Dapsone is a synthetic sulfone antimicrobial agent with a well-established history in clinical medicine, primarily recognized for its dual role in treating infectious diseases and modulating inflammatory responses. Its mechanism of action involves inhibition of bacterial dihydrofolic acid synthesis, analogous to sulfonamides, and suppression of neutrophil-mediated inflammation, making it a versatile therapeutic option. This agent is indicated for a spectrum of dermatological and systemic conditions, offering a targeted approach where conventional antibiotics or anti-inflammatory agents may be insufficient. Its utility spans from leprosy management to dermatoses characterized by neutrophil infiltration, underpinned by decades of clinical evidence and a predictable pharmacokinetic profile.

Features

• Chemical structure: 4,4’-diaminodiphenyl sulfone
• Mechanism: Competitive antagonist of para-aminobenzoic acid (PABA), inhibiting bacterial folate synthesis; also inhibits neutrophil myeloperoxidase and chemotaxis
• Formulations: Oral tablets (25 mg, 100 mg); topical gel (5%, 7.5%)
• Bioavailability: 70-80% following oral administration
• Protein binding: 70-90%
• Metabolism: Hepatic via N-acetylation and N-hydroxylation (CYP2E1, CYP3A4)
• Half-life: 20-30 hours (range 10-50 hours)
• Excretion: Primarily renal (unchanged drug and metabolites)

Benefits

• Provides bactericidal activity against Mycobacterium leprae, crucial for multibacillary and paucibacillary leprosy regimens.
• Offers effective anti-inflammatory control in neutrophilic dermatoses such as dermatitis herpetiformis, reducing blister formation and pruritus.
• Serves as a second-line agent for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in sulfa-allergic patients, particularly those with HIV/AIDS.
• Demonstrates efficacy in managing acne vulgaris, especially inflammatory papules and pustules, via its antimicrobial and anti-inflammatory properties.
• Used off-label in conditions like linear IgA disease, subcorneal pustular dermatosis, and leukocytoclastic vasculitis, expanding its therapeutic utility.
• Allows for once-daily dosing in most indications due to its prolonged half-life, enhancing patient adherence.

Common use

Dapsone is primarily employed in the management of leprosy (Hansen’s disease), both multibacillary and paucibacillary forms, as part of World Health Organization (WHO)-recommended multidrug therapy (MDT). In dermatology, it is a first-line treatment for dermatitis herpetiformis, often resulting in rapid symptomatic relief. It is also utilized for prophylaxis against Pneumocystis jirovecii pneumonia in immunocompromised individuals, particularly when trimethoprim-sulfamethoxazole is not tolerated. Off-label uses include inflammatory acne, linear IgA bullous dermatosis, and other neutrophil-predominant disorders. Topical dapsone is approved for acne vulgaris, providing localized effect with minimized systemic exposure.

Dosage and direction

Dosage must be individualized based on indication, patient weight, and clinical response. For leprosy: adults typically receive 100 mg daily unsupervised or 100 mg daily supervised in MDT regimens (combined with rifampicin and clofazimine). For dermatitis herpetiformis: initial dose is 50 mg daily, titrated upward to 100-300 mg daily based on symptom control, then maintained at the lowest effective dose. For PCP prophylaxis: 100 mg daily or 50 mg twice daily. For acne vulgaris (oral): 50-100 mg daily; topical gel is applied twice daily to affected areas. Administration with food may reduce gastrointestinal upset. Regular monitoring of complete blood count (CBC) and liver function tests is recommended during therapy.

Precautions

Dapsone therapy requires vigilant monitoring due to potential hematological, hepatic, and neurological effects. Baseline glucose-6-phosphate dehydrogenase (G6PD) level must be assessed prior to initiation to identify patients at risk for hemolytic anemia. CBC should be performed weekly for the first month, monthly for the next five months, and semi-annually thereafter. Liver function tests and peripheral neuropathy assessments are advised periodically. Use with caution in patients with cardiopulmonary disease due to risk of methemoglobinemia. Pregnancy Category C: use only if potential benefit justifies potential risk to the fetus. Not recommended during lactation due to secretion in breast milk.

Contraindications

Dapsone is contraindicated in patients with known hypersensitivity to dapsone or other sulfone drugs. It must not be used in those with severe G6PD deficiency due to high risk of severe hemolysis. Contraindicated in patients with methemoglobin reductase deficiency. Avoid use in individuals with a history of dapsone-induced agranulocytosis, aplastic anemia, or other severe blood dyscrasias. Not recommended in combination with drugs that inhibit hepatic CYP enzymes without careful monitoring.

Possible side effect

Common adverse effects include hemolytic anemia (dose-related), methemoglobinemia (cyanosis, dyspnea), nausea, vomiting, headache, and dizziness. Less frequently, agranulocytosis, peripheral neuropathy, rash, photosensitivity, and hepatic enzyme elevations may occur. Rare but serious effects include dapsone hypersensitivity syndrome (fever, rash, lymphadenopathy, hepatitis), toxic epidermal necrolysis, and sulfone syndrome. Topical application may cause local dryness, erythema, or peeling.

Drug interaction

Dapsone interacts with drugs that induce or inhibit CYP3A4 and CYP2E1. Rifampin decreases dapsone levels by inducing metabolism. Protease inhibitors (e.g., ritonavir) may increase dapsone concentrations. Concurrent use with other hemolytic agents (e.g., primaquine) increases risk of anemia. Trimethoprim may elevate dapsone levels. Dapsone may reduce the efficacy of oral contraceptives. Concurrent use with methotrexate or other myelosuppressive drugs requires extreme caution.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose. Do not double the dose to make up for a missed one. Consistent daily dosing is important to maintain therapeutic levels, especially for antimicrobial or prophylactic indications.

Overdose

Overdose may exacerbate common adverse effects, particularly methemoglobinemia (evidenced by cyanosis, fatigue, tachycardia) and hemolysis. Gastric lavage or activated charcoal may be considered if ingestion is recent. Methylene blue (1-2 mg/kg IV) is the antidote for significant methemoglobinemia. Supportive care, including oxygen and transfusion, may be necessary. 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 freeze. Keep out of reach of children and pets. Do not use beyond the expiration date.

Disclaimer

This information is for educational purposes and does not constitute medical advice. Dapsone is a prescription medication and must be used under the supervision of a qualified healthcare professional. Dosage, indications, and monitoring requirements should be determined by a physician based on individual patient factors. Always report adverse effects to your healthcare provider.

Reviews

Clinical studies and long-term use support dapsone’s efficacy in indicated conditions, particularly dermatitis herpetiformis and leprosy. Dermatologists frequently note rapid response in reducing itch and blistering in DH patients. Hematological monitoring is emphasized in all expert guidelines due to toxicity risks. Some patients report gastrointestinal tolerance issues, which often improve with dose adjustment or administration with food. Overall, it remains a valued agent in dermatological and infectious disease therapeutics.