dapsone (DDS)
Avlosulfon ◆

Available forms
Available by prescription only
Tablets: 25 mg, 100 mg

Indications and dosages
 Multibacillary leprosy. Adults: 100 mg P.O. daily plus rifampin and clofazimine for 12 months.
Children ages 10 to 14: 50 mg daily P.O. plus rifampin and clofazimine for 12 months.
Children younger than age 10: Give appropriately adjusted dosage plus rifampin and clofazimine for 12 months.
 Paucibacillary leprosy. Adults: 100 mg P.O. daily plus rifampin for 6 months.
Children ages 10 to 14: 50 mg daily P.O. plus rifampin for 6 months.
Children younger than age 10: Give appropriately adjusted dosage plus rifampin for 6 months.
 Prophylaxis for people in close contact with leprosy patient. Adults and children age 12 and older: 50 mg P.O. daily.
Children ages 6 to 12: 25 mg P.O. daily.
Children ages 2 to 5: 25 mg P.O. three times weekly.
Infants ages 6 months to 23 months: 12 mg P.O. three times weekly.
Infants younger than age 6 months: 6 mg P.O. three times weekly.
 Dermatitis herpetiformis. Adults: Initially, 50 mg P.O. daily; may increase dose usually up to 400 mg daily, p.r.n., to obtain full control.
≡ Dosage adjustment. Dapsone levels are influenced by acetylation rates. Patients with high acetylation rates may need dosage adjustments.
 Malaria suppression or prophylaxis. Adults: 100 mg P.O. weekly with pyrimethamine 12.5 mg P.O. weekly. Continue prophylaxis throughout exposure and 6 months after exposure.
Children: 2 mg/kg P.O. weekly with pyrimethamine 0.25 mg/kg weekly. Continue prophylaxis throughout exposure and 6 months after exposure.
 Treatment of Pneumocystis carinii pneumonia ◇. Adults: 100 mg P.O. daily. Usually given with trimethoprim, 5 mg/kg t.i.d., for 21 days.
 Prophylaxis of P. carinii pneumonia ◇. Adults: 50 mg b.i.d. or 100 mg daily P.O.
Children age 1 month and older: 2 mg/kg (maximum 100 mg) once daily or 4 mg/kg (maximum 200 mg) once weekly.
 Prophylaxis of toxoplasmosis in HIV-infected patients ◇. Adults and adolescents: 50 mg daily with pyrimethamine 50 mg once weekly and leucovorin 25 mg once weekly, P.O.
Children age 1 month and older: 2 mg/kg or 15 mg/m² (maximum 25 mg) P.O. once daily plus pyrimethamine and leucovorin.

Pharmacodynamics
Antibiotic action: Drug is bacteriostatic and bactericidal; like sulfonamides, it probably acts mainly by inhibiting folic acid. It acts against Mycobacterium leprae and Mycobacterium tuberculosis and has some activity against P. carinii and Plasmodium.

Pharmacokinetics
Absorption: Drug is rapidly and almost completely absorbed.
Distribution: Distributed widely into most body tissues and fluids; 70% to 90% is protein-bound.
Metabolism: Undergoes acetylation by liver enzymes; rate varies and is genetically determined. Almost 50% of blacks and whites are slow acetylators, and more than 80% of Chinese, Japanese, and Inuits are fast acetylators.
Excretion: Excreted primarily in urine. Small amounts are excreted in feces. Substantial amounts appear in breast milk. Dapsone undergoes enterohepatic circulation; half-life in adults ranges from 10 to 50 hours (average 28 hours). Orally administered charcoal may enhance excretion. Dapsone is dialyzable.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal, hepatic, or CV disease; refractory types of anemia; and G6PD deficiency.

Interactions
Drug-drug. Activated charcoal: Decreases GI absorption of dapsone. Monitor patient carefully.
Didanosine: May cause dapsone to fail, leading to an increase in infection. Avoid use together.
Folic acid antagonists such as methotrexate: Increases risk of adverse hematologic reactions. Avoid use together.
Para-aminobenzoic acid: May antagonize effect of dapsone by interfering with the primary mechanism of action. Monitor patient for lack of efficacy.
Probenecid: Reduces urinary excretion of dapsone metabolites, increasing plasma levels. Monitor patient closely.
Rifampin: Increases hepatic metabolism of dapsone. Monitor patient for lack of efficacy.
Trimethoprim: Serum levels of both drugs may increase, possibly increasing their pharmacologic and toxic effects. Monitor patient carefully.
Drug-lifestyle. Sun exposure: Photosensitivity reactions may occur. Advise patient to take precautions.

