (tretinoin) [prescribing information]. Fort Worth, TX: Coria Laboratories, LTD.; July 2016. Revised July 2016. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b45969-a64a-4ce3-b3b6-157d2568a301&type=display Accessed February 13, 2024.
 
Amerge® (naratriptan HCl) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; Revised October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=13f4a8ec-75a3-4c51-b3bc-6244f3c79e95&type=display. Accessed February 13, 2024.
 
Arazlo™ (tazarotene) [prescribing information]. Quebec, Canada: Bausch Health Companies Inc. May 2021. Available at: https://www.bauschhealth.com/portals/25/pdf/pi/arazlo-pi.pdf. Accessed February 13, 2024.
 
Aricept® (donepezil) [prescribing information]. Teaneck, NJ: Pfizer, Inc.; November 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e451e1-e4d7-4439-a675-c5457ba20975. Accessed February 13, 2024
 
Ativan ® (lorazepam) [prescribing information]. Eatontown, NJ: West-ward Pharmaceuticals; February 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017794s034s035lbl.pdf. Accessed February 13, 2024.

Atorvaliq® (atorvastatin calcium) [prescribing information]. Farmville, NC: CMP Pharma Inc. Feb 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213260s000lbl.pdf. Accessed February 13, 2024
 
Auvi-Q™ (epinephrine) [prescribing information]. Bridgewater, NJ. Sanofi-Aventis U.S. LLC. Revised September 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6180fb40-7fca-4602-b3da-ce62b8cd2470&type=display Accessed February 13, 2024.
 
Avita® (tretinoin) [prescribing information]. Research Triangle Park, NC: Bertek Pharmaceuticals, Inc.; July 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=302ca95f-5a7e-4971-870a-5cfea618d7a7 Accessed February 13, 2024.
 
Avodart® (dutasteride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January 2020. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Avodart/pdf/AVODART-PI-PIL.PDF Accessed February 13, 2024.
 
Briviact® (brivaracetam) [prescribing information]. Smyrna, GA: UCB, Inc. March 2022. Available at: https://www.briviact.com/briviact-PI.pdf. Accessed February 13, 2024.
 
butorphanol tartrate [prescribing information]. Toronto, Ontario: Apotex Corp.; August 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b8e48063-0b40-ee43-85c1-4ef2de80c404. Accessed February 13, 2024.
 
Casey, David A., et al. Drugs for Alzheimer's Disease: Are They Effective? U.S. National Library of Medicine, Apr. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2873716/. Accessed February 13, 2024.
 
Caverject® (alprostadil injection) [prescribing information]. New York, NY: Pfizer Inc. December 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a295fc1e-d82c-4f44-bc2d-a552bf594c98. Accessed February 13, 2024.
 
Doxycycline [prescribing information]. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b52e0a7-f024-4d8a-a59e-374946e60b44. Accessed November 25, 2020. Accessed February 13, 2024.
 
Edex® (alprostadil injection) [prescribing information]. Malvern, PA: Endo Pharmaceuticals, Inc. July 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8b8ec8d-1318-43e4-a182-446e9f9579de. Accessed February 13, 2024.
 
Entadfi™ (finasteride and tadalafil) [prescribing information]. Miami, FL: ery Inc. December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=112bf653-8322-4444-8d4d-03234b11c38c. Accessed December 28, 2022.
 
Firvanq® (vancomycin HCL) [prescribing information]. Wilmington, MA: Cutis Pharma; December 2021. Available at: https://firvanq.com/assets/pdf/FIRVANQ-PI-R1.pdf. Accessed February 13, 2024
 
Flolipid® (simvastatin suspension) [prescribing information]. Brooskville, FL: Salerno Pharmaceuticals LP. June 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ee17d10-6eb1-452a-99e8-02381368b3fe. Accessed February 13, 2024.
 
Furadantin® (nitrofurantoin suspension) [prescribing information]. Parsippany, NJ: Activis Pharma, Inc. December 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8c5b015-626e-4d57-9b91-392fb53575fa. Accessed February 13, 2024.
 
