Drug Interactions between Dual Action Complete and taletrectinib

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.

ADJUST DOSING INTERVAL: Coadministration with antacids or other agents with acid neutralizing or reducing effects may decrease the gastrointestinal absorption and plasma concentrations of taletrectinib due to increased gastric pH. Taletrectinib displays pH-dependent aqueous solubility, with increased solubility at lower pH. The magnitude of interaction may be dose-dependent and related to the degree of acid suppression achieved.

MANAGEMENT: The possibility of a reduced or subtherapeutic response to taletrectinib should be considered during coadministration with antacids or other agents that can increase gastric pH. If an antacid is required, the antacid should be taken 2 hours before or 2 hours after administration of taletrectinib. The same precaution may be applicable to other drugs with antacid effects. 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.

ADJUST DOSING INTERVAL: Coadministration with antacids or other agents with acid neutralizing or reducing effects may decrease the gastrointestinal absorption and plasma concentrations of taletrectinib due to increased gastric pH. Taletrectinib displays pH-dependent aqueous solubility, with increased solubility at lower pH. The magnitude of interaction may be dose-dependent and related to the degree of acid suppression achieved.

MANAGEMENT: The possibility of a reduced or subtherapeutic response to taletrectinib should be considered during coadministration with antacids or other agents that can increase gastric pH. If an antacid is required, the antacid should be taken 2 hours before or 2 hours after administration of taletrectinib. The same precaution may be applicable to other drugs with antacid effects. 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.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.