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Dolutegravir (S/GSK1349572) with multivitamins or acid reducing agents

hiv-druginteractions.org

Dolutegravir (S/GSK1349572) is an unboosted, once-daily, next-generation HIV integrase inhibitor. The effects of multivitamins (One-A-Day Maximum, single tablet), antacid (Maalox 20 mL single dose with or 2 hours after dolutegravir) and omeprazole (40 mg once daily for 5 days) on single doses of dolutegravir (50 mg) were studied in HIV-negative subjects.

Coadministration of the multivitamin modestly decreased dolutegravir AUC and Cmax by 33% and 35%, respectively.  Concurrent antacid co-administration reduced dolutegravir AUC and Cmax by 74% and 72%, respectively.  Staggered antacid dosing significantly diminished this interaction, with a reduction in dolutegravir AUC of 26% and Cmax of 18%. Omeprazole did not significantly affect dolutegravir exposure (no change in AUC, 9% decrease in Cmax).

Dolutegravir can be taken with proton pump inhibitors and multivitamins without dose adjustment but should be administered 2 hours before or 6 hours after antacids. The mechanism of the antacid interaction with dolutegravir is likely to result from chelation with metal cations in the antacid rather than an effect of pH and would be consistent with the omeprazole data.

Source: hiv-druginteractions.org (23 June 2011).

Ref: Patel P et al. Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. J Antimicrob Chemother, 2011, 66(7): 1567-1572.

http://www.ncbi.nlm.nih.gov/pubmed/21493648

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