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ribavirin (Virazole, Rebetol, Copegus)

Tradenames: Virazole, Rebetol, Copegus. Indications: - treatment of patients with respiratory syncytial virus (RSV) - especially for treatment of severe lower respiratory tract infections due to RSV in patients with pre-existing pulmonary compromise - treatment of influenza A & influenza B - treatment of adenovirus - adjunctive therapy with interferon-alpha for hepatitis C - other viral infections - Rift valley fever - Lassa fever virus [10] Contraindications: 1) hypersensitivity to ribavirin 2) pregnant women or women who may become pregnant during exposure to ribavirin (teratogenic) [7.8] 3) autoimmune hepatitis (& decompensated liver disease [Canada]) Dosage: 1) use with Viratek small particle aerosol generator at a concentration of 20 mg/mL 2) 6 g reconstituted with 300 mL of sterile water without preservatives 3) aerosol: 12-18 hours/day X 3-7 days. 4) no dosage adjustment with renal failure; caution recommended [3] 5) Copegus: a) for oral administration in combination with peginterferon alpha-2a b) 1000-1200 mg/day, divided BID (Hepatitis C gentotype 1 or 4) c) 800 mg/day, divided BID (Hepatitis C gentotype 2 or 3) d) take with food Powder for aerosol: 6 g (100 mL). Pharmacokinetics: 1) systemically absorbed from the respiratory tract following nasal & oral administration of aerosol 2) maximal absorbtion occurs with use of an aerosolized generator via an endotracheal tube 3) food increased absorption after oral administration (Copegus) 3) highest concentration of drug achieved in the respiratory tract & erythrocytes 4) crosses placenta & appears in breast milk 5) does not cross blood-brain barrier 6) peak serum concentration in 60-90 minutes 7) metabolism: a) intracellular metabolism may be necessary for activity b) hepatic metabolism is the major route of elimination 8) elimination 1/2life: a) plasma: 24 hours (adult) b) plasma: 6.5-11 hours (children) c) erythrocyte 1/2life is 16-40 days or longer [7] Monitor: - liver function tests baseline & periodically - in clinical trials, serum ALT, serum AST & serum biliribin were measured at 2,4,6,8, & 12 weeks, then every 6 weeks [8] Adverse effects: 1) not common (1-10%) - fatigue, headache, insomnia, nausea, anorexia, anemia 2) uncommon (< 1%) - hypotension, cardiac arrest, digitalis toxicity, rash, skin irritation, conjunctivitis, mild bronchospasm, worsening of respiratory function, apnea, accumulation of fluid in ventilator tubing 3) other [9] - hemolytic anemia - hyperuricemia - teratogen Laboratory: - ribavirin in serum/plasma Mechanism of action: 1) appears to interfere with viral DNA & RNA synthesis [5] 2) generally greater inhibition of viral DNA & RNA synthesis than cellular DNA & RNA synthesis in viral-infected cells 3) antiviral activity dependent on conversion to ribavirin- triphosphate & ribavirin-monophosphate 4) ribavirin interferes with purine metabolism by inhibiting inosine monophosphate dehydrogenase [6] a) result is diminished cellular GTP b) results in disruption of viral RNA synthesis 5) ribavirin has minimal effect on the host immune response

Interactions

drug interactions

General

antiviral agent inosine-5'-monophosphate dehydrogenase inhibitor; IMP dehydrogenase inhibitor

Properties

MISC-INFO: elimination route LIVER LUNG 1/2life 24 HOURS 6.5-11 HOURS 16-40 DAYS pregnancy-category X safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Sanford Guide to antimicrobial therapy 2001
  4. Prescriber's Letter 10(1):3 2003
  5. AHFS Drug Information, American Society of Health-System Pharmacists, Bethesda, (2003)
  6. Harrison's Online (2003)
  7. Physician's Desk Reference (PDR) 56th edition, Medical Economics, 2002
  8. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  9. Medical Knowledge Self Assessment Program (MKSAP) 16 American College of Physicians, Philadelphia 2012
  10. Deprecated Reference

Component-of

IFN-alpha 2b/ribavirin (Rebetron)