Substances that are inducers of CYP3A4 activity increase the metabolism of gefitinib and decrease its plasma concentrations. In patients receiving a potent CYP3A4 inducer such as rifampicin or phenytoin, a dose increase to 500 mg daily should be considered in the absence of severe adverse drug reaction, and clinical response and adverse events should be carefully monitored (see CLINICAL PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and DOSAGE AND ADMINISTRATION-Dosage Adjustment sections).
International Normalized Ratio (INR) elevations and/or bleeding events have been reported in some patients taking warfarin while on IRESSA therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR (see CLINICAL PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and ADVERSE REACTIONS sections).
Substances that are potent inhibitors of CYP3A4 activity (eg, ketoconazole and itraconazole) decrease gefitinib metabolism and increase gefitinib plasma concentrations. This increase may be clinically relevant as adverse experiences are related to dose and exposure; therefore, caution should be used when administering CYP3A4 inhibitors with IRESSA (see CLINICAL PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and ADVERSE REACTIONS sections).
Drugs that cause significant sustained elevation in gastric pH (histamine H2-receptor antagonists such as ranitidine or cimetidine) may reduce plasma concentrations of IRESSA and therefore potentially may reduce efficacy (see CLINICAL PHARMACOLOGY-Drug-Drug Interactions section).
Phase II clinical trial data, where IRESSA and vinorelbine have been used concomitantly, indicate that IRESSA may exacerbate the neutropenic effect of vinorelbine.