Dapsone


Article Author:
George Kurien
Radia Jamil


Article Editor:
Charles Preuss


Editors In Chief:
Wanda Wright
Cynthia Oster


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
6/11/2019 9:53:08 AM

Indications

Dapsone is indicated for a number of conditions, both dermatologic and non-dermatologic. The FDA-approved indications are leprosy and dermatitis herpetiformis.

The non-FDA approved indications include the following:[1]

  • Linear IgA bullous dermatosis, chronic bullous dermatosis of childhood, bullous systemic lupus erythematosus, and erythema elevatum diutinum
  • Autoimmune bullous dermatoses such as bullous pemphigoid, cicatricial pemphigoid, IgA pemphigus, subcorneal pustular dermatosis, pemphigus vulgaris, pemphigus foliaceous, and epidermolysis bullosa acquisita
  • Vasculitic dermatoses such as leukocytoclastic vasculitis and urticarial vasculitis
  • Neutrophilic dermatoses such as Sweet syndrome, pyoderma gangrenosum, and Behcet syndrome
  • Other dermatoses such as subacute cutaneous lupus erythematosus, relapsing polychondritis, granuloma annulare, loxoscelism, granuloma faciale, rosacea, panniculitis, pustular psoriasis, nodulocystic acne, and rhinosporidiosis

Non-dermatologic indications are malaria and Pneumocystis (carinii) jiroveci prophylaxis and treatment.[2]

Mechanism of Action

When treating leprosy, dapsone is bacteriostatic against Mycobacterium leprae at concentrations of 1 - 10 mg/L. It acts via inhibition of the folic acid pathway. In particular, it prevents the bacteria from utilizing para-aminobenzoic acid (PABA) for the synthesis of folic acid by competitively antagonizing PABA. It is a competitive inhibitor of dihydropteroate synthase.[3]

In treating conditions with neutrophilic infiltrates in the skin, the drug acts by affecting neutrophilic functions. Dapsone inhibits the myeloperoxidase-peroxide halide-mediated cytotoxic system, which is a component of neutrophil respiratory burst. Thereby, it controls the degree of neutrophil-induced destruction in lesions. In leprosy treatment, dapsone exerts its therapeutic effect by inhibiting the folic acid pathway. In conditions with neutrophilic infiltrates in the skin, the drug acts by affecting neutrophilic functions. It also may inhibit synthesis of chemotactic lipids and interfere with LTB4 (leukotriene B4) mediated chemotaxis in neutrophils and migration of neutrophils to lesions. Dapsone also decreases the adhesion of neutrophils to IgA.[4]

Though the actual mechanism of action of dapsone is not known for dermatologic conditions, the drug does have a specific effect on human neutrophils, perhaps by both moderating the level of damage by neutrophils at the site of lesions and by decreasing neutrophil migration to lesions.

Dapsone also may have an action on eosinophils and monocytes. The efficacy of the drug in conditions like granuloma annulare and eosinophilic cellulitis, in which monocytes and eosinophils have major roles respectively, points to this hypothesis.

Administration

Leprosy

According to the World Health Organization Expert Committee on Leprosy: Eighth report, there are 3 standard first-line drugs: rifampin, clofazimine, and dapsone. These are to be used in multidrug regimens of fixed duration, and none should be used as monotherapy. For multibacillary leprosy, the standard adult dose of dapsone is 100 mg daily for 12 months. The standard child dose is 50 mg daily for 12 months. For paucibacillary leprosy, the standard adult dose of dapsone is 100 mg daily for 6 months. The standard child dose is 50 mg daily for 6 months. Children under 10 years of age should receive appropriately reduced doses of dapsone at 2 mg/kg body weight per day.

Dapsone is administered orally. The drug is well absorbed from the gut, with approximately 70% to 80% of the single oral dose absorbed. N-acetylation and N-hydroxylation metabolize it. Dapsone and its metabolites are formed in the liver as dapsone glucuronide, which is water soluble and rapidly excreted via kidneys.

