Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus

Background. Dapsone is an alternative drug for Pneumocystis carinii pneumon ia (PCP) prophylaxis in individuals intolerant to trimethoprimsulfamethoxaz ole (T/S). There are, however, few data on the pharmacokinetics, toxicity o r efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with w eekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S. Methods. Hematologic and hepatic toxicity was monitored, as well as the occ urrence of skin rash, PCP or death. Results. Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic t oxicities were marginally greater in children receiving the daily 2 mg/kg c ompared with the weekly regimen. Allergic skin rashes were similar in child ren receiving the daily and weekly regimens (17% in both) and were not asso ciated with prior history of rash with T/S. PCP occurred most frequently wi th the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequent ly with the daily 2-mg/kg regimen (0 case/100 patient years) and at interme diate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regim en (8 vs. 2, respectively), although the deaths were not directly attributa ble to dapsone treatment. Conclusion. Although a weekly dapsone regimen of 4 mg/kg produced less hema tologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.