Drug Interactions between interferon alfa-2b / ribavirin and Zerit XR

MONITOR: Ribavirin, a nucleoside analog, has been shown to antagonize the in vitro antiviral activity of stavudine against HIV. The mechanism is feedback inhibition of thymidine kinase induced by ribavirin, resulting in decreased intracellular phosphorylation of stavudine to its active triphosphate metabolite. The clinical relevance of this finding is unknown. Preliminary data from a small number of HCV-HIV coinfected patients receiving interferon-ribavirin therapy and different antiretroviral regimens containing stavudine do not support a major clinical impact related to the in vitro effect. However, the potential for diminished antiretroviral activity should be considered, as three patients in one study had an increase in HIV viral load of more than 0.5 log after 3 to 6 months of interferon-ribavirin therapy which led to discontinuation of ribavirin in one. In addition, the risk of mitochondrial toxicities such as lipodystrophy, peripheral neuropathy, pancreatitis, and lactic acidosis associated with nucleoside reverse transcriptase inhibitors may be increased during coadministration with ribavirin. Nucleoside analogs alone and in combination have been associated with these and other toxicities.

MANAGEMENT: Coadministration of ribavirin with stavudine should be undertaken with caution and only if the benefit is anticipated to outweigh the potential risks. Patients should be advised to promptly seek medical attention if they experience symptoms of toxicity such as nausea, vomiting, abdominal pain/distention, fatigue, infection, unexplained weight loss, tachypnea, dyspnea, motor weakness, numbness, tingling, and pain in hands and feet. Dosage reduction or discontinuation of ribavirin should be considered if worsening toxicities are observed.

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MONITOR: The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. Patient risk factors include diabetes and age older than 60 years. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

MANAGEMENT: Caution is advised during concomitant use of agents with neurotoxic effects. Patients should be monitored closely for symptoms of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Since the development of peripheral neuropathy may be dose-related for many drugs, the recommended dosages should generally not be exceeded. Consideration should be given to dosage reduction or immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If feasible, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, permanent dosage reductions may be required.

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