Hillebrand, G.G., et al. “New Wrinkles on Wrinkling: an 8‐Year Longitudinal Study on the Progression of Expression Lines into Persistent Wrinkles." British Journal of Dermatology, Wiley/Blackwell (10.1111), 22 Feb. 2010, onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2133.2010.09709.x. Accessed February 13, 2024.
 
Hycodan® (hydrocodone bitartrate and homatropine methylpromide) [prescribing information]. Allentown, PA: Genus Lifesciences Inc.; December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=901d4115-f71a-4681-bd0e-c9b691151b78. Accessed February 13, 2024
 
Imitrex® (sumatriptan succinate) [prescribing information]. Canada: GlaxoSmithKiline LLC. December 2020. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32f6d89b-4aea-5396-e054-00144ff88e88. Accessed February 13, 2024.
 
Indocin® (indomethacin suspension) [prescribing information]. Wayne, PA: Zyla Life Sciences US Inc. April 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73878376-1d24-423b-9f37-3666e83c95da. Accessed February 13, 2024
 
Katerzia® (amlodipine suspension) [prescribing information]. Greenwood Village, CO, Silvergate Pharmaceuticals Inc. October 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=df673a4d-acb8-444c-a472-c87ab8cbd366&type=display. Accessed February 13, 2024.
 
Luebberding, Stefanie, et al. Quantification of Age-Related Facial Wrinkles in Men and... : Dermatologic Surgery. Oxford University Press, 2014, journals.lww.com/dermatologicsurgery/pages/articleviewer.aspx?year=2014&issue=01000&article=00003&type=abstract.  February 13, 2024
 
Lyrica® (pregabalin) oral solution [prescribing information]. New York, NJ: Pfizer. June 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60185c88-ecfd-46f9-adb9-b97c6b00a553.. Accessed February 13, 2024
 
Maxalt® (rizatriptan benzoate) [prescribing information]. Whitehouse Station, NJ: Merck& Co., Inc.; 2012. Revised June 2021.  https://www.merck.com/product/usa/pi_circulars/m/maxalt/maxalt_pi.pdf Accessed February 13, 2024.
 
Meltzer EO, Welch MJ, Ostrom NK. Pill swallowing ability and training in children 6 to 11 years of age. Clin Pediatr. 2006;45:725-33. Accessed February 13, 2024
 
Mestinon® (pyridostigmine bromide) [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC. December 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a851795e-b7a8-40c3-9922-5e79d3eb4d92. Accessed February 13, 2024.
 
Muse® (alprostadil urethral suppository) [prescribing information]. Somerset, NJ: Meda Pharmaceuticals. April 2018. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c55f3f9-c4cf-11df-851a-0800200c9a66. Accessed July 21, 2021.
 
Namenda® (memantine HCl) [prescribing information]. St. Louis, MO: Forest Laboratories, Inc.; 2012. Revised November 2018.  https://www.allergan.com/assets/pdf/namenda_pi Accessed February 13, 2024.
 
Namzaric™ (Memantine/ donepezil) [prescribing information]. St. Louis, MO: Forest Laboratories, Inc.; January 2019. https://www.allergan.com/assets/pdf/namzaric_pi Accessed February 13, 2024.
 
Naprosyn® (naproxen) [prescribing information]. Athens, GA: Athena Bioscience. August 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f9b4173d-7836-4d7d-b149-1d96f9377ad0. February 13, 2024.
 
Neurontin® (gabapentin) [prescribing information]. New York, NY: Parke-Davis, Division of Pfizer Inc. April 2020. Available at: http://labeling.pfizer.com/ShowLabeling.aspx?id=630. Accessed February 13, 2024.
 
Norliqva® (amlodipine) [prescribing information]. Farmville, NC: CMP Pharma Inc; February 2022. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c1730a51-4383-4c61-a9a1-7e1326bd0abe. Accessed February 13, 2024.
 
Nortriptyline [prescribing information]. Greensville, SC: Pharmaceutical Associates, Inc. February 2019. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fcabf90-357a-4a06-b680-9572dc28bcfe. Accessed February 13, 2024.
 
Nurtec® ODT (rimegepant) [prescribing information]. New Haven, CT: Biohaven Pharmaceuticals, Inc.; April 2022. Available from: https://www.nurtec.com/pi. Accessed February 13, 2024.
 
