Co-administration of raltegravir with aluminium and/or magnesium antacids is not recommended. Co-administration of raltegravir with antacids containing divalent metal cations may reduce raltegravir absorption by chelation, resulting in a decrease of raltegravir plasma levels. Taking an aluminium and magnesium antacid within 6 hours of raltegravir administration significantly decreased raltegravir plasma levels. When raltegravir (400 mg twice daily) and an antacid containing aluminium and magnesium hydroxide (20 ml single dose) were administered simultaneously, raltegravir AUC, Cmin and Cmax decreased by 49%, 63% and 44%. Coadministration of the antacid 2 h before raltegravir decreased raltegravir AUC, Cmin and Cmax by 51%, 56% and 51%. Coadministration of the antacid 2 h after raltegravir decreased raltegravir AUC, Cmin and Cmax by 30%, 57% and 24%. Coadministration of the antacid 6 h before raltegravir decreased raltegravir AUC, Cmin and Cmax by 13%, 50% and 10%. Coadministration of the antacid 6 h after raltegravir decreased raltegravir AUC, Cmin and Cmax by 11%, 49% and 10%. Therefore, coadministration of raltegravir with aluminium and/or magnesium-containing antacids is not recommended.
Isentress Summary of Product Characteristics, Merck Sharp & Dohme Ltd, November 2014.

Coadministration or staggered administration of aluminum and/or magnesium hydroxide-containing antacids and raltegravir is not recommended. When raltegravir (400 mg twice daily) and an antacid containing aluminium and magnesium hydroxide (20 ml single dose) were administered simultaneously, raltegravir Cmax, AUC and Cmin decreased by 44%, 49% and 63% (n=25). Coadministration of the antacid 2 h before raltegravir decreased raltegravir Cmax, AUC and Cmin by 51%, 51% and 56% (n=23). Coadministration of the antacid 2 h after raltegravir decreased raltegravir Cmax, AUC and Cmin by 22%, 30% and 57% (n=23). Coadministration of the antacid 4 h before raltegravir decreased raltegravir Cmax, AUC and Cmin by 22%, 19% and 60% (n=17). Coadministration of the antacid 4 h after raltegravir decreased raltegravir Cmax, AUC and Cmin by 30%, 32% and 62% (n=16). Coadministration of the antacid 6 h before raltegravir decreased raltegravir Cmax, AUC and Cmin by 10%, 13% and 50% (n=16). Coadministration of the antacid 6 h after raltegravir decrease raltegravir Cmax, AUC and Cmin by 10%, 11% and 49% (n=16). Therefore, coadministration of raltegravir with aluminium and/or magnesium-containing antacids is not recommended.
Isentress Prescribing Information, Merck & Co Inc, February 2015.

 

The effects of pH, metal salts, and omeprazole on the cellular permeativity of raltegravir were determined using Caco-2 monolayers. Cellular accumulation studies were used to determine the effect of interplay between pH and ABCB1 transport on raltegravir accumulation. Raltegravir cellular permeativity was heavily influenced by changes in extracellular pH, where apical-to-basolateral permeativity was reduced 9-fold (P < 0.05) when apical pH was increased from 5 to 8.5. Raltegravir cellular permeativity was also reduced in the presence of magnesium and calcium. Omeprazole did not alter raltegravir cellular permeativity. Gastrointestinal pH and polyvalent metals can potentially alter the pharmacokinetic properties of raltegravir, and these data provide an explanation for the variability in raltegravir exposure in patients. The evaluation of how divalent-metal-containing products, such as multivitamins, that do not affect gastric pH alter raltegravir pharmacokinetics in patients is now justified.