Drug Interaction Report

MONITOR: The concomitant or sequential use of epirubicin with agents known to induce hepatotoxicity may potentiate the risk of liver injury. Epirubicin undergoes elimination through the hepatobiliary system.

MANAGEMENT: Caution and clinical and laboratory monitoring for signs of liver injury are advisable before, during, or after use of epirubicin with other agents that are potentially hepatotoxic.

CONTRAINDICATED: Coadministration with inhibitors of CYP450 1A2 such as caffeine may significantly increase the plasma concentrations of fezolinetant, which is primarily metabolized by the isoenzyme. The interaction has not been studied with caffeine but has been reported for other CYP450 1A2 inhibitors. Consumption of caffeine-containing food or beverages (e.g., chocolate, coffee, cola drinks, energy drinks, tea) could result in an interaction with fezolinetant. In clinical drug interaction studies, coadministration of the potent CYP450 1A2 inhibitor fluvoxamine increased the peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 840%, respectively. Likewise, the moderate CYP450 1A2 inhibitor, mexiletine, is predicted through physiologically based pharmacokinetic (PBPK) modeling to increase the Cmax and AUC of fezolinetant by 40% and 360%, respectively. The weak CYP450 1A2 inhibitor cimetidine is also predicted via PBPK to increase the Cmax and AUC of fezolinetant by 30% and 100%, respectively.

MANAGEMENT: Concomitant use of fezolinetant with CYP450 1A2 inhibitors such as caffeine, including caffeine-containing food or beverages, is considered contraindicated.