Brand name: Dapsone Aczone™

Description: Used to treat leprosy and skin infections.

Dapsone is a versatile drug. It is a synthetic sulfone and is chemically similar to sulfonamides, but cross-sensitivity has not been substantiated. It is used as an antiinfective (for leprosy, Pneumocystis carinii pneumonia (PCP), and prophylaxis of malaria) and as an immunosuppressive agent (for relapsing polychondritis and systemic lupus erythematosus). Dapsone also has been used to treat various dermatologic disorders such as actinomycotic mycetoma, dermatitis herpetiformis, pemphigoid, subcorneal pustular dermatosis, granuloma annulare, and pyoderma gangrenosum.

In addition, dapsone is commonly used to treat Loxosceles reclusa (e.g., brown recluse spider) bites; however, both human and animal data to support its routine use are conflicting. A few case reports and small case series indicate efficacy in humans, but prospective human trials supporting its use are not available. Furthermore, in addition to the lack of evidence to support its use, dapsone can cause serious, life-threatening toxicities (e.g., hemolytic anemia, hepatitis, methemoglobinemia). A prospective epidemiologic study found that patients treated with dapsone for suspected loxoscelism experienced a nonsignificant increase in healing time and scarring.

The benefits of administering dapsone for the treatment of loxoscelism should be carefully balanced against the risks; supportive therapy and wound care are the treatment modalities of choice in patients presenting with loxoscelism.[8838] [8840] Dapsone is currently the agent of choice in the treatment of all forms of leprosy, unless the organism exhibits dapsone resistance. Dapsone can be used for prophylaxis of PCP either as a single agent or in combination with pyrimethamine. In combination with trimethoprim, dapsone is effective for treatment of PCP.[189] In combination with pyrimethamine, dapsone is effective for prevention of toxoplasmosis in patients with AIDS.[191] Acedapsone is a long-acting repository form. In Canada, a commonly used brand name of oral dapsone is Alvosulfon.

Dapsone was originally approved by the FDA in 1955. A 5% topical dapsone gel (Aczone™) was approved for use in treating acne vulgaris on July 7, 2005.

Mechanism of Action: Similar to sulfonamides, dapsone inhibits dihyropteroate synthase in susceptible organisms. Other proposed mechanisms for dapsone include inhibition of the neutrophilic-cytotoxic system and interference with the alternate pathway of the complement system. Although the mechanism of dapsone in dermatologic disorders is unknown, it has been suggested that it may act as an immunomodulator.

For many years, dapsone was the main therapy for leprosy (Mycobacterium leprae). Unfortunately, years of monotherapy has lead to significant resistance in this organism. Resistance to M. leprae develops in 2—10% of patients after prolonged administration. Nevertheless, dapsone remains a component of combination therapy for leprosy.

Pharmacokinetics:

Dapsone is administered orally and is almost completely absorbed from the GI tract. Peak serum levels are reached in 2—8 hours. Dapsone is widely distributed and is retained in the skin, muscles, kidneys, and liver. The drug also crosses the placenta and is distributed into breast milk (see Contraindications).

Dapsone and its primary acetylated metabolite, monoacetyldapsone (MADDS), undergo enterohepatic recirculation. Acetylation is accomplished via N-acetyltransferase. Unlike with other acetylated compounds, slow and fast acetylators have exhibited no differences in pharmacokinetics, side effects, or therapeutic response. Minor metabolites include diacetyl derivatives and hydroxylamine dapsone (NOH-DDS). The latter metabolite appears to be associated with methemoglobinemia and hemolysis, which have been reported during therapy. The hydroxylamine metabolite is primarily produced by N-hydroxylation via CYP3A and CYP2C9 enzymes. The average half-life of both dapsone and MADDS is 30 hours. About 20% of a dose is excreted unchanged in the urine, while 70—85% is excreted as metabolites. A small amount can be detected in the feces.