N-acetylcysteine treatment and the risk of toxic reactions to trimethoprim-sulphamethoxazole in primary Pneumocystis carinii prophylaxis in HIV-infected patients.
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.
Akerlund
B
B
Department of Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Sweden.
Tynell
E
E
Bratt
G
G
Bielenstein
M
M
Lidman
C
C
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D003545:Cysteine / Q000172:deficiency; D005076:Exanthema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D011010:Pneumocystis; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine