Dapsone is an orally (Tablets formulation) available antibiotic drug that is primarily used to treat patients with leprosy (in combination with clofazimine and rifampicin).

Dapsone Uses:

• Used in the treatment of leprosy (due to susceptible strains of Mycobacterium leprae) and dermatitis herpetiformis

• Off Label Uses of Dapsone in Adults:

  • Used in severe aphthous ulcers
  • Used in bullous systemic lupus erythematosus
  • Used in immune thrombocytopenia
  • Used in pemphigus vulgaris (oral)
  • Used in pneumocystis pneumonia (PCP) prophylaxis in HIV-infected patients
  • Used in pneumocystis pneumonia (PCP) treatment in HIV-infected patients
  • Used in relapsing polychondritis
  • Used in Toxoplasma gondii encephalitis prophylaxis in HIV-infected patients

Dapsone Dose in Adults

Dapsone Dose in the treatment of Dermatitis herpetiformis:

• Oral: Start at 50 mg once in a day, increase to 300 mg once in a day, or higher to achieve full control, reduce to minimum maintenance dosage as soon as possible

Dapsone Dose in the treatment of Leprosy: Oral:

• Tuberculoid (paucibacillary):

  • National Hansen's Disease Program:
    • 100 mg each day in combination with rifampin for 12 months.
  • World Health Organization:
    • 100 mg each day in combination with rifampin for 6 months.

• Lepromatous (multibacillary):

  • National Hansen's Disease Program:
    • 100 mg each day in combination with rifampin and clofazimine for 24 months.
  • World Health Organization:
    • 100 mg each day in combination with clofazimine and rifampin for 12 months.

Dapsone Dose in the treatment of severe Aphthous ulcers (off-label): Oral:

• Initial:
  • 25 mg each day for 3 days;
  • Increase dose in increments of 25 mg per day every 3 days up to 100 mg per day for 3 days, then increase by 25 mg per day every 7 days up to 150 mg every day.
  • Administer in 2 divided doses (75 mg dose is administered in 3 divided doses).
• Maintenance:
  • 100 to 150 mg per day in 2 divided doses with or without concomitant colchicine.

Dapsone Dose in the treatment of Bullous systemic lupus erythematosus (off-label):

• Oral: 100 mg once in a day with or without prednisone.

Dapsone Dose in the treatment of Immune thrombocytopenia (ITP) (off-label):

• Oral: 75 to 100 mg per day or 1 to 2 mg per kg per day;
• duration of therapy is 21 days or more than 21 days.

Dapsone Dose in the treatment of Pemphigus Vulgaris (off-label):

• Oral: 25 mg each day for 7 days, then increase the dose in increments of 25 mg in a day every 7 days up to 100 mg per day for 7 days (4 weeks total therapy) with concomitant prednisone.
• Administer in 2 divided doses (a 75 mg dose is administered in 3 divided doses).

Note:

• If the patient becomes lesion free, taper, and discontinue gradually by decreasing the dose to 25 mg per day over 7 days.
• If no new lesions are seen, a gradual taper is continued.
• If lesions recur, the dose is increased by 25 mg daily at 7-day intervals until the patient develops no new lesions.
• The taper is usually ~4 weeks total.

Dapsone Dose in the treatment of Pneumocystis pneumonia (PCP) in HIV-infected patients: Oral:

• Prophylaxis (primary or secondary; alternative to preferred therapy):

  • 100 mg daily once in a day  or in 2 divided doses as monotherapy or 50 mg in a day in combination with weekly pyrimethamine and leucovorin or
  • 200 mg weekly in combination with weekly pyrimethamine and leucovorin

• Treatment (mild to moderate disease; an alternative to preferred therapy):

  • 100 mg once in a day in combination with trimethoprim for 21 days

Dapsone Dose in the treatment of Toxoplasma gondii encephalitis in HIV-infected patients (alternative to preferred therapy) (off-label):

• Primary prophylaxis:

  • Oral: 50 mg every day, in combination with weekly pyrimethamine and leucovorin  or
  • 200 mg in a weak  in combination with weekly pyrimethamine and leucovorin.