Adverse reactions
CNS: insomnia, psychosis, headache, paresthesia, peripheral neuropathy, vertigo, fever.
CV: tachycardia.
EENT: tinnitus, blurred vision.
GI: anorexia, abdominal pain, nausea, vomiting, pancreatitis.
GU: albuminuria, nephrotic syndrome, renal papillary necrosis, male infertility.
Hematologic: hemolytic anemia, agranulocytosis, aplastic anemia.
Respiratory: pulmonary eosinophilia.
Skin: lupus erythematosus, phototoxicity, exfoliative dermatitis, toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria, erythema nodosum.
Other: infectious mononucleosis-like syndrome, sulfone syndrome (fever, malaise, jaundice [with hepatic necrosis], exfoliative dermatitis,lymphadenopathy, methemoglobinemia, hemolytic anemia), leprosy reactional states.

Effects on lab test results
• May decrease hemoglobin, hematocrit, and granulocyte count.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, and hyperexcitability occurring within minutes or up to 24 hours after ingestion; methemoglobin-induced depression, cyanosis, and seizures may occur. Hemolysis is a late complication (up to 14 days after ingestion).
 Treatment is by gastric lavage, followed by activated charcoal. Patients with dapsone-induced methemoglobinemia (without G6PD deficiency) can be given methylene blue. Hemodialysis also may be used to enhance elimination.

Special considerations
• Give drug with or after meals to avoid gastric irritation. Ensure adequate fluid intake.
• Specimens for culture and sensitivity testing should be obtained before first dose, but therapy may begin before test results are complete; repeat tests periodically to detect drug resistance.
• Isolation of patient with inactive leprosy isn’t required; however, make sure to disinfect surfaces that contact discharge from nose or skin lesions.
• Therapeutic effect on leprosy may not be evident for 3 to 6 months after therapy starts.
• Because drug is dialyzable, patients undergoing hemodialysis may need dosage adjustments.
• During therapy for leprosy, two types of leprosy reactional states related to the effectiveness of dapsone therapy may occur. Type I, reversal reaction, includes erythema followed by swelling of skin and nerve lesions in tuberculoid patients. Skin lesions may ulcerate and multiply, and acute neuritis may cause neural dysfunction. Severe cases require hospitalization, analgesics, corticosteroids, and nerve trunk decompression while dapsone therapy is continued. Type II, erythema nodosum leprosum, is seen mainly with lepromatous leprosy and occurs about 50% of the time during the first year of therapy. Signs and symptoms include tender erythematous skin nodules, fever, malaise, orchitis, neuritis, albuminuria, iritis, joint swelling, epistaxis, and depression; skin lesions may ulcerate. Treatment includes one or more of the following drugs while dapsone is continued: corticosteroids, analgesics, and thalidomide. Additional treatment guidelines are available from the National Hansen’s Disease Center at the U.S. Public Health Service in Carville, LA.
• Monitor dapsone serum levels periodically to maintain effective levels. Levels of 0.1 to 7 mcg/ml (average 2.3 mcg/ml) are usually effective and safe.
• Monitor vital signs frequently during early weeks of drug therapy. Frequent or high fever may require reduced dosage or discontinuation of drug.
• Patient requires observation for adverse effects and monitoring of hematologic and liver function test results to minimize toxicity.
• Watch skin and mucous membranes for early signs of allergic reactions or leprosy reactional states.
Breast-feeding patients
• Dapsone appears in breast milk and is tumorigenic. An alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Use drug cautiously in children.
Geriatric patients
• These patients commonly have decreased renal function, which decreases drug excretion. Use cautiously.

Patient education
• Explain disease process and rationale for long-term therapy to patient and family; emphasize that improvement may not occur for 3 to 6 months and that treatment must continue for 1 to 2 years or longer.
• Teach signs and symptoms of hypersensitivity and other adverse reactions, and emphasize need to report these promptly. Explain possibility of cumulative effects. Urge patient to report any unusual effects or reactions and to report loss of appetite, nausea, or vomiting promptly.
• Teach patient how to take drug. Emphasize the need to comply with prescribed regimen. Encourage patient to report symptoms that worsen or that don’t improve after 3 months of treatment. Urge patient not to stop drug without medical approval.
• Explain the importance of follow-up visits and the need to monitor close contacts at 6- to 12-month intervals for 10 years.
• Teach sanitary disposal of secretions from nose or skin lesions.
• Assure patient and family that inactive leprosy is no barrier to employment or school attendance.
• New mothers need not be separated from infant during therapy; teach signs of cyanosis and methemoglobinemia.
• Caution patient regarding photosensitivity; advise patient to avoid prolonged exposure to sunlight and ultraviolet light.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use