Drug Interactions between dacomitinib and Yosprala

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.

Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates.