Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.08 Subsection: Anti-infective Agents Original Policy Date: January 1, 2006 Subject: Pegasys Ribavirin Page: 1 of 6 Last Review Date: March 18, 2016 Pegasys Ribavirin Description Pegasys (peginterferon alfa-2a) with Ribavirin (Copegus, Moderiba, Rebetol, RibaPak, Ribasphere, RibaTab, ribavirin tablets/capsules - all strengths) Background Hepatitis C is a viral disease caused by the hepatitis C virus (HCV) that leads to inflammation of the liver. Most people who were recently infected with hepatitis C do not have symptoms, but most people infected with hepatitis C develop a chronic infection. Untreated, chronic infection can lead to liver cirrhosis and/or liver cancer. Six genotypes of the hepatitis C virus exist and genotyping is essential to effective treatment. Hepatitis C infection may be detected in the blood by the HCV RNA assay. Disease status may be monitored by assays of biochemical liver tests or liver biopsy (1). The goals of HCV treatment are to remove the virus from the blood and reduce the risk of cirrhosis and liver cancer that can result from long-term HCV infection. The most common treatment regimens are based on combinations of pegylated interferon alfa, ribavirin, and a protease inhibitor (1). Regulatory Status FDA-approved indications: Pegasys is an antiviral indicated for the treatment of chronic hepatitis C (CHC) in patients 5 years of age and older with compensated liver disease. Pegasys monotherapy is indicated for CHC only if patient has contraindication to or significant intolerance to other HCV antiviral drugs (2).
Subject: Pegasys Ribavirin Page: 2 of 6 Limitations of Use: Pegasys alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with CHC who previously failed therapy with an interferon-alfa. Pegasys is not recommended for treatment of patients with CHC who have had solid organ transplantation (2). If Pegasys is administered with other antiviral agents, the contraindications to those agents also apply to the combination regimen (2). Ribavirin may cause birth defects and fetal death: avoid pregnancy in female patients and female partners of male patients (3,4). Related policies Intron A, PegIntron Policy This policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims. Pegasys with ribavirin may be considered medically necessary for the treatment of chronic hepatitis C in patients age 5 years and older with a detectable viral load in the serum; compensated liver disease; viral genotype must be provided and if genotype 1 must not be an appropriate candidate for treatment with a protease inhibitor; without renal failure if age 5 to 17; without pregnancy or a partner who is pregnant; and with instruction to practice effective contraception during therapy and for six months after stopping ribavirin therapy. A viral load will be required to be drawn at treatment week 24 if not coinfected with HIV to determine if continuation of treatment is medically necessary. Pegasys with ribavirin is considered investigational for patients below 5 years of age and for all other indications. Prior-Approval Requirements Age 5 years of age or older Diagnosis
Subject: Pegasys Ribavirin Page: 3 of 6 Patient must have the following: 1. Chronic hepatitis C AND ALL of the following: a. Detectable viral load in the serum b. Compensated liver disease c. Viral genotype must be provided and if genotype 1 must NOT be an appropriate candidate for treatment with a protease inhibitor d. NOT diagnosed with renal failure if age 5 to 17 e. Neither the patient nor the partner of the patient is pregnant f. Will be instructed to practice effective contraception during therapy and for 6 months after stopping ribavirin therapy if either the patient or their partner are of child bearing age g. Viral load will be drawn at treatment week 24 if not coinfected with HIV Prior Approval Renewal Requirements Diagnosis Patient must have ALL of the following: 1. UNDETECTABLE hepatitis C viral load after initial 24 weeks of therapy 2. Genotype 1, 4, 5 or 6 3. NOT already treated for 12 months (HIV co-infected) OR ONE of the following: 1. History of null or partial response to previous (non-protease inhibitor) treatment 2. Presence of cirrhosis Policy Guidelines Pre - PA Allowance None Prior - Approval Limits Duration 7 months if NOT co-infected with HIV (all genotypes) 12 months if co-infected with HIV (all genotypes)
Subject: Pegasys Ribavirin Page: 4 of 6 Prior - Approval Renewal Limits Duration 5 months (if age 5 to 17) 12 months (if age 18 or older) Rationale Summary Hepatitis C is a viral disease caused by the hepatitis C virus (HCV) that leads to inflammation of the liver. Untreated, chronic infection can lead to liver cirrhosis and/or liver cancer. The most common treatment regimens are based on combinations of pegylated interferon alfa, ribavirin, and a protease inhibitor (1). Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of Pegasys with ribavirin while maintaining optimal therapeutic outcomes. References 1. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009; 49(4):1335-1374. 2. Pegasys [package insert]. South San Francisco, CA: Genentech USA, Inc; March 2015. 3. Copegus [package insert]. South San Francisco, CA. Genentech USA, Inc. August 2015. 4. Ribasphere tablets [package insert]. Warrendale, PA: Three Rivers Pharmaceuticals, LLC; August 2014. Policy History Date January 2006 November 2007 July 2009 Action Criteria updated to reflect a process change to allow patients on Hepatitis C Combination Therapy to switch between ribavirin products during their authorization period without needing a new prior authorization record being set. Criteria updated to include criteria for renewal. Requirement that patients have not been previously unsuccessfully treated with pegylated interferon and ribavirin deleted. Criteria updated to remove Roferon A, which was discontinued by manufacturer.
Subject: Pegasys Ribavirin Page: 5 of 6 September 2011 September 2012 March 2014 December 2014 March 2015 March 2016 Criteria rewritten to follow current practice guidelines and package inserts, with genotype requirements, as follows: Patients with genotype 1, 4, 5 or 6 should be ideally treated for a full 48 weeks of therapy with peginterferon plus ribavirin. However, for genotypes 1, 4, 5 or 6 therapy should be discontinued if the patient has failed to achieve an undetectable viral load after 24 weeks of therapy. If the viral load remains detectable at 24 weeks of therapy it is unlikely the patient will respond to additional treatment and therapy should be stopped. Three important revisions have been to the Pegasys package insert as follows:first, FDA has approved the combination of Pegasys and Copegus for the treatment of chronic hepatitis C virus infection in pediatric patients 5 through 17 years of age. The criteria were changed to match the package insert: patients 5 years of age and older with compensated liver disease not previously treated with interferon alpha (3). Second, guidelines for patients with renal impairment were revised. Adult patients ages 18 and older with renal impairment may now be treated with appropriate renal monitoring and dose reductions. No data is available for pediatric patients (ages 5-17) with renal impairment; therefore, renal impairment will remain in the criteria as a contraindication for members ages 5 through 17 (2). And the third change: studies identified a negative impact on growth in pediatric patients treated with Pegasys plus ribavirin. Retreatment of pediatric patients has not been studied beyond 48 weeks. For these two reasons, treatment of patients age 5 through 17 will not be covered beyond 12 months of therapy (2). Annual editorial and reference update Annual editorial and reference update Limitations of use added to Regulatory Status section Annual editorial and reference update. Addition of Moderiba Annual editorial review and reference update Annual editorial review and reference update Policy number changed from 5.03.08 to 5.01.08 Keywords
Subject: Pegasys Ribavirin Page: 6 of 6 This policy was approved by the FEP Pharmacy and Medical Policy Committee on March 18, 2016 and is effective April 1, 2016. Deborah M. Smith, MD, MPH