Drug Interactions between pexidartinib and Yosprala

GENERALLY AVOID: Coadministration with proton pump inhibitors (PPIs) may significantly decrease the bioavailability and therapeutic effects of pexidartinib. The proposed mechanism is a pH-dependent reduction in drug dissolution and/or absorption. Concomitant administration of esomeprazole, a proton pump inhibitor, decreased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 50%, respectively. The effect of coadministration with an H2-receptor antagonist or locally-acting antacids on pexidartinib pharmacokinetics is unknown.

MANAGEMENT: Concomitant use of pexidartinib with proton pump inhibitors should be avoided. If acid-suppression therapy is required, pexidartinib may be administered 2 hours before or 2 hours after taking a locally-acting antacid, or if using an H2-receptor antagonist, administer pexidartinib at least 2 hours before or 10 hours after taking the H2-receptor antagonist.

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.