Usage
Dapsone is prescribed for the treatment of dermatitis herpetiformis, leprosy (all forms except dapsone-resistant), and actinomycotic mycetoma. It is also used for prophylaxis of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis, particularly in immunocompromised individuals. It is classified as a sulfone antibacterial and antileprotic agent.
Dapsone’s mechanism of action involves inhibiting dihydropteroate synthase, a bacterial enzyme necessary for folate synthesis. This action disrupts bacterial DNA synthesis and ultimately leads to bacterial cell death.
Alternate Names
Dapsone is also known as diaminodiphenyl sulfone (DDS) and Avlosulfon (brand name). Various brand names exist depending on the region.
How It Works
Pharmacodynamics: Dapsone acts primarily by competitively inhibiting dihydropteroate synthase. This enzyme plays a crucial role in the folic acid synthesis pathway in susceptible organisms, preventing their growth and replication.
Pharmacokinetics: Dapsone is readily absorbed after oral administration, with peak plasma concentrations reached in 2-8 hours. It undergoes hepatic metabolism with both N-acetylation and N-hydroxylation pathways. N-hydroxy metabolites are associated with adverse reactions like methemoglobinemia and hemolysis. Dapsone is eliminated primarily through hepatic metabolism and renal excretion. The elimination half-life is variable, ranging from 10 to 50 hours, averaging around 28 hours.
Mode of Action: Dapsone targets dihydropteroate synthase by competing with para-aminobenzoic acid (PABA). This competition prevents the synthesis of dihydrofolic acid, an essential precursor in the folate pathway required for bacterial DNA synthesis.
Receptor Binding/Enzyme Inhibition: The primary mode of action is competitive inhibition of dihydropteroate synthase.
Elimination Pathways: Primarily hepatic metabolism with subsequent renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Dermatitis Herpetiformis: Initially 50-100 mg orally once daily. May be increased up to 300 mg daily, then titrated to lowest effective maintenance dose.
- Leprosy: 100 mg orally once daily (1-2 mg/kg/day). As part of multi-drug therapy:
- Multibacillary Leprosy: 100 mg daily self-administered along with rifampicin and clofazimine.
- Paucibacillary Leprosy: 100 mg daily self-administered along with rifampicin.
- Actinomycotic Mycetoma: 100 mg orally twice daily, often in combination with streptomycin or trimethoprim-sulfamethoxazole.
- PCP Prophylaxis: 100 mg orally once daily.
- Toxoplasmosis Prophylaxis: 50 mg orally once daily or 200 mg once weekly as part of combination therapy.
Children:
- Leprosy: 1-2 mg/kg orally once daily. Children aged 10-14 years: 50 mg orally once daily or 1-2 mg/kg/day if body weight is low.
- PCP Prophylaxis: 2 mg/kg/day (up to 100 mg) orally once daily, or 4 mg/kg once weekly (up to 200 mg).
- Toxoplasmosis Prophylaxis: 2 mg/kg/day (up to 25 mg) orally once daily as part of combination therapy.
Special Cases:
- Elderly Patients: Dose adjustments may be needed based on renal/hepatic function.
- Patients with Renal Impairment: Caution advised. Dosage adjustments may be necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution advised. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Careful monitoring is recommended, especially for those with G6PD deficiency, anemia, cardiac, pulmonary, or hepatic disease.
Clinical Use Cases
Dapsone’s use in settings like intubation, surgical procedures, mechanical ventilation, or the ICU is limited to its role in preventing/treating PCP. It is not indicated for sedation or other specific uses in these settings. For status epilepticus or cardiac arrest, it’s not typically indicated.
Dosage Adjustments
Dose modifications are required for patients with renal/hepatic impairment. Patients with G6PD deficiency are at increased risk of hemolysis and may require lower doses or alternative therapies.
Side Effects
Common Side Effects:
Headache, nausea, vomiting, loss of appetite, abdominal pain.
Rare but Serious Side Effects:
Methemoglobinemia, hemolytic anemia (especially in patients with G6PD deficiency), agranulocytosis, peripheral neuropathy, hypersensitivity reactions (fever, rash, jaundice, hepatitis), drug-induced lupus.
