Dapsone

Source: Wikipedia, the free encyclopedia.
Dapsone
Clinical data
Trade namesAczone, others
AHFS/Drugs.comMonograph
MedlinePlusa682128
License data
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability70 to 80%
Protein binding70 to 90%
MetabolismLiver (mostly CYP2E1-mediated)
Elimination half-life20 to 30 hours
ExcretionKidney
Identifiers
  • 4-[(4-aminobenzene)sulfonyl]aniline
JSmol)
Melting point175 to 176 °C (347 to 349 °F)
  • O=S(=O)(c1ccc(N)cc1)c2ccc(N)cc2
  • InChI=1S/C12H12N2O2S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8H,13-14H2 checkY
  • Key:MQJKPEGWNLWLTK-UHFFFAOYSA-N checkY
  (verify)

Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS),

acne, dermatitis herpetiformis, and various other skin conditions.[4] Dapsone is available both topically and by mouth.[5]

Severe side effects may include a decrease in blood cells, red blood cell breakdown especially in those with glucose-6-phosphate dehydrogenase deficiency (G-6-PD), or hypersensitivity.[3] Common side effects include nausea and loss of appetite.[5] Other side effects include liver inflammation, methemoglobinemia,[6] and a number of types of skin rashes.[3] While the safety of use during pregnancy is not entirely clear some physicians recommend that it be continued in those with leprosy.[3] It is of the sulfone class.[3]

Dapsone was first studied as an antibiotic in 1937.[4] Its use for leprosy began in 1945.[4] It is on the World Health Organization's List of Essential Medicines.[7] The form, which is taken by mouth, is available as a generic drug and not very expensive.[3][8]

Medical uses

Infections

Dapsone is commonly used in combination with rifampicin and clofazimine for the treatment of leprosy.[3] It is also used to both treat and prevent pneumocystis pneumonia (PCP).[3][9] It is also used for toxoplasmosis in people unable to tolerate trimethoprim with sulfamethoxazole.[9]

Dapsone by mouth was one of the first medications used to treat moderate to severe acne vulgaris, and is still occasionally prescribed for the treatment of severe cases.[10][11] A topical form of dapsone is also effective with potentially less side effects.[12]

It is unclear if the combination with pyrimethamine is useful in the prevention of malaria.[13]

Autoimmune disease

  • Cutaneous lupus erythematosis. Dapsone is effective and safe in persons with moderate, severe, or refractory cutaneous lupus erythematosis.[14]
  • Idiopathic thrombocytopenic purpura. Dapsone is effective and safe for adjunctive glucocorticoid-sparing treatment of persons with idiopathic thrombocytopenic purpura and is preferred over danazol or interferon alpha in those people with antinuclear antibodies.[15]
  • Chronic spontaneous urticaria. Dapsone is effective and safe for treatment of second-line therapy for people with chronic spontaneous urticaria in those for whom antihistamines and other first-line agents have failed.[16][17]
  • Relapsing polychondritis. There are no clinical trials but there are many case reports that dapsone is effective at doses of 25 mg/day to 200 mg/day for treatment of relapsing polychondritis.[18]

Other

Dermatitis herpetiformis in combination with a gluten-free diet.[3]

Dapsone may be used to treat

necrotic.[19]

Dapsone is the recommended treatment for erythema elevatum diutinum, as a review found that using oral dapsone alone was effective in 80% of early cases of the disease. However, dapsone can potentially cause severe side effects, meaning that sometimes steroids or other antibiotics should be used instead, although these alternative treatments are much less effective.[20]

An August 2015 review notes that dapsone is reported to be effective against generalized granuloma annulare.[21]

Dapsone has been used as a monomer in the design of dye adsorbent polymers.[22]

Contraindications and precautions

People with

G6PD deficiency, and liver impairment are at higher risks of adverse effects when using dapsone.[9]

Adverse effects

Hypersensitivity reactions occur in 1.4% of persons treated with dapsone, and can be fatal in medical settings with low resources.

