Drug Interaction Report

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.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.