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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31829ecd3b
Clinical Science

Pharmacokinetics of Once-Daily Boosted Elvitegravir When Administered in Combination With Acid-Reducing Agents

Ramanathan, Srinivasan PhD; Mathias, Anita PhD; Wei, Xuelian PhD; Shen, Gong PhD; Koziara, Joanna PhD; Cheng, Andrew MD, PhD; Kearney, Brian P. PharmD

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Background: Acid-reducing agents are commonly used co-medications by HIV-1–infected patients receiving antiretroviral treatment. The effects of various representative acid-reducing agents on the pharmacokinetics (PK) of boosted elvitegravir were evaluated by 1-way interaction in 4 studies.

Methods: Healthy subjects received ritonavir-boosted elvitegravir (EVG/r; 50/100 mg QD) administered alone or with antacid simultaneously in Study 1, staggered (±2 or ±4 hours) or with omeprazole in Study 2; Studies 3 and 4 evaluated cobicistat-boosted elvitegravir (EVG/co; 150/150 mg QD) administered simultaneously or staggered (+12 hours) with famotidine or omeprazole. Lack of PK alteration was defined as 90% confidence intervals about the geometric least squares means ratio (coadministration:alone) being within 70%–143% for elvitegravir Cmax (maximum concentration), Ctau (trough), and AUCtau (area under plasma concentration–time curve; 0–24 hours); cobicistat PK were explored.

Results: EVG exposures were 40%–50% lower upon simultaneous dosing of EVG/r and antacids, probably due to local complexation with cations in gastrointestinal tract, and were unaffected with ≥2 hours staggered dosing. No relevant drug interactions were observed between EVG/co and famotidine or between EVG/r or EVG/co and omeprazole, indicating the absence of a broader pH effect on boosted EVG PK. In all studies, study treatments were well tolerated, with adverse events being generally mild to moderate in severity and primarily gastrointestinal disorders.

Conclusions: There are no clinically relevant interactions between boosted elvitegravir, and thus elvitegravir/cobicistat/emtricitabine/tenofovir DF single-tablet regimen, and H2-receptor antagonists or proton pump inhibitors; staggered antacid administration by ≥2 hours is recommended.

© 2013 by Lippincott Williams & Wilkins


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