Raltegravir + Aluminum = Prohibited

Effect on Concentration

Raltegravir
Decrease
Applies within class?
No
Aluminum
Unknown
Applies within class?
No

Pharmacologic Effects

Raltegravir
Effect
N/A
Applies within class?
No
Aluminum
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Divalent metals and pH alter raltegravir disposition in vitro. ^

Study Design

This was a randomized, crossover study of 12 subjects to determine the effects of an antacid containing aluminum, magnesium and simethicone on the pharmacokinetics of a single dose of raltegravir (RAL) in HIV-seronegative adult men and women. Subjects received an oral dose of 400mg of raltegravir, with or without 30ml of an antacid containing aluminum, magnesium and simethicone (Maalox Plus Extra Strength). Twelve blood samples were obtained within 24 hours of study medication ingestion and then at 48 hours for each group. After a 5-12 day washout, subjects returned to crossover into the other group and obtain the same blood sampling over a 48 hour period. In a separate study conducted by the manufacturer, the effect of an antacid containing magnesium and aluminum on the pharmacokinetics (PK) of raltegravir was evaluated using several different dosing schedules as follows: 20ml single dose antacid given with RAL, as well as 20ml single dose given 2, 4 and 6 hours before and after administration of RAL. RAL was administered as 400mg BID.

Study Results

For the first study, RAL AUC(0-12) and Cmax were not significantly changed in either group. However, the Tmax had a significant change to 1hr versus 3hr and the C12 was significantly lower, with 9 of 12 subjects having a C12 <15ng/ml (the IC95 for raltegravir). The authors did note interindividual variability in the extent of the interaction. Using geometric mean ratios and 90% confidence intervals, the Cmax, AUC and Cmin of RAL observed in the manufacturer's study were as follows: -RAL + antacid (n=25): 0.56 (0.42-0.73), 0.51 (0.40-0.65) and0.37 (0.29-0.48), respectively. -2 hrs before RAL (n=23): 0.49 (0.33-0.71), 0.49 (0.35-0.67) and 0.44 (0.34-0.55), respectively. -2 hrs after RAL (n=23): 0.78 (0.53-1.13), 0.70 (0.50-0.96) and 0.43 (0.34-0.55), respectively. -4 hrs before RAL (n=17): 0.78 (0.55-1.10), 0.81 (0.63-1.05) and 0.40 (0.31-0.52), respectively. -4 hrs after RAL (n=18): 0.70 (0.48-1.04), 0.68 (0.50-0.92) and 0.38 (0.30-0.49), respectively. -6 hrs before RAL (n=16): 0.90 (0.58-1.40), 0.87 (0.64-1.18) and 0.50 (0.39-0.65), respectively. -6 hrs after RAL (n=16): 0.90 (0.58-1.41), 0.89 (0.64-1.22) and 0.51 (0.40-0.64), respectively.

Study Conclusions

The manufacturer states that coadministration or staggered administration (2 hours before or 2 hours after) of magnesium hydroxide-aluminum containing antacids with RAL is not recommended.

References

Moss DM, Siccardi M, Murphy M, Piperakis MM, Khoo SH, Back DJ, Owen A. Divalent metals and ph alter raltegravir disposition in vitro. Antimicrobial Agents And Chemotherapy . 2012; 6: 3020-3026.