DRESS syndrome or a DRESS syndrome-like reaction occurs.[25][26]

Blood

Hemolysis is the most prominent side-effect, occurring in about 20 % of patients treated with dapsone,[27] although it is dose-related. It may lead to hemolytic anemia and methemoglobinemia.[28] 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.[29][30] A case of hemolysis in a neonate from dapsone in breast milk has been reported.[31] Agranulocytosis occurs rarely when dapsone is used alone but more frequently in combination regimens for malaria prophylaxis.[32] Abnormalities in white blood cell formation, including aplastic anemia, are rare, yet are the cause of the majority of deaths attributable to dapsone therapy.[33][34][35]

blood gas analysis result, methemoglobinemia may be suspected.[36]

Liver

Toxic

isozymes CYP2D6, CYP2B6, CYP3A4, and CYP2C19.[37] Dapsone metabolites produced by the cytochrome P450 2C19 isozyme are associated with the methemoglobinemia side effect of the drug.[citation needed
]

Skin

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.[38]

Dapsone hypersensitivity syndrome

Hypersensitivity reactions occur in some patients. This reaction may be more frequent in patients receiving multiple-drug therapy.[39][40][41]

The reaction always involves a

DRESS syndrome (see above).[25][42][43][44][45][46] In general, these symptoms will occur within the first six weeks of therapy or not at all, and may be ameliorated by corticosteroid therapy.[9]

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.[47]

Mechanism of action

As an

antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthase, thereby inhibiting nucleic acid synthesis.[48] Though structurally distinct from dapsone, the sulfonamide group of antibacterial drugs also work in this way.[citation needed
]

As an anti-inflammatory, dapsone inhibits the myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonucleocytes.[49] As part of the respiratory burst that neutrophils use to kill bacteria, myeloperoxidase converts hydrogen peroxide (H
2O
2) 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.[50][51][52][53][54] Myeloperoxidase inhibition has also been suggested as a neuron-sparing mechanism for reducing inflammation in neurodegenerative diseases such as Alzheimer's disease and stroke.[55]

Dapsone's anti-inflammatory and immunomodulatory effects[56] are thought to be its mechanism of action in treating dermatitis herpetiformis.[57]

Dapsone is an odorless white to creamy-white crystalline powder with a slightly bitter taste.[citation needed]

History

Discovery

4-nitrochlorobenzene by E. Fromm and J. Wittmann, 1908[58]

In the early 20th century, the German chemist

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),[59] then with that of dapsone independently by Ernest Fourneau[60] in France and Gladwin Buttle[61] in the United Kingdom.[62]

Proposed use in antimalarial drugs

The spread of drug-resistant

Lapdap, a combination drug consisting of chlorproguanil and dapsone. Lapdap was licensed in the United Kingdom starting in October 2003.[30]

One advantage of Lapdap was that chlorproguanil and dapsone are both low-cost drugs. Another was that by virtue of being a combination drug, it was less likely to cause drug resistance. However, because dapsone causes hemolytic anemia in patients with G6PD deficiency, and because G6PD deficiency affects 10-25% of the population of sub-Saharan Africa, it was discovered that Lapdap is not safe for use in Africa. It was available in many African countries for four years before GlaxoSmithKline took it off the market in February 2008.[30]

Dapsone gel

Dapsone had been reported in a few cases to effectively treat acne, but the risk of hemolytic anemia kept it from being widely used for this purpose. For many years scientists attempted to develop a topical formulation of dapsone that would be as effective against acne as oral dapsone, but without the hemolysis side effect. This was difficult to accomplish because dapsone is highly insoluble in aqueous solvents. In the early 2000s QLT USA developed Aczone, a 5% dapsone gel that was shown to be effective against acne without causing clinically significant declines in hemoglobin levels, even in subjects with G6PD deficiency.[63] In February 2016, the FDA approved a 7.5% dapsone gel. This higher strength has the advantage of a once-daily application, versus twice-daily application of the 5% formulation.[64]

Other uses

4,4-Diaminodiphenyl sulfone also finds uses as a

glass-transition temperature
.

