Dapsone

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Dapsone chemical structure
Dapsone
Systematic (IUPAC) name
4,4'sulfonyldianiline
Identifiers
CAS number 80-08-0
ATC code J04BA02
PubChem 2955
DrugBank APRD00345
Chemical data
Formula C12H12N2O2S 
Mol. weight 248.302 gmol-1
Pharmacokinetic data
Bioavailability 70 to 80%
Protein binding 70 to 90%
Metabolism Hepatic (mostly CYP2E1-mediated)
Half life 20 to 30 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

B2(AU) C(US)
Legal status

℞-only (U.S.), POM (UK)
Routes Oral

Dapsone is an pharmacological medication most commonly used for the treatment of Mycobacterium leprae infections (leprosy).

Contents

[edit] History

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. Further investigation into the active chemicals involved led to the discoveries both of dapsone and of the antibacterial sulfonamides.[1]

[edit] Mechanism of action

As an antibacterial, dapsone inhibits bacterial 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.

[edit] Indications

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 jirovici pneumonia (PCP) in patients with HIV and to treat idiopathic thrombocytopenic purpura. It is used prophyactically to prevent P. jiroveci pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole.[1]

[edit] Administration

Dapsone is administered orally as a 100mg tablet or alternatively as 25mg tablets.

[edit] Adverse effects

[edit] Effects on the blood

The most prominent side effects of this drug are dose-related haemolysis (which may lead to haemolytic anemia) and methemoglobinemia.[2] Agranulocytosis occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis.[3] Abnormalities in white blood cell formation, including aplastic anaemia, are rare but the cause of the majority of deaths due to dapsone therapy.[4][5][6]

[edit] 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).

[edit] 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.[7]

[edit] Dapsone reaction

Hypersensitivity reactions occur in some patients. This reaction may be more frequent in patients receiving multiple drug therapy.[8][9][10]

The reaction always involves a rash and may also include fever, jaundice, and eosinophilia.[11][12][13][14][15] These symptoms will generally occur within the first six weeks of therapy or not at all, and may be ameliorated by corticosteroid therapy.[1]

[edit] Specific considerations

Certain patients are at higher risks of adverse effects when using dapsone. Some specific issues which should be considered are:[1]

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

[edit] References

  1. ^ a b c Rossi S, ed. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  2. ^ Jopling WH. Side-effects of antileprosy drugs in common use. Lepr Rev 1983; 54: 261–70.
  3. ^ Firkin FC, Mariani AF. Agranulocytosis due to dapsone. Med J Aust 1977; 2: 247–51.
  4. ^ Foucauld J, et al. Dapsone and aplastic anemia. Ann Intern Med 1985; 102: 139.
  5. ^ Meyerson MA, Cohen PR. Dapsone-induced aplastic anaemia in a woman with bullous systemic lupus erythematosus. Mayo Clin Proc 1994; 69: 1159–62.
  6. ^ Björkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull WHO 1991; 69: 297–304.
  7. ^ Jaffuel D, et al. Eosinophilic pneumonia induced by dapsone. BMJ 1998; 317: 181.
  8. ^ Richardus JH, Smith TC. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy. Lepr Rev 1989; 60: 267–73.
  9. ^ Kumar RH, et al. Dapsone syndrome—a five year retrospective analysis. Indian J Lepr 1998; 70: 271–6.
  10. ^ Rao PN, Lakshmi TSS. Increase in the incidence of dapsone hypersensitivity syndrome—an appraisal. Lepr Rev 2001; 72: 57–62.
  11. ^ Joseph MS. Hypersensitivity reaction to dapsone. Lepr Rev 1985; 56: 315–20.
  12. ^ Jamrozik K. Dapsone syndrome occurring in two brothers. Lepr Rev 1986; 57: 57–62.
  13. ^ Hortaleza AR, et al. Dapsone syndrome in a Filipino man. Lepr Rev 1995; 66: 307–13.
  14. ^ Tomecki KJ, Catalano CJ. Dapsone hypersensitivity: the sulfone syndrome revisited. Arch Dermatol 1981; 117: 38–9.
  15. ^ Kromann NP, et al. The dapsone syndrome. Arch Dermatol 1982; 118: 531–2.

[edit] External links


Antimycobacterials (J04) edit
Tuberculosis:

Aminosalicylic acid, Calcium aminosalicylate, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Morinamide, Protionamide, Pyrazinamide, Rifabutin, Rifampicin, Rifamycin, Rifapentin, Sodium aminosalicylate, Terizidone, Tiocarlide
Leprosy:

Aldesulfone sodium, Clofazimine, Dapsone
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