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Systematic (IUPAC) name
Clinical data
Trade names Aczone
AHFS/Drugs.com monograph
MedlinePlus a682128
Pregnancy cat.
Legal status
  • ℞-only (U.S.), POM (UK)
Routes Oral, Topical
Pharmacokinetic data
Bioavailability 70 to 80%
Protein binding 70 to 90%
Metabolism Hepatic (mostly CYP2E1-mediated)
Half-life 20 to 30 hours
Excretion Renal
CAS number 80-08-0 YesY
ATC code D10AX05 J04BA02
PubChem CID 2955
DrugBank DB00250
ChemSpider 2849 YesY
UNII 8W5C518302 YesY
KEGG D00592 YesY
Chemical data
Formula C12H12N2O2S 
Mol. mass 248.302 gmol-1
 YesY (what is this?)  (verify)

Dapsone (diamino-diphenyl sulfone) is an antibacterial most commonly used in combination with rifampicin and clofazimine as multidrug therapy (MDT) for the treatment of Mycobacterium leprae infections (leprosy). It is also second-line treatment for prophylaxis (prevention) against Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (formerly P. carinii) in HIV patients in whom CD4 counts are below 200/mm3.[1]

Dapsone is an odorless white to creamy-white crystalline powder with a slightly bitter taste, used in combination with pyrimethamine in the treatment of malaria.[2][3] Dapsone is commercially available in both topical and oral formulations. Topical dapsone is available in a 5% gel formulation that is sold under the brand name Aczone and is produced by Allergan. Oral dapsone is also available but is less commonly used than other sulfonamide antibiotics, many of which have a lower incidence of adverse effects.[4]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[5]

Medical uses[edit]

As well as being used in leprosy, dapsone can also be used to treat mucous membrane pemphigoid,[6] (an autoimmune blistering disease of skin and mucous membranes), dermatitis herpetiformis and Linear immunoglobulin A dermatosis, (both blistering skin diseases that are effectively treated with a long-time treatment with dapsone), and other skin conditions including lichen planus. Dapsone is also used in the treatment of pyostomatitis vegetans, an oral manifestation of inflammatory bowel disease, commonly seen in patients with ulcerative colitis.

It is also sometimes used to prevent Pneumocystis pneumonia (PCP) in immunosuppressed patients and to treat idiopathic thrombocytopenic purpura.

It is used prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole.[7]

Dapsone is also used to treat Brown recluse spider bites.[8] In presumed cases of brown recluse spider bites, dapsone is often used effectively, but clinical trials do not demonstrate similar effectiveness;[9] however, dapsone may be effective at treating many "spider bites" because many such cases are actually misdiagnosed microbial infections.[10]

Oral dapsone was one of the first medications used to treat moderate to severe acne vulgaris, and is still occasionally prescribed for the treatment of severe and abnormal acne (e.g. acne conglobata and acne fulminans).[11] Oral dapsone is generally reserved for cases where conventional treatments for severe acne, such as isotretinoin and first-line antibiotics, are found to be ineffective.[12] In December 2008, a 5% dapsone gel called Aczone was introduced to the prescription market as a topical treatment for moderate to severe acne.[1]. Preliminary reports suggest that topical dapsone is a safe and moderately effective acne treatment.[13]

Adverse effects[edit]

The dapsone hypersensitivity syndrome develops in 0.5-3.6% of persons treated with the drug, and is associated with a mortality of 9.9%.[14]

Effects on the blood[edit]

The most prominent side-effects of this drug are dose-related hemolysis (which may lead to hemolytic anemia) and methemoglobinemia.[15] About 20% of patients treated with dapsone suffer hemolysis [16] and the side-effect is more common and severe in those with glucose-6-phosphate dehydrogenase deficiency, leading to the dapsone-containing antimalarial combination Lapdap being withdrawn from clinical use.[17][18] A case of hemolysis in a neonate from dapsone in breast milk has been reported.[19] Agranulocytosis occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis.[20] Abnormalities in white blood cell formation, including aplastic anemia, are rare, yet are the cause of the majority of deaths attributable to dapsone therapy.[21][22][23]

Effects on the liver[edit]

Toxic hepatitis and cholestatic jaundice have been reported by the manufacturer. Jaundice may also occur as part of the dapsone reaction or dapsone syndrome (see below). Dapsone is metabolized by the Cytochrome P450 system, specifically isozymes CYP2D6, CYP2B6, CYP3A4, and CYP2C19.[24] Dapsone metabolites produced by the cytochrome P450 2C19 isozyme are associated with the methemoglobinemia side effect of the drug.


