Drug Interactions between interferon alfa-2b / ribavirin and zalcitabine

MONITOR: Concomitant use of oral ribavirin and nucleoside reverse transcriptase inhibitors (NRTIs) may increase the risk of symptomatic hyperlactatemia and lactic acidosis. Ribavirin itself is a nucleoside analogue, and these agents alone and in combination have been associated with the syndrome of lactic acidosis and severe hepatomegaly with steatosis. Other mitochondrial toxicities associated with the use of nucleoside analogues include lipodystrophy, peripheral neuropathy, and pancreatitis.

MANAGEMENT: Coadministration of ribavirin and NRTIs 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, unexplained weight loss, tachypnea, dyspnea, motor weakness, numbness, tingling, and pain in hands and feet.

GENERALLY AVOID: Zalcitabine can cause peripheral neuropathy in up to one-third of patients with advanced HIV disease, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Zalcitabine-related peripheral neuropathy is a sensorimotor neuropathy characterized initially by numbness and burning dysesthesia involving the distal extremities. These symptoms may be followed by sharp shooting pains or severe continuous burning pain if the drug is not withdrawn, and progress to severe pain requiring narcotic analgesics. The neuropathy is potentially irreversible. However, with prompt discontinuation of zalcitabine, it is usually slowly reversible, although symptoms may initially progress following discontinuation.

MANAGEMENT: Use of zalcitabine with other drugs that have the potential to cause peripheral neuropathy should be avoided whenever possible. Otherwise, careful monitoring is recommended for symptoms of neuropathy such as burning, tingling, pain, numbness, or weakness in the extremities, particularly in patients with a low CD4 cell count or diabetes. Since the development of peripheral neuropathy appears to be dose-related, the recommended dosage of zalcitabine should not be exceeded. Patients should be advised to promptly discontinue zalcitabine therapy and contact their physician if neuropathy develops. Therapy may be reinstituted following resolution of neuropathy symptoms, but dosage should be reduced to one-half the initially recommended dosage. Zalcitabine should be permanently discontinued in patients who develop severe peripheral neuropathy during treatment.