What are the indications and dosing guidelines for dapsone?

Indications and Dosing Guidelines for Dapsone

Dapsone is primarily indicated for leprosy, dermatitis herpetiformis, Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV patients, and acne vulgaris, with dosing regimens that vary by indication and patient age. 1, 2

Indications and Dosing

Leprosy

• Adult dosing: 100 mg daily without interruption, as part of multidrug therapy 1
• Duration:
  • Tuberculoid/indeterminate: Continue for 3 years after clinical activity control
  • Borderline tuberculoid: Continue for 5 years after clinical activity control
  • Lepromatous/borderline lepromatous: Continue for 10 years to life 1
• Pediatric dosing: Correspondingly smaller doses based on weight 1
• Must be used in combination with other anti-leprosy drugs (typically rifampin) to prevent resistance 1

Dermatitis Herpetiformis

• Adult dosing: Start at 50 mg daily, titrate individually within range of 50-300 mg daily 1
• Pediatric dosing: Correspondingly smaller doses based on weight 1
• Dosage should be reduced to minimum maintenance level as soon as possible 1
• Gluten-free diet may allow for dosage reduction (average time 8 months) or elimination (average time 29 months) 1

PCP Prophylaxis in HIV Patients

• Adult dosing: 100 mg daily or 200 mg weekly 2
• Pediatric dosing: 2 mg/kg body weight (max 100 mg) daily or 4 mg/kg body weight (max 200 mg) weekly 2
• Used as alternative when TMP-SMX is not tolerated 2

Acne Vulgaris (Topical Formulation)

• Indication: Topical treatment of acne vulgaris 2
• Dosing: Apply pea-sized amount in thin layer to affected areas twice daily 2
• Duration: If no improvement after 12 weeks, treatment should be reassessed 2, 3
• Age restriction: Safety and efficacy not established in patients <12 years 2, 3

Monitoring and Safety Considerations

Pre-Treatment Assessment

• Check for G6PD deficiency before starting oral dapsone (not required for topical formulation) 2, 3
• Baseline complete blood count, liver and renal function tests 4

Adverse Effects Monitoring

1. Hematologic effects (most significant):

   • Hemolytic anemia (dose-related, more common at doses >200 mg/day)
   • Methemoglobinemia
   • Agranulocytosis (rare)
   • Monitor CBC regularly 2, 4

2. Dermatologic effects:

   • Rash
   • Exfoliative dermatitis (part of "sulfone syndrome") 2

3. Neurologic effects:

   • Peripheral neuropathy (primarily motor function)
   • Insomnia, headache, vertigo 5

4. Gastrointestinal effects:

   • Abdominal pain, anorexia
   • Nausea, vomiting 5, 4

5. Hepatic effects:

   • Hepatotoxicity
   • Increased liver enzymes 2, 4

6. Hypersensitivity reactions:

   • "Sulfone syndrome" (fever, exfoliative dermatitis, hepatic dysfunction, methemoglobinemia) typically occurring 1-4 weeks into therapy 2

Special Populations

• Pregnancy: Category C for topical dapsone 2, 3
• Nursing: Excreted in human milk; consider risks vs. benefits 2
• G6PD deficiency: Higher risk of hemolysis, even at lower doses (50 mg/day) 4

Drug Interactions

• Oral dapsone:

  • Rifampin (may decrease dapsone levels)
  • Probenecid (may increase dapsone levels) 4

• Topical dapsone:

  • Trimethoprim/sulfamethoxazole
  • Topical benzoyl peroxide (may cause orange-brown skin discoloration)
  • Rifampin
  • Anticonvulsants
  • St. John's wort
  • Folic acid antagonists 2, 3

Clinical Pearls

• Oral dapsone has linear pharmacokinetics within therapeutic range with elimination half-life of approximately 30 hours 6
• Therapeutic serum concentration range is 0.5-5 mg/L for oral dapsone 6
• Acetylation ratio shows genetic variation (slow vs. rapid acetylators) 6
• Activated charcoal can be used in cases of dapsone overdose due to enterohepatic circulation 6
• Topical dapsone has significantly lower systemic absorption compared to oral administration, reducing risk of serious side effects 7

Remember to check for G6PD deficiency before initiating oral dapsone therapy, as this is a critical safety consideration that can prevent potentially serious hemolytic reactions.