Drug Interactions between Acid Controller Complete and neratinib

GENERALLY AVOID: Coadministration with proton pump inhibitors or H2-receptor antagonists may significantly decrease the oral bioavailability of neratinib. The solubility of neratinib is pH-dependent and increases as neratinib becomes protonated at acidic pH, thus an increase in pH may interfere with its absorption. According to the product labeling, neratinib is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximate pH 5.0 and above (0.08 mg/mL or less). When a single 240 mg dose of neratinib was administered to 15 healthy adult subjects on day 5 of treatment with lansoprazole 30 mg orally once daily for 7 days, mean neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 65%, respectively, compared to neratinib administered alone. In addition, the Cmax and AUC of neratinib were reduced by 55% and 47%, respectively, when neratinib was administered 2 hours after a 300 mg dose of ranitidine.

MANAGEMENT: Concomitant use of neratinib with proton pump inhibitors and H2-receptor antagonists should generally be avoided. According to some authorities, if H2-receptor antagonist therapy is required, neratinib should be administered at least 2 hours before or 10 hours after the H2-receptor antagonist. In addition, short-acting antacids could be considered if acid-suppression therapy is required, with neratinib dosing separated by at least three hours after antacid administration. If coadministered with a gastric acid reducing agent, increasing the dose of neratinib is unlikely to compensate for the loss of bioavailability.

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of neratinib. The solubility of neratinib is pH-dependent and increases as neratinib becomes protonated at acidic pH, thus an increase in pH may interfere with its absorption. According to the product labeling, neratinib is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximate pH 5.0 and above (0.08 mg/mL or less). When a single 240 mg dose of neratinib was administered to 15 healthy adult subjects on day 5 of treatment with lansoprazole 30 mg orally once daily for 7 days, mean neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 65%, respectively, compared to neratinib administered alone. Concomitant use with other pH lowering agents was not studied, but a decrease in neratinib AUC is also considered likely.

MANAGEMENT: Concomitant use of neratinib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with neratinib dosing separated by at least three hours after antacid administration.

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of neratinib. The solubility of neratinib is pH-dependent and increases as neratinib becomes protonated at acidic pH, thus an increase in pH may interfere with its absorption. According to the product labeling, neratinib is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximate pH 5.0 and above (0.08 mg/mL or less). When a single 240 mg dose of neratinib was administered to 15 healthy adult subjects on day 5 of treatment with lansoprazole 30 mg orally once daily for 7 days, mean neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 65%, respectively, compared to neratinib administered alone. Concomitant use with other pH lowering agents was not studied, but a decrease in neratinib AUC is also considered likely.

MANAGEMENT: Concomitant use of neratinib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with neratinib dosing separated by at least three hours after antacid administration.

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.