Drug Interactions between cannabidiol 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.

ADJUST DOSING INTERVAL: Food may affect the plasma concentrations of cannabidiol. In healthy volunteers, administration of cannabidiol with a high-fat/high-calorie meal increased cannabidiol peak plasma concentration (Cmax) by 5-fold and systemic exposure (AUC) by 4-fold and reduced the total variability compared with administration in the fasted state.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cannabidiol. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of cannabidiol by certain compounds present in grapefruit. The interaction has not been studied, but the product labeling for cannabidiol recommends consideration of a dosage reduction when used with strong or moderate inhibitors of CYP450 3A4. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: Cannabidiol should be taken about the same time each day consistently either with or without food. Patients should limit the consumption of grapefruit and grapefruit juice. If they are coadministered, cannabidiol levels should be monitored and the dosage adjusted as necessary.