When used topically, dapsone can cause mild skin irritation, redness, dry skin, burning and itching. When used together with benzoyl peroxide products, temporary yellow or orange skin discolorations can occur.[25][26]

Other adverse effects[edit]

Other adverse effects include nausea, headache, and rash (which are common), and insomnia, psychosis, and peripheral neuropathy. Effects on the lung occur rarely and may be serious, though are generally reversible.[27]

Dapsone reaction[edit]

Hypersensitivity reactions occur in some patients. This reaction may be more frequent in patients receiving multiple-drug therapy.[28][29][30]

The reaction always involves a rash and may also include fever, jaundice, and eosinophilia.[31][32][33][34][35] In general, these symptoms will occur within the first six weeks of therapy or not at all, and may be ameliorated by corticosteroid therapy.[7]

Mechanism of action[edit]

As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthetase.[36] Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way.

When used for the treatment of skin conditions in which bacteria do not have a role, the mechanism or action of dapsone is not well understood. Dapsone has anti-inflammatory and immunomodulatory effects,[37] which are thought to come from the drug's blockade of myeloperoxidase. This is thought to be its mechanism of action in treating dermatitis herpetiformis.[38]

As part of the respiratory burst that neutrophils use to kill bacteria, myeloperoxidase converts hydrogen peroxide (H2O2) into hypochlorous acid (HOCl). HOCl is the most potent oxidant generated by neutrophils, and can cause significant tissue damage during inflammation. Dapsone arrests myeloperoxidase in an inactive intermediate form, reversibly inhibiting the enzyme. This prevents accumulation of hypochlorous acid, and reduces tissue damage during inflammation.[39][40][41][42][43]

Myeloperoxidase inhibition has also been suggested as a neuron-sparing mechanism for reducing inflammation in neurodegenerative diseases such as Alzheimer's disease and stroke.[44]

Though dapsone is an anti-inflammatory agent and not a steroid, it does not fit the usual definition of an NSAID. By definition, NSAIDs block cyclo-oxygenase as their primary mechanism of action, which dapsone does not do.


To deal with dapsone-resistant leprosy cases, multidrug therapy was introduced by WHO in 1981; dapsone is administered along with rifampin and clofazimine or other antileprotic drugs.

Specific considerations[edit]

Certain patients are at higher risks of adverse effects when using dapsone. Some specific issues that should be considered are:[7]

  • Related to allergy:
    • Sulfonamide allergy is associated with dapsone allergy

Patients with Diabetes mellitus have been seen to exhibit unexpectedly low HbA1c results when taking Dapsone, and HbA1c i an unreliable test in states of increased red cell turnover, e.g. a drug induced haemolytic anaemia.


In the early 20th century, the German chemist Paul Ehrlich was developing theories of selective toxicity based largely on the ability of certain dyes to kill microbes. Gerhard Domagk, who would later win a Nobel Prize for his efforts, made a major breakthrough in 1932 with the discovery of the antibacterial prontosil red (sulfonamidochrysoidine). Further investigation into the involved chemicals opened the way to sulfa drug and sulfone therapy, first with the discovery of sulfanilamide, the active agent of prontosil, by Daniel Bovet and his team at Pasteur Institute (1935),[45] then with of dapsone independently by Ernest Fourneau[46] in France and Gladwin Buttle[47] in United-Kingdom.[48]


