Drug Interaction Report

MONITOR: Coadministration with enzalutamide may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-glycoprotein (P-gp) efflux transporter. The proposed mechanism involves accelerated clearance via these routes due to enzalutamide-mediated induction. The resulting plasma concentrations will depend on the sensitivity of the affected drugs to these isoenzymes.

MANAGEMENT: Caution is advised when enzalutamide is used concomitantly with drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever enzalutamide is added to or withdrawn from therapy.

GENERALLY AVOID: Coadministration with large amounts of certain fruit juices, including grapefruit, orange and apple, may decrease the oral bioavailability of fexofenadine. The proposed mechanism is inhibition of drug efflux via intestinal organic anion transporting polypeptides (e.g., P-glycoprotein), of which fexofenadine is a substrate. In a five-way crossover study with 10 healthy volunteers, 1/4-strength grapefruit juice, grapefruit juice, orange juice and apple juice (300 mL with drug administration and 150 mL every 1/2 hour for up to 3 hours, total volume 1.2 L) reduced the mean area under the plasma concentration-time curve (AUC) of a 120 mg dose of fexofenadine by 23%, 67%, 72% and 77%, respectively, compared to water. Mean peak plasma concentration (Cmax) was similarly affected. The clinical significance of these changes is unknown. However, results from studies using histamine-induced skin wheals and flares found that the size of wheal and flare was significantly larger when fexofenadine was administered with either grapefruit or orange juices compared to water.

MANAGEMENT: To maximize plasma levels and therapeutic effects, fexofenadine should be taken with water. In addition, patients should refrain from consuming large amounts of grapefruit, orange, or apple juice.