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CROI 2006; Denver, Colorado; February 5-8, 2006

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The Body Covers: The 13th Conference on Retroviruses and Opportunistic Infections
Acid-Reducing Agents Reduce Atazanavir Drug Levels but Not Lopinavir/Ritonavir Levels

February 7, 2006

Some protease inhibitors (PIs) -- notably atazanavir (ATV, Reyataz) -- have impaired absorption when coadministered with acid-reducing agents. In addition, antacids, H2 blockers and proton pump inhibitors are available over-the-counter and widely used in both the HIV-infected and HIV-uninfected populations. This industry-sponsored study evaluated the effect of the H2 blocker ranitidine (Tritec, Zantac) and the proton pump inhibitor omeprazole (Prilosec) on the pharmacokinetics of the new tablet formulation of lopinavir/ritonavir (LPV/r, Kaletra) and boosted atazanavir.

Seventy-one healthy seronegative adults were enrolled into this multiple dose, pharmacokinetic study. Patients received one of three PI regimens:

  1. lopinavir/ritonavir tablets twice daily,

  2. lopinavir/ritonavir once daily or

  3. atazanavir + ritonavir (RTV, Norvir) once daily.

After receiving these regimens for 10 days, trial participants then received either five days of omeprazole 40 mg a day or ranitidine 150 mg for one day.

Serial plasma samples were obtained for lopinavir, ritonavir and atazanavir both with and without the acid-reducing agents. Using several different pharmacokinetic parameters, neither the use of omeprazole nor ranitidine altered exposure to lopinavir or ritonavir. By contrast, atazanavir exposure was reduced by 48%-62% with both drugs, contrasting an earlier report in which atazanavir levels were not influenced by famotidine (Pepcid) administration.

These results encouragingly show no drug-drug interaction with lopinavir/ritonavir tablets and acid-reducing agents, while confirming that stomach acid is required for adequate atazanavir absorption. Since acid-reducing drugs of all types are over-the-counter and heavily marketed directly to consumers, physicians may not be aware that their patients are taking these drugs. Clinicians should remember to ask patients specifically about both proton pump inhibitor and H2 blocker use even if they are not prescribed.


Abstract: Lack of effect of acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir tablet (Poster 578)
Authored by: C Klein, YL Chiu, Y Cai, K Beck, K King, S Causemaker, T Doan, HU Esslinger, T Podsadecki, and G Hanna

Affiliations: Abbott Labs, Abbott Park, IL, US; Abbott GmbH & Co KG Ludwigshafen, German
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