Drug Interactions between famotidine / ibuprofen and sotorasib

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.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.