Drug Interactions between Acid Controller Complete and lamivudine / raltegravir

GENERALLY AVOID: Coadministration with aluminum-, magnesium-, and/or calcium-containing antacids may reduce the oral bioavailability of raltegravir. The proposed mechanism is chelation of raltegravir by polyvalent cations, but changes in solubility and lipophilicity of raltegravir related to pH increases may also contribute. In drug interaction studies, raltegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 44%, 49% and 63%, respectively, when a single 20 mL dose of aluminum and magnesium hydroxide antacid was administered simultaneously with raltegravir (400 mg twice daily). The Cmax, AUC and Cmin of raltegravir decreased by 51%, 51% and 56%, respectively, when the antacid was given 2 hours before raltegravir, and by 22%, 30% and 57%, respectively, when the antacid was given 2 hours after raltegravir. When given 4 hours apart, raltegravir Cmax, AUC and Cmin decreased by 22%, 19% and 60% with antacid administered first, and by 30%, 32% and 62% with raltegravir administered first. Minimal changes in raltegravir Cmax and AUC were observed when administration was staggered by 6 hours; however, Cmin was still diminished by approximately 50% regardless of whether antacid was administered before or after raltegravir. When raltegravir 400 mg twice daily was given with a single dose of antacid containing calcium carbonate 3000 mg, raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%, respectively. These changes are not considered clinically significant by the manufacturer. However, when a single 1200 mg dose of raltegravir was coadministered with the calcium carbonate antacid, raltegravir Cmax, AUC and Cmin decreased by 74%, 72% and 58%, respectively. Staggering the doses by administering the calcium carbonate antacid 12 hours after raltegravir resulted in minimal changes in raltegravir Cmax and AUC, but Cmin was still reduced by 57%.

MANAGEMENT: Concomitant use of raltegravir with aluminum- and/or magnesium-containing antacids should generally be avoided, even if administration is staggered. Antacids containing calcium carbonate should not be used with once-daily raltegravir (HD formulation), but may be used without dose adjustment for other raltegravir products.

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GENERALLY AVOID: Coadministration with aluminum-, magnesium-, and/or calcium-containing antacids may reduce the oral bioavailability of raltegravir. The proposed mechanism is chelation of raltegravir by polyvalent cations, but changes in solubility and lipophilicity of raltegravir related to pH increases may also contribute. In drug interaction studies, raltegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 44%, 49% and 63%, respectively, when a single 20 mL dose of aluminum and magnesium hydroxide antacid was administered simultaneously with raltegravir (400 mg twice daily). The Cmax, AUC and Cmin of raltegravir decreased by 51%, 51% and 56%, respectively, when the antacid was given 2 hours before raltegravir, and by 22%, 30% and 57%, respectively, when the antacid was given 2 hours after raltegravir. When given 4 hours apart, raltegravir Cmax, AUC and Cmin decreased by 22%, 19% and 60% with antacid administered first, and by 30%, 32% and 62% with raltegravir administered first. Minimal changes in raltegravir Cmax and AUC were observed when administration was staggered by 6 hours; however, Cmin was still diminished by approximately 50% regardless of whether antacid was administered before or after raltegravir. When raltegravir 400 mg twice daily was given with a single dose of antacid containing calcium carbonate 3000 mg, raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%, respectively. These changes are not considered clinically significant by the manufacturer. However, when a single 1200 mg dose of raltegravir was coadministered with the calcium carbonate antacid, raltegravir Cmax, AUC and Cmin decreased by 74%, 72% and 58%, respectively. Staggering the doses by administering the calcium carbonate antacid 12 hours after raltegravir resulted in minimal changes in raltegravir Cmax and AUC, but Cmin was still reduced by 57%.

MANAGEMENT: Concomitant use of raltegravir with aluminum- and/or magnesium-containing antacids should generally be avoided, even if administration is staggered. Antacids containing calcium carbonate should not be used with once-daily raltegravir (HD formulation), but may be used without dose adjustment for other raltegravir products.

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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.

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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.

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Since raltegravir solubility is increased at higher pH, coadministration with agents that elevate gastric pH may theoretically increase the plasma concentrations of raltegravir. However, concurrent use of proton pump inhibitors or H2-receptor antagonists in clinical trials did not result in meaningful differences in the safety of raltegravir. Based on these data, no dosage adjustment of raltegravir is necessary when used together with proton pump inhibitors or H2-receptor antagonists.

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