Dapsone (oral): Difference between revisions

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{{Drugbox|
{{DrugProjectFormSinglePage
|IUPAC_name = 4,4'sulfonyldianiline
|authorTag={{KS}}
| image=Dapsone.svg
|genericName=dapsone
| image2=Dapsone3d.png
|aOrAn=an
| CAS_number=80-08-0
|drugClass=[[anti-infective agent]]
| ATC_prefix=J04
|indicationType=treatment
| ATC_suffix=BA02
|indication=[[acne vulgaris]], [[dermatitis herpetiformis]], and [[leprosy]]
| PubChem=2955
|adverseReactions=[[nausea]], [[vomiting]], [[abdominal pain]], [[pancreatitis]], [[vertigo]], [[blurred vision]], and [[tinnitus]]
| DrugBank=APRD00345
|fdaLIADAdult=====Indications====
| 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
}}
{{SI}}


* '''Dermatitis herpetiformis'''
* '''Leprosy''': All forms of [[leprosy]] except for cases of proven Dapsone resistance.


'''Dapsone'''(diamino-diphenyl sulphone) 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]]).
====Dosage====


'''Dermatitis herpetiformis''':


== History ==
* The dosage should be individually titrated starting in adults with 50 mg daily and correspondingly smaller doses in children. If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried. Dosage should be reduced to a minimum maintenance level as soon as possible. In responsive patients there is a prompt reduction in [[pruritus]] followed by clearance of skin lesions. There is no effect on the gastrointestinal component of the disease. Dapsone levels are influenced by acetylation rates. Patients with high acetylation rates, or who are receiving treatment affecting acetylation may require an adjustment in dosage.


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]
* A strict gluten free diet is an option for the patient to elect, permitting many to reduce or eliminate the need for Dapsone; the average time for dosage reduction is 8 months with a range of 4 months to 2 1/2 years and for dosage elimination 29 months with a range of 6 months to 9 years.


== Mechanism of action ==
'''Leprosy''':


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.
* In order to reduce secondary Dapsone resistance, the WHO Expert Committee on Leprosy and the USPHS at Carville, LA, recommended that Dapsone should be commenced in combination with one or more anti-leprosy drugs. In the multidrug program Dapsone should be maintained at the full dosage of 100 mg daily without interruption (with corresponding smaller doses for children) and provided to all patients who have sensitive organisms with new or recrudescent disease or who have not yet completed a two year course of Dapsone monotherapy. For advice and other drugs, the USPHS at Carville, LA (1-800-642-2477) should be contacted. Before using other drugs consult appropriate product labeling.


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.
* In bacteriologically negative tuberculoid and indeterminate disease, the recommendation is the coadministration of Dapsone 100 mg daily with six months of Rifampin 600 mg daily. Under WHO, daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. The Dapsone is continued until all signs of clinical activity are controlled - usually after an additional six months. Then Dapsone should be continued for an additional three years for tuberculoid and indeterminate patients and for five years for borderline tuberculoid patients.


== Indications ==
* In lepromatous and borderline lepromatous patients, the recommendation is the co-administration of Dapsone 100 mg daily with two years of Rifampin 600 mg daily. Under WHO daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. One may elect the concurrent administration of a third anti-leprosy drug, usually either Clofazamine 50-100 mg daily or Ethionamide 250-500 mg daily. Dapsone 100 mg daily is continued 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year. Dapsone should then be continued for an additional 10 years for borderline patients and for life for lepromatous patients.


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 patients with [[HIV]] 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>
* Secondary Dapsone resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving Dapsone treatment relapses clinically and bacteriologically, solid staining bacilli being found in the smears taken from the new active lesions. If such cases show no response to regular and supervised Dapsone therapy within three to six months or good compliance for the past 3-6 months can be assured, Dapsone resistance should be considered confirmed clinically. Determination of drug sensitivity using the mouse footpad method is recommended and, after prior arrangement, is available without charge from the USPHS, Carville, LA. Patients with proven Dapsone resistance should be treated with other drugs.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Dapsone in adult patients.
|offLabelAdultNoGuideSupport===Indications==
* '''Erythema elevatum diutinum'''
|fdaLIADPed=====Indications====
* '''Acne vulgaris'''
* '''Dermatitis herpetiformis'''
* '''Leprosy''', in combination with other anti-leprosy medications


== Administration ==
====Dosing====


Dapsone is administered orally as a 100mg tablet or alternatively as 25mg tablets.
* '''Acne vulgaris''': (12 yr and older) topically rub small amount into clean, dry, acne affected areas twice daily.


