Drug Detail:Rebetol (Ribavirin (oral) [ rye-ba-vye-rin ])
Generic Name: ribavirin 200mg
Dosage Form: capsule, oral solution
Drug Class: Inhaled anti-infectives Purine nucleosides
General Dosing Information
Do not open, crush or break REBETOL capsules. REBETOL should be taken with food [see Clinical Pharmacology (12.3)].
REBETOL/PegIntron Combination Therapy
Adult Patients
The recommended dose of REBETOL when used in combination with PegIntron is 800 mg to 1,400 mg based on patient body weight in two divided doses (see Table 1). Refer to PegIntron labeling for PegIntron dosing information.
Duration of Treatment – Interferon Alpha-naïve Patients
The treatment duration for patients with genotype 1 is 48 weeks. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of hepatitis C virus (HCV)-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy. Patients with genotype 2 and 3 should be treated for 24 weeks.
Duration of Treatment – Re-treatment with PegIntron/REBETOL of Prior Treatment Failures
The treatment duration for patients who previously failed therapy is 48 weeks, regardless of HCV genotype. Re-treated patients who fail to achieve undetectable HCV-RNA at Week 12 of therapy, or whose HCV-RNA remains detectable after 24 weeks of therapy, are highly unlikely to achieve SVR and discontinuation of therapy should be considered [see Clinical Studies (14.1)].
| Body Weight (kg) |
REBETOL Daily Dose | REBETOL Number of Capsules |
|---|---|---|
| Less than 66 | 800 mg/day | 2 × 200-mg capsules AM 2 × 200-mg capsules PM |
| 66-80 | 1,000 mg/day | 2 × 200-mg capsules AM 3 × 200-mg capsules PM |
| 81-105 | 1,200 mg/day | 3 × 200-mg capsules AM 3 × 200-mg capsules PM |
| Greater than 105 | 1,400 mg/day | 3 × 200-mg capsules AM 4 × 200-mg capsules PM |
Pediatric Patients
Dosing of REBETOL in pediatric patients is determined by body weight. The recommended dose of REBETOL when used in combination with PegIntron in pediatric patients ages 3-17 years is 15 mg/kg/day in two divided doses (see Table 2). Refer to PegIntron labeling for PegIntron dosing information. The treatment duration for patients with genotype 1 is 48 weeks. Patients with genotype 2 and 3 should be treated for 24 weeks.
| Body Weight (kg) |
REBETOL Daily Dose | REBETOL Number of Capsules |
|---|---|---|
|
||
| Less than 47 | 15 mg/kg/day | Use REBETOL Oral Solution* |
| 47-59 | 800 mg/day | 2 × 200-mg capsules AM 2 × 200-mg capsules PM |
| 60-73 | 1,000 mg/day | 2 × 200-mg capsules AM 3 × 200-mg capsules PM |
| Greater than 73 | 1,200 mg/day | 3 × 200-mg capsules AM 3 × 200-mg capsules PM |
REBETOL/INTRON A Combination Therapy
Adults
Duration of Treatment – Interferon Alpha-naïve Patients
The recommended dose of REBETOL when used in combination with INTRON A depends on the patient's body weight (see Table 3). Refer to Intron A labeling for interferon dosing information. The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. The duration of treatment should be individualized to the patient depending on baseline disease characteristics, response to therapy, and tolerability of the regimen [see Indications and Usage (1.1), Adverse Reactions (6.1), and Clinical Studies (14)]. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data for treatment duration lasting longer than 48 weeks in the previously untreated patient population.
Duration of Treatment – Re-treatment with INTRON A/REBETOL in Relapse Patients
In patients who relapse following nonpegylated interferon monotherapy, the recommended duration of treatment is 24 weeks.
| Body Weight | REBETOL Capsules |
|---|---|
| At least 75 kg | 2 × 200-mg capsules AM 3 × 200-mg capsules PM daily orally |
| Greater than 75 kg | 3 × 200-mg capsules AM 3 × 200-mg capsules PM daily orally |
Pediatrics The recommended dose of REBETOL when used in combination with INTRON A is 15 mg/kg per day orally in two divided doses (see Table 2). Refer to Intron A labeling for interferon dosing information.
The recommended duration of treatment is 48 weeks for pediatric patients with genotype 1. After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by this time. The recommended duration of treatment for pediatric patients with genotype 2 and 3 is 24 weeks.
Testing Prior to Initiation of REBETOL
The following laboratory tests are recommended in all patients treated with REBETOL prior to initiation of treatment and periodically thereafter.
- Standard hematologic tests - including hemoglobin (pretreatment, Week 2 and Week 4 of therapy, and as clinically appropriate [see Warnings and Precautions (5.2, 5.6)], complete and differential white blood cell counts, and platelet count.
- Blood chemistries - liver function tests and TSH.
- Pregnancy - in women of childbearing potential.
- ECG [see Warnings and Precautions (5.2)].
Dose Modifications
If severe adverse reactions or laboratory abnormalities develop during REBETOL combination therapy, modify or discontinue the dose until the adverse reaction abates or decreases in severity (see Table 4) [see Warnings and Precautions (5)]. If intolerance persists after dose adjustment, combination therapy should be discontinued. Refer to PegIntron labeling for additional information regarding dose reduction of PegIntron.
Dose reduction in pediatric patients is accomplished by modifying the recommended REBETOL dose from the original starting dose of 15 mg/kg daily in a two-step process to 12 mg/kg/day, then to 8 mg/kg/day, if needed (see Table 4).
REBETOL is contraindicated in patients with creatinine clearance less than 50 mL/min [see Contraindications (4)]. Patients with impaired renal function and those over the age of 50 should be carefully monitored with respect to development of anemia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), and Clinical Pharmacology (12.3)].
REBETOL should be administered with caution to patients with pre-existing cardiac disease. Assess cardiovascular status before initiation of treatment and during therapy. If there is any deterioration of cardiovascular status, discontinue combination therapy [see Warnings and Precautions (5.2)].
In patients with a history of stable cardiovascular disease, a permanent dose reduction is required if the hemoglobin decreases by 2 g/dL or more during any 4-week period. If the hemoglobin level remains below 12 g/dL after 4 weeks on a reduced dose, discontinue combination therapy.
Modify or discontinue REBETOL dosing in any patient whose hemoglobin level falls below 10 g/dL (see Table 4) [see Warnings and Precautions (5.2)].
Refer to labeling for INTRON A or PegIntron for additional information about how to reduce an INTRON A or PegIntron dose.
Discontinuation of Dosing
Adults In HCV genotype 1, interferon-alfa-naïve patients receiving PegIntron in combination with ribavirin, discontinue therapy if there is not at least a 2 log10 drop or loss of HCV-RNA at 12 weeks of therapy, or if HCV-RNA levels remain detectable after 24 weeks of therapy. Regardless of genotype, previously treated patients who have detectable HCV-RNA at Week 12 or 24 are highly unlikely to achieve SVR and discontinuation of therapy should be considered.
