Drug Interactions between cimetidine and Veozah

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.

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.