Ribavirin
REBETOL
What it isGuanosine analogue with multiple antiviral mechanisms; hepatitis C in older regimens and RSV.
Why this oneHistorically part of every hepatitis C cure before the direct-acting antivirals.
What limits it⚑ Hemolytic anemia is dose-limiting, and it is powerfully teratogenic with a six-month washout for both partners.
FDA label
Read the full label on DailyMed ↗
BOXED WARNING Embryo-fetal toxicity (contraindicated in pregnancy and in male partners of pregnant women; avoid pregnancy 9 mo post-therapy for female patients, 6 mo for female partners of male patients); hemolytic anemia may worsen cardiac disease (fatal/nonfatal MI); monotherapy not effective for chronic hepatitis C.
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Chronic hepatitis C, with PegIntron | Adults <66 kg | 400 mg AM + 400 mg PM (800 mg/day) | 800 mg/day in 2 divided doses | 800 mg/day |
| Chronic hepatitis C, with PegIntron | Adults 66-80 kg | 400 mg AM + 600 mg PM (1,000 mg/day) | 1,000 mg/day in 2 divided doses | 1,000 mg/day |
| Chronic hepatitis C, with PegIntron | Adults 81-105 kg | 600 mg AM + 600 mg PM (1,200 mg/day) | 1,200 mg/day in 2 divided doses | 1,200 mg/day |
| Chronic hepatitis C, with PegIntron | Adults >105 kg | 600 mg AM + 800 mg PM (1,400 mg/day) | 1,400 mg/day in 2 divided doses | 1,400 mg/day |
| Chronic hepatitis C, with PegIntron | 3-17 yr | 15 mg/kg/day in 2 divided doses (47-59 kg: 800 mg/day; 60-73 kg: 1,000 mg/day; >73 kg: 1,200 mg/day; <47 kg: use oral solution) | 15 mg/kg/day BID | 1,200 mg/day |
| Chronic hepatitis C, with INTRON A | Adults ≤75 kg | 400 mg AM + 600 mg PM (1,000 mg/day) | 1,000 mg/day in 2 divided doses | 1,000 mg/day |
| Chronic hepatitis C, with INTRON A | Adults >75 kg | 600 mg AM + 600 mg PM (1,200 mg/day) | 1,200 mg/day in 2 divided doses | 1,200 mg/day |
| Chronic hepatitis C, with INTRON A | Pediatric | 15 mg/kg/day in 2 divided doses | 15 mg/kg/day BID | 1,200 mg/day |
Renal Contraindicated if CrCl <50 mL/min; monitor for anemia in renal impairment and age >50
Hepatic Undefined
Must be used in combination with interferon (PegIntron or INTRON A) — never as monotherapy
Instructions
- Take with food; do not open, crush, or break capsules
- Duration (PegIntron combo): genotype 1 48 wks; genotypes 2-3 24 wks; re-treatment of prior failures 48 wks regardless of genotype
- Duration (INTRON A combo): treatment-naive 24-48 wks; relapse after nonpegylated interferon 24 wks
- Discontinue if <2 log10 HCV-RNA drop at wk 12 or detectable HCV-RNA at wk 24
- Dose-reduce for hemoglobin 8.5-<10 g/dL (adults: -200 mg/day steps; 1,400 mg dose: first step -400 mg/day; peds: 15→12→8 mg/kg/day); discontinue if Hgb <8.5 g/dL
- Stable cardiac disease: reduce dose if Hgb drops ≥2 g/dL in any 4-wk period; discontinue if Hgb <12 g/dL after 4 wks at reduced dose
- Baseline and periodic labs: hemoglobin (pretreatment, wk 2, wk 4), CBC with differential, platelets, LFTs, TSH, pregnancy test, ECG
Contraindications
- Pregnancy, women planning pregnancy, and men whose female partners are pregnant
- Autoimmune hepatitis
- Hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia)
- CrCl <50 mL/min
- Coadministration with didanosine (fatal hepatic failure, peripheral neuropathy, pancreatitis, lactic acidosis reported)
Cautions
- Hemolytic anemia (~10%; onset within 1-2 wks) — may precipitate fatal/nonfatal MI; do not use with significant or unstable cardiac disease
- Embryo-fetal toxicity: negative pregnancy test before start; effective contraception + monthly tests during and 9 mo (female) / 6 mo (male partner) after therapy
- Pancreatitis — suspend for signs/symptoms; discontinue if confirmed
- Pulmonary disorders (dyspnea, infiltrates, pneumonitis, pulmonary hypertension; occasional fatal pneumonia)
- Severe neutropenia/thrombocytopenia and hematologic, endocrine (TSH), hepatic abnormalities with combination therapy
- Pancytopenia with concomitant azathioprine — do not reintroduce combination
- Growth inhibition (reduced adult height in some) in pediatric patients; suicidal ideation more frequent in adolescents
- Dental/periodontal disorders with long-term combination therapy
Adverse reactions
- Hemolytic anemia (>10%)
- Injection site reaction, fatigue/asthenia, headache, rigors, fever (≥40% with interferon combo)
- Nausea, myalgia, anxiety/emotional lability/irritability
- Peds: pyrexia, headache, neutropenia, fatigue, anorexia, injection-site erythema, vomiting
Pregnancy Contraindicated — significant teratogenic/embryocidal effects in all animal species; registry shows higher birth-defect rate; avoid pregnancy during and 9 mo (6 mo for male partners) after therapy
Lactation No data on presence in human milk; weigh benefits of breastfeeding against risk
⚠ BOXED WARNINGS
- Hemolytic anemia
- Embryo-fetal toxicity
- Not for monotherapy in hepatitis C
Classes and tags
Clinical profile
Mechanism of action: Ribavirin ballicule
