Continuing Education Activity
Dapsone is indicated for a variety of conditions, both dermatologic and non-dermatologic. The FDA-approved indications are leprosy and dermatitis herpetiformis. The non-FDA-approved indications include a wide range of dermatoses and malaria and Pneumocystis (carinii) jiroveci prophylaxis and treatment. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of dapsone, pertinent for interprofessional team members in treating conditions where dapsone is indicated.
Objectives:
- Identify the mechanisms of action of dapsone.
- Summarize the indications for dapsone, both FDA and non-FDA approved.
- Describe the potential adverse effects of dapsone.
- Review the importance of improving care coordination among interprofessional team members to improve patient outcomes for whom dapsone is appropriate to treat their condition.
Indications
Dapsone has indications for several 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 to 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 the 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 the 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 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 significant roles, respectively, points to this hypothesis.
Administration
Leprosy
According to the World Health Organization Expert Committee on Leprosy: Eighth report, there are three standard first-line drugs: rifampin (rifampicin), 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 six months. The standard child dose is 50 mg daily for six months. Children under ten years of age should receive appropriately reduced doses of dapsone at 2 mg/kg body weight per day.
Dapsone administration is via the oral route. 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 the drug. Dapsone and its metabolites are formed in the liver as dapsone glucuronide, which is water-soluble and rapidly excreted via kidneys.[5]
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, and 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.[6][7][6]
Pneumocystis (carinii) jiroveci
Dapsone is used, off-label, for the prophylaxis and treatment of Pneumocystis jiroveci (carinii), 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 the oral route. For patients greater than one 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 the treatment of Pneumocystis jiroveci (carinii), the adult dose is 100 mg daily in combination with trimethoprim for 21 days. The dose is 2 mg/kg daily in conjunction with trimethoprim for 21 days for pediatric patients greater than one month of age. For adolescents, the dose is 100 mg daily in combination with trimethoprim for 21 days.
Toxoplasmosis Prophylaxis
Dapsone is also used off-label for prophylaxis against toxoplasmosis. The dose is 50 mg oral each day. It is not considered a first-line agent and should be given with pyrimethamine and leucovorin.
Dose Adjustments
No dose adjustments are necessary for patients with renal impairment. If the patient is on hemodialysis, dosing should be after dialysis, with consideration for a supplemental dose if the subsequent maintenance dose is not due immediately after dialysis. Peritoneal dialysis requires no dose adjustment and no supplemental dose.
Hepatic dosing has no specific recommendations, but caution is advised.
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.[9]
Relative contraindications to the use of dapsone include allergy to sulfonamide antimicrobials, 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 the benefits outweigh the risks.[10]
According to the American Academy of Pediatrics, dapsone is listed as a "maternal medication usually compatible with breastfeeding."
Toxicity
Dapsone-induced methemoglobinemia typically is the result of acute poisoning, either by accidental ingestion or suicidal intent. Methemoglobinemia is treatable with vitamin E and C, cimetidine, or intravenous (IV) methylene blue.
Enhancing Healthcare Team Outcomes
The entire interprofessional healthcare team, e.g., clinicians (MDs, DOs, NPs, PAs), nursing staff, and 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. Open communication can preclude adverse events and make all team members aware of any concerns that may arise during monitoring. This interprofessional approach will drive optimal patient outcomes. [Level 5]
Dapsone