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 can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.