Dapsone Dose in Childrens

Dapsone Dose in the treatment of Dermatitis herpetiformis:

• Infants, Children, and Adolescents:

  • Oral: Initial: 0.5 to 2 mg per kg per day in 1 to 2 divided doses.
  • The maximum initial daily dose in adults: 50 mg per day;
  • increase dose as needed to achieve control;
  • The usual adult dose: 300 mg per dose; once lesions controlled, some have reported that dose may be decreased as tolerated for chronic therapy to a reported range: 0.125 to 0.5 mg per kg per day.

Dapsone Dose in the treatment of refractory Idiopathic thrombocytopenic purpura (ITP): Limited data available:

• Children ≥3 years and Adolescents:

  • Oral: 1 to 2 mg per kg per day for at least 2 months.
  • Dosing based on two retrospective reviews.
  • The first was a retrospective cohort analysis of adult and pediatric (age range: 3 to 61 years, including 35 patients less than 16 years) with chronic ITP ( more than 6 months with diagnosis) who failed steroid therapy and observed an overall similar response rate for children (65.7 percent ) and adults.
  • Adverse effects occurred in three patients (one with acute hemolysis and two with an erythematous rash).
  • The second was a small retrospective report of seven pediatric patients with acute or chronic refractory, symptomatic ITP (age range: 6 to 15 years) which also showed a similar response rate (60 percent ); however, a higher incidence (two of seven patients [29 percent ]) of methemoglobinemia was observed.

Dapsone Dose in the treatment of Leprosy (Hansen's disease):

Note:

• Treatment should be managed in consultation with a leprosy expert;
• The use of multidrug therapy is important to prevent drug resistance.

The recommended duration varies:

• Paucibacillary (Tuberculoid) leprosy (1 to 5 patches):

  • National Hansen's Disease Program Recommendations:

    • Infants, Children, and Adolescents:
      • Oral: 1 mg per kg per dose once in a day for 12 months;
      • The maximum dose: 100 mg per dose;
      • Use in combination with rifampin.

  • WHO Recommendations (WHO 2016):

    • Infants and Children <10 years and weighing <20 kg:
      • Oral: 2 mg per kg per dose once in a day for 6 months;
      • use in combination with rifampin
    • Children ≥10 years and Adolescents ≤14 years:
      • 20 to 40 kg: Oral:
        • 25 mg once in a day for 6 months;
        • use in combination with rifampin
      • >40 kg: Oral:
        • 50 mg once in a day for 6 months;
        • use in combination with rifampin
    • Adolescents >14 years:
      • Oral: 100 mg once in a day for 6 months;
      • use in combination with rifampin

• Multibacillary (Lepromatous) leprosy (≥6 patches):

  • National Hansen's Disease Program Recommendations:

    • Infants, Children, and Adolescents: Oral:
      • 1 mg per kg per dose once in a day for 24 months;
      • The maximum dose: 100 mg per dose;
      • Use in combination with rifampin and clofazimine.

  • WHO Recommendations (WHO 2016):

    • Infants and Children <10 years and weighing <20 kg: Oral:
      • 2 mg per kg per dose once in a day for 12 months;
      • use in combination with rifampin and clofazimine
    • Children ≥10 years and Adolescents ≤14 years:
      • 20 to 40 kg: Oral:
        • 25 mg once in a day  for 12 months; use in combination with rifampin and clofazimine
      • >40 kg: Oral:
        • 50 mg once in a day for 12 months; use in combination with rifampin and clofazimine
    • Adolescents >14 years: Oral:
      • 100 mg once in a day  for 12 months;
      • use in combination with rifampin and clofazimine

Dapsone Dose in the treatment of Linear IgA bullous dermatosis (LABD):

• Infants, Children, and Adolescents:

  • Oral: 0.5 to 2 mg per kg per day in 1 to 2 divided doses with or without prednisone
  • may increase if needed at weekly intervals until symptoms controlled;
  • The maximum reported daily dose: 4 mg per kg per day;
  • The usual adult dose: 25 to 150 mg per day.

