Drug Interaction Report

GENERALLY AVOID: Coadministration of erdafitinib with potent inhibitors of CYP450 2C9 or 3A4 may increase the plasma concentrations and risk of toxicity of erdafitinib, which is a substrate of these isoenzymes. When coadministered with fluconazole, a strong CYP450 2C9 inhibitor and moderate CYP450 3A4 inhibitor, erdafitinib mean ratios for Cmax and AUC were 121% and 148%, respectively, relative to erdafitinib alone. Similarly, when coadministered with itraconazole, a strong CYP450 3A4 inhibitor, erdafitinib mean ratios for Cmax and AUC were 105% and 134%, respectively, relative to erdafitinib alone.

MANAGEMENT: Coadministration of erdafitinib with potent inhibitors of CYP450 2C9 or 3A4 should generally be avoided. If concomitant use is unavoidable, patients should be closely monitored for the development of adverse effects. Dosage adjustments as well as clinical and laboratory monitoring of erdafitinib should be considered whenever a CYP450 2C9 or 3A4 inhibitor is added to or withdrawn from therapy.

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.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.