dapsone

Sulfone antibiotic· Brands: Aczone, Avlosulfon, Dapson-FatolPOTOP

Mechanism of action

Dapsone is a sulfone antibiotic that inhibits bacterial folate synthesis by competing with para-aminobenzoic acid for the active site of dihydropteroate synthase. This action prevents the formation of dihydrofolic acid and thus disrupts the production of nucleic acids essential for bacterial growth. It is primarily bacteriostatic and is active against Mycobacterium leprae and some protozoa. Its anti-inflammatory properties are also used in dermatological conditions.

Pharmacokinetics

Dapsone is well absorbed orally, with peak plasma concentrations occurring within 2 to 6 hours. It is widely distributed throughout the body, including skin, liver, and kidneys. Approximately 70% to 90% of the drug is bound to plasma proteins. Dapsone is metabolised in the liver via N-acetylation and N-hydroxylation, primarily by CYP2C9 and CYP2E1. The hydroxylamine metabolite is associated with methaemoglobinaemia and haemolysis. The elimination half-life is about 20 to 30 hours, and the drug and its metabolites are excreted in urine. Dapsone has a long half-life, allowing once-daily or weekly dosing in some regimens.

Indications & dosing

Leprosy (Hansen's disease)

In combination with rifampicin and clofazimine for multibacillary leprosy.

adult · PO: 100 mg once daily · In combination with rifampicin and clofazimine for multibacillary leprosy.

Dermatitis herpetiformis

Dose adjusted to control lesions; may be increased up to 200 mg daily if needed.

adult · PO: 50–100 mg once daily · Dose adjusted to control lesions; may be increased up to 200 mg daily if needed.

Pneumocystis jirovecii pneumonia (PCP) prophylaxis

Alternative prophylaxis in patients intolerant to trimethoprim-sulfamethoxazole.

adult · PO: 100 mg once daily · Alternative prophylaxis in patients intolerant to trimethoprim-sulfamethoxazole.

Acne vulgarisoff-label

Off-label use; typically as adjunctive therapy.

adult · PO: 50–100 mg once daily · Off-label use; typically as adjunctive therapy.

Contraindications & precautions

Hypersensitivity to dapsone or other sulfonamides · Includes rash, angio-oedema or anaphylaxis.
Porphyria · Dapsone may precipitate acute porphyric attacks.
Severe anaemia · May worsen anaemia; use with caution and monitor.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency · Risk of severe haemolysis; avoid if possible, otherwise monitor closely.
Monitor full blood count at baseline and regularly during treatment, especially in the first few months.
Avoid in G6PD deficiency unless essential; if used, monitor closely for haemolysis.
Monitor for signs of methaemoglobinaemia, such as cyanosis, fatigue or dyspnoea, particularly at higher doses.
Advise patients to report any rash, fever, sore throat or oral ulceration immediately.
Use caution in hepatic impairment; consider dose adjustment and monitoring of liver function.
Use cautiously in pregnancy and breastfeeding; only if the potential benefit outweighs the risk.

Adverse effects

Haemolytic anaemiaserious
Methaemoglobinaemiaserious
Nausea and vomiting
Headache
Skin rash
Agranulocytosisserious
Stevens-Johnson syndrome / toxic epidermal necrolysisserious
Dapsone syndrome (hypersensitivity reaction with fever, rash, lymphadenopathy, hepatitis)serious

Renal & hepatic adjustment

Hepatic impairment (mild): No specific dose adjustment required; monitor liver function tests.
Hepatic impairment (moderate): Use with caution; monitor liver function and signs of hepatic toxicity.
Hepatic impairment (severe): Avoid use; seek alternative therapy. (avoid)

Monitoring, pregnancy & toxicity

G6PD status · Baseline
Full blood count with differential · Baseline, then every 2 weeks for the first month, then periodically
Liver function tests · Baseline, then periodically
Methemoglobin level · If symptoms of cyanosis or unexplained hypoxia
Signs of hypersensitivity (fever, rash, jaundice) · Throughout treatment
Pregnancy: Dapsone may be used in pregnancy if clearly indicated. Evidence suggests low risk of fetal harm, but caution is advised near term due to the risk of neonatal haemolysis and methaemoglobinaemia.
Toxicity: Methaemoglobinaemia: dose-related, presents with cyanosis, headache, fatigue, and dyspnoea. · Discontinue dapsone, administer methylthioninium chloride (methylene blue) for severe cases, and monitor methemoglobin levels.
Toxicity: Haemolysis: occurs in G6PD deficiency or with high doses; presents with anaemia, jaundice, and dark urine. · Discontinue dapsone, provide supportive care, and transfuse if severe.
Toxicity: Agranulocytosis: rare, idiosyncratic; presents with sore throat, fever, and neutropenia. · Discontinue immediately, do not restart, and provide supportive measures.
Toxicity: Dapsone hypersensitivity syndrome: fever, rash, eosinophilia, lymphadenopathy, and hepatitis. · Discontinue dapsone, consider corticosteroids, and provide supportive care.

Antidotes & reversal

Methylene blue · For methaemoglobinaemia (>20-30%): 1-2 mg/kg IV; cimetidine as adjunct; prolonged observation (long t-half).

Clinical notes

Dapsone is used for the treatment of leprosy, usually in combination with rifampicin and clofazimine, and for the prevention and treatment of Pneumocystis jirovecii pneumonia in immunocompromised patients. It is also used as a second-line agent for acne vulgaris, dermatitis herpetiformis, and other inflammatory dermatoses. Common adverse effects include haemolytic anaemia, methaemoglobinaemia, and skin reactions, which are more common in patients with glucose-6-phosphate dehydrogenase deficiency. Regular monitoring of full blood count, methaemoglobin levels, and liver function is recommended. Dapsone should be used with caution in patients with porphyria or severe anaemia. Interactions with other drugs that affect cytochrome P450 enzymes or cause haemolysis should be considered.

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BNF; local formulary