Dapsone Dose in the treatment of Pneumocystis jirovecii pneumonia (PCP) as an alternative agent (patients unable to take trimethoprim/ sulfamethoxazole):

• Prophylaxis (primary or secondary):

  • Multiple regimens (daily or weekly dosing) and combinations presented

• HIV-exposed/-positive: Oral:

  • • Infants and Children:
      • 2 mg per kg per dose once in a day  (maximum daily dose: 100 mg per day) or 4 mg per kg per dose once in a weak (maximum weekly dose: 200 mg per week).
    • Adolescents:
      • 100 mg per day in 1 or 2 divided doses as monotherapy or 50 mg once in a day  in combination with weekly pyrimethamine and leucovorin or
      • 200 mg once in a week in combination with weekly pyrimethamine and leucovorin;
      • monotherapy should not be used in patients who are seropositive for Toxoplasma gondii.

• Hematopoietic stem cell transplant recipient: Oral:

  • • Infants and Children:
      • 2 mg per kg per dose once in a day;
      • maximum dose: 100 mg per dose
    • Adolescents:
      • 100 mg per day in 1 or 2 divided doses

  • Treatment of mild to moderate disease:

    • Infants, Children, and Adolescents (HIV-positive/-exposed):
      • Oral: 2 mg per kg per dose once in a day in combination with trimethoprim for 21 days;
      • The maximum dose: 100 mg per dose.

Dapsone dose as an alternative agent for the primary prophylaxis of Toxoplasma gondii infection in HIV-exposed/-positive patients); (patients unable to tolerate trimethoprim/sulfamethoxazole):

Note: Multiple regimens (daily or weekly dosing), combinations, and dosing units (mg per kg, mg per m² ) presented; use caution.

• Infants and Children:

  • Oral: 2 mg per kg per dose or 15 mg per m² per dose once in a day in combination with pyrimethamine and leucovorin;
  • maximum dose: 25 mg per dose.

• Adolescents:

  • Oral:
    • 50 mg once in a day in combination with weekly pyrimethamine and leucovorin or
    • 200 mg once in a weak in combination with weekly pyrimethamine and leucovorin.

Dapsone Pregnancy Risk Factor C

• Dapsone crosses over the placenta.
• You may also consider Dapsone as an alternative treatment for Pneumocystis Jirovecii pneumonia (PCP), or Toxoplasma gondii Encephalitis in HIV-infected pregnant women.
• According to the manufacturer, dapsone does not increase the risk of congenital anomalies if it is given in all three trimesters.
• Numerous reports have reported adverse effects on newborns after in utero dapsone exposure, including neonatal hemolytic disorder, methemoglobinemia and hyperbilirubinemia.
• Pregnant women who have leprosy or dermatitis mypetiformis may use dapsone.
• Neonatal care providers should be aware that maternal dapsone may increase the risk of hyperbilirubinemia or kernicterus.

Dapsone use during breastfeeding:

• Dapsone can be found in breast milk, and in the serum of nursing babies.
• The manufacturer suggests that the mother decide whether to stop nursing her infant or discontinue using the drug.
• This is in consideration of the possibility of serious adverse reactions.
• A breast-fed infant has been diagnosed with hemolytic anemia.

Dapsone Dose in Kidney Disease:

No dosage adjustment required.

Dapsone Dose in Liver disease:

Manufacturer’s labeling doesn't provide any dosage adjustments; use with caution

Side effects of Dapsone:

• Hematologic:

  • Reticulocyte increase
  • Leukopenia
  • Hemolysis
  • Hemoglobin decrease
  • Methemoglobinemia
  • Red cell life span shortened
  • Agranulocytosis
  • Anemia
  • Pure red cell aplasia (case report)

• Cardiovascular:

  • Tachycardia

• Central nervous system:

  • Headache
  • Insomnia
  • Psychosis
  • Fever
  • Vertigo

• Dermatologic:

