Hansen's Disease (Leprosy)

Current and Future Pharmacotherapy and Treatment of Disease-related Immunologic Reactions

Davey P. Legendre, Pharm.D.; Christina A. Muzny, M.D.; Edwin Swiatlo, M.D., Ph.D.

Disclosures

Pharmacotherapy. 2012;32(1):27-37. 

In This Article

Dapsone

Sulfones have long been the cornerstone for treatment of Hansen's disease. Dapsone exerts weakly bactericidal activity against M. leprae by inhibiting dihydropteroate synthase, ultimately preventing folic acid synthesis. In a mouse footpad model, oral dapsone therapy killed 99.4% of viable organisms as evidenced by a lag of an average of 78 days for M. leprae growth curves in dapsone-treated versus control animals.[39] It is taken orally once/day with or without meals, with nearly complete absorption and peak serum concentrations of 2–8 hours. There is no dosage adjustment needed for patients with renal dysfunction, but patients with hepatic impairment should be monitored closely. Dapsone may cause hepatitis and cholestatic jaundice, but no dosage adjustment guidelines are available for those with liver disease.

Dapsone was initially used as monotherapy, but resistance, estimated at 2–10%, has become problematic.[40] One proposed mechanism of resistance is a mutant folP1 gene, which encodes a resistant dihydropteroate synthase capable of folic acid synthesis under a variety of extreme conditions.[41] In an effort to prevent the emergence of resistance expected with monotherapy, multidrug therapy is the standard of care.

The adverse effects of dapsone can be quite limiting with the most profound being methemoglobinemia and hemolysis related to glucose-6-phosphate dehydrogenase (G6PD) deficiency.[42] All patients should be screened for G6PD deficiency before starting dapsone, and those with mild G6PD deficiency may be started at 25 mg/day with close monitoring.[35] Dapsone is used in pregnant patients, although it is a category C drug. It is excreted substantially in breast milk and is potentially harmful to nursing infants with G6PD deficiency. Cutaneous manifestations that may be confused with worsening disease are also possible, sometimes accompanied with lymphadenopathy, fever, hepatitis, leukopenia, anemia, and acute psychosis.[43] There are also reports of peripheral neuropathy, although this adverse effect is rare.[44]

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