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and laboratory monitoring of erdafitinib should be considered whenever a CYP450 2C9 or 3A4 inhibitor is added to or withdrawn from therapy.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.