Drug Interactions between esomeprazole / naproxen and gefitinib

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.

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GENERALLY AVOID: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered.

MANAGEMENT: Concomitant use of these drugs is generally not recommended.

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