Drug Interaction Report

GENERALLY AVOID: Coadministration with erdafitinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter, resulting in increased toxicity of these drugs. In vitro, erdafitinib has been shown to be an inhibitor of P-gp. However, no pharmacokinetic data are available from drug interaction studies.

MANAGEMENT: Concomitant use of erdafitinib and P-gp substrates should generally be avoided. If concomitant use is required, administer erdafitinib at least 6 hours before or after administration of P-gp substrates with narrow therapeutic ranges.

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.