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N-acetylcysteine treatment and the risk of toxic reactions to trimethoprim-sulphamethoxazole in primary Pneumocystis carinii prophylaxis in HIV-infected patients.

Author(s): Akerlund B, Tynell E, Bratt G, Bielenstein M, Lidman C

Affiliation(s): Department of Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Sweden.

Publication date & source: 1997-09, J Infect., 35(2):143-7.

Publication type: Clinical Trial; Randomized Controlled Trial

In a randomized double blind placebo controlled trial, HIV sero-positive patients with CD4+ cell count less than 200 x 10(6)/l or an AIDS diagnosis were evaluated for drug reactions to trimethoprim-sulphamethoxazole (TMP-SMX) during treatment, including pretreatment, with N-acetylcysteine (NAC) 800 mg daily or placebo. TMP-SMX (one double-strength tablet containing 160 mg of trimethoprim and 800 mg of sulphamethoxazole) was given three times weekly as primary Pneumocystis carinii (PCP) prophylaxis. Thirty percent (n = 15) of the patients experienced adverse reactions 8-20 (mean 12.7) days after starting with TMP-SMX. At entry, low cysteine and glutathione levels in plasma were found in the HIV-positive patients. Age, sex, CD4+ count, plasma cysteine and glutathione levels were not risk factors for adverse reactions to TMP-SMX. However, concomitant therapy with nucleoside analogues was associated with increased risk for TMP-SMX reactions. Oral NAC 800 mg daily was well tolerated, but replenished neither cysteine nor glutathione levels in plasma. NAC 800 mg/day did not significantly decrease the risk of adverse reactions to TMP-SMX in this study, and could thus not be recommended for this purpose. A prolonged pretreatment period and/or higher dose of NAC may be necessary for clinical effect.

Page last updated: 2006-01-31

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