dapsone
Brand: Aczone (topical), Dapsone
Prototype Drug
Drug Class: sulfone antibiotic
Drug Family: antibiotic
Subclass: anti-leprosy and anti-pneumocystis agent
Organ Systems: infectious-disease
Mechanism of Action
Inhibits DHPS by competing with PABA, blocking folate synthesis; bacteriostatic/static against M. leprae and Pneumocystis jirovecii; mechanism is identical to sulfonamides.
dihydropteroate synthase (DHPS)
Indications
- leprosy (Hansen's disease — part of multidrug therapy)
- Pneumocystis jirovecii pneumonia (PCP) prophylaxis in HIV
- PCP treatment (in combination with trimethoprim)
- dermatitis herpetiformis
Contraindications
- dapsone hypersensitivity
- G6PD deficiency (relative — major hemolysis risk)
- sulfonamide hypersensitivity (cross-reactivity possible)
Adverse Effects
Common
- dose-related methemoglobinemia (universal, usually mild)
- hemolytic anemia (dose-related; exacerbated by G6PD deficiency)
- GI upset
Serious
- severe methemoglobinemia (at high doses or G6PD deficiency)
- DRESS syndrome (dapsone hypersensitivity syndrome)
- agranulocytosis
- peripheral neuropathy
- hepatotoxicity
Pharmacokinetics (ADME)
| Absorption | 86–95% oral bioavailability; unaffected by food |
| Distribution | widely distributed; enters red blood cells (accumulation causes methemoglobinemia) |
| Metabolism | hepatic acetylation (NAT2-dependent — slow vs. fast acetylators) and CYP oxidation (forms toxic hydroxylamine metabolite) |
| Excretion | renal (70–85%) |
| Half-life | 20–30 hours |
| Onset | 1–4 hours |
| Peak | 2–8 hours |
| Duration | 24 hours |
| Protein Binding | 73% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| pyrimethamine/trimethoprim | folate antagonism combined with dapsone's DHPS inhibition provides synergy against PCP | beneficial |
| rifampin | CYP induction reduces dapsone levels; reduced efficacy for leprosy | major |
| probenecid | reduces renal excretion of dapsone metabolites | minor |
Nursing Considerations
- Screen for G6PD deficiency before initiating therapy; G6PD-deficient patients are at high risk for severe hemolytic anemia.
- Monitor CBC and methemoglobin level; cyanosis or oxygen saturation that does not improve with supplemental oxygen may indicate methemoglobinemia.
- Methemoglobin >30% requires IV methylene blue 1–2 mg/kg; instruct caregivers on signs of methemoglobinemia.
- Monitor for dapsone hypersensitivity syndrome (DRESS): fever, rash, lymphadenopathy, hepatitis — occurs 3–8 weeks after initiation; requires immediate discontinuation.
Clinical Pearls
- Dapsone universally causes methemoglobinemia to some degree due to formation of hydroxylamine metabolite in red blood cells; healthy patients tolerate methemoglobin levels of 5–10% without symptoms, but G6PD-deficient patients may develop severe hemolytic anemia.
- For PCP prophylaxis in G6PD-normal HIV patients, dapsone 100 mg daily is an acceptable alternative when trimethoprim-sulfamethoxazole is not tolerated due to sulfonamide allergy.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.