Lexiva: Blood Levels Not Lowered When Taken Simultaneously With Nexium

On April 29, 2005 GlaxoSmithKline announced that a drug-interaction trial of Lexiva (fosamprenavir) with Nexium (esomeprazole, a proton-pump inhibitor, often used to reduce stomach acidity for relief of reflux, the unwanted flow of stomach acid into the esophagus), had found no reduction in the in the blood level of amprenavir. The data were presented at the 6th International Workshop on Clinical Pharmacology of HIV Therapy, in Quebec.¹

The FDA-approved "label" for Lexiva (the official prescribing information for physicians) urges caution in using the drug together with proton-pump inhibitors, because experience with other drugs suggested that the blood level of the antiviral might be decreased, making it less effective (no test with Lexiva and Nexium had been done). But the company's randomized crossover trial in 48 HIV-negative volunteers who took Lexiva for two weeks with Nexium, and later for two weeks without, found that this did not happen, at least with the 20 mg dose of Nexium tested (the drug is supplied in 20 and 40 mg doses) -- whether or not the Lexiva was "boosted" with a small dose of Norvir.

There was speculation that the timing of the doses might be important -- that because they were taken simultaneously in this study, the Lexiva might be absorbed before the Nexium had time to reduce stomach acidity. A previous study had shown a 30% reduction in blood concentration of amprenavir when Zantac (another drug for reducing stomach acidity) was given one hour before Lexiva.²

Currently (June 2005) the official prescribing information is still the December 2004 version. Glaxo is seeking FDA permission to change it, in view of the new data. Any version with a later date should reflect the FDA's evaluation of the new information.

The current prescribing information is available here. Look for the date at the end of the file.

Note: At the same conference Glaxo presented a similar study showing that tenofovir (Viread) did not affect amprenavir levels when used with Lexiva. This is consistent with prior information.

Comment

We urgently need more drug-interaction trials to guide physicians and reduce guesswork when multiple medications are prescribed. Companies that try to save money by skipping these trials put at risk a far larger investment, if their major drugs cannot be used optimally. These trials could aim for simple rules (such as choice of acid-reducing drugs, and delays when necessary) to avoid problems with antiretrovirals or other critical drugs that require stomach acidity in order to be fully absorbed. And small drug-level tests should check that results developed with HIV-negative volunteers do work for HIV-positive patients.

References

1. Shelton MJ, Ford SL, Wire MB, and others. Coadministration of esomeprazole (ESO) with fosamprenavir (fAPV) has no impact on steady-state plasma amprenavir (APV) pharmacokinetics (APV10031). 6th International Workshop on Clinical Pharmacology of HIV Therapy, April 28-30, 2005, Quebec City, Quebec [Abstract 24].

2. See "Gastric pH Modifiers" section on the Medscape (you need to register first, but that is free).

ISSN # 1052-4207

Copyright 2005 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.