  1. ^ Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine, by Sabatine, 3rd Edition
  2. ^ Croft, A. M. (Nov 2007). "Malaria: prevention in travellers". Clinical evidence 2007: 0903. PMC 2943798. PMID 19450348.  edit
  3. ^ Alkadi, H. O. (2007). "Antimalarial drug toxicity: a review". Chemotherapy 53 (6): 385–391. doi:10.1159/000109767. ISSN 0009-3157. PMID 17934257.  edit
  4. ^ Zhu, et al., YI; Stiller, MJ (2001). "Dapsone and sulfones in dermatology: overview and update". Journal of the American Academy of Dermatology 45 (3): 420–34. doi:10.1067/mjd.2001.114733. PMID 11511841. 
  5. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  6. ^ Rogers RS, Seehafer JR, Perry HO (February 1982). "Treatment of cicatricial (benign mucous membrane) pemphigoid with dapsone". J. Am. Acad. Dermatol. 6 (2): 215–. doi:10.1016/S0190-9622(82)70014-3. PMID 7037880. 
  7. ^ a b c Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide. ISBN 0-9757919-2-3. 
  8. ^ Rees RS, Altenbern DP, Lynch JB, King LE (November 1985). "Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision". Ann. Surg. 202 (5): 659–63. doi:10.1097/00000658-198511000-00020. PMC 1250983. PMID 4051613. 
  9. ^ Elston, DM; Miller, SD; Young Rj, 3rd; Eggers, J; McGlasson, D; Schmidt, WH; Bush, A (2005). "Comparison of colchicine, dapsone, triamcinolone, and diphenhydramine therapy for the treatment of brown recluse spider envenomation: A double-blind, controlled study in a rabbit model". Archives of dermatology 141 (5): 595–7. doi:10.1001/archderm.141.5.595. PMID 15897381. 
  10. ^ Vetter R, Bush S (2002). "The diagnosis of brown recluse spider bite is overused for dermonecrotic wounds of uncertain etiology". Ann Emerg Med 39 (5): 544–6. doi:10.1067/mem.2002.123594. PMID 11973562. 
  11. ^ Ross, et al., CM (1961). "The treatment of acne vulgaris with dapsone". British Journal of Dermatology 73 (10): 367–70. doi:10.1111/j.1365-2133.1961.tb14398.x. PMID 14494150. 
  12. ^ "Dapsone and Acne Vulgaris". ScienceOfAcne.com. 2012-10-10. Retrieved 2012-08-17. 
  13. ^ Draelos, et al., ZD; Carter, E; Maloney, JM; Elewski, B; Poulin, Y; Lynde, C; Garrett, S; United States/Canada Dapsone Gel Study Group (2007). "Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris". Journal of the American Academy of Dermatology 56 (3): 439.e1–10. doi:10.1016/j.jaad.2006.10.005. PMID 17208334. 
  14. ^ Zhang FR, Liu, H; Irwanto, A; et al. (Oct 24, 2013). "HLA-B*13:01 and the dapsone hypersensitivity syndrome.". N Engl J Med. 369 (17): 1620–8. doi:10.1056/NEJMoa1213096. PMID 24152261. 
  15. ^ Jopling WH. Side-effects of antileprosy drugs in common use. Lepr Rev 1983; 54: 261–70.
  16. ^ Puavilai S, Chutha S, Polnikorn N, et al. (July 1984). "Incidence of anemia in leprosy patients treated with dapsone". J Med Assoc Thai 67 (7): 404–7. PMID 6512448. 
  17. ^ http://www.who.int/medicines/publications/drugalerts/Alert_117_LapDap.pdf
  18. ^ Luzzatto L (August 2010). "The rise and fall of the antimalarial Lapdap: a lesson in pharmacogenetics". Lancet 376 (9742): 739–41. doi:10.1016/S0140-6736(10)60396-0. PMID 20599264. 
  19. ^ Sanders SW, Zone JJ, Foltz RL, Tolman KG, Rollins DE. (Apr 1, 1982). "Hemolytic anemia induced by dapsone transmitted through breast milk.". Ann Intern Med. 96 (4): 465–6. doi:10.7326/0003-4819-96-4-465. PMID 7065565. 
  20. ^ Firkin FC, Mariani AF. Agranulocytosis due to dapsone. Med J Aust 1977; 2: 247–51.
  21. ^ Foucauld J, et al. Dapsone and aplastic anemia. Ann Intern Med 1985; 102: 139.
