Drug Interactions between azathioprine and Moderiba

GENERALLY AVOID: Published case reports suggest that ribavirin may potentiate the myelotoxic effects of 6-mercaptopurine and its prodrug, azathioprine. The proposed mechanism is inhibition of inosine monophosphate dehydrogenase by ribavirin, which interferes with one of the metabolic pathways of 6-mercaptopurine and leads to accumulation of the myelotoxic metabolite 6-methylthioinosine monophosphate (6-MTIMP). Pancytopenia and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the concomitant administration of pegylated interferon/ribavirin and azathioprine. Myelotoxicity was reversible within 4 to 6 weeks upon withdrawal of both the hepatitis C antiviral and azathioprine treatments, and did not recur upon reintroduction of either treatment alone. Theoretically, inhibition of inosine monophosphate dehydrogenase may also reduce the pharmacologic effects of 6-mercaptopurine and azathioprine by inhibiting conversion to the active metabolite; however, this was not observed in the case reports.

MANAGEMENT: The use of ribavirin in combination with 6-mercaptopurine or azathioprine should generally be avoided if possible. Patients receiving the combination should have complete blood counts, including platelet counts, monitored weekly for the first month, twice monthly for the second and third months, then monthly or more frequently if dosage or other therapy changes are necessary. Treatment with these medications should be discontinued promptly if pancytopenia develops, and the combination should not be reintroduced following recovery.

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