Onfi® (clobazam) [prescribing information]. Winchester, KY: Catalent Pharma Solutions, LLC. February 2021. Available at: https://www.lundbeck.com/upload/us/files/pdf/Products/ONFI_PI_US_EN.pdf. Accessed February 13, 2024.
 
Oxazepam [prescribing information]. Princeton, NJ: Sandoz Inc.; 2011. Revised February 2021. Accessed February 13, 2024.
 
Proscar® (finasteride) [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; June 2021.  Accessed February 13, 2024.
 
“Prostate Enlargement (Benign Prostatic Hyperplasia)." National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, 1 Sept. 2014, www.niddk.nih.gov/health-information/urologic-diseases/prostate-problems/prostate-enlargement-benign-prostatic-hyperplasia.
 
Prozac® (fluoxetine) oral solution [prescribing information]. Greenville, SC: Pharmaceutical Associates, Inc. December 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=180a07fd-1f6a-4617-b8e0-f938c65ba273. Accessed February 13, 2024.
 
Qbrelis® (lisinopril) [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals; July 2020. Available from: https://qbrelis.com/Qbrelis-Prescribing-Info.pdf. Accessed February 13, 2024.
 
Qdolo™ (tramadol) [prescribing information]. Athens, GA: Athena Bioscience, LLC. September 2020. Available at: https://qdolo.com/wp-content/uploads/2020/10/QDOLO-Prescribing-Information.pdf. Accessed February 13, 2024.
 
Qiu, Chengxuan, et al. Epidemiology of Alzheimer's Disease: Occurrence, Determinants, and Strategies toward Intervention. U.S. National Library of Medicine, June 2009, www.ncbi.nlm.nih.gov/pmc/articles/PMC3181909/. Accessed February 13, 2024.
 
Razadyne ER ® (galantamine) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2016. Revised October 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021169s033,021615s024lbl.pdf. Accessed February 13, 2024.
 
Relenza® (zanamivir) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2012. Revised October 2021. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Relenza/pdf/RELENZA-PI-PIL-COMBINED.PDF. Accessed February 13, 2024.
 
Relpax® (eletriptan) [prescribing information]. New York, NY: Roerig (Pfizer Inc.); 2012. Revised March 2020. http://labeling.pfizer.com/ShowLabeling.aspx?id=621 Accessed February 13, 2024.
 
Restoril™ (Temazepam) [prescribing information]. Webster Groves, MO: Mallinckrodt; 2016. Revised February 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018163s065lbl.pdf. Accessed February 13, 2024.
 
Retin-A® (tretinoin) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America; 2016. Revised September 2019. Accessed February 13, 2024.
 
Retin-A Micro® (tretinoin) [prescribing information].  Bridgewater, NJ: Valeant Pharmaceuticals North America; 2016. Revised October 2017. Accessed February 13, 2024.
 
Reyvow® (lasmiditan) [prescribing information]. Indianapolis, IN: Lilly USA, LLC; September 2022. Available from: http://pi.lilly.com/us/reyvow-uspi.pdf. Accessed February 13, 2024.
 
Riomet® (metformin hydrochloride) oral solution [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; November 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021591s007lbl.pdf. Accessed February 13, 2024.
 
Riomet ER™ (metformin hydrochloride for extended-release oral suspension) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; August 2019. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212595s000lbl.pdf. Accessed February 13, 2024.
 
Tegretol® (carbamazepine) [prescribing information]. East Hanover, NJ: Norvatis Pharmaceuticals Corporations. March 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d409411-aa9f-4f3a-a52c-fbcb0c3ec053. Accessed  February 13, 2024
 
Thyquidity™ (levothyroxine sodium) oral solution [prescribing information]. Largo, FL: Vertice Specialty Group. December 2020. Available at: https://www.thyquidity.com/pdf/Prescribing-Information.pdf. Accessed February 13, 2024
 
Tosymra (sumatriptan) nasal spray [prescribing information]. Maple Grove, MN: Upsher-Smith Laboratories, LLC. February 2021. Available from: www.upsher-smith.com/wp-content/uploads/TOS-MI.pdf. Accessed February 13, 2024.
 
