Drug Interaction Report

GENERALLY AVOID: Coadministration with drugs that elevate gastric pH may decrease the plasma concentrations of gefitinib. According to the manufacturer, the solubility of gefitinib is pH-dependent and decreases sharply between pH 4 and 6, becoming practically insoluble above pH 7. When gefitinib 250 mg was administered to healthy male volunteers (n=26) one hour following two oral 450 mg doses of ranitidine with sodium bicarbonate as needed to achieve a sustained gastric pH above 5.0, mean gefitinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 47%, respectively, compared to administration of gefitinib alone. The interaction has not been studied with proton pump inhibitors.

MANAGEMENT: Concomitant use of gefitinib with proton pump inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends administering gefitinib 12 hours after the last dose or 12 hours before the next dose of the proton pump inhibitor.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.