Drug interactions of Gefitinib

Drugs Affecting Gefitinib Exposure

CYP3A4 Inducers

Strong CYP3A4-inducing drugs increase the metabolism of gefitinib and decrease its plasma concentrations. For patients receiving treatment with strong CYP3A4 inducers (e.g., rifampicin, phenytoin, or tricyclic antidepressants), increase the gefitinib dose to 500 mg once daily, and resume the 250 mg dose of gefitinib 7 days after discontinuing the strong inducer.

CYP3A4 Inhibitors

Strong CYP3A4 inhibitors (e.g., ketoconazole and itraconazole) decrease the metabolism of gefitinib and increase its plasma concentrations. Monitor for adverse reactions when a strong CYP3A4 inhibitor is co-administered with gefitinib.

Drugs Affecting Gastric pH

Drugs that increase gastric pH (e.g., proton pump inhibitors, histamine H2-receptor antagonists, and antacids) may decrease gefitinib plasma concentrations. If possible, avoid co-administration of gefitinib with proton pump inhibitors. If treatment with a proton pump inhibitor is necessary, take gefitinib 12 hours after the last dose of the proton pump inhibitor or 12 hours before the next dose of the proton pump inhibitor. Take gefitinib 6 hours after or 6 hours before administration of an H2-receptor antagonist or antacid.

Bleeding in Patients Taking Warfarin

Some patients taking warfarin have reported elevated international normalized ratio (INR) and/or bleeding during treatment with gefitinib. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR.

FDA，2021.05