Drug Interactions between Effervescent Pain Relief and gefitinib

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.

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.