Dapsone

(BAN, USAN, rINN)
Dapsone Chemical formula
Synonyms: DADPS; Dapson; Dapsona; Dapsonas; Dapsoni; Dapsonum; Dapszon; DDS; Diaminodiphenylsulfone; Diaphenylsulfone; Disulone; NSC6091; 4,4′-Sulfonylbis-benzenamine; Sulphonyldianiline. Bis(4-aminophenyl) sulphone.
Cyrillic synonym: Дапсон.

💊 Chemical information

Chemical formula: C12H12N2O2S = 248.3.
CAS — 80-08-0.
ATC — J04BA02.
ATC Vet — QJ04BA02.

Pharmacopoeias.

In Chin., Eur., Int., US, and Viet.

Ph. Eur. 6.2

(Dapsone). A white or slightly yellowish-white, crystalline powder. Very slightly soluble in water; sparingly soluble in alcohol; freely soluble in acetone. It dissolves freely in dilute mineral acids. Protect from light.

USP 31

(Dapsone). A white or creamy-white, odourless crystalline powder. Very slightly soluble in water, freely soluble in alcohol; soluble in acetone and in dilute mineral acids. Protect from light.

Stability.

A study 1 of the stability of two extemporaneous oral

suspensions of dapsone prepared

from commercially available tablets found them to be stable for 3 months when stored at 4° and at 25°. 1. Nahata MC, et al. Stability of dapsone in two oral liquid dosage forms. Ann Pharmacother 2000; 34: 848–50.

💊 Adverse Effects

Varying degrees of dose-related haemolysis and methaemoglobinaemia are the most frequently reported adverse effects of dapsone, and occur in most patients given more than 200 mg daily; doses of up to 100 mg daily do not cause significant haemolysis, but patients with G6PD deficiency are affected by doses above about 50 mg daily. Although agranulocytosis has been reported rarely with dapsone when used alone, reports have been more common when it has been used with other drugs in the prophylaxis of malaria. Deaths due to agranulocytosis, aplastic anaemia, and other blood dyscrasias have been reported. Rash and pruritus may develop. Serious cutaneous hypersensitivity reactions occur rarely and include maculopapular rash, exfoliative dermatitis, toxic epidermal necrolysis, and Stevens-Johnson syndrome. Fixed drug eruptions have occurred. A ‘dapsone syndrome’ may occur after 4 to 8 weeks of treatment and resembles mononucleosis in its presentation (see Hypersensitivity Reactions, below). Peripheral neuropathy with motor loss has been reported in patients on dapsone for dermatological conditions. Peripheral neuropathy may occur as part of leprosy reaction states and is not an indication to stop dapsone. Other adverse effects occur infrequently and include nausea, vomiting, anorexia, headache, hepatitis, insomnia, psychosis, and tachycardia.

Carcinogenicity.

A survey of 1678 leprosy patients admitted for treatment to the National Hansen’s Disease Center in the USA between 1939 and 1977 indicated that, although dapsone has been implicated as a carcinogen in animals, the use of dapsone did not appear to affect significantly the risk of cancer in these patients.1 The International Agency for Research on Cancer concluded2 that there was limited evidence for the carcinogenicity of dapsone in animals and insufficient data to be able to classify the carcinogenic risk in humans.
1. Brinton LA, et al. Cancer mortality among patients with Hansen’s disease. J Natl Cancer Inst 1984; 72: 109–14
2. IARC/WHO. Some pharmaceutical drugs. IARC monographs on the evaluation of carcinogenic risks to humans volume 24 1980. Also available at: http://monographs.iarc.fr/ENG/Monographs/ vol24/volume24.pdf Updated 07/04/88. (accessed 03/10/07)

Effects on the blood.