Dermatitis Herpetiformis

In patients who are responsive to dapsone, there is a quick reduction in pruritus followed by the clearance of skin lesions. However, there is no effect on the gastrointestinal aspect of the disease. The starting dose for treating dermatitis herpetiformis is 50 mg daily administered orally. Dapsone should be titrated up to 300 mg per day to achieve the desired effect. A higher dose is given only if the patient is not responsive to a lower dose. The dose should be reduced to the minimum effective dose within the range of 50 to 300 mg per day as soon as possible to avoid potential adverse effects. Dapsone is not indicated in the pediatric patient for this condition.

The dosing schedule for other dermatoses is the same as that of dermatitis herpetiformis.[5]

Pneumocystis (carinii) jiroveci

Dapsone is used, off-label, for the prophylaxis and treatment of Pneumocystis (carinii) jiroveci which is classified as a fungus. For prophylaxis, the adult dose is 100 mg daily administered by oral route or divided twice a day as monotherapy. It also can be administered orally at 50 mg daily in combination with weekly pyrimethamine and leucovorin. The pediatric dose also is administered by oral route. For patients greater than 1 month of age, the dose is 2 mg/kg daily not to exceed 100 mg per day, or 4 mg/kg/dose weekly not to exceed 200 mg/week. The adolescent dose is orally administered at 100 mg daily or divided twice a day as monotherapy. It also can be administered orally at 50 mg daily in combination with weekly pyrimethamine and leucovorin.

For treatment of Pneumocystis (carinii) jiroveci, the adult dose is 100 mg daily in combination with trimethoprim for 21 days. For the pediatric patient greater than 1 month of age, the dose is 2 mg/kg daily in combination with trimethoprim for 21 days. For adolescents, the dose is 100 mg daily in combination with trimethoprim for 21 days.

Adverse Effects

Adverse effects include:

  • Hematologic: Hemolytic anemia, methemoglobinemia, leukopenia, and agranulocytosis
  • Cutaneous hypersensitivity reactions: Mebilliform eruption, exfoliative erythroderma, drug-induced lupus erythematosus, and toxic epidermal necrolysis
  • Neurologic: Peripheral neuropathy, predominantly motor loss
  • Psychiatric: Psychosis and insomnia
  • Eyes: Blurred vision
  • Ear, nose, and throat: Tinnitus and vertigo
  • Cardiac: Tachycardia
  • Pulmonary: Pulmonary Eosinophilia
  • Hepatic: Hepatitis, dapsone syndrome, cholestatic jaundice, and hypoalbuminemia without proteinuria
  • Gastrointestinal: Nausea, vomiting, abdominal pain, anorexia, and pancreatitis
  • Renal: Nephrotic syndrome, albuminuria, and renal papillary necrosis
  • Dapsone syndrome: Usually develops after 2 to 6 weeks of dapsone therapy. It is characterized by fever, rash, and hepatitis. The clinical picture may resemble infectious mononucleosis. Blood work will show peripheral eosinophilia and elevated liver enzymes. It can be life-threatening if not properly treated[6]

Contraindications

Absolute contraindications to the use of dapsone are prior hypersensitivity to dapsone or its derivatives including agranulocytosis and hypersensitivity syndrome. Deaths from agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported with dapsone administration.

Relative contraindications to the use of dapsone include allergy to sulfonamide antibiotics, significant cardiopulmonary disease, significant liver or renal function impairment, or pre-existing peripheral neuropathy.

For the treatment of women who are pregnant, dapsone is a category C drug. Therefore, it should be used with caution only if benefits outweigh risks. 

According to the American Academy of Pediatrics, dapsone is listed as a "maternal medication usually compatible with breastfeeding."

Monitoring

Baseline

Complete history and physical with emphasis on cardiopulmonary, gastrointestinal, neurologic, and renal systems.

Lab: Complete blood count, differential count, liver function tests, renal function tests, G6PD level, and urinalysis

Follow-up

Complete blood count (CBC) with differential every week for 4 weeks, then every 2 weeks until week 12, then every 3 to 4 months.

Reticulocyte count as needed

Liver function tests and renal function tests every 3 to 4 months

Methemoglobin level as clinically indicated

Toxicity

Dapsone-induced methemoglobinemia typically is the result of acute poisoning, either by accidental ingestion or suicidal intent. Methemoglobinemia may be treated with vitamin E and C, cimetidine, or intravenous (IV) methylene blue.

