REBETOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REBETOL (REBETOL).
Ribavirin, a guanosine analog, inhibits viral RNA-dependent RNA polymerase and inosine monophosphate dehydrogenase, leading to a decrease in intracellular guanosine triphosphate pools and impairment of viral RNA synthesis.
| Metabolism | Phosphorylated intracellularly. Elimination via renal excretion of parent drug and metabolites; hepatic metabolism minimal. |
| Excretion | Renal: 10-15% unchanged; biliary/fecal: 60-70% as metabolites; pulmonary excretion of CO2 contributes to elimination of ribavirin's triazole moiety. Approximately 10-20% excreted in feces as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life: 120-200 hours (multiple doses, due to extensive accumulation in erythrocytes). Single dose: 24-36 hours. Clinically, steady state is reached in approximately 4 weeks. |
| Protein binding | Not significantly bound to plasma proteins (approximately 0-5% binding). |
| Volume of Distribution | Apparent Vd: 10 L/kg (large, indicating extensive tissue distribution, particularly to liver and red blood cells). Mean Vd: 2000-3000 L. |
| Bioavailability | Oral: 45-65% (absolute bioavailability of capsule formulation). Inhalation: systemic bioavailability is variable and depends on delivery system, but typically 5-10%. |
| Onset of Action | Oral: peak serum concentrations at 1-2 hours; clinical antiviral effect (as part of combination therapy for hepatitis C) typically observed after several weeks of treatment. Inhalation (aerosolized): clinical effect on respiratory syncytial virus may be seen within 3-5 days. |
| Duration of Action | Oral: The drug persists in erythrocytes with a half-life of 40 days; clinical effect duration is prolonged due to slow release from red blood cells. Duration of therapy for hepatitis C is typically 24-48 weeks. Inhalation: usually administered for 3-7 days. |
| Molecular Weight | 244.21 |
| Action Class | Antiviral (Non-HIV) drugs |
| Brand Substitutes | Heptos 200mg Capsule, Ribasure Capsule, Heplovir Capsule, Rinhib 200mg Capsule, Virofix 200mg Capsule |
Oral: 400-600 mg twice daily (800-1200 mg/day) based on body weight (≤75 kg: 400 mg twice daily; >75 kg: 600 mg twice daily) in combination with interferon alfa or peginterferon alfa.
| Dosage form | CAPSULE |
| Renal impairment | If eGFR <50 mL/min: REBETOL is contraindicated. For eGFR 30-50 mL/min: alternate dosing (200 mg alternating with 400 mg every other day) may be considered with close monitoring; however, use is generally not recommended. |
| Liver impairment | Child-Pugh Class B and C: Contraindicated. No adjustment needed for mild hepatic impairment (Child-Pugh Class A) but monitor closely. |
| Pediatric use | For children ≥3 years: Weight-based dosing: 15 mg/kg/day divided twice daily (max 1200 mg/day). Typically: 25-36 kg: 200 mg twice daily; 37-49 kg: 200 mg morning, 400 mg evening; 50-61 kg: 400 mg twice daily; >61 kg: 600 mg twice daily. |
| Geriatric use | No specific dose adjustment based solely on age, but use with caution due to increased risk of renal impairment (assess creatinine clearance and adjust accordingly) and anemia; initiate at lower end of dosing range. |
| 1st trimester | Avoid. Ribavirin is teratogenic in animal studies; use contraindicated due to significant teratogenic and embryocidal effects. |
| 2nd trimester | Avoid. Continued teratogenic risk; contraindicated throughout pregnancy. |
| 3rd trimester | Avoid. Risks persist; contraindicated in all trimesters. |
Clinical note
Comprehensive clinical and safety monograph for REBETOL (REBETOL).
| Placental transfer | Ribavirin crosses the placenta extensively in animal models; human data confirm placental transfer. Accumulation in fetal tissues noted. |
| Breastfeeding | Ribavirin is excreted in breast milk in animal studies; unknown in humans. Due to potential for serious adverse effects in nursing infants, breastfeeding is not recommended during therapy and for at least 7 days after last dose. |
■ FDA Black Box Warning
Monotherapy is not effective for chronic hepatitis C. Risk of hemolytic anemia, which may exacerbate cardiac disease. Avoid in pregnancy due to teratogenicity; avoid in men with pregnant partners.
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraceptionMale partners of pregnant womenSevere hypersensitivity to ribavirin or any component
| Precautions | Hemolytic anemia, cardiac disease exacerbation, pulmonary toxicity, pancreatitis, immunosuppression, hypersensitivity, ophthalmic effects, weight loss, growth impairment in children. |
| Food/Dietary | Take with high-fat meal to improve absorption. Avoid grapefruit juice as it may alter ribavirin levels. No specific food restrictions otherwise, but maintain adequate hydration. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | Rebetol (ribavirin) is contraindicated in pregnancy (Category X). It has significant teratogenic effects in all trimesters, including cranial, skeletal, and gastrointestinal malformations, as well as embryolethal effects. |
| Fetal Monitoring | Female patients must have a negative pregnancy test prior to therapy, monthly pregnancy tests during treatment, and for 6 months after discontinuation. Male patients with female partners must use effective contraception during and for 6 months post-therapy. |
| Fertility Effects | Ribavirin may impair spermatogenesis and cause reversible infertility in males. Effects on female fertility include potential ovarian toxicity. |
| Clinical Pearls | REBETOL (ribavirin) is used in combination with interferon alfa for chronic hepatitis C. It is teratogenic; both male and female patients must use effective contraception during and for 6 months after therapy. Monitor hemoglobin closely due to dose-dependent hemolytic anemia. Dose adjust for renal impairment (CrCl <50 mL/min: not recommended). |
| Patient Advice | Take this medication with food to reduce gastrointestinal upset. · Use two reliable forms of contraception during treatment and for 6 months after stopping; do not become pregnant or father a child. · Report severe fatigue, shortness of breath, or pale skin immediately as these may indicate anemia. · Avoid alcohol and limit sun exposure; report any new or worsening symptoms to your healthcare provider. · Do not stop taking this medication without consulting your doctor. |