Haemolysis is the most frequent serious adverse effect of dapsone and may occur at doses of 200 mg or higher daily.1 Red blood cells may contain Heinz bodies and there is a reduction in their life span. Well-known risk factors include G6PD deficiency, methaemoglobin reductase deficiency, and haemoglobin M trait; haemoglobin E trait may also increase susceptibility to haemolytic reactions.2 Haemolytic anaemia has been reported in a neonate after ingestion of dapsone in breast milk.3 Methaemoglobinaemia, although common, is rarely symptomatic.1 However, severe cyanosis was associated with methaemoglobinaemia after an inadvertent overdose with dapsone in an HIV-positive patient with suspected pneumocystis pneumonia.4Methaemoglobinaemia has also been reported in an HIV-negative patient with severe renal impairment, who had previously undergone liver and kidney transplantations and who was receiving dapsone for prophylaxis of pneumocystis pneumonia.5 The metabolite dapsone hydroxylamine is probably responsible for the methaemoglobinaemia and haemolysis associated with dapsone. Studies have shown6,7 that use of dapsone with cimetidine, which inhibits production of the N-hydroxy metabolite, has resulted in a decrease in methaemoglobin levels, at least in the short term. Agranulocytosis has occurred rarely on use of dapsone in leprosy and skin disease. More cases have been observed when used for malaria prophylaxis8 and dermatitis herpetiformis.9 The reaction is usually self-limiting once the drug is withdrawn, but fatalities have occurred.9,10 Aplastic anaemia has been reported.11,12 Of 11 fatalities attributed to dapsone reported to the British and Swedish adverse reaction registers13 between 1968 and 1988, seven were due to white blood cell dyscrasias; none were attributed to red cell dyscrasias, although such reactions formed almost half of all serious reactions reported for dapsone. Pure red cell aplasia has been reported in an elderly patient taking oral dapsone daily for granuloma annulare.14 Thrombocytosis was reported in a patient with AIDS receiving dapsone prophylactically.15 See also Hypoalbuminaemia, below.
1. Jopling WH. Side-effects of antileprosy drugs in common use. Lepr Rev 1983; 54: 261–70
2. Lachant NA, Tanaka KR. Case report: dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait. Am J Med Sci 1987; 294: 364–8
3. Sanders SW, et al. Hemolytic anemia induced by dapsone transmitted through breast milk. Ann Intern Med 1982; 96: 465–6
4. Seaton RA, et al. Blue and breathless. Hosp Med 1999; 60: 530
5. Ward KE, McCarthy MW. Dapsone-induced methemoglobinemia. Ann Pharmacother 1998; 32: 549–53
6. Coleman MD, et al. The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man. Br J Clin Pharmacol 1990; 30: 761–7
7. Rhodes LE, et al. Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy. Br J Dermatol 1995; 132: 257–62
8. Firkin FC, Mariani AF. Agranulocytosis due to dapsone. Med J Aust 1977; 2: 247–51
9. Cockburn EM, et al. Dapsone-induced agranulocytosis: spontaneous reporting data. Br J Dermatol 1993; 128: 702–3
10. Barss P. Fatal dapsone agranulocytosis in a Melanesian. Lepr Rev 1986; 57: 63–6
11. Foucauld J, et al. Dapsone and aplastic anemia. Ann Intern Med 1985; 102: 139
12. Meyerson MA, Cohen PR. Dapsone-induced aplastic anaemia in a woman with bullous systemic lupus erythematosus. Mayo Clin Proc 1994; 69: 1159–62
13. Björkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull WHO 1991; 69: 297–304
14. Borrás-Blasco J, et al. Pure red cell aplasia associated with dapsone therapy. Ann Pharmacother 2005; 39: 1137–8
15. Wynn RF, et al. Case report of dapsone-related thrombocytosis in an AIDS patient. Am J Med 1995; 98: 602.

Effects on the eyes.

There have been rare reports1-4 of ocular toxicity, usually resulting in permanent loss of visual acuity, after overdoses with dapsone. Toxic effects included blurring of vision,1,2 optic atrophy,1 ischaemic retinopathy, ischaemic optic neuropathy,3 and bilateral macular infarction.4 These effects were thought to be due to acute hypoxia and obstruction with red cell fragments. A case of anterior ischaemic optic neuropathy5has also been reported in a patient taking usual doses of dapsone for dermatitis herpetiformis.
1. Daneshmend TK. The neurotoxicity of dapsone. Adverse Drug React Acute Poisoning Rev 1984; 3: 43–58
2. Alexander TA, et al. Presumed DDS ocular toxicity. Indian J Ophthalmol 1989; 37: 150–1.
3. Seo M-S, et al. Dapsone maculopathy. Korean J Ophthalmol 1997; 11: 70–3
4. Chakrabarti M, et al. Bilateral macular infarction due to diaminodiphenyl sulfone (4,4′ DDS) toxicity. Retina 1999; 19: 83–4
5. Chalioulias K, et al. Anterior ischaemic optic neuropathy associated with Dapsone. Eye 2006; 20: 943–5.

