COPEGUS, Ribavirin (Hepatitis C) RIBASPHERE RIBAPAK, Ribavirin (Hepatitis C) RIBASPHERE, Ribavirin (Hepatitis C) MODERIBA, Ribavirin (Hepatitis C) REBETOL, Ribavirin (Hepatitis C) Form

Ribavirin (Rebetol® and Ribasphere® RibaPak®) is a nucleoside analogue. FDA Approved Indication(s) Ribasphere Ribapak is indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with Pegasys (peginterferon alfa-2a) in patients 5 years of age and older with compensated liver disease not previously treated with interferon alpha, and in adult CHC patients coinfected with HIV. Rebetol is indicated for the treatment of CHC in combination with interferon alfa-2b (pegylated and nonpegylated) for the treatment of CHC in patients 3 years of age or older with compensated liver disease. The following points should be considered when initiating Rebetol combination therapy with PegIntron® or Intron A®:
• Combination therapy with Rebetol/PegIntron is preferred over Rebetol/Intron A as this combination provides substantially better response rates.
• Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. • No safety and efficacy data are available for treatment duration lasting longer than one year.
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 Rebetol and Ribasphere Ribapak are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Hepatitis C Infection (must meet all):

1. Diagnosis of chronic hepatitis C virus (HCV) infection as evidenced by detectable serum HCV RNA levels by quantitative assay in the last 6 months;

2. Prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or provider who has expertise in treating HCV based on a certified training program (see Appendix E);
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   Ribavirin

3. Member meets prior authorization criteria for Epclusa®, Harvoni®, Mavyret®, Sovaldi®, Zepatier®, Viekira Pak®, or Vosevi® for combination use;
4. For brand Rebetol or Ribasphere Ribapak requests, member must use generic ribavirin, unless contraindicated or clinically significant adverse effects are experienced;
5. Member meets one of the following (a or b): a. Ribasphere Ribapak: Age ≥ 5 years; b. Rebetol: Age ≥ 3 years;
6. Dose does not exceed: a. Ribasphere Ribapak: 1,200 mg per day; b. Rebetol: 1,400 mg per day. Approval duration: Coincides with duration for Epclusa, Harvoni, Mavyret, Sovaldi, Zepatier, Viekira Pak, or Vosevi authorization B. Other diagnoses/indications (must meet 1 or 2):
7. 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: CP.CPA.190 for commercial, 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
8. 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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Chronic Hepatitis C Infection (must meet all):
   
   1. 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);
   2. Member is responding positively to therapy;
   3. For brand Rebetol or Ribasphere Ribapak requests, member must use generic ribavirin, unless contraindicated or clinically significant adverse effects are experienced;

9. If request is for a dose increase, new dose does not exceed: a. Ribasphere Ribapak: 1,200 mg per day; Page 2 of 7

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   Ribavirin b. Rebetol: 1,400 mg per day. Approval duration: Coincides with duration for Epclusa, Harvoni, Mavyret, Sovaldi, Zepatier, Viekira Pak, or Vosevi authorization B. Other diagnoses/indications (must meet 1 or 2):

10. 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: CP.CPA.190 for commercial, 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

11. 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: CP.CPA.09 for commercial, 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 – CP.CPA.09 for commercial, 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 CHC: chronic hepatitis C FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable HCV: hepatitis C virus HIV: human immunodeficiency virus Appendix C: Contraindications/Boxed Warnings • Rebetol and Ribasphere Ribapak are contraindicated in: o Women who are pregnant o Men whose female partners are pregnant o Patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia) o Coadministration with didanosine
    o Patients with autoimmune hepatitis (when in combination with Pegasys) o When used in combination with Pegasys: Ribasphere Ribapak is additionally contraindicated in patients with hepatic decompensation (Child-Pugh B or C) in cirrhotic CHC patients. Page 3 of 7

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    Ribavirin • Rebetol only: o Patients with known hypersensitivity reactions such as Stevens-Johnson syndrome, toxic, epidermal necrolysis, and erythema multiforme to ribavirin or any component of the product o Creatinine clearance less than 50 mL/min • Boxed warning(s):
    o Ribasphere Ribapak: risk of serious disorders and ribavirin-associated effects o Rebetol: embryo-fetal toxicity, hemolytic anemia, and monotherapy not recommended Appendix D: General Information • Ribasphere brands are no longer commercially being manufactured. Appendix E: Healthcare Provider HCV Training
    • Acceptable HCV training programs and/or online courses include, but are not limited to the following: • Hepatitis C online course (https://www.hepatitisc.uw.edu/): University of Washington is funded by the Division of Viral Hepatitis to develop a comprehensive, online self-study course for medical providers on diagnosis, monitoring, and management of hepatitis C virus infection. Free CME and CNE credit available. • Fundamentals of Liver Disease (https://liverlearning.aasld.org/fundamentals-of- liverdisease): The AASLD, in collaboration with ECHO, the American College of Physicians (ACP), CDC, and the Department of Veterans Affairs, has developed Fundamentals of Liver Disease, a free, online CME course to improve providers’ knowledge and clinical skills in hepatology. • Clinical Care Options: http://www.clinicaloptions.com/hepatitis.aspx
    • CDC training resources: https://www.cdc.gov/hepatitis/resources/professionals/trainingresources.htm V. Dosage and Administration Indication Dosing Regimen CHC The daily dose of administered orally in two divided doses. The dose should be individualized to the patient depending on baseline disease characteristics (e.g., genotype), response to therapy, and tolerability of the regimen. Maximum Dose 1,400 mg/day Body Weight kg (lbs) < 66 (< 144) 66-80 (145-177) Rebetol Daily Dose Rebetol Number of Capsules 800 mg/day 1000 mg/day 2 x 200-mg capsules A.M. 2 x 200-mg capsules P.M. 2 x 200-mg capsules A.M. 3 x 200-mg capsules P.M. Page 4 of 7

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    Ribavirin Indication Dosing Regimen Maximum Dose 81-105 (178-231) 1,200 mg/day 3 x 200-mg capsules A.M. 3 x 200-mg capsules P.M.

    105 (231) 1,400 mg/day 3 x 200-mg capsules A.M. 4 x 200-mg capsules P.M. VI. Product Availability Drug Ribavirin (Rebetol) Ribavirin (Ribasphere RibaPak) Availability
    Capsule: 200 mg
    Tablets: 200 mg, 400 mg, 600 mg (brand version no longer being manufactured) RibaPak compliance pack, tablets: 800 mg/day, 1,000 mg/day, 1,200 mg/day (brand version no longer being manufactured) VII.