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

Kenneth McIntosh*, Ellen Cooper, Jing Xu, Mark Mirochnick, Jane Lindsey, David Jacobus, Lynne Mofenson, Ram Yogev, Stephen A. Spector, John L. Sullivan, Henry Sacks, Andrea Kovacs, Sharon Nachman, John Sleasman, Vincent Bonagura, James McNamara

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background. Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprimsulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (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 occurrence 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 toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment. Conclusion. Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.

Original languageEnglish (US)
Pages (from-to)432-439
Number of pages8
JournalPediatric Infectious Disease Journal
Volume18
Issue number5
DOIs
StatePublished - May 1 1999

Keywords

  • Dapsone
  • Pediatric human immunodeficiency virus infection
  • Pneumocystis carinii pneumonia

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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