Drug interactions between interferon alfa-2b/ribavirin and Trizivir

zidovudine ↔ interferon alfa-2b

Applies to:Trizivir (abacavir/lamivudine/zidovudine) and interferon alfa-2b/ribavirin

MONITOR CLOSELY: The coadministration of interferons and zidovudine (AZT) may result in severe bone marrow toxicity, most often manifested as granulocytopenia and/or thrombocytopenia. These agents are individually myelotoxic, with potentially additive or synergistic effects.

MANAGEMENT: Caution is advised if concomitant therapy is necessary, particularly with the alfa interferons. Complete blood counts, differential and platelet counts should be performed regularly and drug dosages adjusted accordingly. Patients should be advised to promptly report symptoms such as chills, fever, sore throat, pale skin, or unusual fatigue to their physician. Cessation of one or all drugs may be necessary if toxicity develops.

zidovudine ↔ ribavirin

Applies to:Trizivir (abacavir/lamivudine/zidovudine) and interferon alfa-2b/ribavirin

GENERALLY AVOID: Ribavirin, a nucleoside analog, has been shown to antagonize the in vitro antiviral activity of zidovudine against HIV. The mechanism is feedback inhibition of thymidine kinase induced by ribavirin, resulting in decreased intracellular phosphorylation of zidovudine 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 zidovudine 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 myelosuppression and 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 zidovudine should generally be avoided. 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.

ribavirin ↔ lamivudine

Applies to:interferon alfa-2b/ribavirin and Trizivir (abacavir/lamivudine/zidovudine)

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.

ribavirin ↔ abacavir

Applies to:interferon alfa-2b/ribavirin and Trizivir (abacavir/lamivudine/zidovudine)

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.