DAPSONE

(dap'sone)

Aczone, Avlosulfon

, DDS
Classifications: antileprosy (sulfone) agent;
Therapeutic: antileprosy; sulfone; immunosuppressant
Pregnancy Category: C

Availability

25 mg, 100 mg tablets; 5% gel

Action

Sulfone derivative chemically related to sulfonamides, with bacteriostatic and bactericidal activity similar to that group. Interferes with bacterial cell growth by competitive inhibition of folic acid synthesis by susceptible organisms. It also interferes with alternative pathways of complement system.

Therapeutic Effect

Drug is effective against dapsone-sensitive multibacillary (borderline, borderline lepromatous, or lepromatous) leprosy, and dapsone-sensitive paucibacillary (indeterminate, tuberculoid, or borderline tuberculoid) leprosy.

Uses

Drug of choice for treatment of all forms of leprosy (unless organism is dapsone resistant). Used in dapsone-sensitive multibacillary leprosy (with clofazimine and rifampin) and in dapsone-sensitive paucibacillary leprosy (with rifampin, clofazimine, or ethionamide). Also used prophylactically in contacts of patients with all forms of leprosy except tuberculoid and indeterminate leprosy. Used for treatment of dermatitis herpetiformis. Gel used for acne vulgaris.

Unlabeled Uses

Chemoprophylaxis of malaria (with pyrimethamine), systemic and discoid lupus erythematosus, pemphigus vulgaris, dermatosis (especially those associated with bullous eruptions, mucocutaneous lesions, inflammation or pustules); rheumatoid arthritis, allergic vasculitis; treatment of initial episodes of P. carinii pneumonia (with trimethoprim) in limited number of adults with AIDS.

Contraindications

Hypersensitivity to sulfones or its derivatives; advanced renal amyloidosis, anemia, methemoglobin reductase deficiency; pregnancy (category C).

Cautious Use

Sulfonamide hypersensitivity; chronic renal, hepatic, pulmonary, or cardiovascular disease, refractory anemias, albuminuria, G6PD deficiency, lactation.

Route & Dosage

Tuberculoid and Indeterminate-type Leprosy
Adult: PO 100 mg/d (with 6 mo of rifampin 600 mg/d) for a minimum of 3 y

Lepromatous and Borderline Lepromatous Leprosy
Adult: PO 100 mg/d for ≥10 y
Child: PO 1–2 mg/kg/d once daily in combination therapy (max: 100 mg/d)

Dermatitis Herpetiformis
Adult: PO 50 mg/d, may be increased to 300 mg/d if necessary (max: 500 mg/d)

Prophylaxis for Close Contacts of Patient with Multibacillary Leprosy
Adult: PO 50 mg/d
Child: PO <6 mo, 6 mg 3 times/wk; 6–23 mo, 12 mg 3 times/wk; 2–5 y, 25 mg 3 times/wk; 6–12 y, 25 mg/d

P. carinii Pneumonia Prophylaxis
Adult: PO 50 mg b.i.d. or 100 mg q.d.
Child: PO 2 mg/kg once daily (max: 100 mg/d)

Acne
Apply pea-sized amount of gel to affected area b.i.d.

Administration

Oral

Give with food to reduce possibility of GI distress.
Store in tightly covered, light-resistant containers at 15°–30° C (59°–86° F). Drug discoloration apparently does not indicate a chemical change.

Topical

Clean skin with soap and water before application.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (cutaneous reactions); erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis (rare), allergic rhinitis, urticaria, fever, infectious mononucleosis-like syndrome. CNS: Headache, nervousness, insomnia, vertigo; paresthesia, muscle weakness. CV: Tachycardia. GI: Anorexia, nausea, vomiting, abdominal pain; toxic hepatitis, cholestatic jaundice (reversible with discontinuation of drug therapy); increased ALT, AST, LDH; hyperbilirubinemia. Hematologic: In patient with or without G6PD deficiency; dose-related hemolysis, Heinz body formation, methemoglobinemia with cyanosis, hemolytic anemia; aplastic anemia (rare), agranulocytosis. Skin: Drug-induced lupus erythematosus, phototoxicity. Special Senses: Blurred vision, tinnitus. Other: Male infertility; sulfone syndrome (fever, malaise, exfoliative dermatitis, hepatic necrosis with jaundice, lymphadenopathy, methemoglobinemia, anemia).

Interactions

Drug: Activated charcoal decreases dapsone absorption and enterohepatic circulation; pyrimethamine, trimethoprim increase risk of adverse hematologic reactions; rifampin decreases dapsone levels 7–10 fold.

Pharmacokinetics

Absorption: Rapidly and nearly completely absorbed from GI tract. Peak: 2–8 h. Distribution: Distributed to all body tissues; high concentrations in kidney, liver, muscle, and skin; crosses placenta; distributed into breast milk. Metabolism: In liver by CYP3A4. Elimination: 70–85% in urine; remainder in feces; traces of drug may be found in body for 3 wk after repeated doses. Half-Life: 20–30 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness that may not appear for leprosy until after 3–6 mo of therapy. Skin lesions respond well; recovery from nerve involvement is usually limited.
Lab tests: Perform baseline then weekly CBC during the first month of therapy, at monthly intervals for at least 6 mo, and semiannually thereafter.
Determine periodic dapsone blood levels.
Perform liver function tests in patients who complain of malaise, fever, chills, anorexia, nausea, vomiting, and have jaundice. Dapsone therapy is usually suspended until etiology is identified.
Monitor severity of anemia. Nearly all patients demonstrate hemolysis. Manufacturer states that Hgb level is generally decreased by 1–2 g/dL; reticulocytes increase by 2–12%; RBC life span is shortened; and methemoglobinemia occurs in most patients receiving dapsone.
Monitor temperature during first few weeks of therapy. If fever is frequent or severe, leprosy reactional state should be ruled out. Reduction of or interruption of therapy may be sufficient for improvement.
Report cyanotic appearance or mucous membranes with brownish hue to physician as possible methemoglobinemia.

Patient & Family Education

Report symptoms of leprosy that do not improve within 3 mo or get worse to physician.
Report the appearance of a rash with bullous lesions around elbows and other joints promptly. Drug-induced or worsening skin lesions require withdrawal of dapsone.
Report symptoms of peripheral neuropathy with motor loss (muscle weakness) promptly.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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