Tranxene® (clorazepate) [prescribing information]. Lebanon, NJ: AbbVie LTD; May 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017105s079lbl.pdf. Accessed February 13, 2024.
 
Treximet® (sumatriptan/naproxen) [prescribing information]. Morristown, NJ. Pernix Therapeutics. April 2021. http://www.treximet.com/Areas/Patient/Contents/pdf/prescribing-information.pdf Accessed February 13, 2024
 
Trileptal® (oxcarbazepine) oral suspension. [prescribing information] East Hanover, NJ: Norvatis. May 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c5c86c8-ab7f-4fcf-bc1b-5a0b1fd0691b. Accessed February 13, 2024.
 
Twyneo® (Tretinoin-benzoyl peroxide) [prescribing information]. Fort Worth, TX: Galderma Laboratories, L.P. July 2021. Available from: https://www.galderma.com/us/sites/default/files/2022-02/Twyneo_PI.pdf. Accessed February 13, 2024.
 
Ubrelvy® (ubrogepant) [prescribing information]. Madison, NJ: Allergan USA, Inc; March 2021. https://media.allergan.com/products/Ubrelvy_pi.pdf. Accessed February 13, 2024
 
Ultracet® (tramadol/acetaminophen) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; April 2022. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ULTRACET-pi.pdf. Accessed February 13, 2024
 
Ultram® (tramadol) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; October 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021692s015lbl.pdf Accessed February 13, 2024
 
Ultram® ER (tramadol ER) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; September 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021692s015lbl.pdf. Accessed February 13, 2024.
 
Valganciclovir (Valcyte) [prescribing information]. San Francisco, CA: Genetech USA, inc. December 2021. VALCYTE Prescribing Information (gene.com). Accessed November 4, 2022. 
 
Xanax® (alprazolam) [prescribing information]. New York, NY: Pharmacia & Upjohn Company; March 2021. http://labeling.pfizer.com/ShowLabeling.aspx?id=547 Accessed February 13, 2024.
 
Xatmep™ (methotrexate) [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals, Inc.; September 2020. https://xatmep.com/Xatmep-Prescribing-Info.pdf. Accessed February 13, 2024.
 
Zavzpret™ (zavegepant) [package insert]. New York, NY: Pfizer Inc. March 2023. Available from: https://labeling.pfizer.com/ShowLabeling.aspx?id=19471. Accessed February 13, 2024
 
Ziana® (tretinoin/clindamycin) [prescribing information]. Brigewater, NJ: Medicis Pharmaceutical Corp; Revised March 2017. Accessed February 13, 2024.
 
Zomig® (zolmitriptan) [prescribing information]. Macclesfield, Cheshire UK: AstraZeneca Pharmaceuticals; 2012. Revised May 2019.  Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=84b51cb9-83f3-4a49-7fa3-1adc0f963658&type=display. Accessed February 13, 2024.
 
Zomig NS® (zolmitriptan nasal) [prescribing information]. Macclesfield, Cheshire UK: AstraZeneca Pharmaceuticals; 2012. Revised April 2019. https://www.azpicentral.com/zomig_nasal/zomig_nasal.pdf#page=1. Accessed February 13, 2024.
 
Zyflo CR® (Zileuton) [prescribing information]. Cary, NC: Chiesi USA, Inc., Revised December 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022052s014lbl.pdf. Accessed February 13, 2024.

