Copeg

• Approved Indications:
• Chronic Hepatitis C Virus (HCV) Infection: Used in combination with direct-acting antivirals (DAAs) or interferon-based regimens for the treatment of chronic HCV infection to achieve sustained virologic response.
• Respiratory Syncytial Virus (RSV) Infection: Aerosolized ribavirin is indicated for severe lower respiratory tract infection caused by RSV in infants and young children at high risk for severe disease.
• Lassa Fever: Intravenous ribavirin is used for treatment of Lassa fever, an arenavirus hemorrhagic fever endemic in West Africa.
• Other Viral Hemorrhagic Fevers: Used off-label for some viral hemorrhagic fevers (e.g., Crimean-Congo hemorrhagic fever, hantavirus infections) under specific protocols.
• Off-label / Clinically Accepted Uses:
• Treatment of other viral infections such as certain paramyxoviruses or arenaviruses where no specific therapy exists.
• Occasionally combined in salvage regimens for difficult viral infections.

• Chronic Hepatitis C (Adults):
• Oral ribavirin capsules or solution, dosed based on body weight:
• <75 kg: 1000 mg/day in divided doses (e.g., 400 mg AM, 600 mg PM)
• ≥75 kg: 1200 mg/day in divided doses (e.g., 600 mg twice daily)
• Duration depends on combination regimen, typically 12 to 48 weeks.
• Respiratory Syncytial Virus (Infants/Children):
• Aerosolized ribavirin via small-particle aerosol generator (SPAG) at 20 mg/mL for 12-18 hours/day over 3-7 days.
• Lassa Fever (Adults and Children):
• Intravenous dosing starts with a loading dose of 30 mg/kg followed by maintenance doses (15 mg/kg every 6 hours for 4 days, then 7.5 mg/kg every 8 hours for 6 days).
• Renal/Hepatic Impairment:
• Dose adjustments recommended in severe renal impairment (e.g., reduce dose or avoid use in dialysis patients).
• Use caution in hepatic impairment; limited data.
• Pediatrics:
• Dosing varies by indication; aerosol form for RSV is primary use in infants.
• Elderly:
• Dose adjustment based on renal function and tolerability.
• Administration Routes:
• Oral (capsules/solution), intravenous infusion, inhalation aerosol.

Ribavirin is a synthetic nucleoside analog with broad-spectrum antiviral activity. It is phosphorylated intracellularly to active ribavirin triphosphate, which interferes with viral RNA metabolism through multiple mechanisms: inhibition of viral RNA-dependent RNA polymerase, induction of lethal mutagenesis by increasing viral mutation rates, inhibition of inosine monophosphate dehydrogenase (IMPDH) leading to depletion of guanosine triphosphate pools, and modulation of host immune response. These actions collectively inhibit viral replication and promote viral clearance.

• Absorption:
• Oral bioavailability is approximately 45-65%.
• Food may reduce peak plasma concentration but does not affect overall absorption.
• Distribution:
• Widely distributed with large volume of distribution (~2 L/kg).
• Crosses the blood-brain barrier and placenta.
• Accumulates in erythrocytes.
• Metabolism:
• Minimal hepatic metabolism; primarily intracellular phosphorylation to active metabolites.
• Elimination:
• Primarily excreted unchanged via kidneys.
• Plasma half-life ranges from 120 to 170 hours (long due to erythrocyte accumulation).
• Clearance prolonged in renal impairment.

• Pregnancy:
• FDA Pregnancy Category X (contraindicated).
• Causes significant teratogenicity and embryocidal effects in animal studies.
• Should not be used in pregnant women; effective contraception required during treatment and for 6 months post-therapy in both men and women.
• Lactation:
• Unknown if excreted in human milk; potential risk to infant.
• Breastfeeding is generally not recommended during treatment.

• Antiviral agent
• Nucleoside analog, broad-spectrum antiviral

• Known hypersensitivity to ribavirin or formulation excipients
• Pregnancy or potential pregnancy in men and women without effective contraception
• Severe anemia or significant cardiac disease contraindicating ribavirin-induced anemia
• Severe renal impairment without dose adjustment
• Coadministration with didanosine (risk of fatal toxicity)

• Hemolytic anemia: Dose-dependent, may be severe and exacerbate cardiac disease; monitor hemoglobin closely.
• Teratogenicity and embryotoxicity: Strict contraception advised; pregnancy testing mandatory.
• Pulmonary toxicity: Caution in patients with preexisting pulmonary disease.
• Psychiatric effects: Depression and suicidal ideation reported, especially in combination therapies.
• Renal impairment: Monitor renal function; dose adjustment needed.
• Infusion-related reactions (IV form): Monitor during administration.

• Common:
• Hemolytic anemia
• Fatigue
• Headache
• Nausea, vomiting
• Insomnia
• Rash
• Serious/Rare:
• Severe anemia requiring transfusion
• Teratogenic effects
• Depression, suicidal ideation
• Pancreatitis (rare)
• Pulmonary dysfunction
• Onset:
• Hemolytic anemia usually develops within 1-2 weeks of therapy initiation.
• Psychiatric symptoms may appear anytime during treatment.

• Didanosine: Contraindicated due to fatal mitochondrial toxicity risk.
• Zidovudine: Increased risk of anemia.
• Azathioprine: Increased myelotoxicity risk.
• Warfarin: May alter anticoagulant effect; monitor INR closely.
• CYP450: Ribavirin is not a significant inhibitor or inducer, but combination antiviral regimens may involve interactions.

• Updated HCV treatment guidelines emphasize ribavirin use primarily as adjunct to newer DAAs in select patient populations (e.g., treatment-experienced or decompensated cirrhosis).
• FDA warnings reinforced regarding teratogenicity and contraception requirements.
• No new major indications added recently.

• Store oral and injectable forms at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Do not freeze.
• Inhalation solution stored refrigerated or as per manufacturer instructions.