Drug Interactions between cannabidiol and Mysoline

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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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.

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