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Rx.01.33 Off Label Use

Rx.01.17 Cosmetic Policy

Rx.01.251 Migraine and Headache agents

Rx.01.197 Opioid Policy

Rx.01.202 Prior authorization requirements for select drugs

Rx.01.33 Off-Label Use

Rx.01.76 Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit​



Drug NameAge Edit:  Prior Authorization Required (years)
Acne Medications
Tretinoin, topical (e.g., Atralin, Avita, Retin-A, Retin-A micro, Altreno, etc.)Age 26 and over
Adapalene (Differin)Age 26 and over
Adapalene/ Benzoyl Peroxide (Epiduo)Age 26 and over
Tretinoin/ clindamycin (Ziana)Age 26 and over
Dapsone (Aczone) 5%Under age 12
Dapsone (Aczone) 7.5%Under age 9
Triafarotene (Aklief)Age 26 and over
Tazarotene (Fabior, Arazlo, Tazorac)Age 26 and over
Tretinoin-benzoyl peroxide (Twyneo)Age 26 and over
Alzheimer's Drugs
Donepezil (Aricept [ODT]), AdlarityUnder age 50
Rivastigmine (Exelon)Under age 50
Memantine (Namenda [XR])Under age 50
Galantamine (Razadyne [ER])Under age 50
Memantine/ donepezil (Namzaric)Under age 50
Anticonvulsant Agents
Clobazam (Onfi) suspension Age 13 and over
Rufinamide (Banzel) suspension Age 13 and over
Carbamazepine (Tegretol) suspension Age 13 and over
Gabapentin (Neurontin) Oral solution Age 13 and over
Brivaracetam (Briviact) oral solution Age 13 and over
Pregabalin solution (Lyrica®)Age 13 and over
Oxcarbazepine suspension (Trileptal®)Age 13 and over
Antidepressants
Nortriptyline solutionAge 13 and over
Fluoxetine solution (Prozac)Age 13 and over
Antidiabetic Agents
Metformin (Riomet) ER solutionAge 13 and over
Metformin (Riomet) suspension                                      Age 13 and over
Acute migraine Agents
Eletriptan (Relpax)Under age 18
Sumatriptan (Imitrex, Onzetra. Xsail, Zembrace Symtouch, Tosymra)Under age 18
Butorphanol tartrate NSUnder age 18
Naratriptan (Amerge)Under age 18
Rizatriptan (Maxalt/ Maxalt MLT)Under age 6
Zolmitriptan (Zomig/Zomig ZMT)Under age 12
Almotriptan    Under age 12
Frovatriptan (Frova)Under age 18
Sumatriptan/naproxen (Treximet)Under age 12
TosymraUnder age 18
Lasmiditan (Reyvow)Under age 18
Ubrogepan (Ubrelvy)Under age 18
Rimegepant (Nurtec ODT)Under age 18
Zavegepant (Zayzpret)Under age 18
Antihypertensives
Amlodipine (Katerzia, Norliqva)Age 13 and over
Enalapril (Epaned)Age 13 and over
Lisinopril (Qbrelis)Age 13 and over
Valsartan oral solutionAge 13 and over
Anti-Infectives
Vancomycin oral solution (Firvanq)Age 13 and over
Zanamivir (Relenza)Under age 5
Nitrofurantoin suspension (Furdantin)Age 13 and over
Doxycycline hyclate DR 75mg, 150mg (Doryx 75mg, 150mg), Doxycycline hyclate 75mg, 150mg (Acticlate 75mg, 150mg), Doxycycline monohydrate /Mondoxyn NL 75mg capsule (Monodox 75mg), Doxycycline monohydrate 150mg capsule and tablet (Adoxa 150mg)Age 18 and over
Valganciclovir oral solution (Valcyte)Age 13 and over
Benign Prostate Hypertrophy
Dutasteride (Avodart)Under age 50
Finasteride (Proscar)Under age 50
Finasteride-Tadalafil (Entadfi)Under age 50
Erectile Dysfunction Agents
Alprostadil (Muse®, Edex®, Caverject®, IFE-PG20)Under age 55
Benzodiazepines
FlurazepamUnder age 15
Triazolam (Halcion)Under age 18
Quazepam (Doral)Under age 18
EstazolamUnder age 18
Temazepam (Restoril)Under age 18
Lorazepam (Ativan)Under age 12
ChlordiazepoxideUnder age 6
OxazepamUnder age12
Clorazepate (Tranxene)Under age 9
Alprazolam (Xanax) Under age 18
Leukotriene Inhibitors
Zafirlukast (Accolate)Under age 5
Zileuton (Zyflo [CR])Under age 12
Pain

Tramadol/Tramadol ER containing products

(e.g., Ultram, Ultram ER, Ultracet, Conzip) 

