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.
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
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
Phase II clinical trial data, where IRESSA and vinorelbine have been used concomitantly, indicate that IRESSA may
exacerbate the neutropenic effect of vinorelbine.