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: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.