Ribavirindosage

Ribavirin tablets should be taken with food. Ribavirin tablets should be given in combination with PEGASYS ®; it is important to note that ribavirin tablets should never be given as monotherapy. See PEGASYS ® Package Insert for all instructions regarding PEGASYS ® dosing and administration.

CHC: Ribavirin tablets are administered according to body weight and genotype CHC with HIV coinfection: 800 mg by mouth daily for a total of 48 weeks, regardless of genotype Dose reduction or discontinuation is recommended in patients experiencing certain adverse reactions or renal impairment

2.1 Chronic

Hepatitis C Monoinfection Adult Patients The recommended dose of ribavirin tablets is provided in Table 1. The recommended duration of treatment for patients previously untreated with ribavirin and interferon is 24 to 48 weeks. The daily dose of ribavirin tablets is 800 mg to 1200 mg 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 (see Table 1 ). Table 1 PEGASYS ® and Ribavirin Tablets Dosing Recommendations Genotypes 2 and 3 showed no increased response to treatment beyond 24 weeks (see Table 10 ). Data on genotypes 5 and 6 are insufficient for dosing recommendations. * See PEGASYS ® Package Insert for further details on PEGASYS ® dosing and administration, including dose modification in patients with renal impairment. Hepatitis C Virus (HCV) Genotype PEGASYS ® Dose* (once weekly) Ribavirin Tablets Dose (daily) Duration Genotypes 1, 4 180 mcg <75 kg = 1000 mg ≥75 kg = 1200 mg 48 weeks 48 weeks Genotypes 2, 3 180 mcg 800 mg 24 weeks Pediatric Patients PEGASYS ® is administered as 180 mcg/1.73m 2 x BSA once weekly subcutaneously, to a maximum dose of 180 mcg, and should be given in combination with ribavirin. The recommended treatment duration for patients with genotype 2 or 3 is 24 weeks and for other genotypes is 48 weeks. Ribavirin tablets should be given in combination with PEGASYS ®. Ribavirin tablets are available only as a 200 mg tablet and therefore the healthcare provider should determine if this sized tablet can be swallowed by the pediatric patient. The recommended doses for ribavirin tablets are provided in Table 2. Patients who initiate treatment prior to their 18 th birthday should maintain pediatric dosing through the completion of therapy. Table 2 Ribavirin Tablets Dosing Recommendations for Pediatric Patients *approximately 15 mg/kg/day Body Weight in kilograms (kg) Ribavirin Tablets Daily Dose* Ribavirin Tablets Number of Tablets 23 to 33 400 mg/day 1 x 200 mg tablet A.M. 1 x 200 mg tablet P.M. 34 to 46 600 mg/day 1 x 200 mg tablet A.M. 2 x 200 mg tablets P.M. 47 to 59 800 mg/day 2 x 200 mg tablets A.M. 2 x 200 mg tablets P.M. 60 to 74 1000 mg/day 2 x 200 mg tablets A.M. 3 x 200 mg tablets P.M. ≥75 1200 mg/day 3 x 200 mg tablets A.M. 3 x 200 mg tablets P.M.

2.2 Chronic

Hepatitis C with HIV Coinfection Adult Patients The recommended dose for treatment of chronic hepatitis C in patients coinfected with HIV is PEGASYS ® 180 mcg subcutaneous once weekly and ribavirin tablets 800 mg by mouth daily for a total duration of 48 weeks, regardless of HCV genotype.

2.3 Dose Modifications

Adult and Pediatric Patients If severe adverse reactions or laboratory abnormalities develop during combination ribavirin tablets/PEGASYS ® therapy, the dose should be modified or discontinued, if appropriate, until the adverse reactions abate or decrease in severity. If intolerance persists after dose adjustment, ribavirin tablets/PEGASYS ® therapy should be discontinued. Table 3 provides guidelines for dose modifications and discontinuation based on the patient’s hemoglobin concentration and cardiac status. Ribavirin tablets should be administered with caution to patients with pre-existing cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped. Table 3 Ribavirin Tablets Dose Modification Guidelines in Adults and Pediatrics Body weight in kilograms (kg) Laboratory Values Hemoglobin <10 g/dL in patients with no cardiac disease, or Decrease in hemoglobin of ≥2 g/dL during any 4 week period in patients with history of stable cardiac disease Hemoglobin <8.5 g/dL in patients with no cardiac disease, or Hemoglobin <12 g/dL despite 4 weeks at reduced dose in patients with history of stable cardiac disease Adult Patients older than 18 years of age Any weight 1 x 200 mg tablet A.M. 2 x 200 mg tablets P.M. Discontinue ribavirin tablets Pediatric Patients 5 to 18 years of age 23 to 33 kg 1 x 200 mg tablet A.M. Discontinue ribavirin tablets 34 to 46 kg 1 x 200 mg tablet A.M. 1 x 200 mg tablet P.M. 47 to 59 kg 1 x 200 mg tablet A.M. 1 x 200 mg tablet P.M. 60 to 74 kg 1 x 200 mg tablet A.M. 2 x 200 mg tablets P.M. ≥75 kg 1 x 200 mg tablet A.M. 2 x 200 mg tablets P.M. The guidelines for ribavirin tablets dose modifications outlined in this table also apply to laboratory abnormalities or adverse reactions other than decreases in hemoglobin values. Adult Patients Once ribavirin tablets have been withheld due to either a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart ribavirin tablets at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that ribavirin tablets be increased to the original assigned dose (1000 mg to 1200 mg). Pediatric Patients Upon resolution of a laboratory abnormality or clinical adverse reaction, an increase in ribavirin tablets dose to the original dose may be attempted depending upon the physician’s judgment. If ribavirin tablets have been withheld due to a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart ribavirin tablets at one-half the full dose.

2.4 Renal Impairment

The total daily dose of ribavirin tablets should be reduced for patients with creatinine clearance less than or equal to 50 mL/min; and the weekly dose of PEGASYS ® should be reduced for creatinine clearance less than 30 mL/min as follows in Table 4. Table 4 Dosage Modification for Renal Impairment Creatinine Clearance PEGASYS ® Dose (once weekly) Ribavirin Tablets Dose (daily) 30 to 50 mL/min 180 mcg Alternating doses, 200 mg and 400 mg every other day Less than 30 mL/min 135 mcg 200 mg daily Hemodialysis 135 mcg 200 mg daily The dose of ribavirin tablets should not be further modified in patients with renal impairment. If severe adverse reactions or laboratory abnormalities develop, ribavirin tablets should be discontinued, if appropriate, until the adverse reactions abate or decrease in severity. If intolerance persists after restarting ribavirin tablets, ribavirin tablets/PEGASYS ® therapy should be discontinued. No data are available for pediatric subjects with renal impairment.

2.5 Discontinuation of

Dosing Discontinuation of PEGASYS ® /ribavirin tablets therapy should be considered if the patient has failed to demonstrate at least a 2 log 10 reduction from baseline in HCV RNA by 12 weeks of therapy, or undetectable HCV RNA levels after 24 weeks of therapy. PEGASYS ® /Ribavirin tablets therapy should be discontinued in patients who develop hepatic decompensation during treatment.