trimethoprim--sulfamethoxazole-drug-combination and Pruritus

Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two-arm trial designed to determine whether gradual initiation of TMP/SMX suspension reduced the incidence of treatment-limiting adverse drug reactions compared with routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372 HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had not previously received TMP/SMX for PCP prophylaxis were randomized to receive either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX suspension. The suspension dose was increased to reach the equivalent of a DS tablet by study day 13. During the first 2 weeks, study subjects also received a matching placebo tablet/suspension. After week 2, all study subjects received TMP/SMX tablets for the next 10 weeks. There were significantly fewer study subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX therapy was initiated gradually (17%) than when initiated in DS tablet formulation (33%) (p =.0002). Gradual initiation was also associated with significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Eruptions; Female; Fever; HIV Infections; HIV-1; Humans; Male; Nausea; Pneumonia, Pneumocystis; Pruritus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Child, Preschool; Chlorpheniramine; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV; HIV Infections; Humans; Nigeria; Prednisolone; Pruritus; Skin Tests; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Allopurinol; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Carbamazepine; Child; Drug Combinations; Drug Eruptions; Eosinophilia; Exanthema; Female; Glucosamine; Gout Suppressants; Humans; Male; Middle Aged; Pruritus; Retrospective Studies; Sulfasalazine; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Drug Eruptions; Female; Fever; Humans; Leukopenia; Liver Function Tests; Middle Aged; Pruritus; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination