HEPSERA, Adefovir Dipivoxil Form

Adefovir (Hepsera®) is a nucleotide analogue and reverse transcriptase inhibitor with activity against human hepatitis B virus.
FDA Approved Indication(s) Hepsera is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Hepsera is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Hepatitis B Infection (must meet all):

1. Diagnosis of chronic hepatitis B virus infection;
   2. Prescribed by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist;
2. Age ≥ 12 years;
   
   4. For Hepsera requests, member must use adefovir, unless contraindicated or clinically significant adverse effects are experienced;
3. For member with lamivudine-resistant hepatitis B virus infection: lamivudine is being used in combination with adefovir;

4. Failure of one of the following, unless clinically significant adverse effects are experienced or all are contraindicated: Pegasys®, entecavir, or tenofovir (preferred formulation is tenofovir disoproxil fumarate); *Prior authorization may be required for Pegasys and entecavir

   7. Hepsera is not prescribed concurrently with tenofovir;
   8. Dose does not exceed both of the following (a and b): a. 10 mg per day; b. 1 tablet per day. Approval duration: 6 months
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   CLINICAL POLICY Adefovir B. Other diagnoses/indications (must meet 1 or 2):

5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Chronic Hepatitis B Infection (must meet all):
   3. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   4. Member is responding positively to therapy;
   5. For Hepsera requests, member must use adefovir, unless contraindicated or clinically significant adverse effects are experienced;
6. For member with lamivudine-resistant hepatitis B virus infection: lamivudine is being used in combination with adefovir;
7. Hepsera is not prescribed concurrently with tenofovir;
   6. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 10 mg per day; b. 1 tablet per day.
      Approval duration: 12 months
      B. Other diagnoses/indications (must meet 1 or 2):

8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY Adefovir

9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALT: alanine aminotransferase AST: aspartate aminotransferase FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen entecavir (Baraclude®) Pegasys® (peginterferon alfa-2a) 0.5 to 1 mg PO QD 180 mcg SC once weekly for 48 weeks tenofovir disproxil fumarate (Viread®) 300 mg PO QD Vemlidy® (tenofovir alafenamide fumarate) 25 mg PO QD Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 300 mg/day 25 mg/day Dose Limit/ Maximum Dose 1 mg/day 180 mcg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity • Boxed warning(s): severe acute exacerbations of hepatitis, nephrotoxicity, HIV resistance, lactic acidosis, and severe hepatomegaly with steatosis Appendix D: General Information • Hepsera labeling warns against coadministration of Hepsera with tenofovir-containing products. Hepsera may increase serum concentrations of tenofovir-containing products and vice versa, resulting in additive nephrotoxicity and diminishing therapeutic effect. In the treatment of chronic hepatitis B, tenofovir should not be administered with Hepsera to avoid multi-drug resistance. In patients with concomitant HIV and chronic hepatitis B, treatment with tenofovir is sufficient. Page 3 of 6

   CLINICAL POLICY Adefovir V. Dosage and Administration
   Indication Chronic hepatitis B
   Dosing Regimen CrCl ≥ 50 mL/min: 10 mg PO QD CrCl 30 to 49 mL/min: 10 mg PO Q48H CrCl 10 to 29 mL/min: 10 mg PO Q72H Hemodialysis: 10 mg every 7 days following dialysis Maximum Dose 10 mg/day VI. Product Availability
   Tablet: 10 mg VII.