Enhancing Healthcare Team Outcomes

The healthcare team, e.g., physicians, nurses, pharmacists must work together to make sure that patients prescribed dapsone correctly take their medications, and most importantly to discuss any serious drug side effects which the patient may encounter, e.g., rash, jaundice, etc. during their treatment.


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Dapsone - Questions

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A 35-year-old woman presents with methemoglobinemia. Which of the following most likely caused the methemoglobinemia in this patient?



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A patient is found to have leprosy and is started on dapsone. What is a side effect of this drug that should be monitored from the patient's blood?



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Which of the following drugs can cause methemoglobinemia?



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What type of drug is dapsone?



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What is an FDA approved indication for dapsone?



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How is dapsone is primarily metabolized?



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What cause the hematotoxicity of dapsone?



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A 45-year-old woman presents with recurrent groups of sterile pustules appearing on subcorneal layers of the skin in an annular pattern located on her intertriginous skin. The patient receives treatment with an oral antimicrobial drug. Which of the following is the most likely mechanism of action for this drug?



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A 29-year-old man receives treatment with dapsone. Which of the following is the most likely therapeutic use of dapsone in this patient?



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What are the features of dapsone syndrome?



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An 18-year-old woman presents with itchy, diffuse, polymorphic skin lesions. A test dose of which of the following would be the most diagnostic in this patient?



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What is the chemical name of dapsone?



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Which enzyme level is estimated before starting dapsone?



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A 65-year-old patient diagnosed with Hansen disease (borderline tuberculoid) developed cyanosis of the fingers after 3 weeks of starting treatment. What is the reason for cyanosis and what is the drug of choice for this condition?



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A 65-year-old patient with poorly controlled diabetes was detected to have Hansen disease. He was put on paucibacillary-multidrug therapy (dapsone and rifampicin) as per the WHO recommendation. After a month of treatment, on routine check-up, his HbA1C level was found to have lowered indicating very good control of diabetes. What is the explanation for this phenomenon?



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A 65-year-old patient with Hansen disease on treatment with dapsone and rifampicin for the last 4 weeks presented with fever, erythematous rashes all over the body, and hepatitis. What is the probable diagnosis?



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A 30-year-old male presents with a fever, sore throat, and a pruritic rash. He has a history of celiac disease and is currently taking dapsone daily for the last 9 weeks. He doesn't use tobacco or alcohol but has a brief history of IV drug use. Blood pressure is 110/90, the pulse is 110/min and regular, the temperature is 38.2 (102 F) and respiration is 24/min. On examination, he has blisters with a watery fluid present on his elbows, knees, buttocks, and back. His liver function tests are within normal limits. What is the most likely cause of this patient's condition?



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Dapsone - References

References

Liang SE,Hoffmann R,Peterson E,Soter NA, Use of Dapsone in the Treatment of Chronic Idiopathic and Autoimmune Urticaria. JAMA dermatology. 2018 Nov 21;     [PubMed]
Ramos FS,Ferreira FR,Rabay FMO,Lira MLA, Neutrophilic dermatosis of the dorsal hands: response to dapsone monotherapy. Anais brasileiros de dermatologia. 2018 Sep-Oct;     [PubMed]
Kumar B, Antimicrobial resistance in leprosy. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018 Dec 21;     [PubMed]
Din RS,Tsiaras WG,Li DG,Mostaghimi A, Efficacy of Systemic Dapsone Treatment for Pyoderma Gangrenosum: A Retrospective Review. Journal of drugs in dermatology : JDD. 2018 Oct 1;     [PubMed]
Wang Y,Yang B,Zhou G,Zhang F, Two Cases of Dermatitis Herpetiformis Successfully Treated with Tetracycline and Niacinamide. Acta dermatovenerologica Croatica : ADC. 2018 Oct;     [PubMed]
Thangaraju P,Venkatesan S, Leprosy cases with respiratory infection - Rule out tuberculosis simultaneously with dapsone syndrome. Indian journal of pharmacology. 2018 Jul-Aug;     [PubMed]

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