Under age 12
Tramadol solution (Qdolo)Under age 18
Codeine containing productsUnder age 12
Indomethacin (Indocin) suspensionAge 13 and over
Naproxen (Naprosyn) suspensionAge 13 and over
Cough/Cold Products
Codeine and hydrocodone containing productsUnder age 18
Miscellaneous
Auvi-Q 0.1mgAge 4 and over
Xatmep (Methotrexate solution)      Age 13 and over
Pyridostigmine (Mestinon) solutionAge 13 and over
Thyquidity solutionAge 13 and over
Simvastatin (Flolipid) suspensionAge 13 and over
Atorvastatin calcium suspension (Atorvaliq)Age 13 and over

 



medications that have age edits medications that have age edits
338
  
4/1/2024Rx.01.259CommercialOyenusi, OluwadamilolaQ4-2023

The antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). These vasculitis are complex, immune-mediated disorders in which tissue injury results from the interplay of an initiating inflammatory event and a highly specific immune response. Part of this response is directed against previously shielded epitopes of neutrophil granule proteins, leading to high-titer autoantibodies known as ANCA. The production of ANCA is one of the hallmarks of the ANCA-associated vasculitis. ANCA are directed against antigens present primarily within the granules of neutrophils and monocytes; these autoantibodies produce tissue damage via interactions with primed neutrophils and endothelial cells.

Avacopan (Tavneos™) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. Avacopan does not eliminate glucocorticoid use.

Avacopan is a complement 5a receptor (C5aR) antagonist that inhibits the interaction between C5aR and the anaphylatoxin C5a. Avacopan blocks C5a-mediated neutrophil activation and migration. The precise mechanism by which avacopan exerts a therapeutic effect in patients with ANCA-associated vasculitis has not been definitively established.



The intent of this policy is to communicate the medical necessity criteria for Avacopan (Tavneos™) as provided under the member's prescription drug benefit. 

INITIAL CRITERIA: Avacopan (Tavneos™) is approved when ALL of the following are met:

  1. Diagnosis of one of the following types of severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis:
    1. Granulomatosis with polyangiitis (GPA); or
    2. Microscopic polyangiitis (MPA); and
  2. Member is receiving concurrent immunosuppressant therapy with one of the following:
    1. Cyclophosphamide; or
    2. Rituximab; and
  3. One of the following:
    1. Member is concurrently on glucocorticoids (e.g., prednisone); or
    2. Inadequate response or inability to tolerate glucocorticoids (e.g., prednisone); and
  4. Member is 18 years of age or older; and
  5. Prescribed by or in consultation with one of the following:
    1. Nephrologist; or
    2. Pulmonologist; or
    3. Rheumatologist


Initial authorization duration: 6 months

REAUTHORIZATION CRITERIA: Avacopan (Tavneos™) is re-approved when ALL of the following are met:

  1. Member does not show evidence of progressive disease while on therapy; and
  2. Member is receiving concurrent immunosuppressant therapy (e.g., azathioprine, cyclophosphamide, methotrexate, rituximab); and
  3. Prescribed by or in consultation with one of the following:
    1. Nephrologist; or
    2. Pulmonologist; or
    3. Rheumatologist


Reauthorization duration: 2 years
 


None

Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis. UpToDate. October 2020. Available at: https://www.uptodate.com/contents/pathogenesis-of-antineutrophil-cytoplasmic-autoantibody-associated-vasculitis?search=antineutrophil%20cytoplasmic%20autoantibody%20associated%20vasculitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed February 13, 2024

Tavneos (avacopan) [package insert]. Cincinnati, OH. ChemoCentryx, Inc. Feburary 2022. Available at:

https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7ea3c60a-45c7-44cc-afc2-d87fa53993c0&type=displayAccessed February 13, 2024


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​Rx.01.33 Off Label Use
Tavneos™Avacopan
339
  
4/1/2024Rx.01.171CommercialOyenusi, OluwadamilolaQ4-2023

Bile acid synthesis disorders (BASD) are extremely rare, genetic, metabolic conditions that exhibit manifestations of liver disease, steatorrhea, and complications from decreased fat soluble vitamin absorption.  Individuals with BASD lack the enzymes needed to synthesize cholic acid.  If untreated, these individuals fail to grow and can develop life-threatening liver injury. 

