Aluminium and magnesium containing antacids reduce raltegravir plasma levels. Co-administration of raltegravir (400 mg twice daily and 1,200 mg once daily) with aluminium and/or magnesium containing antacids is not recommended. No dose adjustment is required for raltegravir (400 mg twice daily) with calcium carbonate antacid; co-administration of raltegravir (1,200 mg once daily) and calcium carbonate antacid is not recommended. When raltegravir (400 mg twice daily) and an antacid containing aluminium and magnesium hydroxide were administered simultaneously, raltegravir AUC, C12 and Cmax decreased by 49%, 63% and 44%. Coadministration of the antacid 2 h before raltegravir decreased raltegravir AUC, C12 and Cmax by 51%, 56% and 51%. Coadministration of the antacid 2 h after raltegravir decreased raltegravir AUC, C12 and Cmax by 30%, 57% and 24%. Coadministration of the antacid 6 h before raltegravir decreased raltegravir AUC, C12 and Cmax by 13%, 50% and 10%. Coadministration of the antacid 6 h after raltegravir decreased raltegravir AUC, C12 and Cmax by 11%, 49% and 10%. Coadministration of an antacid containing aluminium and magnesium hydroxide 6 h after raltegravir (1,200 mg single dose) decreased raltegravir AUC, C12 and Cmax by 14%, 58% and 14%. Simultaneous coadministration of raltegravir (400 mg twice daily) with a calcium carbonate antacid decreased raltegravir AUC, C12 and Cmax by 55%, 32% and 52%, respectively. Simultaneous coadministration of raltegravir (1,200 mg single dose) with a calcium carbonate antacid decreased raltegravir AUC, C12 and Cmax by 72%, 48% and 74%, respectively. Coadministration of the antacid 12 h after raltegravir decreased raltegravir AUC, C12 and Cmax by 10%, 57% and 2%.
Isentress Summary of Product Characteristics, Merck Sharp & Dohme Ltd, September 2021.

Aluminium and/or magnesium containing antacids decrease raltegravir concentrations. Coadministration or staggered administration is not recommended with twice daily or once daily raltegravir. Calcium carbonate antacid decreases raltegravir concentrations. No dose adjustment is required with twice daily raltegravir; coadministration is not recommended with once daily raltegravir. 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=18). 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 decreased raltegravir Cmax, AUC and Cmin by 10%, 11% and 49% (n=16). Coadministration of the antacid 12 h after raltegravir (1200 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 14%, 14% and 58% (n=19). Simultaneous coadministration of raltegravir (400 mg twice daily) with a calcium carbonate antacid (3000 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 52%, 55% and 32% (n=24). Simultaneous coadministration of raltegravir (1200 mg single dose) with a calcium carbonate antacid (3000 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 74%, 72% and 48% (n=19). Coadministration of the antacid 12 h after raltegravir (1200 mg single dose) decreased raltegravir Cmax, AUC and Cmin by 2%, 10% and 57% (n=19).
Isentress Prescribing Information, Merck & Co Inc, August 2021.

Coadministration of raltegravir (400 mg single dose) and an antacid containing aluminium/magnesium hydroxide (Maalox Plus, 30 ml single dose) was studied in HIV-negative subjects. Simultaneous coadministration decreased raltegravir Cmax, Cmin and AUC by 5%, 27% and 17%, respectively (n=11). When the antacid was administered 2 h before raltegravir, raltegravir Cmax, Cmin and AUC decreased by 15%, 37% and 22%, respectively (n=10).
The effect of antacids and multivitamins on raltegravir. Reynolds H, Lewis J, Egan D, et al. CROI 2018, Boston, March 2018, abstract 470.

The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in 20 HIV-infected patients. Drug administration was as follows: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as Tums® Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (period 2), magnesium/aluminium hydroxide antacid as 20 ml Maalox® Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS® US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Metal-cation antacids variably affected the pharmacokinetics of 1200 mg once daily raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC0-24 , Cmax and C24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg once daily dosing, the GMR (90% CI) values for AUC0-24 and Cmax were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively. Overall, the use of metal-cation antacids with 1200 mg once daily raltegravir is not recommended.
Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir. Krishna R, et al. J Pharm Pharmacol, 2016, 68 (11): 1359-65.

The pharmacokinetics of single-dose raltegravir (400 mg) were studied in healthy volunteers with and without an antacid (Maalox Plus containing both magnesium and aluminium hydroxide).  Although raltegravir AUC and Cmax were unchanged with simultaneous antacid administration, the time to peak occurred 2 hours sooner and there was a 67% reduction in C12h. The authors speculate that antacid may have two effects on raltegravir pharmacokinetics.  First to cause a faster and more uniform dissolution (earlier Tmax and less variability) and secondly binding of raltegravir to the antacid which offsets the potential for an increase in extend of absorption.  However, it is not known if the reduction in raltegravir C12h would compromise the efficiency of the drug.
Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Kiser J, Bumpass JB, Meditz AL, et al. Antimicrob Agents Chemother, 2010, 54(12): 4999-5003.

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.
Moss DM, Siccardi M, Murphy M et al. Divalent metals and pH alter raltegravir disposition in vitro. Antimicrob Agents Chemother. 2012, 56(6): 3020-6.