== Adverse effects ==
* '''Dermatitis herpetiformis''': initial and maintenance dose schedule is the same as in adults, but given in correspondingly smaller doses.


=== Effects on the blood ===
* '''Leprosy''', in combination with other anti-leprosy medications: 1 to 2 mg/kg orally once a day, maximum 100 mg/day
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Dapsone in pediatric patients.
|offLabelPedNoGuideSupport===Indications==
* '''Malaria'''
|contraindications=* Hypersensitivity to Dapsone and/or its derivatives.
|warnings=* The patient should be warned to respond to the presence of clinical signs such as [[sore throat]], [[fever]], [[pallor]], [[purpura]] or [[jaundice]]. Deaths associated with the administration of Dapsone have been reported from [[agranulocytosis]], [[aplastic anemia]] and other blood [[dyscrasias]]. Complete blood counts should be done frequently in patients receiving Dapsone. The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Dapsone should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Dapsone the patient should be monitored more frequently. Patients on weekly pyrimethamine and Dapsone have developed [[agranulocytosis]] during the second and third month of therapy.


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>
* Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.


=== Effects on the liver ===
* Cutaneous reactions, especially bullous, include [[exfoliative dermatitis]] and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic [[erythema]], [[erythema multiforme]], [[toxic epidermal necrolysis]], morbilliform and scarlatiniform reactions, [[urticaria]] and [[erythema nodosum]]. If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Dapsone and do not require discontinuation. See special section.
|clinicalTrials=In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Dapsone.


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.
'''Hematologic Effects''': Dose-related [[hemolysis]] is the most common adverse effect and is seen in patients with or without [[G6PD deficiency]]. Almost all patients demonstrate the inter-related changes of a loss of 1-2 g of [[hemoglobin]], an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methemoglobin. G6PD deficient patients have greater responses.


=== Other adverse effects ===
'''Nervous System Effects''': [[Peripheral neuropathy]] is a definite but unusual complication of dapsone therapy in non-leprosy patients. Motor loss is predominant. If muscle weakness appears, Dapsone should be withdrawn. Recovery on withdrawal is usually substantially complete. The mechanism of recovery is reported by axonal regeneration. Some recovered patients have tolerated retreatment at reduced dosage. In leprosy this complication may be difficult to distinguish from a leprosy reactional state.


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>
'''Body As A Whole''': In addition to the warnings and adverse effects reported above, additional adverse reactions include: [[nausea]], [[vomiting]], [[abdominal pain]]s, [[pancreatitis]], [[vertigo]], [[blurred vision]], [[tinnitus]], [[insomnia]], [[fever]], [[headache]], [[psychosis]], [[phototoxicity]], pulmonary [[eosinophilia]], [[tachycardia]], [[albuminuria]], the [[nephrotic syndrome]], [[hypoalbuminemia]] without proteinuria, renal papillary necrosis, male infertility, drug-induced [[Lupus erythematosus]] and an infectious mononucleosis-like syndrome. In general, with the exception of the complications of severe anoxia from overdosage (retinal and optic nerve damage, etc.) these adverse reactions have regressed off drug.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of Dapsone in the drug label.
|drugInteractions=* [[Rifampin]] lowers Dapsone levels 7 to 10-fold by accelerating plasma clearance; in leprosy this reduction has not required a change in dosage. Folic acid antagonists such as pyrimethamine may increase the likelihood of hematologic reactions.


=== Dapsone reaction ===
* A modest interaction has been reported for patients receiving 100 mg Dapsone daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Dapsone alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to 12.4 ± 4.5 μg/mL for patients not receiving Dapsone. Thus, there is a mutual interaction between Dapsone and trimethoprim in which each raises the level of the other about 1.5 times.