  • Bullous and exfoliative dermatitis
  • Morbilliform and scarlatiniform reactions
  • Phototoxicity
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Erythema nodosum
  • Exfoliative dermatitis
  • Urticaria

• Endocrine & metabolic:

  • Hypoalbuminemia (without proteinuria)
  • Male infertility

• Gastrointestinal:

  • Nausea
  • Pancreatitis
  • Abdominal pain
  • Vomiting

• Hepatic:

  • Cholestatic jaundice
  • Hepatitis

• Neuromuscular & skeletal:

  • Lower motor neuron toxicity (prolonged therapy)
  • Lupus-like syndrome
  • Peripheral neuropathy (rare, nonleprosy patients)

• Ophthalmic:

  • Blurred vision

• Otic:

  • Tinnitus

• Renal:

  • Albuminuria
  • Nephrotic syndrome
  • Renal papillary necrosis

• Respiratory:

  • Interstitial pneumonitis
  • Pulmonary eosinophilia

• Miscellaneous:

  • Infectious mononucleosis-like syndrome (rash, fever, lymphadenopathy, hepatic dysfunction)

Contraindications to Dapsone:

• Hypersensitivity to any component of the formulation or dapsone

Warnings and precautions

• Blood dyscrasias:

  • Aplastic anemia, agranulocytosis and other severe blood disorders (some fatal) were reported. Monitor for signs/symptoms (eg pallor, purpura jaundice fever sore throat).
  • If hemopoiesis, leukocytes, or platelets are reduced, discontinue therapy.

• Dermatologic reactions

  • Rarely have serious dermatologic reactions been reported, including toxic epidermal necrolysis, scarlatiniform reactions and scarlatiniform reactions.
  • If severe or new dermatologic reactions occur, discontinue therapy. Leprosy reactional states (eg erythema nososum leprosum), however, do not need to be stopped.

• Hepatic effects

  • There have been reports of toxic hepatitis, cholestatic jaundice and toxic liver disease. Patients with G6PD may experience hyperbilirubinemia more often.
  • If liver function is abnormal, discontinue use.

• Peripheral neuropathy:

  • Reports of motor loss and weakness have been made; stop using if you develop peripheral neuropathy symptoms.
  • Most patients recover after stopping treatment. Some patients can tolerate retreatment at lower doses.

• Allergy to sulfonamide

  • Patients with hypersensitivity to other Sulfonamides should be cautious.
  • Sulfone reactions can also cause potentially fatal hypersensitivity reactions and require drug discontinuation.

• Superinfection

  • Extended use can lead to fungal or bacterial overinfections, such as pseudomembranous and C. difficile-associated diarrhea. CDAD has been documented >2 months after antibiotic treatment.

• Anemia:

  • Patients with severe anemia should be treated before you start therapy.

Dapsone (systemic): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Check G6PD levels (prior to initiation);
• CBC (weekly for the first month, monthly for 6 months and semiannually thereafter);
• reticulocyte counts;
• liver function tests (baseline and periodic).
• Monitor patients for signs of hemolysis, jaundice, and blood dyscrasias.

How to administer Dapsone Tablets?

It is administered orally with meals if GI upset occurs.

Mechanism of action of Dapsone:

It is a competitive antagonist to para-aminobenzoic (PABA) which prevents normal bacterial use of PABA for synthesis of Folic Acid.

Absorption:

• Rapid and almost complete

Protein binding:

• Dapsone: 70 percent  to 90 percent ;
• Metabolite: ~99 percent

Metabolism:

• Hepatic (acetylation and hydroxylation);
• forms multiple metabolites

Half-life elimination:

• Children: 15.1 hours
• Adults: 28 hours (range: 10 to 50 hours)

Time to peak:

• 4 to 8 hours

Excretion:

• Urine (~85 percent  as metabolites)

International Brand Names of Dapsone:

• MAR-Dapsone
• Daps
• Dapsomed
• Pyrisone
• Dapson
• Dapson-Fatol
• Dapsona
• Dapsone
• Disulone
• Dopsan
• Lennon-Dapsone
• Lepsone

Dapsone Brand Names in Pakistan: