Drug Interaction Report

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.

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.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of ribavirin. Administration of a single oral dose of ribavirin following a high-fat meal delayed absorption (Tmax was doubled) but increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by up to 70% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, ribavirin should be administered with or immediately after a meal.

Food increases the extent of absorption and slows the rate of absorption of dolutegravir. When administered with a low-, moderate- or high-fat meal, dolutegravir peak plasma concentration (Cmax) increased by 46%, 52% and 67%, systemic exposure (AUC) increased by 33%, 41% and 66%, and time to reach Cmax (Tmax) increased from 2 hours to 3, 4 and 5 hours, respectively, compared to administration under fasted conditions. Dolutegravir may be taken with or without food.