Drug Interactions between dacomitinib and rabeprazole

GENERALLY AVOID: Coadministration with proton pump inhibitors (PPIs) may decrease the plasma concentrations of dacomitinib. The proposed mechanism is a pH-dependent reduction in dissolution or absorption of dacomitinib due to prolonged gastric acid suppression induced by PPIs. When a single 45 mg dose of dacomitinib was coadministered with rabeprazole (40 mg once daily for 7 days) in 24 healthy subjects, dacomitinib peak plasma concentration (Cmax) and systemic exposure (AUC 0 to 96 hours) decreased by approximately 51% and 39%, respectively, compared to dacomitinib administered alone. By contrast, administration of dacomitinib with a local antacid (aluminum hydroxide-magnesium hydroxide 400 mg-400 mg/5 mL) did not cause clinically relevant changes in dacomitinib concentrations. The lack of a significant interaction may be due to the shorter duration of action of antacids relative to PPIs. The interaction has not been studied with H2-receptor antagonists. Based on pooled data in clinical study patients, H2-receptor antagonists had no apparent effect on steady-state trough concentration of dacomitinib.

MANAGEMENT: Concomitant use of dacomitinib with PPIs should generally be avoided. If acid suppression therapy is required, locally-acting antacids or H2-receptor antagonists may be considered. The manufacturer recommends taking dacomitinib at least 6 hours before or 10 hours after H2-receptor antagonists.

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