Effects on the liver.

Toxic hepatitis and cholestatic jaundice have been reported by licensed product information to occur early in dapsone therapy. Jaundice may also form part of the dapsone syndrome (see Hypersensitivity Reactions, below). Deterioration in liver function tests during dapsone treatment has been noted in a patient with dermatitis herpetiformis and primary sclerosing cholangitis.1
1. Kirby B, et al. Abnormal liver function tests induced by dapsone in a patient with dermatitis herpetiformis and primary sclerosing cholangitis. Br J Dermatol 1999; 141: 172–3.

Effects on the lungs.

Hypersensitivity reactions to dapsone usually affect the skin, but there have been rare reports of dapsone hypersensitivity presenting with fever, wheezing, and pulmonary eosinophilia.1-4 Pulmonary eosinophilia occurred in one patient taking dapsone for urticaria1 and in another taking dapsone as part of the WHO multidrug treatment regimen for leprosy.2 In both patient symptoms resolved when dapsone was stopped and occurred again on rechallenge. Another patient3known to develop fever and wheezing when taking dapsone for leprosy was given a dapsone challenge for 5 days. He became acutely ill and had a high absolute eosinophil count; symptoms resolved 2 weeks after stopping dapsone.
1. Jaffuel D, et al. Eosinophilic pneumonia induced by dapsone. BMJ 1998; 317: 181
2. Kaur J, et al. Dapsone-induced eosinophilic pneumonitis in a leprosy patient. Indian J Lepr 2005; 77: 267–71
3. Arunthathi S, Raju S. Dapsone induced pulmonary eosinophilia without cutaneous allergic manifestations—an unusual encounter—a case report. Acta Leprol 1998; 11: 3–5
4. Janier M, et al. Pulmonary eosinophilia associated with dapsone. Lancet 1994; 343: 860–1.

Effects on mental state.

Psychiatric adverse effects have been reported in leprosy patients receiving dapsone, but the role of dapsone in this effect is poorly defined.1-4 Manic-depressive reactions have been reported in 2 patients2,3 with skin disorders and psychosis4 was reported in a patient being treated for leprosy. These reactions appeared to be idiosyncratic reactions to dapsone. In all cases symptoms resolved when dapsone was stopped.
1. Daneshmend T. Idiosyncratic dapsone induced manic depression. BMJ 1989; 299: 324
2. Carmichael AJ, Paul CJ. Idiosyncratic dapsone induced manic depression. BMJ 1989; 298: 1524. Correction. ibid.; 299: 56
3. Gawkrodger D. Manic depression induced by dapsone in patient with dermatitis herpetiformis. BMJ 1989; 299: 860
4. Balkrishna, Bhatia MS. Dapsone-induced psychosis. J Indian Med A prospective clinical study1 of 31 patients with brown recluse spider bites indicated that treatment with dapsone 100 mg daily for 14 days followed by delayed surgical intervention if necessary reduced the incidence of wound complications and residual scarring compared with treatment by immediate surgical excision. A dose of 100 mg twice daily has also been given for 14 days.2 An evaluation3 of the management of brown recluse spider bites found that common treatments did not reduce healing time or scarring; dapsone was associated with slower healing rate and an increased risk of scarring.
1. Rees RS, et al. Brown recluse spider bites: a comparison of early surgical excision versus dapsone and delayed surgical excision. Ann Surg 1985; 202: 659–63
2. King LE, Rees RS. Dapsone treatment of a brown recluse bite. JAMA 1983; 250: 648
3. Mold JW, Thompson DM. Management of brown recluse spider bites in primary care. J Am Board Fam Pract 2004; 17: 347–52.

💊 Preparations

BP 2008: Dapsone Tablets; USP 31: Dapsone Tablets.

Proprietary Preparations

Arg.: Daps; Canad.: Aczone; Israel: Avlosulfon†; Mex.: Dapsoderm-X; Novasulfon†; Philipp.: Lepravir; Port.: Sulfona; Spain: Sulfona; Thai.: Dopsan; Servidapsone†; USA: Aczone. Multi-ingredient: Austral.: Maloprim; Austria: Isoprodian; Fr.: Disulone; Ger.: Isoprodian†; Irl.: Maloprim†; S.Afr.: Maloprim†; Singapore: Pyrisone.
Published January 31, 2019.