ribavirin (Virazole, Rebetol, Copegus)

Introduction

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

Contraindications

• hypersensitivity to ribavirin
• pregnant women or women who may become pregnant during exposure to ribavirin (teratogenic) [7.8]
• autoimmune hepatitis (& decompensated liver disease [Canada])

pregnancy category = x

safety in lactation = -

Dosage

• use with Viratek small particle aerosol generator at a concentration of 20 mg/mL
• 6 g reconstituted with 300 mL of sterile water without preservatives
• aerosol: 12-18 hours/day X 3-7 days.
• no dosage adjustment with renal failure; caution recommended
• Copegus:
  • for oral administration in combination with peginterferon alpha-2a
  • 1000-1200 mg/day, divided BID (Hepatitis C gentotype 1 or 4)
  • 800 mg/day, divided BID (Hepatitis C gentotype 2 or 3)
  • take with food

Powder for aerosol: 6 g (100 mL).

Pharmacokinetics

• systemically absorbed from the respiratory tract following nasal & oral administration of aerosol
• maximal absorbtion occurs with use of an aerosolized generator via an endotracheal tube
• food increased absorption after oral administration (Copegus)
• highest concentration of drug achieved in the respiratory tract & erythrocytes
• crosses placenta & appears in breast milk
• does not cross blood-brain barrier
• peak serum concentration in 60-90 minutes
• metabolism:
  • intracellular metabolism may be necessary for activity
  • hepatic metabolism is the major route of elimination
• elimination 1/2life:
  • plasma: 24 hours (adult)
  • plasma: 6.5-11 hours (children)
  • erythrocyte 1/2life is 16-40 days or longer

elimination via liver

elimination via lung

1/2life = 24 hours plasma, adults

1/2life = 6.5-11 hours plasma, children

1/2life = 16-40 days erythrocyte

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

Adverse effects

• not common (1-10%)
  • fatigue, headache, insomnia, nausea, anorexia, anemia
• uncommon (< 1%)
  • hypotension, cardiac arrest, digitalis toxicity, rash, skin irritation, conjunctivitis, mild bronchospasm, worsening of respiratory function, apnea, accumulation of fluid in ventilator tubing
• other
  • hemolytic anemia
  • hyperuricemia
  • teratogen

Laboratory

• ribavirin in serum/plasma

Mechanism of action

• appears to interfere with viral DNA & RNA synthesis
• generally greater inhibition of viral DNA & RNA synthesis than cellular DNA & RNA synthesis in viral-infected cells
• antiviral activity dependent on conversion to ribavirin- triphosphate & ribavirin-monophosphate
• ribavirin interferes with purine metabolism by inhibiting inosine monophosphate dehydrogenase
  • result is diminished cellular GTP
  • results in disruption of viral RNA synthesis
• ribavirin has minimal effect on the host immune response

More general terms

• antiviral agent
• IMP dehydrogenase inhibitor

Component of

• IFN-alpha 2b/ribavirin (Rebetron)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=37542
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5064