Interactions between virazole(ribavirin) and Didanosine delayed release capsule (didanosine)
didanosine and ribavirin (Major Drug-Drug)
GENERALLY AVOID: Coadministration with ribavirin, a nucleoside analogue, may increase exposure to didanosine (ddI) or its active triphosphate metabolite. Both the antiretroviral effect and clinical toxicities of ddI may be enhanced. The mechanism is inhibition of inosine 5'-monophosphate (IMP) dehydrogenase by an initial metabolite of ribavirin, resulting in decreased synthesis of guanine nucleotides that would otherwise compete with the active ddI metabolite for HIV-1 reverse transcriptase. In addition, ddI phosphorylation to the active metabolite may be enhanced by the accumulation of IMP, which is an efficient phosphate donor. Pharmacodynamically, the risk of mitochondrial toxicities such as lipodystrophy, peripheral neuropathy, pancreatitis, and lactic acidosis associated with ddI and other nucleoside reverse transcriptase inhibitors may also be increased during coadministration with ribavirin. Nucleoside analogues alone and in combination have been associated with these and other toxicities. Isolated cases of fatal hepatic failure have also been reported during coadministration of ribavirin and didanosine.
MANAGEMENT: The concomitant use of oral ribavirin and didanosine is not recommended.
