Drug Interaction Report

GENERALLY AVOID: Coadministration with strong or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations and anti-cancer activity of mobocertinib, which is primarily metabolized by the isoenzyme. Based on drug interaction studies using model-informed approaches, coadministration of mobocertinib with multiple doses of rifampin (a strong CYP450 3A4 inducer) is predicted to decrease the steady-state combined molar AUC (systemic exposure) of mobocertinib and its active metabolites by 92%, while coadministration with multiple doses of efavirenz (a moderate CYP450 3A4 inducer) is predicted to decrease this value by 58%.

MANAGEMENT: Coadministration of mobocertinib with strong or moderate CYP450 3A4 inducers should be avoided.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mobocertinib. The mechanism may involve inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice. Based on drug interaction studies using model-informed approaches, coadministration of mobocertinib with multiple doses of itraconazole or ketoconazole (strong CYP450 3A4 inhibitors) is predicted to increase the steady-state combined molar AUC (systemic exposure) of mobocertinib and its active metabolites by 374% to 419%, while coadministration with multiple doses of a moderate CYP450 3A4 inhibitor is predicted to increase this value by approximately 100% to 200%. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Elevated plasma concentrations of mobocertinib may increase the risk for adverse effects such as QT prolongation, heart failure or reduced ejection fraction, cardiomyopathy, heart block, diarrhea, rash, stomatitis, fatigue, and musculoskeletal pain.

MANAGEMENT: Patients should avoid consumption of grapefruit and grapefruit juice during treatment with mobocertinib.