  22. ^ Meyerson MA, Cohen PR. Dapsone-induced aplastic anaemia in a woman with bullous systemic lupus erythematosus. Mayo Clin Proc 1994; 69: 1159–62.
  23. ^ Björkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull WHO 1991; 69: 297–304.
  24. ^ Ganesan, S; Sahu, R; Walker, LA; Tekwani, BL (April 2010). "Cytochrome P450-dependent toxicity of dapsone in human erythrocytes". J Appl Toxicol 30 (3): 271–5. doi:10.1002/jat.1493. PMID 19998329. Retrieved 7 March 2013. 
  25. ^ Aczone(Dapsone) Package insert. Irvine CA: Allergan Inc; September 2008
  26. ^ http://pharmacistanswers.com/medications-for-acne-guide.html
  27. ^ Jaffuel D, et al. Eosinophilic pneumonia induced by dapsone. BMJ 1998; 317: 181.
  28. ^ Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy. Lepr Rev 1989; 60: 267–73.
  29. ^ Kumar RH, et al. Dapsone syndrome—a five year retrospective analysis. Indian J Lepr 1998; 70: 271–6.
  30. ^ Rao PN, Lakshmi TSS. Increase in the incidence of dapsone hypersensitivity syndrome—an appraisal. Lepr Rev 2001; 72: 57–62.
  31. ^ Joseph MS. Hypersensitivity reaction to dapsone. Lepr Rev 1985; 56: 315–20.
  32. ^ Jamrozik K. Dapsone syndrome occurring in two brothers. Lepr Rev 1986; 57: 57–62.
  33. ^ Hortaleza AR, et al. Dapsone syndrome in a Filipino man. Lepr Rev 1995; 66: 307–13.
  34. ^ Tomecki KJ, Catalano CJ. Dapsone hypersensitivity: the sulfone syndrome revisited. Arch Dermatol 1981; 117: 38–9.
  35. ^ Kromann NP, et al. The dapsone syndrome. Arch Dermatol 1982; 118: 531–2.
  36. ^ "Medscape.com". Retrieved 2009-02-24. 
  37. ^ Begon E, Chosidow O, Wolkenstein P (December 2004). "[Disulone]". Ann Dermatol Venereol (in French) 131 (12): 1062–73. doi:10.1016/S0151-9638(04)93842-2. PMID 15692440. 
  38. ^ Uetrecht JP (1995). "Myeloperoxidase as a generator of drug free radicals". Biochem. Soc. Symp. 61: 163–70. PMID 8660393. 
  39. ^ Bozeman P, Learn D, Thomas E. Assay of the human leukocyte encymes myeloperoxidase and eosinophil peroxidase. J Immunol Methods 1990; 126:125-133.
  40. ^ Bozeman P, Learn D, Thomas E. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochem Pharmacol 1992; 44:553-563.
  41. ^ Stendahl O, Molin L, Lindroth M. Granulocyte-mediated release of histamine from mast cells. Effect of myeloperoxidase and its inhibition by antiinflammatory sulfone compounds. Int Arch Allergy Appl Immunol 1983; 70:277-284.
  42. ^ Kettle A, Gedye C, Winterbourn C. Superoxide is an antagonist of antiinflammatory drugs that inhibit hypochlorous acid production by myeloperoxidase. Biochem Pharmacol 1993; 45:2003-2010.
  43. ^ Kettle A, Winterbourn C. Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs. Biochem Pharmacol 1991; 41:1485-1492.
  44. ^ Diaz-Ruiz A, Zavala C, Montes S, et al. (November 2008). "Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats". J. Neurosci. Res. 86 (15): 3410–9. doi:10.1002/jnr.21775. PMID 18615706. 
  45. ^ J. et T. Tréfouël, F. Nitti et D. Bovet, « Activité du p.aminophénylsulfamide sur l’infection streptococcique expérimentale de la souris et du lapin », C. R. Soc. Biol., 120, 23 novembre 1935, p. 756.
  46. ^ E. Fourneau, Th. et J. Tréfouël, F. Nitti, D. Bovet, « Action antistreptococcique des dérivés sulfurés organiques », C. R. Acad. Sci., vol. 204, 1937, p. 1763.
  47. ^ G. Buttle, Y. Smith, G. Foster, « Treatment of streptococcal infections in mice with 4:4'diamino-dipheni-sulphone », Lancet, vol. 1, 1937, p. 133.
  48. ^ "Leprosy | 14 History of dapsone and dyes". Retrieved 2009-02-24.  (1937)

External links[edit]