Effect of Carbamazepine on the Pharmacokinetics of Erdafitinib in Healthy Participants

Abstract

AbstractErdafitinib, a selective and potent oral pan‐FGFR inhibitor, is metabolized mainly through CYP2C9 and CYP3A4 enzymes. This phase 1, open‐label, single‐sequence, drug‐drug interaction study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of erdafitinib alone and when co‐administered with steady state oral carbamazepine, a dual inducer of CYP3A4 and CYP2C9, in 13 healthy adult participants (NCT04330248). Compared with erdafitinib administration alone, carbamazepine co‐administration decreased total and free maximum plasma concentrations of erdafitinib (Cmax) by 35% (95% CI 30%‐39%) and 22% (95% CI 17%‐27%), respectively. The areas under the concentration‐time curve over the time interval from 0 to 168 hours, to the last quantifiable data point, and to time infinity (AUC168h, AUClast, AUCinf), were markedly decreased for both total erdafitinib (56%‐62%) and free erdafitinib (48%‐55%). The safety profile of erdafitinib was consistent with previous clinical studies in healthy participants, with no new safety concerns when administered with or without carbamazepine. Co‐administration with carbamazepine may reduce the activity of erdafitinib due to reduced exposure. Concomitant use of strong CYP3A4 inducers with erdafitinib should be avoided.