indication

For the treatment of chronic hepatitis C and for respiratory syncytial virus (RSV).

pharmacology

Ribavirin is an anti-viral drug active against a number of DNA and RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to it's resemblence to building blocks of the RNA molecules. The oral form is used in the treatment of hepatitis C, in combination with interferon drugs. The aerosol form is used to treat respiratory syncytial virus-related diseases in children. The primary serious adverse effect of ribavirin is hemolytic anemia, which may worsen preexisting cardiac disease.

mechanism of action

Ribavirin is readily phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is a potent competitive inhibitor of inosine monophosphate (IMP) dehydrogenase, viral RNA polymerase and messenger RNA (mRNA) guanylyltransferase (viral) and can be incorporated into RNA in RNA viral species.. Guanylyltranserase inhibition stops the capping of mRNA. These diverse effects result in a marked reduction of intracellular guanosine triphosphate (GTP) pools and inhibition of viral RNA and protein synthesis. Ribavirin is also incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity.

toxicity

Side effects include "flu-like" symptoms, such as headache, fatigue, myalgia, and fever. The LD₅₀ in mice is 2 g/kg orally and is associated with hypoactivity and gastrointestinal symptoms (estimated human equivalent dose of 0.17 g/kg, based on body surface area conversion).

biotransformation

Hepatic. Results of in vitro studies using both human and rat liver microsome preparations indicated little or no cytochrome P450 enzyme-mediated metabolism of ribavirin, with minimal potential for P450 enzyme-based drug interactions. Ribavirin has two pathways of metabolism: (1) a reversible phosphorylation pathway in nucleated cells; and (2) a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite.

absorption

Rapidly and extensively absorbed following oral administration. However, due to first-pass metabolism, the absolute bioavailability averages 64%.

half life

9.5 hours

drug interactions

Abacavir: Ribavirin may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.

Zalcitabine: Ribavirin may increase the hepatotoxicity of zalcitabine. May cause lactic acidosis. MOnitor for lactic acidosis during concomitant therapy.

Zidovudine: Increased risk or severity of anemia. Consider alternate therapy or monitor more closely for anemia.