Dapsone

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Indications

  • Leprosy (FDA-approved).
  • Dermatitis herpetiformis (FDA-approved ).
  • Bullous eruption of SLE : 50 mg daily.
  • Linear IgA bullous dermatosis.
  • Erythema elevatum diutinum.
  • Behçet disease.
  • Cutaneous small vessel vasculitis.
  • Mucous membrane (cicatricial) pemphigoid.
  • IgA pemphigus.
  • Sweet syndrome.
  • Pyoderma gangrenosum.
  • Subacute cutaneous lupus erythematosus.
  • Relapsing polychondritis.
  • Granuloma annulare.
  • Granuloma faciale.
  • Rosacea (granulomatous).
  • Pustular psoriasis.
  • Panniculitis.
  • Nodulocystic acne.

Dosage

  • Most conditions require 50–200 mg/day.

Mechanism of action

  • Dapsone is most useful in the treatment of dermatologic diseases involving neutrophilic infltrates.
  • It inhibits neutrophil myeloperoxidase, thus reducing damage from the neutrophil respiratory burst mediated by this enzyme.
  • Dapsone inhibits neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (fMLP) and to interfere with the CD11b/CD18-mediated neutrophil binding that induces chemoattractant signal transduction.
  • It also inhibits eosinophil myeloperoxidase activity.

Baseline Monitoring

  • Any cardiopulmonary or neurologic symptoms should be assessed prior to therapy.
  • Complete blood count.
  • Liver function tests.
  • G6PD level.
  • Renal function tests

Follow Up Monitoring

  • CBC with differential every week for four weeks, then every two weeks until week 12, then every 3 to 4 months.
  • Reticulocyte count if anemia develops.
  • Liver function tests every 3–4 months.
  • Renal function tests every 3–4 months.

Each visit :

  • Assessment of peripheral motor function.
  • Evaluation for the signs and symptoms of methemoglobinemia.
  • Assessment for peripheral neuropathy (e.g. motor strength,reflexes).
  • Methemoglobin level if clinically indicated.
  • Increase monitoring frequency when dose is increased.

Side effects

  • Blood (common)
    • Hemolysis, methemoglobinemia (symptoms include headache, lethargy).
  • GIT(uncommon)
    • dyspepsia, anorexia.
  • Rare
    • Agranulocytosis (idiosyncratic reaction).
    • Peripheral neuropathy, Dapsone hypersensitivity syndrome.

Contraindications

  • Absolute
    • Prior hypersensitivity to dapsone.
  • Relative
    • Low (G6PD) level.
    • Significant cardiopulmonary disease.
    • Allergy to sulfonamide antibiotics.
    • Signifcant liver or renal function impairment.
    • Pre-existing peripheral neuropathy.

Interactions

  • Drugs that may increase dapsone levels (and side effects) are probenecid (via decreased renal clearance), trimethoprim, and other folate antagonists such as methotrexate.
  • Sulfonamides and hydroxychloroquine increase the oxidative stress on RBCs and may worsen hemolysis.
  • Dapsone levels may be reduced by activated charcoal, paraaminobenzoic acid (PABA), and rifampin.

Pregnancy &Lactation

  • Pregnancy category C.
  • Dapsone is able to cross the placenta and is excreted into breast milk.
  • However, it is approved by the American Academy of Pediatrics for use during lactation when required.
  • Hemolysis has been demonstrated to occur in nursing infants of mothers taking dapsone.

Precautions

  • Patients must be warned against self-medication and self adjustment of the dosage of dapsone in response to small changes in disease activity.
  • They should be instructed to discontinue the medication if they develop persistent fevers or flu-like symptoms.
  • Patients should be educated about DHS and instructed to discontinue therapy and notify their medical provider if any signs or symptoms of the dapsone hypersensitivity syndrome develop.

Drug Info

  • Dapsone has along elimination half-life >> remaining in the circulation for as long as 30 days after a single oral dose.
  • The major hemotoxicity of dapsone is related to the N-hydroxy metabolites of dapsone.
  • Dapsone-induced hemolysis is that it may result in falsely low levels of HgbA1c in patients with poorly controlled diabetes mellitus.
  • There is not a clear relationship between the hemolytic anemia associated with dapsone and the formation of methemoglobin
  • Vitamin E (800 IU daily) may provide a small amount of protection against the formation of methemoglobin and hemolysis.
  • Cimetidine (400 mg 3 times daily) has been demonstrated to reduce methemoglobin formation in humans.
  • In an emergency, oral methylene blue (100–300 mg daily) can also be used acutely to reduce methemoglobin levels, although this drug is contraindicated and ineffective if the patient is G6PD defcient.
  • Granulocyte colony-stimulating factor (G-CSF) has been used successfully to speed granulocyte recovery in case of agranulocytosis.
  • Most patients recover completely from peripheral neuropathy with discontinuation of the dapsone, which can take from several weeks to up to 2 years.

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