Dapsone is a synthetic sulfone antimicrobial agent with a well-established history in dermatology and infectious disease. Its primary mechanisms of action involve inhibition of bacterial folate synthesis and suppression of neutrophil-mediated inflammation, making it a uniquely versatile therapeutic agent. This medication is indicated for a range of conditions where its dual antibacterial and anti-inflammatory properties provide significant clinical benefit, particularly in managing chronic dermatoses and specific infections. Its use requires careful patient selection and monitoring due to a distinct side effect 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%
• Metabolism: Hepatic, primarily via N-acetylation (polymorphic) and N-hydroxylation
• Half-life: 20-30 hours (range: 10-50 hours)
• Excretion: Primarily renal

Benefits

• Provides potent antibacterial activity against Mycobacterium leprae and a spectrum of other organisms.
• Offers significant anti-inflammatory effects, particularly for neutrophil-predominant dermatoses like dermatitis herpetiformis.
• Serves as a second-line treatment for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in sulfonamide-allergic patients.
• Effective for managing acne vulgaris, especially inflammatory and pustular forms, when conventional therapies fail.
• Can be used as a steroid-sparing agent in various immune-mediated conditions.

Common use

Dapsone is FDA-approved for the treatment of leprosy (always used in multi-drug regimens to prevent resistance) and dermatitis herpetiformis. It is widely used off-label for a variety of dermatological conditions, including acne vulgaris, linear IgA disease, subcorneal pustular dermatosis, and pemphigus vulgaris/foliaceus. It is also a critical agent for prophylaxis against Pneumocystis jirovecii pneumonia in immunocompromised individuals, such as those with HIV/AIDS or on immunosuppressive therapies, who have a contraindication to trimethoprim-sulfamethoxazole.

Dosage and direction

Dosage is highly indication-specific and must be individualized.

• Dermatitis Herpetiformis: Initiate at 50 mg daily, titrating upward as needed to a typical maintenance dose of 25-300 mg daily. A gluten-free diet can reduce dosage requirements.
• Leprosy: As part of multi-drug therapy (MDT). For multibacillary leprosy: 100 mg daily unsupervised plus other agents for 12 months. For paucibacillary leprosy: 100 mg daily unsupervised plus other agents for 6 months.
• PJP Prophylaxis: 100 mg daily or 50 mg twice daily.
• Acne Vulgaris: Typically 50-100 mg daily, often initiated at 25 mg daily to assess tolerance.
• Administration: Can be taken with or without food. Taking with food may mitigate gastrointestinal upset.

Precautions

• G6PD Deficiency Screening is MANDATORY: Must be performed prior to initiation due to the high risk of dose-related hemolysis and methemoglobinemia. Use is contraindicated in severe deficiency.
• Complete Blood Count (CBC) Monitoring: Baseline CBC is required. Monitor periodically (e.g., weekly for first month, monthly for next 5 months, then semi-annually) for signs of hemolytic anemia, agranulocytosis, and leukopenia.
• Peripheral Neuropathy: Monitor for motor loss and muscle weakness, which can be irreversible.
• Hypersensitivity Reactions: Dapsone hypersensitivity syndrome (fever, rash, lymphadenopathy, hepatitis) is a serious, potentially fatal reaction requiring immediate discontinuation.
• Hepatic and Renal Function: Use with caution in patients with significant hepatic or renal impairment; dosage adjustment may be necessary.

Contraindications

• Known hypersensitivity to dapsone or any component of the formulation.
• Severe anemia.
• Known severe G6PD deficiency.
• History of dapsone hypersensitivity syndrome.

Possible side effect

Common and less serious side effects include:

• Hemolytic anemia (dose-related, especially in G6PD deficiency)
• Headache
• Nausea, vomiting
• Dizziness
• Mild skin rash
• Elevated liver enzymes

Serious side effects requiring medical attention include:

• Methemoglobinemia (cyanosis, shortness of breath, fatigue)
• Agranulocytosis
• Peripheral neuropathy (motor loss)
• Dapsone Hypersensitivity Syndrome (DHS): fever, rash, hepatitis, eosinophilia
• Exfoliative dermatitis, Stevens-Johnson syndrome
• Cholestatic jaundice
• Psychosis

Drug interaction

• Probenecid: May increase dapsone levels.
• Rifampin: Significantly increases dapsone metabolism, reducing its plasma levels.
• Trimethoprim: Increases levels of both dapsone and its hydroxylamine metabolite, increasing the risk of hematologic toxicity.
• Didanosine: Coadministration may reduce the absorption and efficacy of dapsone for PJP prophylaxis.
• Other Hemolytic Agents: Increased risk of hemolysis when combined with other drugs that cause oxidative stress (e.g., primaquine).
• Methotrexate: May increase the risk of pancytopenia.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Do not double the dose to make up for a missed one.

Overdose

Overdose exacerbates the drug’s primary toxicities. Symptoms include severe nausea, vomiting, hyperexcitability, seizures, and profound methemoglobinemia (evidenced by cyanosis). Hemolysis may occur 5-7 days post-overdose. Treatment is supportive and includes gastric lavage if presented early, administration of activated charcoal, and management of methemoglobinemia with methylene blue (contraindicated in G6PD deficiency). Exchange transfusion may be necessary in severe cases.

Storage

Store at room temperature (20°C to 25°C or 68°F to 77°F) in a tight, light-resistant container. Keep out of reach of children and pets. Do not flush medication down the toilet or pour it into a drain. Dispose of unused medication via a official medicine take-back program.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

• “Dapsone has been a game-changer for my patients with refractory dermatitis herpetiformis. The rapid control of pruritus and blistering is remarkable, though vigilant monitoring for hematologic effects is non-negotiable.” – Board-Certified Dermatologist
• “An indispensable tool in our MDT regimens for leprosy. Its efficacy is proven, but the necessity of combination therapy to curb resistance cannot be overstated.” – Infectious Disease Specialist, Leprosy Mission
• “As a prophylactic agent for PJP in sulfa-allergic transplant patients, dapsone is effective, though the side effect profile demands careful patient education and consistent follow-up.” – Transplant Pharmacist
• “For inflammatory acne unresponsive to oral antibiotics and retinoids, low-dose dapsone can be highly effective. Starting low and titrating slowly is key to managing initial side effects like headache.” – Aesthetic Practitioner