Drug Interaction Report

Coadministration with osimertinib may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. In vitro, osimertinib has been shown to be a competitive inhibitor as well as inducer of CYP450 3A4. However, a clinically significant inhibitory effect on CYP450 3A4 has not been demonstrated in clinical drug interaction studies. In a pharmacokinetic study of 49 patients with non-small cell lung cancer, coadministration of osimertinib with the sensitive CYP450 3A4 substrate simvastatin decreased the area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of simvastatin by approximately 9% and 23%, respectively. These reductions are also not considered clinically significant. Based on these observations, osimertinib may be administered with CYP450 3A4 substrates without the need for increased clinical monitoring.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.