[[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>
* A crossover study1 designed to assess the potential of a drug interaction between Dapsone, 100 mg/day and trimethoprim, 200 mg every 12 hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524 cells/mm3) demonstrated that there was not a significant drug intreraction between Dapsone and trimethoprim. However, an earlier report2 also by Lee et al, in 78 HIV infected patients with acute Pneumocystis carinii pneumonia, receiving Dapsone, 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated that the serum levels of Dapsone were increased by 40% and trimethoprim levels were increased by 48% when the drugs were administered concurrently.
|useInPregnancyFDA=Pregnancy: Teratogenic Effects. Pregnancy Category C: Animal reproduction studies have not been conducted with Dapsone. Extensive, but uncontrolled experience and two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can affect reproduction capacity. Because of the lack of animal studies or controlled human experience, Dapsone should be given to a pregnant woman only if clearly needed. In general, for leprosy, USPHS at Carville recommends maintenance of Dapsone. Dapsone has been important for the management of some pregnant D.H. patients.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


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"> </ref>
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dapsone in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of Dapsone during labor and delivery.
|useInNursing=Dapsone is excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. See section on hemolysis. Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of drug to the mother.
|useInPed=Pediatric patients are treated on the same schedule as adults but with correspondingly smaller doses. Dapsone is generally not considered to have an effect on the later growth, development and functional development of the pediatric patient.
|useInGeri=There is no FDA guidance on the use of Dapsone with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of Dapsone with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of Dapsone with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of Dapsone in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of Dapsone in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of Dapsone in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of Dapsone in patients who are immunocompromised.
|administration=* Oral
|monitoring=There is limited information regarding <i>Monitoring</i> of Dapsone in the drug label.


== Specific considerations ==
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of Dapsone in the drug label.
|overdose=[[Nausea]], [[vomiting]], hyperexcitability can appear a few minutes up to 24 hours after ingestion of an overdosage. Methemoglobin induced depression, convulsions or severe cyanosis requires prompt treatment. In normal and methemoglobin reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given slowly intravenously, is the treatment of choice. The effect is complete in 30 minutes, but may have to be repeated if methemoglobin reaccumulates. For non-emergencies, if treatment is needed, methylene blue may be given orally in doses of 3-5 mg/kg every 4-6 hours. Methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD deficient patients.
|drugBox=[[File:Dapsone structure01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|mechAction=The mechanism of action in Dermatitis herpetiformis has not been established. By the kinetic method in mice, Dapsone is bactericidal as well as bacteriostatic against Mycobacterium leprae.
|structure=*Dapsone-USP, 4,4'-diaminodiphenylsulfone (DDS), is a primary treatment for Dermatitis herpetiformis. It is an antibacterial drug for susceptible cases of leprosy. It is a white, odorless crystalline powder, practically in-soluble in water and insoluble in fixed and vegetable oils.


Certain patients are at higher risks of adverse effects when using dapsone. Some specific issues which should be considered are:<ref name="AMH"> </ref>
* Dapsone is issued on prescription in tablets of 25 and 100 mg for oral use.


* Related to the blood (a [[full blood count]] should be obtained prior to initiating therapy):
[[File:Dapsone structure.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
** [[Porphyria]]
** [[Anaemia]]
** [[Cardiac disease]]
** [[Pulmonary disease]]
** [[HIV]] infection
** [[G6PD deficiency]]


* Related to the liver (obtain [[liver function test]]s before starting therapy):
Inactive Ingredients: Colloidal silicone dioxide, magnesium stearate, microcrystalline cellulose and corn starch.
** Liver impairment
|PD=There is limited information regarding <i>Pharmacodynamics</i> of Dapsone in the drug label.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of  Dapsone in the drug label.
|nonClinToxic='''Carcinogenesis, mutagenesis''': Dapsone has been found carcinogenic (sarcomagenic) for male rats and female mice causing mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female rats. Dapsone is not mutagenic with or without microsomal activation in S. typhimurium tester strains 1535, 1537, 1538, 98, or 100.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of Dapsone in the drug label.
|howSupplied=* Dapsone Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15). The blisters are light and child-resistant. NDC 49938-102-30.


