In vitro studies have shown that the metabolism of gefitinib is predominantly via CYP3A4.
Co-administration with rifampicin (a known potent CYP3A4 inducer) in healthy volunteers reduced mean gefitinib AUC by 83% of that without rifampicin (see Precautions).
Co-administration with itraconazole (a CYP3A4 inhibitor) resulted in an 80% increase in the mean AUC of gefitinib in healthy volunteers. This increase may be clinically relevant since adverse experiences are related to dose and exposure.
Co-administration of ranitidine at a dose that caused sustained elevations in gastric pH (≥ 5), resulted in a reduced mean gefitinib AUC by 47% in healthy volunteers (see Precautions and Pharmacology: Pharmacokinetics under Actions).
INR elevations and/or bleeding events have been reported in some patients taking warfarin (see Precautions).