Drug Interactions between sotorasib and Yosprala

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of sotorasib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of sotorasib decreases from 1.3 mg/mL at pH 1.2 to 0.03 mg/mL at pH 6.8. When a single 960 mg dose of sotorasib was coadministered with multiple doses of the proton pump inhibitor omeprazole, sotorasib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 65% and 57%, respectively, under fed conditions, and by 57% and 42%, respectively, under fasted conditions. Coadministration of a single dose of the H2-receptor antagonist famotidine given 10 hours before and 2 hours after a single 960 mg dose of sotorasib under fed conditions decreased sotorasib Cmax by 35% and AUC by 38%. The interaction may similarly occur with other acid reducing or neutralizing agents, which may reduce the efficacy of sotorasib.

MANAGEMENT: Concomitant use of sotorasib with proton pump inhibitors, H2-receptor antagonists, or other acid reducing agents should generally be avoided. If acid suppression therapy is required, locally acting antacids may be considered. The manufacturer recommends taking sotorasib 4 hours before or 10 hours after administration of a locally acting antacid.

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.