Dapsone is a synthetic sulfone antimicrobial agent with a well-established history in dermatological and infectious disease therapeutics. Its primary mechanism of action involves inhibition of bacterial folate synthesis and potent anti-inflammatory effects, particularly through the suppression of neutrophil-mediated responses. This dual functionality makes it a cornerstone in the management of a range of complex conditions, from leprosy and dermatitis herpetiformis to certain forms of acne and autoimmune bullous diseases. Its efficacy is supported by decades of clinical use and a robust understanding of its pharmacokinetic profile.

Features

• Chemical Class: Synthetic sulfone
• Mechanism of Action: Competitive antagonist of para-aminobenzoic acid (PABA), inhibiting bacterial dihydrofolic acid synthesis; also inhibits neutrophil myeloperoxidase and chemotaxis
• Bioavailability: 70-80% following oral administration
• Protein Binding: 70-90%
• Half-Life: Approximately 30 hours (range 10-50 hours)
• Metabolism: Hepatic, primarily via N-acetylation and N-hydroxylation (CYP2E1, CYP3A4)
• Excretion: Primarily renal (unchanged drug and metabolites)
• Available Formulations: Oral tablets (25 mg, 100 mg); topical gel (5%, 7.5%)

Benefits

• Provides targeted antibacterial action against Mycobacterium leprae, making it a first-line agent in multibacillary leprosy regimens.
• Offers significant anti-inflammatory effects, rapidly controlling the intense pruritus and blistering associated with dermatitis herpetiformis.
• Serves as a effective steroid-sparing agent in the management of chronic inflammatory dermatoses, reducing long-term corticosteroid exposure.
• Demonstrates efficacy in treating acne vulgaris, particularly inflammatory papules and pustules, when other treatments have failed.
• Used in the prophylaxis and treatment of Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients, often in combination with other agents.
• Provides a well-tolerated long-term maintenance option for certain chronic conditions due to its predictable pharmacokinetics.

Common use

Dapsone is indicated for the treatment of leprosy (Hansen’s disease), always as part of a multidrug therapy regimen as recommended by the World Health Organization to prevent resistance. It is a first-line therapy for dermatitis herpetiformis, providing rapid symptomatic relief and controlling disease activity. In dermatology, it is used off-label for various neutrophilic dermatoses, including linear IgA disease, bullous lupus erythematosus, and subcorneal pustular dermatosis. It is also employed in the management of inflammatory acne, particularly in cases resistant to conventional antibiotics. In infectious disease, it is used for PJP prophylaxis in HIV-positive patients and other immunocompromised states, as well as for the treatment of certain protozoal infections like malaria (in combination) and toxoplasmosis.

Dosage and direction

Dosage is highly indication-specific and must be individualized based on patient weight, clinical response, and tolerability.

For leprosy:

• Adults: 100 mg daily as part of multidrug therapy (with rifampicin and clofazimine)
• Children: 1-2 mg/kg/day (maximum 100 mg/day)

For dermatitis herpetiformis:

• Adults: Initial dose 50 mg daily, may increase to 300 mg daily based on response. Maintenance dose is often the lowest effective dose.
• Children: 0.5-2 mg/kg/day

For acne vulgaris:

• Adults: 50-100 mg daily, often starting at lower doses
• Not typically recommended for children for this indication

For PJP prophylaxis:

• Adults: 100 mg daily or 50 mg twice daily
• Children: 2 mg/kg/day (maximum 100 mg/day) or 4 mg/kg once weekly (maximum 200 mg)

Administration should be with food to minimize gastrointestinal upset. Regular monitoring of complete blood count (CBC), liver function tests (LFTs), and glucose-6-phosphate dehydrogenase (G6PD) levels is mandatory before and during therapy.