Long-Term Effects:
Peripheral neuropathy, dose-related hemolytic anemia.
Adverse Drug Reactions (ADR):
Agranulocytosis, methemoglobinemia, hemolytic anemia, hypersensitivity syndrome.
Contraindications
Hypersensitivity to dapsone or any component of the formulation; severe anemia (treat before starting dapsone).
Drug Interactions
Drugs that induce or inhibit CYP450 enzymes can affect dapsone metabolism. Concomitant use of other drugs that cause hemolysis (e.g., primaquine) increases this risk. Antacids and didanosine may decrease dapsone absorption. Co-administration with zidovudine increases hematological toxicity. Rifampin and clofazimine are frequently used concomitantly in leprosy treatment.
Pregnancy and Breastfeeding
Dapsone is classified as Pregnancy Category C. While there is no definitive evidence of harm, caution is advised. Dapsone is excreted in breast milk, potential for neonatal side effects. Benefits of breastfeeding should be weighed against potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits dihydropteroate synthase, disrupting bacterial folate synthesis.
- Side Effects: Headache, nausea, vomiting, hemolytic anemia, methemoglobinemia, hypersensitivity reactions, peripheral neuropathy.
- Contraindications: Hypersensitivity to dapsone, severe anemia.
- Drug Interactions: CYP450 inducers/inhibitors, primaquine, antacids, didanosine, zidovudine, rifampin, clofazimine.
- Pregnancy & Breastfeeding: Category C; caution advised. Excreted in breast milk.
- Dosage: Variable depending on indication; adult leprosy: 100 mg daily; dermatitis herpetiformis: 50-300 mg daily.
- Monitoring Parameters: Complete blood count, liver function tests, methemoglobin levels (if indicated), G6PD status.
Popular Combinations
- Leprosy: Rifampicin, clofazimine.
- PCP prophylaxis: Pyrimethamine, leucovorin.
- Actinomycotic Mycetoma: Streptomycin or trimethoprim-sulfamethoxazole
Precautions
- General Precautions: Screen for G6PD deficiency and anemia prior to starting therapy. Monitor complete blood count and liver function.
- Specific Populations: Use with caution in pregnancy and during breastfeeding; adjust dosage in patients with renal/hepatic impairment.
- Lifestyle Considerations: No specific lifestyle restrictions unless experiencing side effects like dizziness or drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dapsone?
A: Dosage varies depending on the indication and patient-specific factors. For leprosy in adults, it’s typically 100 mg daily. For dermatitis herpetiformis, it can range from 50-300 mg daily. Pediatric and other dosages are outlined above.
Q2: What is the mechanism of action of Dapsone?
A: Dapsone competitively inhibits dihydropteroate synthase, a key enzyme in bacterial folate synthesis.
Q3: What are the most common side effects of Dapsone?
A: Common side effects include headache, nausea, vomiting, and abdominal pain.
Q4: What are the serious side effects of Dapsone?
A: Serious side effects include hemolytic anemia (especially in patients with G6PD deficiency), methemoglobinemia, agranulocytosis, and hypersensitivity reactions.
Q5: Is Dapsone safe to use during pregnancy?
A: Dapsone is Pregnancy Category C. Caution is advised. Potential benefits should outweigh potential risks. Consult with a specialist.
Q6: Can Dapsone be used in children?
A: Yes, but the dosage is adjusted based on weight or age.
Q7: What should be monitored in patients taking Dapsone?
A: Complete blood counts and liver function tests should be monitored. Methemoglobin levels may be checked as needed, especially if signs of methemoglobinemia develop.
Q8: What are the drug interactions of Dapsone?
A: Dapsone can interact with drugs that affect CYP450 enzymes, those causing hemolysis (primaquine), antacids, didanosine, and zidovudine.
Q9: What are the contraindications for Dapsone use?
A: Contraindications include hypersensitivity to dapsone and severe anemia.
Q10: What is the role of Dapsone in leprosy treatment?
A: Dapsone is a key component of multi-drug therapy for leprosy. It is used in combination with other antileprosy agents to prevent the development of drug resistance.
