A randomized trial of N-acetylcysteine for prevention of trimethoprim-sulfamethoxazole hypersensitivity reactions in Pneumocystis carinii pneumonia prophylaxis (CTN 057). Canadian HIV Trials Network 057 Study Group.
Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.
Walmsley
S L
SL
Department of Medicine, University of Toronto, Ontario, Canada. swalmsley@torhosp.toronto.on.ca
Khorasheh
S
S
Singer
J
J
Djurdjev
O
O
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D011322:Primary Prevention; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D016166:Free Radical Scavengers; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000111:Acetylcysteine