Drug Interaction Report

ADJUST DOSING INTERVAL: Coadministration with drugs that elevate gastric pH such as H2-receptor antagonists and antacids 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. High doses of short-acting antacids may have a similar effect if taken regularly in close proximity to gefitinib administration.

MANAGEMENT: The possibility of a diminished therapeutic response to gefitinib should be considered during coadministration with H2-receptor antagonists or antacids. If concomitant treatment is required, the manufacturer recommends administering gefitinib 6 hours before or 6 hours after an H2-receptor antagonist or antacid.

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.