* Related to [[allergy]]:
* Dapsone Tablets USP, 100 mg are available as round white scored tablets, debossed “100” above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15).The blisters are light and child-resistant. NDC 49938-101-30.
** Sulfonamide allergy is associated with dapsone allergy


== References ==
* Dapsone Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-102-28.


<div class="references-small"><references/></div>
* Dapsone Tablets USP, 100 mg are available as round white scored tablets, debossed“100" above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-101-28.
 
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of Dapsone in the drug label.
== External links ==
|alcohol=* Alcohol-Dapsone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
 
|brandNames=Dapsone<ref>{{cite web | title = DAPSONE - dapsone tablet  | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6a00b4-4546-4af9-a8e7-f4722b753441 }}</ref>
*[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682128.html MedlinePlus Drug Information]
|drugShortage=
 
}}
{{Antimycobacterials}}
{{PillImage
[[Category:Sulfonamide antibiotics]]
|fileName=No image.jpg
[[Category:Leprosy]]
}}
{{LabelImage
|fileName=Dapsone ingredients and appearance.png
}}
{{LabelImage
|fileName=Dapsone fig01.jpg
}}


[[es:Dapsona]]
[[Category:Drug]]
[[fr:Dapsone]]
[[no:Dapson]]
[[pt:Dapsona]]
[[tr:Dapsone]]
{{WH}}
{{WikiDoc Sources}}

Latest revision as of 19:35, 18 August 2015

Dapsone (oral)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Disclaimer

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Overview

Dapsone (oral) is an anti-infective agent that is FDA approved for the treatment of acne vulgaris, dermatitis herpetiformis, and leprosy. Common adverse reactions include nausea, vomiting, abdominal pain, pancreatitis, vertigo, blurred vision, and tinnitus.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • Dermatitis herpetiformis
  • Leprosy: All forms of leprosy except for cases of proven Dapsone resistance.

Dosage

Dermatitis herpetiformis:

  • The dosage should be individually titrated starting in adults with 50 mg daily and correspondingly smaller doses in children. If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried. Dosage should be reduced to a minimum maintenance level as soon as possible. In responsive patients there is a prompt reduction in pruritus followed by clearance of skin lesions. There is no effect on the gastrointestinal component of the disease. Dapsone levels are influenced by acetylation rates. Patients with high acetylation rates, or who are receiving treatment affecting acetylation may require an adjustment in dosage.
  • A strict gluten free diet is an option for the patient to elect, permitting many to reduce or eliminate the need for Dapsone; the average time for dosage reduction is 8 months with a range of 4 months to 2 1/2 years and for dosage elimination 29 months with a range of 6 months to 9 years.

Leprosy:

  • In order to reduce secondary Dapsone resistance, the WHO Expert Committee on Leprosy and the USPHS at Carville, LA, recommended that Dapsone should be commenced in combination with one or more anti-leprosy drugs. In the multidrug program Dapsone should be maintained at the full dosage of 100 mg daily without interruption (with corresponding smaller doses for children) and provided to all patients who have sensitive organisms with new or recrudescent disease or who have not yet completed a two year course of Dapsone monotherapy. For advice and other drugs, the USPHS at Carville, LA (1-800-642-2477) should be contacted. Before using other drugs consult appropriate product labeling.
  • In bacteriologically negative tuberculoid and indeterminate disease, the recommendation is the coadministration of Dapsone 100 mg daily with six months of Rifampin 600 mg daily. Under WHO, daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. The Dapsone is continued until all signs of clinical activity are controlled - usually after an additional six months. Then Dapsone should be continued for an additional three years for tuberculoid and indeterminate patients and for five years for borderline tuberculoid patients.
  • In lepromatous and borderline lepromatous patients, the recommendation is the co-administration of Dapsone 100 mg daily with two years of Rifampin 600 mg daily. Under WHO daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. One may elect the concurrent administration of a third anti-leprosy drug, usually either Clofazamine 50-100 mg daily or Ethionamide 250-500 mg daily. Dapsone 100 mg daily is continued 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year. Dapsone should then be continued for an additional 10 years for borderline patients and for life for lepromatous patients.
  • Secondary Dapsone resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving Dapsone treatment relapses clinically and bacteriologically, solid staining bacilli being found in the smears taken from the new active lesions. If such cases show no response to regular and supervised Dapsone therapy within three to six months or good compliance for the past 3-6 months can be assured, Dapsone resistance should be considered confirmed clinically. Determination of drug sensitivity using the mouse footpad method is recommended and, after prior arrangement, is available without charge from the USPHS, Carville, LA. Patients with proven Dapsone resistance should be treated with other drugs.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Dapsone in adult patients.

