What is the recommended dosing for dapsone (diaphenylsulfone) in adults?

Dapsone Dosing in Adults

For adults, dapsone dosing varies by indication: 50-100 mg daily for dermatitis herpetiformis (starting at 50 mg and titrating up to a maximum of 300 mg if needed), 100 mg daily for leprosy (in combination with other anti-leprosy drugs), and 100 mg daily or 100-200 mg weekly for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in HIV-infected patients. 1, 2

Leprosy Treatment

• Standard dosing is 100 mg daily as part of multidrug therapy, never as monotherapy to prevent secondary resistance 1
• For tuberculoid and indeterminate disease, combine dapsone 100 mg daily with rifampin 600 mg daily for 6 months, then continue dapsone alone until clinical activity is controlled (typically an additional 6 months), followed by 3 years for tuberculoid patients or 5 years for borderline tuberculoid patients 1
• For lepromatous and borderline lepromatous disease, combine dapsone 100 mg daily with rifampin 600 mg daily for 2 years, then continue dapsone for 3-10 years until all clinical activity is controlled, followed by an additional 10 years for borderline patients or lifelong for lepromatous patients 1
• A third anti-leprosy drug (clofazimine 50-100 mg daily or ethionamide 250-500 mg daily) may be added for lepromatous cases 1

Dermatitis Herpetiformis

• Start with 50 mg daily and titrate upward based on response 1
• The typical effective range is 50-300 mg daily, though higher doses may be tried if control is not achieved 1
• Reduce to minimum maintenance dose as soon as possible 1
• Patients on a strict gluten-free diet may reduce or eliminate dapsone after an average of 8 months (range 4 months to 2.5 years) 1

PCP Prophylaxis in HIV-Infected Adults

• For daily dosing: 100 mg once daily 2
• For weekly dosing: 100-200 mg once weekly 2
• Daily dosing of 100 mg showed less than 1% PCP recurrence rate over 16 months for secondary prophylaxis 2
• Weekly dosing of 100-200 mg demonstrated zero failure rate for primary prophylaxis and 8% recurrence for secondary prophylaxis 2
• Dapsone is particularly useful in the approximately 60% of TMP-SMX-intolerant patients who can tolerate it 2

Toxoplasmosis Prophylaxis in HIV

• Dapsone 50 mg daily combined with pyrimethamine 50 mg weekly plus leucovorin 25 mg weekly provides dual protection against both PCP and toxoplasmosis 2

Critical Safety Considerations

Mandatory Pre-Treatment Screening

• G6PD deficiency screening is mandatory before initiating therapy due to hemolysis risk, particularly in males of African, Mediterranean, or Asian ancestry 3, 2

Monitoring Requirements

• Complete blood count with differential and platelet count at baseline and monthly intervals to assess for hemolytic anemia, methemoglobinemia, and neutropenia 4, 2
• Liver function tests for hepatotoxicity monitoring 2

Dose-Related Toxicity

• Hemolysis risk increases significantly when daily doses exceed 200 mg 2
• Starting at lower doses (50 mg daily) and titrating upward minimizes hematologic side effects while maintaining therapeutic benefit 3
• Most dermatologic conditions are controlled on 100 mg daily or less 3

Drug Interactions

• Trimethoprim-sulfamethoxazole increases dapsone toxicity risk, including methemoglobinemia, requiring more frequent monitoring if co-administered 3
• Rifampin, anticonvulsants, and St. John's wort may affect dapsone levels through acetylation rate changes 4, 1
• Topical benzoyl peroxide can interact with topical dapsone formulations 4

Hypersensitivity Reactions

• "Sulfone syndrome" is a rare but serious reaction occurring 1-4 weeks into therapy, characterized by fever, exfoliative dermatitis, hepatic dysfunction, and methemoglobinemia 2
• Dapsone is permanently contraindicated after pancytopenia develops, and other sulfonamide-containing medications should be avoided due to cross-reactivity risk 5

Pharmacokinetic Considerations

• Dapsone has an elimination half-life of approximately 24-30 hours, supporting once-daily dosing 6, 7
• Peak plasma concentrations occur at approximately 4 hours after oral administration 6
• The drug is 70-90% protein bound with a volume of distribution of approximately 1.5 L/kg 6
• Therapeutic serum concentration range is 0.5-5 mg/L 6
• A daily dose of 100 mg maintains plasma therapeutic concentrations above 0.5 mcg/mL throughout 24 hours at steady state 8

Management of Methemoglobinemia

• Methylene blue (1-2 mg/kg IV) is the definitive treatment for symptomatic methemoglobinemia, acting as a cofactor to reduce methemoglobin back to hemoglobin 3
• Severe methemoglobinemia (levels exceeding 50-70%) can cause cardiovascular collapse and death 3