DAPSONE

Clinical safety rating: caution

Animal studies have proved adverse effects but may be safe for humans

How it works

Dapsone is a sulfone antibiotic that inhibits bacterial synthesis of dihydrofolic acid via competition with para-aminobenzoic acid for the active site of dihydropteroate synthase. It also has anti-inflammatory and immunomodulatory properties, including inhibition of neutrophil myeloperoxidase and suppression of neutrophil chemotaxis.

What the body does with it

Metabolism	Metabolized primarily in the liver via N-acetylation and N-hydroxylation. Acetylation is mediated by N-acetyltransferase (NAT); hydroxylation is mediated by cytochrome P450 (CYP) enzymes, particularly CYP2E1 and CYP3A4. The N-hydroxy metabolite is responsible for hemolytic and methemoglobinemic effects.
Excretion	Primarily renal (70-85% as metabolites, <20% unchanged). Biliary/fecal excretion accounts for 10-15%.
Half-life	Terminal elimination half-life is 20-30 hours (mean 28 hours). In patients with renal impairment, half-life may be prolonged up to 48 hours.
Protein binding	70-90% bound to plasma proteins, primarily albumin.
Volume of Distribution	1.5 L/kg (range 1.0-2.0 L/kg), indicating extensive tissue distribution, especially to skin, liver, and kidneys.
Bioavailability	Oral: ~90-100% (well absorbed). Topical: Minimal systemic absorption (<10%).
Onset of Action	Oral: Time to clinical effect is 4-7 days for dermatitis herpetiformis; for leprosy, clinical improvement noted within 1-3 weeks. Topical: Not applicable.
Duration of Action	Oral: Duration is 48-72 hours after a single dose. Steady-state achieved in 7-10 days. For chronic therapy, continuous effect requires daily dosing.

Classification & Brands

Action Class

Anti leprotic

Dosing & administration

100 mg orally once daily for leprosy or dermatitis herpetiformis.

Dosage form	GEL
Renal impairment	GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 50-100% of dose; GFR <10 mL/min: not recommended or use with extreme caution.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Leprosy: 1-2 mg/kg orally once daily, max 100 mg/day. Dermatitis herpetiformis: 2 mg/kg/day in divided doses, not to exceed adult dose.
Geriatric use	Start at lower end of dosing range due to age-related renal and hepatic decline; monitor for hemolysis and methemoglobinemia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Rifampin decreases levels trimethoprim increases levels Can cause hemolytic anemia and methemoglobinemia especially in G6PD deficiency.

Breastfeeding

Dapsone is excreted into breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.2–0.5. Estimated infant dose is about 2–5% of maternal weight-adjusted dose. No significant adverse effects have been reported in breastfed infants, though there is a theoretical risk of hemolysis in G6PD-deficient infants. Dapsone is generally considered compatible with breastfeeding with monitoring.

Teratogenic Risk

Dapsone is not a major teratogen. Limited data do not suggest a significantly increased risk of major birth defects. However, hemolytic anemia and methemoglobinemia have been reported in neonates whose mothers took dapsone during pregnancy, especially near term. First trimester use may be associated with a slight increase in cardiovascular defects, but data are conflicting. Overall, risk appears low if clinically indicated.

Warnings & precautions

■ FDA Black Box Warning

Dapsone can cause severe hemolytic anemia and methemoglobinemia, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This reaction can be dose-related and potentially fatal.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to dapsone or sulfones.","Severe anemia.","G6PD deficiency (relative contraindication; use with extreme caution and monitoring).","Acute porphyria (may precipitate crisis)."]

Clinical Precautions

Precautions

["Hemolytic anemia: risk increased in G6PD deficiency; monitor hemoglobin and reticulocyte count.","Methemoglobinemia: measure methemoglobin levels if cyanosis or dyspnea occurs; may require methylene blue.","Agranulocytosis: rare but serious; monitor white blood cell counts.","Peripheral neuropathy: may occur with long-term use.","Sulfone syndrome: triad of fever, malaise, and exfoliative dermatitis; requires discontinuation.","Hepatotoxicity: monitor liver function tests.","Photosensitivity: advise sun protection."]

Clinical Tips & Counseling

Drug interactions

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