Non–Guideline-Supported Use

Indications

  • Erythema elevatum diutinum

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications

  • Acne vulgaris
  • Dermatitis herpetiformis
  • Leprosy, in combination with other anti-leprosy medications

Dosing

  • Acne vulgaris: (12 yr and older) topically rub small amount into clean, dry, acne affected areas twice daily.
  • Dermatitis herpetiformis: initial and maintenance dose schedule is the same as in adults, but given in correspondingly smaller doses.
  • Leprosy, in combination with other anti-leprosy medications: 1 to 2 mg/kg orally once a day, maximum 100 mg/day

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Dapsone in pediatric patients.

Non–Guideline-Supported Use

Indications

  • Malaria

Contraindications

  • Hypersensitivity to Dapsone and/or its derivatives.

Warnings

  • The patient should be warned to respond to the presence of clinical signs such as sore throat, fever, pallor, purpura or jaundice. Deaths associated with the administration of Dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. Complete blood counts should be done frequently in patients receiving Dapsone. The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Dapsone should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Dapsone the patient should be monitored more frequently. Patients on weekly pyrimethamine and Dapsone have developed agranulocytosis during the second and third month of therapy.
  • Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.
  • Cutaneous reactions, especially bullous, include exfoliative dermatitis and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and erythema nodosum. If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Dapsone and do not require discontinuation. See special section.

Adverse Reactions

Clinical Trials Experience

In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Dapsone.

Hematologic Effects: Dose-related hemolysis is the most common adverse effect and is seen in patients with or without G6PD deficiency. Almost all patients demonstrate the inter-related changes of a loss of 1-2 g of hemoglobin, an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methemoglobin. G6PD deficient patients have greater responses.

Nervous System Effects: Peripheral neuropathy is a definite but unusual complication of dapsone therapy in non-leprosy patients. Motor loss is predominant. If muscle weakness appears, Dapsone should be withdrawn. Recovery on withdrawal is usually substantially complete. The mechanism of recovery is reported by axonal regeneration. Some recovered patients have tolerated retreatment at reduced dosage. In leprosy this complication may be difficult to distinguish from a leprosy reactional state.

Body As A Whole: In addition to the warnings and adverse effects reported above, additional adverse reactions include: nausea, vomiting, abdominal pains, pancreatitis, vertigo, blurred vision, tinnitus, insomnia, fever, headache, psychosis, phototoxicity, pulmonary eosinophilia, tachycardia, albuminuria, the nephrotic syndrome, hypoalbuminemia without proteinuria, renal papillary necrosis, male infertility, drug-induced Lupus erythematosus and an infectious mononucleosis-like syndrome. In general, with the exception of the complications of severe anoxia from overdosage (retinal and optic nerve damage, etc.) these adverse reactions have regressed off drug.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Dapsone in the drug label.