Cholic acid is a primary bile acid synthesized from cholesterol in the liver. In bile acid synthesis disorders due to single enzyme deficiencies (SEDs) in the biosynthetic pathway, and in peroxisomal disorders (PDs) including Zellweger spectrum disorders, deficiency of primary bile acids leads to unregulated accumulation of intermediate bile acids and cholestasis. Bile acids facilitate fat digestion and absorption by forming mixed micelles, and facilitate absorption of fat-soluble vitamins in the intestine.

Endogenous bile acids, including cholic acid, enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions.

Cholic acid (Cholbam®) is indicated for:

  1. The treatment of BASD due to SEDs
  2. Adjunctive treatment of PDs including Zellweger spectrum disorders, in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption.​

Treatment with cholic acid (Cholbam®) is approved for children aged 3 weeks and older, and adults.


The intent of this policy is to communicate the medical necessity criteria for cholic acid (Cholbam®) as provided under the member's prescription drug benefit.

INITIAL CRITERIA Cholic acid (Cholbam®) is approved when ALL of the following are met:

  1. One of the following:
    1. Treatment of bile acid synthesis disorder due to single enzyme defect; or
    2. Adjunctive treatment of peroxisomal disorder including Zellweger spectrum disorder in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat soluble vitamin absorption; and
  2. Prescribed by or in consultation with one of the following:
    1. hepatologist; or
    2. gastroenterologist; or
    3. medical geneticist; or
    4. other specialist that treats inborn errors of metabolism; and
  3. No documentation of extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders including Zellweger spectrum disorder

 

Initial authorization duration: 3 months

 

REAUTHORIZATION CRITERIA Cholic acid (Cholbam®) is re-approved when there is documentation of improved liver function tests (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]) from the start of treatment.

 

Reauthorization duration: 2 years


None
Cholbam® (Cholic acid) [package insert]. Baltimore MD. Asklepion Pharmaceuticals, LLC. May 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf. Accessed February 13, 2024

Cholic acid. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO.  Available from: http://www.micromedexsolutions.com. Accessed February 13, 2024

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Rx.01.33 Off-Label Use 
Cholbam®cholic acid
340
  
4/1/2024Rx.01.136CommercialOyenusi, OluwadamilolaQ4-2023

Cystinosis is a rare, genetic disorder in which the amnio acid cystine accumulates in tissues and organs, most commonly the kidneys and eyes.  Treatment with cysteamine should be initiated as soon as the diagnosis is made to preserve kidney function, prevent hypothyroidism, and improve growth in affected children.  Orally administered cysteamine does not reach the cornea, thus ophthalmic administration is necessary for accumulation of corneal cystine crystals.

Cysteamine acts as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides.  The result is a reduction in cystine crystals.

Cysteamine hydrochloride (Cystaran®/Cystadrops®) is indicated for the treatment of corneal cystine crystal accumulation in adults and children with cystinosis. 

Cysteamine bitartrate (Cystagon®/Procysbi®) is indicated for the treatment of nephropathic cystinosis in adult and children.


The intent of this policy is to communicate the medical necessity criteria for cysteamine Hydrochloride (Cystaran®/Cystadrops®) and cysteamine bitartrate (Cystagon®/ Procysbi®) as provided under the member's prescription drug benefit.

Cystinosis
 
INITIAL CRITERIA: Cysteamine hydrochloride (Cystaran®/Cystadrops®) Ophthalmic Solution is approved when BOTH of the following are met:

  1. Diagnosis of cystinosis; and
  2. Member has corneal cystine crystal accumulation; and
  3. Prescribed by or in consultation with an ophthalmologist or a specialist with experience in treating cystinosis with corneal cystine crystal accumulation

 

Initial authorization duration: 2 years

 
REAUTHORIZATION CRITERIA Cysteamine hydrochloride (Cystaran®, Cystadrops®) is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years 
___________________________________________________________________________________________

Nephrotic Cystinosis
 
INITIAL CRITERIA: Cysteamine bitartrate (Cystagon®) is approved when there is a diagnosis of nephrotic cystinosis.

Initial authorization: 2 years

REAUTHORIZATION CRITERIA Cysteamine bitartrate (Cystagon®) is re-approved when there is documentation of positive clinical response to therapy.

