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and laboratory monitoring of erdafitinib should be considered whenever a CYP450 2C9 or 3A4 inhibitor is added to or withdrawn from therapy.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: Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.

MANAGEMENT: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• ceritinib
• erdafitinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.