Precautions

Dapsone requires careful hematological monitoring due to its potential to cause hemolytic anemia and methemoglobinemia, particularly in patients with G6PD deficiency. Baseline G6PD testing is essential before initiation. Regular CBC monitoring (weekly for first month, then monthly) is recommended to detect anemia, leukopenia, or agranulocytosis. Liver function should be monitored periodically. Patients should be advised about the risk of peripheral neuropathy with long-term use. Caution is advised in patients with cardiac or pulmonary disease due to reduced oxygen-carrying capacity from methemoglobinemia. Hypoalbuminemia may increase the risk of adverse reactions. Dapsone syndrome (fever, rash, lymphadenopathy, hepatitis) may occur typically within the first 6 weeks of therapy and requires immediate discontinuation.

Contraindications

Dapsone is contraindicated in patients with known hypersensitivity to dapsone or other sulfone drugs. It is absolutely contraindicated in patients with severe G6PD deficiency due to the high risk of severe hemolysis. It should not be used in patients with severe anemia. Contraindicated in combination with drugs that cause significant methemoglobinemia (e.g., primaquine, nitrites). Avoid use in patients with severe hepatic impairment.

Possible side effect

• Hematologic: Hemolytic anemia (dose-related), methemoglobinemia, agranulocytosis, leukopenia, thrombocytopenia
• Gastrointestinal: Nausea, vomiting, abdominal pain, pancreatitis, hepatitis
• Neurologic: Peripheral neuropathy, headache, insomnia, vertigo
• Dermatologic: Rash, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity
• Other: Dapsone hypersensitivity syndrome (fever, rash, lymphadenopathy, hepatitis), hypoalbuminemia, nephrotic syndrome, pulmonary eosinophilia, psychosis

Drug interaction

• Rifampicin: Decreases dapsone levels by inducing metabolism
• Probenecid: Increases dapsone levels by reducing renal excretion
• Trimethoprim: Increases dapsone levels and risk of adverse effects
• Methotrexate: Increased risk of hematologic toxicity
• Didanosine: Reduces absorption of dapsone
• Folic acid antagonists: Additive antifolate effects
• Other hemolytic agents (e.g., primaquine): Increased risk of hemolysis
• CYP2E1/CYP3A4 inducers/inhibitors: May alter dapsone metabolism

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one. Maintaining consistent blood levels is important for efficacy, particularly in infectious indications.

Overdose

Overdose may cause severe hemolytic anemia, methemoglobinemia (cyanosis, chocolate-brown blood, dyspnea, fatigue, tachycardia), nausea, vomiting, and hyperexcitability. Heinz body formation may be observed on blood smear. Management is supportive and includes gastric lavage if presented early, methylene blue for methemoglobinemia (1-2 mg/kg IV slowly), and blood transfusion for severe hemolysis. Hemodialysis is not effective due to high protein binding.

Storage

Store at controlled room temperature (20-25°C or 68-77°F). Protect from light and moisture. Keep in the original container tightly closed. Do not store in bathroom or damp areas. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Dapsone is a prescription medication that should only be used under the supervision of a qualified healthcare professional. The prescribing physician should be consulted for specific diagnostic and therapeutic decisions. Individual patient response and tolerability may vary. Always follow the prescribed dosage and monitoring guidelines.

Reviews

“Dapsone has been transformative in managing my patients with dermatitis herpetiformis. The rapid relief from pruritus and control of blistering is remarkable, often within 48-72 hours. While the monitoring requirements are significant, the benefit-to-risk profile is favorable in appropriately selected patients.” - Board-Certified Dermatologist, 15 years experience

“As an infectious disease specialist working in leprosy-endemic areas, dapsone remains an essential component of our multidrug therapy regimens. Its efficacy against M. leprae is well-documented, though the emergence of resistance underscores the importance of combination therapy.” - Infectious Disease Specialist

“The anti-inflammatory properties of dapsone make it invaluable in my rheumatology practice for patients with refractory cutaneous lupus. It has allowed us to reduce corticosteroid doses significantly in several challenging cases.” - Rheumatologist