Drug Detail:Copegus (Ribavirin (oral) [ rye-ba-vye-rin ])
Generic Name: Ribavirin 200mg
Dosage Form: tablet, film coated
Drug Class: Inhaled anti-infectives Purine nucleosides
COPEGUS should be taken with food. COPEGUS should be given in combination with PEGASYS; it is important to note that COPEGUS should never be given as monotherapy. See PEGASYS Package Insert for all instructions regarding PEGASYS dosing and administration.
Chronic Hepatitis C Monoinfection
Adult Patients
The recommended dose of COPEGUS 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 COPEGUS 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).
| Hepatitis C Virus (HCV) Genotype | PEGASYS Dose* (once weekly) |
COPEGUS Dose (daily) |
Duration |
|---|---|---|---|
| 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. | |||
|
|||
| 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/1.73m2 × 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.
COPEGUS should be given in combination with PEGASYS. COPEGUS is 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 COPEGUS are provided in Table 2. Patients who initiate treatment prior to their 18th birthday should maintain pediatric dosing through the completion of therapy.
| Body Weight in kilograms (kg) | COPEGUS Daily Dose* | COPEGUS Number of Tablets |
|---|---|---|
|
||
| 23 – 33 | 400 mg/day | 1 × 200 mg tablet A.M. 1 × 200 mg tablet P.M. |
| 34 – 46 | 600 mg/day | 1 × 200 mg tablet A.M. 2 × 200 mg tablets P.M. |
| 47 – 59 | 800 mg/day | 2 × 200 mg tablets A.M. 2 × 200 mg tablets P.M. |
| 60 – 74 | 1000 mg/day | 2 × 200 mg tablets A.M. 3 × 200 mg tablets P.M. |
| ≥75 | 1200 mg/day | 3 × 200 mg tablets A.M. 3 × 200 mg tablets P.M. |
Dose Modifications
Adult and Pediatric Patients
If severe adverse reactions or laboratory abnormalities develop during combination COPEGUS/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, COPEGUS/PEGASYS therapy should be discontinued. Table 3 provides guidelines for dose modifications and discontinuation based on the patient's hemoglobin concentration and cardiac status.
COPEGUS 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 [see Warnings and Precautions (5.2)].
| 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 × 200 mg tablet A.M. 2 × 200 mg tablets P.M. |
Discontinue COPEGUS |
| Pediatric Patients 5 to 18 years of age | ||
| 23 – 33 kg | 1 × 200 mg tablet A.M. | Discontinue COPEGUS |
| 34 – 46 kg | 1 × 200 mg tablet A.M. 1 × 200 mg tablet P.M. |
|
| 47 – 59 kg | 1 × 200 mg tablet A.M. 1 × 200 mg tablet P.M. |
|
| 60 – 74 kg | 1 × 200 mg tablet A.M. 2 × 200 mg tablets P.M. |
|
| ≥75 kg | 1 × 200 mg tablet A.M. 2 × 200 mg tablets P.M. |
|
The guidelines for COPEGUS dose modifications outlined in this table also apply to laboratory abnormalities or adverse reactions other than decreases in hemoglobin values.
Adult Patients
Once COPEGUS has been withheld due to either a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart COPEGUS at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that COPEGUS 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 COPEGUS dose to the original dose may be attempted depending upon the physician's judgment. If COPEGUS has been withheld due to a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart COPEGUS at one-half the full dose.
Renal Impairment
The total daily dose of COPEGUS 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 [see Use in Specific Populations (8.7), Pharmacokinetics (12.3), and PEGASYS Package Insert].
| Creatinine Clearance | PEGASYS Dose (once weekly) |
COPEGUS 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 COPEGUS should not be further modified in patients with renal impairment. If severe adverse reactions or laboratory abnormalities develop, COPEGUS should be discontinued, if appropriate, until the adverse reactions abate or decrease in severity. If intolerance persists after restarting COPEGUS, COPEGUS/PEGASYS therapy should be discontinued.
No data are available for pediatric subjects with renal impairment.
Discontinuation of Dosing
Discontinuation of PEGASYS/COPEGUS therapy should be considered if the patient has failed to demonstrate at least a 2 log10 reduction from baseline in HCV RNA by 12 weeks of therapy, or undetectable HCV RNA levels after 24 weeks of therapy.
PEGASYS/COPEGUS therapy should be discontinued in patients who develop hepatic decompensation during treatment [see Warnings and Precautions (5.3)].