Reauthorization duration: 2 years

INITIAL CRITERIA: Cysteamine bitartrate (Procysbi®) is approved when ALL of the following are met:

  1. Diagnosis of nephrotic cystinosis; and
  2. Member is 1 year of age or older; and
  3. Inadequate response or titration from cysteamine bitartrate immediate release capsules (Cystagon®)

 
Initial Authorization duration: 2 years

 
REAUTHORIZATION CRITERIA: Cysteamine bitartrate (Procysbi®) is re-approved when there is documentation of positive clinical response to therapy.
 

Reauthorization duration: 2 years

 


None

Cystadrops® [package insert] Lebanon, NJ. Recordati Rare Diseases Inc. August 2020. Available from: https://www.cystadrops.com/wp-content/uploads/cystadrops-prescribing-information.pdf. Accessed February 13, 2024.

Cystagon® [package insert]. Morgantown WV. Mylan Pharmaceuticals Inc. August 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020392s010lbl.pdf. Accessed December 28,, 2022.

Cystanosis. National Organization for Rare Disorders. Available at: http://rarediseases.org/rare-diseases/cystinosis/. Accessed February 13, 2024.

Cystaran® [package insert]. Amityville NY. Sigma-Tau Pharmaceuticals, Inc. February 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/200740s000lbl.pdf.  Accessed February 13, 2024.

Niaudet P. Cystinosis. UpToDate. February 2020. Available at: https://www.uptodate.com/contents/cystinosis?source=search_result&search=cystinosis&selectedTitle=1~31. Accessed February 13, 2024.

Procysbi® [package insert]. Novato CA. Raptor Pharmaceuticals Inc. February 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203389s010lbl.pdf. Accessed February 13, 2024.


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Rx. 01.33 Off-Label Use 
Rx.01.76 ​Quantity Level Limits for Pharmaceuticals Covered Under the Prescription Drug Benefit 
Brand NameGeneric Name
Cystagon®Cysteamine Bitartrate
Cystaran®/Cystadrops®Cysteamine Hydrochloride
Procysbi®Cysteamine Bitartrate

Cystaran®/Cystadrops®, Cystagon®/ Procysbi®cysteamine Hydrochloride, cysteamine bitartrate
341
  
4/1/2024Rx.04.9Claim Payment PolicyOyenusi, OluwadamilolaQ4-2023
​A cosmetic drug is intended to be used for cleansing, beautifying, promoting attractiveness, or altering the appearance of human body from which no significant improvement in physiologic function can be expected. 
The intent of this policy is to communicate the coverage of cosmetic drugs under the member’s prescription drug benefit.

Coverage is subject to the terms, conditions, and limitations of the member's contract.
Cosmetic drugs, or drugs prescribed for cosmetic purposes, are not covered under the pharmacy benefit. Cosmetic drugs or drugs prescribed for cosmetic purposes are:

  • Used for other than the treatment of illness, injuries, congenital birth defect or restoration of physiological function; and
  • Used for cleansing, beautifying, promoting attractiveness or altering the appearance of any part of the human body


 
Examples of drugs prescribed for cosmetic use include, but are not limited to:

Brand Name         Generic Name   FDA Indication     
EgriftaTesamorelinReduction of excess abdominal fat in HIV-infected patients with lipodystrophy.
Renova, Refissa (branded product only)TretinoinAdjunctive agent for use in the mitigation (palliation) of fine wrinkles, mottled hyperpigmentation, and tactile roughness of facial skin in patients who do not achieve such palliation using comprehensive skin care and sun avoidance programs alone
Propecia 1mgFinasteride 1mgMale pattern alopecia
Multiple (e.g., Lustra)HydroquinoneDiscoloration of skin; Hyperpigmentation of skin
Latisse 0.03% solutionBimatoprostHypotrichosis of the eyelashes
Vaniqa 13.9% creamEflornithineReduction of unwanted facial hair in women
Multiple (e.g., Rogaine)Minoxidil topicalMale pattern alopecia; hair regrowth in women

N/A
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Rx.01.2 Applicable Age Edits 

Rx.01.33 Off-Label Use 

Rx.01.202 Prior Authorization Requirements for Select Drugs 

12.01.03a​ Cosmetic Procedure medical policy 


cosmetic drugscosmetic drugs
342