Drug Interactions between taletrectinib and Yosprala

GENERALLY AVOID: Coadministration with inhibitors of the proton pump (PPIs), potassium-competitive acid blockers (PCABs), and H2 receptor antagonists (H2RAs) may decrease the gastrointestinal absorption and plasma concentrations of taletrectinib, which may reduce the therapeutic effectiveness of the drug. Taletrectinib displays pH-dependent aqueous solubility, with increased solubility at lower pH. In a clinical study, coadministration of the PPI omeprazole (40 mg daily) decreased taletrectinib peak plasma concentration (Cmax) by 65% and systemic exposure (AUC) by 40%. While specific clinical data with PCABs and H2RAs are not available, the possibility of reduced or subtherapeutic effectiveness of taletrectinib should be considered.

MANAGEMENT: Concomitant use of taletrectinib with PPIs, PCABs, and H2RAs should be avoided. If acid suppression is necessary, consider alternatives such as locally acting antacids administered at least 2 hours before or 2 hours after taletrectinib dosing. Patients should be advised to contact their doctor if their symptoms worsen or their condition changes, as reduced drug absorption may lead to decreased therapeutic effectiveness.

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.