Drug Interactions

  • Rifampin lowers Dapsone levels 7 to 10-fold by accelerating plasma clearance; in leprosy this reduction has not required a change in dosage. Folic acid antagonists such as pyrimethamine may increase the likelihood of hematologic reactions.
  • A modest interaction has been reported for patients receiving 100 mg Dapsone daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Dapsone alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to 12.4 ± 4.5 μg/mL for patients not receiving Dapsone. Thus, there is a mutual interaction between Dapsone and trimethoprim in which each raises the level of the other about 1.5 times.
  • A crossover study1 designed to assess the potential of a drug interaction between Dapsone, 100 mg/day and trimethoprim, 200 mg every 12 hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524 cells/mm3) demonstrated that there was not a significant drug intreraction between Dapsone and trimethoprim. However, an earlier report2 also by Lee et al, in 78 HIV infected patients with acute Pneumocystis carinii pneumonia, receiving Dapsone, 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated that the serum levels of Dapsone were increased by 40% and trimethoprim levels were increased by 48% when the drugs were administered concurrently.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Pregnancy: Teratogenic Effects. Pregnancy Category C: Animal reproduction studies have not been conducted with Dapsone. Extensive, but uncontrolled experience and two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can affect reproduction capacity. Because of the lack of animal studies or controlled human experience, Dapsone should be given to a pregnant woman only if clearly needed. In general, for leprosy, USPHS at Carville recommends maintenance of Dapsone. Dapsone has been important for the management of some pregnant D.H. patients.
Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dapsone in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Dapsone during labor and delivery.

Nursing Mothers

Dapsone is excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. See section on hemolysis. Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of drug to the mother.

Pediatric Use

Pediatric patients are treated on the same schedule as adults but with correspondingly smaller doses. Dapsone is generally not considered to have an effect on the later growth, development and functional development of the pediatric patient.

Geriatic Use

There is no FDA guidance on the use of Dapsone with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Dapsone with respect to specific gender populations.

Race

There is no FDA guidance on the use of Dapsone with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Dapsone in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Dapsone in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Dapsone in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Dapsone in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Dapsone in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Dapsone in the drug label.

Overdosage

Nausea, vomiting, hyperexcitability can appear a few minutes up to 24 hours after ingestion of an overdosage. Methemoglobin induced depression, convulsions or severe cyanosis requires prompt treatment. In normal and methemoglobin reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given slowly intravenously, is the treatment of choice. The effect is complete in 30 minutes, but may have to be repeated if methemoglobin reaccumulates. For non-emergencies, if treatment is needed, methylene blue may be given orally in doses of 3-5 mg/kg every 4-6 hours. Methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD deficient patients.

Pharmacology

This image is provided by the National Library of Medicine.

Mechanism of Action

The mechanism of action in Dermatitis herpetiformis has not been established. By the kinetic method in mice, Dapsone is bactericidal as well as bacteriostatic against Mycobacterium leprae.

Structure

  • Dapsone-USP, 4,4'-diaminodiphenylsulfone (DDS), is a primary treatment for Dermatitis herpetiformis. It is an antibacterial drug for susceptible cases of leprosy. It is a white, odorless crystalline powder, practically in-soluble in water and insoluble in fixed and vegetable oils.
  • Dapsone is issued on prescription in tablets of 25 and 100 mg for oral use.
This image is provided by the National Library of Medicine.

Inactive Ingredients: Colloidal silicone dioxide, magnesium stearate, microcrystalline cellulose and corn starch.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Dapsone in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Dapsone in the drug label.

Nonclinical Toxicology

Carcinogenesis, mutagenesis: Dapsone has been found carcinogenic (sarcomagenic) for male rats and female mice causing mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female rats. Dapsone is not mutagenic with or without microsomal activation in S. typhimurium tester strains 1535, 1537, 1538, 98, or 100.

Clinical Studies

There is limited information regarding Clinical Studies of Dapsone in the drug label.

How Supplied

  • Dapsone Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15). The blisters are light and child-resistant. NDC 49938-102-30.
  • Dapsone Tablets USP, 100 mg are available as round white scored tablets, debossed “100” above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15).The blisters are light and child-resistant. NDC 49938-101-30.
  • Dapsone Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-102-28.
  • Dapsone Tablets USP, 100 mg are available as round white scored tablets, debossed“100" above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-101-28.

Storage

There is limited information regarding Dapsone (oral) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Dapsone in the drug label.

Precautions with Alcohol

  • Alcohol-Dapsone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Dapsone[1]

Look-Alike Drug Names

There is limited information regarding Dapsone (oral) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ "DAPSONE - dapsone tablet".

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