Clinical Review
Dapsone and sulfones in dermatology: Overview and update☆

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Abstract

In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been used successfully to treat a range of dermatologic disorders, most successfully those characterized by abnormal neutrophil and eosinophil accumulation. This article reviews and updates the chemistry, pharmacokinetics, clinical application, mechanism of action, adverse effects, and drug interactions of dapsone and the sulfones in dermatology. (J Am Acad Dermatol 2001;45:420-34.)

Section snippets

Chemistry of sulfones

Dapsone (4-4′-diaminodiphenylsulfone, DDS) is structurally the simplest of the sulfones, all of which share the characteristic structure: a sulfur atom linking to two carbon atoms (Fig 1).

. Structures of dapsone and sulfoxone sodium.

Absorption

Orally ingested dapsone is absorbed readily from the gastrointestinal tract with bioavailability of more than 86%.19 Absorption is reduced in severe leprosy.20 The disubstituted sulfones, such as sulfoxone, are poorly absorbed after oral administration, and large amounts are excreted in the feces.21 In healthy volunteers, after 100 mg of oral dapsone, peak serum dapsone concentrations between 1.10 and 2.33 mg/L were reached within 0.5 to 4 hours.22 The elimination half-life ranged from 12 to 30

Antimicrobial action

As an antibiotic, dapsone acts in the same way as sulfonamides, inhibiting the synthesis of dihydrofolic acid through competition with para-aminobenzoate for the active site of dihydropteroate synthetase.45 Therefore dapsone inhibits the growth of microorganisms that are dependent on endogenous folic acid synthesis.

Anti-inflammatory action

Dapsone is effective in dermatoses with abnormal neutrophil accumulation, through many potential mechanisms. Dapsone interferes with neutrophil chemotactic migration46 and β2

Clinical indications

Dapsone is both an antibiotic and an anti-inflammatory agent. It is bacteriostatic against Mycobacterium leprae and is an essential component of leprosy treatment. It has also been used successfully to treat actinomycetoma,64, 65, 66 in prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP),67, 68, 69 and for malaria.70

As an anti-inflammatory agent, dapsone has been used to treat many skin diseases characterized by the abnormal infiltration of neutrophils or eosinophils, such as

Adverse effects

Overall, the risk of dapsone-dependent side effects is very low if the plasma concentration is below 5 mg/L.24 Although the therapeutic range for leprosy was estimated to be 0.5 to 5 mg/L, the ranges for other indications are not known. Metabolism of dapsone by cytochrome P-450 to hydroxylamines is responsible for some dapsone side effects including methemoglobinemia, hemolysis, and fatal agranulocytosis, but the mechanism by which hydroxylamines cause these side effects is unclear (Table III).

How to increase tolerance to dapsone

Use of a metabolic inhibitor such as cimetidine to reduce hepatic oxidation of dapsone to hydroxylamine has successfully decreased its adverse effects.181 Methemoglobin formation in the presence of cimetidine was maintained at 30% below control levels for almost 3 months, and the incidence of reported side effects such as headache and lethargy were significantly reduced.182 Long-term concurrent cimetidine administration increased plasma dapsone levels without increased hemolysis and reduced

Use during pregnancy and lactation

Pregnancy may be a trigger of leprosy and other dermatologic diseases because of the changes in cell-mediated and humoral immunity during gestation.186, 187 First appearance of leprosy, reactivation of the disease, and relapse in “cured” patients are likely to occur particularly in the third trimester of pregnancy.188 Because up to 20% of children born to mothers with leprosy may experience leprosy by puberty,188 pregnant women with leprosy require treatment.

Treatment with dapsone for various

Drug interactions

Drugs that affect the pharmacokinetics and efficacy of dapsone are listed in Table V.

. Drugs affecting dapsone and other sulfones

Names of drugsEffects on dapsone
TrimethoprimIncreases plasma concentration and adverse effects of dapsone248
RifampinInduces dapsone metabolism by causing a proliferation of the smooth endoplasmic reticulum and an increase of cytochrome P-450 content in the liver249; also enhances urinary excretion of dapsone250
Pyrimethamine (together with dapsone as Maloprim)Increases

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    Reprint requests: Matthew J. Stiller, MD, Department of Dermatology, New York-Presbyterian Medical Center, 161 Fort Washington Ave, New York, NY 10032.

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    Copyright © 2001 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.