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ACUTE EXPOSURE INFORMATION

  1. USES: Dapsone is an sulfone antimicrobial that is used as a topical gel for acne and as an oral tablet for leprosy, dermatitis herpetiformis, and Pneumocystis carinii pneumonia.
  1. PHARMACOLOGY: It is a competitive antagonist of para-aminobenzoic acid (PABA), and thus inhibits normal bacterial utilization of PABA for folic acid synthesis.
  1. TOXICOLOGY: the primary toxic effects are due to its P-450 metabolites. Dapsone metabolites oxidize the ferrous iron hemoglobin complex to the ferric state, resulting in methemoglobinemia. These metabolites can sulfate the pyrrole hemoglobin ring in an irreversible reaction, resulting in sulfhemoglobinemia. Finally, oxidative stress with depletion of glutathione may contribute to hemolysis.
  1. EPIDEMIOLOGY: Dapsone is not widely used in the United States, and thus significant exposures are rare.
  1. WITH THERAPEUTIC USE
    1. ADVERSE EFFECTS: ORAL: Adverse reactions from oral formulations include: hematologic abnormalities, seen in greater than 10% of patients and include hemolysis (usually dose related and may occur in patients with and without G6PD deficiency), decreases in hemoglobin (1 to 2 g/dL [observed in most patients]), reticulocyte increases from 2% to 12%, methemoglobinemia, and a shortened red blood cell life span. Other potential adverse reactions from oral formulations may include: tachycardia, fever, headache, insomnia, psychosis, vertigo, dermatologic effects (eg, bullous or exfoliative dermatitis, erythema nodosum, morbilliform or scarlatiniform reactions, phototoxicity, Stevens-Johnson syndrome, toxic epidural necrolysis and urticaria), hypoalbuminemia without proteinuria, abdominal pain, nausea, vomiting, pancreatitis, agranulocytosis, anemia, leucopenia, cholestatic jaundice, hepatitis, drug-induced lupus erythematosus, lower motor neuron toxicity (prolonged drug therapy), peripheral neuropathy (rare), blurred vision, tinnitus, albuminuria, nephritic syndrome, renal papillary necrosis, interstitial pneumonitis, pulmonary eosinophilia, and an infectious mononucleosis-like syndrome (ie, rash, fever, lymphadenopathy, and hepatic dysfunction). TOPICAL: Reported adverse reactions from topical formulations include: facial edema, depression, psychosis, suicide attempt, tonic clonic movements, abdominal pain, pancreatitis, vomiting, and sinusitis.
  1. WITH POISONING/EXPOSURE
    1. MILD TO SEVERE TOXICITY: Hemotoxicity (eg, hemolytic anemia, methemoglobinemia, sulfhemoglobinemia), tachycardia, hypertension, agitation, hallucinations, confusion, nausea, vomiting, diarrhea, hepatotoxicity, hematuria, cold perspiration and blue-gray cyanosis may develop following overdose. Cases of dapsone toxicity have all occurred following oral exposure; significant toxicity is very unlikely from dermal exposure.
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