Drug Interaction Report

MONITOR: Concomitant use of remdesivir with other agents that are known to induce hepatotoxicity may theoretically increase the risk of liver injury. Data from investigational use and clinical studies suggest that remdesivir may be associated with transaminase elevations. Transient treatment-emergent Grade 1 or Grade 2 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed during multiple-dose Phase 1 studies in healthy volunteers. The mechanism of potential hepatotoxicity is unknown and the contribution of remdesivir is difficult to determine, as transaminase elevations have also been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir.

MANAGEMENT: Caution and increased monitoring may be required if remdesivir is given concurrently with other agents associated with liver injury. Hepatic function should be evaluated prior to starting remdesivir and during treatment as clinically appropriate. The manufacturer of remdesivir recommends considering discontinuation of remdesivir if ALT levels increase to greater than 10 times the upper limit of normal. Additionally, the manufacturer recommends discontinuing remdesivir if ALT elevation is accompanied by signs or symptoms of liver inflammation. The labeling of the other agent(s) involved should also be consulted as they may contain dose adjustment or discontinuation recommendations for those agent(s) in the event of hepatotoxicity.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.