Dapsone
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2008-07-04T16:14:16Z
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{{Drugbox|
|IUPAC_name = 4,4'sulfonyldianiline
| image=Dapsone.svg
| image2=Dapsone3d.png
| CAS_number=80-08-0
| ATC_prefix=J04
| ATC_suffix=BA02
| PubChem=2955
| DrugBank=APRD00345
| C = 12 |H = 12 |N = 2 |O = 2 |S = 1
| molecular_weight = 248.302 [[Gram|g]][[Mole (unit)|mol]]<sup>-1</sup>
| bioavailability= 70 to 80%
| protein_bound = 70 to 90%
| metabolism = [[Liver|Hepatic]] (mostly [[CYP2E1]]-mediated)
| elimination_half-life= 20 to 30 [[hour]]s
| excretion = [[Kidney|Renal]]
| pregnancy_AU = B2
| pregnancy_US = C
| legal_status = ℞-only <small>(U.S.)</small>, [[Prescription drug|POM]] <small>([[United Kingdom|UK]])</small>
| routes_of_administration= Oral
}}
'''Dapsone'''(diamino-diphenyl sulfone) is an [[pharmacology|pharmacological]] [[medication]] most commonly used in combination with [[rifampicin]] and [[clofazimine]] as multidrug therapy (MDT) for the treatment of ''[[Mycobacterium leprae]]'' infections ([[leprosy]]).
== History ==
In the early 20th century the [[Germany|German]] chemist [[Paul Ehrlich]] was developing theories of [[selective toxicity]] based largely on the ability of certain [[dye]]s to kill [[microbe]]s. [[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|prontosil red]]. Further investigation into the active chemicals involved led to the discoveries both of dapsone and of the [[Sulfonamide (medicine)|antibacterial sulfonamides]].[http://www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/22_Leprosyp14.htm]
As an [[antibacterial]], dapsone inhibits [[bacteria]]l synthesis of [[dihydrofolic acid]]. 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 less well understood.
== Indication ==
As well as being used in leprosy, dapsone can also be used to treat [[dermatitis herpetiformis]] and other skin conditions including [[lichen planus]]. It is also sometimes used to prevent [[Pneumocystis pneumonia]] (PCP) in people who are immunosupressed and to treat [[idiopathic thrombocytopenic purpura]]. It is used [[prophylaxis|prophylactically]] to prevent [[Pneumocystis pneumonia]] and [[toxoplasmosis]] in patients unable to tolerate [[trimethoprim]] with [[sulfamethoxazole]].<ref name="AMH">Rossi S, ed. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref> Dapsone is also used to treat [[Brown recluse spider]] bites.
== Administration ==
Dapsone is administered orally as a 100mg tablet or alternatively as 25mg tablets.
To deal with dapsone resistant leprosy cases, multidrug therapy was introduced by WHO in 1981.So, Dapsone is administered along with rifampin and clofazimine or other antileprotic drugs.
== Adverse effects ==
=== Effects on the blood ===
The most prominent side effects of this drug are dose-related [[hemolysis]] (which may lead to [[hemolytic anemia]]) and [[methemoglobinemia]].<ref>Jopling WH. Side-effects of antileprosy drugs in common use. Lepr Rev 1983; 54: 261–70.</ref> [[Agranulocytosis]] occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis.<ref>Firkin FC, Mariani AF. Agranulocytosis due to dapsone. Med J Aust 1977; 2: 247–51.</ref> Abnormalities in [[white blood cell]] formation, including [[aplastic anaemia]], are rare but the cause of the majority of deaths due to dapsone therapy.<ref>Foucauld J, et al. Dapsone and aplastic anemia. Ann Intern Med 1985; 102: 139.</ref><ref>Meyerson MA, Cohen PR. Dapsone-induced aplastic anaemia in a woman with bullous systemic lupus erythematosus. Mayo Clin Proc 1994; 69: 1159–62.</ref><ref>Björkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull WHO 1991; 69: 297–304.</ref>
=== Effects on the liver ===
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 also known to inhibit the Cytochrome P450 system.
=== Other adverse effects ===
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.<ref>Jaffuel D, et al. Eosinophilic pneumonia induced by dapsone. BMJ 1998; 317: 181.</ref>
=== Dapsone reaction ===
[[Hypersensitivity]] reactions occur in some patients. This reaction may be more frequent in patients receiving multiple drug therapy.<ref>Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy. Lepr Rev 1989; 60: 267–73.</ref><ref>Kumar RH, et al. Dapsone syndrome—a five year retrospective analysis. Indian J Lepr 1998; 70: 271–6.</ref><ref>Rao PN, Lakshmi TSS. Increase in the incidence of dapsone hypersensitivity syndrome—an appraisal. Lepr Rev 2001; 72: 57–62.</ref>
The reaction always involves a [[rash]] and may also include [[fever]], jaundice, and [[eosinophilia]].<ref>Joseph MS. Hypersensitivity reaction to dapsone. Lepr Rev 1985; 56: 315–20.</ref><ref>Jamrozik K. Dapsone syndrome occurring in two brothers. Lepr Rev 1986; 57: 57–62.</ref><ref>Hortaleza AR, et al. Dapsone syndrome in a Filipino man. Lepr Rev 1995; 66: 307–13.</ref><ref>Tomecki KJ, Catalano CJ. Dapsone hypersensitivity: the sulfone syndrome revisited. Arch Dermatol 1981; 117: 38–9.</ref><ref>Kromann NP, et al. The dapsone syndrome. Arch Dermatol 1982; 118: 531–2.</ref> These symptoms will generally occur within the first six weeks of therapy or not at all, and may be ameliorated by [[corticosteroid]] therapy.<ref name="AMH" />
== Specific considerations ==
Certain patients are at higher risks of adverse effects when using dapsone. Some specific issues which should be considered are:<ref name="AMH" />
* Related to the blood (a [[full blood count]] should be obtained prior to initiating therapy):
** [[Porphyria]]
** [[Anaemia]]
** [[Cardiac disease]]
** [[Pulmonary disease]]
** [[HIV]] infection
** [[G6PD deficiency]]
* Related to the liver (obtain [[liver function test]]s before starting therapy):
** Liver impairment
* Related to [[allergy]]:
** Sulfonamide allergy is associated with dapsone allergy
== References ==
{{reflist}}
== External links ==
*[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682128.html MedlinePlus Drug Information]
{{Antimycobacterials}}
[[Category:antibiotics]]
[[Category:Leprosy]]
[[Category:Sulfones]]
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