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Minimal Erythema Dose (MED) Testing
Published on: May 28, 2013
Dapsone-induced methemoglobinemia: a dose-related occurrence?
Adam J Esbenshade1, Richard H Ho, Ayumi Shintani
1Department of Pediatrics, Vanderbilt University School of Medicine and the Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN 37232, USA. adam.esbenshade@vanderbilt.edu
Cancer
|January 20, 2011
Summary
Higher dapsone doses increase methemoglobinemia risk in pediatric oncology patients receiving it for Pneumocystis pneumonia (PCP) prophylaxis. Cytochrome b5 reductase enzyme activity did not influence this risk.
Area of Science:
- Pediatric Oncology
- Pharmacology
- Hematology
Background:
- Dapsone is frequently used for Pneumocystis pneumonia (PCP) prophylaxis in pediatric oncology.
- Dapsone use is linked to an increased risk of methemoglobinemia.
- The role of cytochrome b5 reductase enzyme activity in dapsone-associated methemoglobinemia is not well understood.
Purpose of the Study:
- To investigate drug-related risk factors for dapsone-associated methemoglobinemia in pediatric oncology patients.
- To determine the contribution of cytochrome b5 reductase enzyme activity to this adverse event.
Main Methods:
- Retrospective analysis of demographic and dapsone treatment data from 167 pediatric patients.
- Evaluation of risk factors using Cox proportional hazards models.
- Assessment of cytochrome b5 reductase enzyme activity in a subgroup of 40 patients.
Main Results:
- Methemoglobinemia was observed in 19.8% of patients.
- Dosing above the target dose (2 mg/kg/d) significantly increased methemoglobinemia risk (HR, 6.25).
- Dosing below the target dose reduced risk (HR, 0.27).
- Cytochrome b5 reductase enzyme activity levels did not differ between patients with and without methemoglobinemia.
Conclusions:
- Methemoglobinemia is a significant risk in pediatric oncology patients on dapsone for PCP prophylaxis.
- Dapsone dosage is a critical factor influencing methemoglobinemia risk.
- Cytochrome b5 reductase enzyme activity does not appear to be a significant risk factor.
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