See also

  • Promin, a more-soluble derivative

References

  1. ^ "Dapsone Use During Pregnancy". Drugs.com. 11 November 2019. Retrieved 17 May 2020.
  2. ISBN 9780781768795. Archived
    from the original on 2016-03-04.
  3. ^ a b c d e f g h i j "Dapsone (Systemic) Monograph for Professionals". The American Society of Health-System Pharmacists. Archived from the original on 2015-01-12. Retrieved January 12, 2015.
  4. ^
    S2CID 39874987
    .
  5. ^
    ISBN 9781449619794. Archived
    from the original on 2016-03-04.
  6. S2CID 40957843
    .
  7. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ISBN 9780199534845. Archived
    from the original on 2016-03-04.
  9. ^
    ISBN 0-9757919-2-3.{{cite book}}: CS1 maint: location missing publisher (link
    )
  10. S2CID 36293895
    .
  11. ^ "Dapsone and Acne Vulgaris". ScienceOfAcne.com. 2012-10-10. Archived from the original on 2012-07-29. Retrieved 2012-08-17.
  12. S2CID 11880942
    .
  13. PMID 19450348
    .
  14. ISBN 978-0-323-47927-1
    .
  15. PMID 28906353
    .
  16. S2CID 52312492
    .
  17. PMID 30476976
    .
  18. PMID 17113965
    .
  19. PMID 11117338
    .
  20. S2CID 30029976
    .
  21. S2CID 20884856
    .
  22. doi:10.1002/app.39069
    .
  23. PMID 22307940
    .
  24. S2CID 34708642
    .
  25. ^
    PMID 9069593
    .
  26. S2CID 4283457
    .
  27. PMID 6512448
    .
  28. PMID 6199637
    .
  29. ^ "Antimalarial chlorproguanil-dapsone (LapDap™) withdrawn following demonstration of post-treatment haemolytic anaemia in G6PD deficient patients in a Phase III trial of chlorproguanil-dapsone-artesunate (Dacart™) versus artemether-lumefantrine (Coartem®) and confirmation of findings in a comparative trial of LapDap™ versus Dacart ™" (PDF). World Health Organization. 4 March 2008. QSM/MC/IEA.1. Archived (PDF) from the original on 21 October 2012.
  30. ^
    S2CID 34866078
    .
  31. PMID 7065565
    .
  32. S2CID 34641425
    .
  33. PMID 3966740
    .
  34. PMID 7967777
    .
  35. PMID 1893504
    .
  36. PMID 24574600
    .
  37. S2CID 33330708
    .
  38. ^ "Aczone (Dapsone) Package insert" (PDF). Irvine CA: Allergan Inc. 2016 – via U.S. Food and Drug Administration.
  39. PMID 2491425
    .
  40. PMID 9801899
    .
  41. PMID 11355519
    .
  42. PMID 4079634
    .
  43. PMID 3702581
    .
  44. PMID 8637384
    .
  45. PMID 6450569
    .
  46. PMID 7092282
    .
  47. PMID 9665900
    .
  48. ^ "Mechanisms of Action of Dapsone in Dermatological Diseases". Dapsone: Clinical Uses in Various Cutaneous Diseases. Medscape Today. Archived from the original on May 17, 2011.
  49. S2CID 53721156
    .
  50. PMID 2154520
    .
  51. PMID 1324677
    .
  52. PMID 6186607
    .
  53. PMID 8390258
    .
  54. PMID 1850278
    .
  55. S2CID 5837071
    .
  56. PMID 15692440
    .
  57. S2CID 12471553
    .
  58. doi:10.1002/cber.190804102131
    .
  59. ^ Tréfouël JT, Nitti F, Bovet D (23 November 1935). "Activité du p.aminophénylsulfamide sur l'infection streptococcique expérimentale de la souris et du lapin". Comptes rendus des séances de la Société de biologie et de ses filiales (in French). 120: 756. Archived from the original on 3 January 2017.
  60. ^ Fourneau E, Tréfouël TJ, Nitti F, Bovet D (1937). "Action antistreptococcique des dérivés sulfurés organiques". Comptes rendus de l'Académie des sciences (in French). 204: 1763. Archived from the original on 2016-02-20.
  61. doi:10.1016/S0140-6736(00)75868-5
    .
  62. ^ "Leprosy | 14 History of dapsone and dyes". Archived from the original on 2009-02-12. Retrieved 2009-02-24.
  63. S2CID 19485887
    .
  64. ^ "Aczone (dapsone) 7.5% Gel Prescribing Information" (PDF). Allergan. February 2016. Retrieved 23 June 2016.
  65. ^ "ECHA dapsone registration dossier".
  66. ^ "LAPOX ASH-10". 3 June 2017.
  67. PMID 34163597
    .

External links

  • "Dapsone". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Dapsone&oldid=1194584262"