Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ulipristal acetate and its pharmacologically active metabolite. Based on in vitro and pharmacokinetic data, ulipristal acetate is thought to be primarily metabolized by CYP450 3A4 to mono-demethylated and di-demethylated metabolites. When a single 30 mg dose of ulipristal acetate was administered following a 9-day treatment with 600 mg once daily of rifampin, a potent CYP450 3A4 inducer, ulipristal acetate peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 90% and 93% respectively, while half-life decreased by 2.2-fold. The Cmax and AUC of monodemethyl-ulipristal acetate, the active metabolite, decreased by 84% and 90%, respectively. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: When used to prevent pregnancy, ulipristal acetate should not be coadministered with CYP450 3A4 inducers due to the potential for loss of therapeutic efficacy. For patients who have used enzyme-inducing drugs within the past 4 weeks and are seeking emergency contraception, ulipristal acetate is not recommended and a non-hormonal method (i.e. a copper intrauterine device (Cu-IUD)) should be considered.

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.