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:
    • Combined with rifampin at a dose of 100 mg each day for 12 months.
  • World Health Organization:
    • For six months, use rifampin and 100 mg each day.

• Lepromatous (multibacillary):

  • National Hansen's Disease Program:
    • For 24 months, use 100 mg every day together with rifampin and clofazimine.
  • World Health Organization:
    • For 12 months, use 100 mg every day along with clofazimine and rifampin.

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

• Initial:
  • 3 days of taking 25 mg every day;
  • Increase the dosage by 25 mg every three days up to 100 mg for three days, then by 25 mg every seven days up to 150 mg every day.
  • Give in two separate doses (75 mg dose is administered in 3 divided doses).
• Maintenance:
  • 100 to 150 mg divided into 2 doses each day, with or without colchicine.

Dapsone Dose for Bullous systemic lupus erythematosus (off-label):

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

Dapsone Dose for Immune thrombocytopenia (ITP) (off-label):

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

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

• Oral: After starting with a dose of 25 mg per day for 7 days, the dosage was increased by 25 mg every 7 days for a total of 100 mg per day for 7 days (4 weeks of treatment), with concurrent 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 once daily or twice daily as monotherapy, 50 mg once daily along with weekly pyrimethamine and leucovorin, or 200 mg once weekly along with weekly pyrimethamine and leucovorin are other options.

• 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: Each day, 50 mg, along with weekly pyrimethamine and leucovorin, or 200 mg, along with weekly pyrimethamine and leucovorin, in a weak dose

Dapsone Dose in Children

Dapsone Dose in the treatment of Dermatitis herpetiformis:

• Infants, Children, and Adolescents:

  • Oral: Initial: 1 to 2 divided dosages of 0.5 to 2 mg per kg each day.
  • 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 kilogramme administered once daily for 12 months; 100 mg is the maximum dose;
      • Use in combination with rifampin.

  • WHO Recommendations (WHO 2016):

    • Infants and Children <10 years and weighing <20 kg:
      • Oral: Use with rifampin at a dose of 2 mg per kilogramme once daily for six months.
    • Children ≥10 years and Adolescents ≤14 years:
      • 20 to 40 kg: Oral:
        • Use in conjunction with rifampin for six months at a dose of 25 mg once daily.
      • >40 kg: Oral:
        • Use in conjunction with rifampin for six months at a dose of 50 mg once daily.
    • Adolescents >14 years:
      • Oral: For six months, use 100 mg once daily while also taking rifampin.

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

  • National Hansen's Disease Program Recommendations:

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

  • WHO Recommendations (WHO 2016):

    • Infants and Children <10 years and weighing <20 kg: Oral:
      • Use in conjunction with rifampin and clofazimine at a dose of 2 mg per kilogramme once daily for 12 months.
    • Children ≥10 years and Adolescents ≤14 years:
      • 20 to 40 kg: Oral:
        • Using 25 mg once daily for 12 months while also taking rifampin and clofazimine
      • >40 kg: Oral:
        • Use in conjunction with rifampin and clofazimine at a dose of 50 mg once daily for 12 months.
    • Adolescents >14 years: Oral:
      • Using 100 mg once daily for 12 months while also taking rifampin and clofazimine

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

• Infants, Children, and Adolescents:

  • Oral: With or without prednisone, administer 0.5 to 2 mg per kilogramme per day in 1 to 2 split doses.
  • 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 daily in 1 or 2 divided doses as monotherapy, 50 mg once day in combination with monthly pyrimethamine and leucovorin, or 200 mg once weekly in combination with weekly pyrimethamine and leucovorin. Patients who are seropositive for Toxoplasma gondii should not receive monotherapy.

• 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 daily, divided into 1 or 2 doses

  • Treatment of mild to moderate disease:

    • Infants, Children, and Adolescents (HIV-positive/-exposed):
      • Oral: Once day in conjunction with trimethoprim at a dose of 2 mg per kilogramme; the maximum dose is 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: In conjunction with pyrimethamine and leucovorin, 2 mg per kg per dosage or 15 mg per m2 per dose given once day; maximum dose: 25 mg.

• Adolescents:

  • Oral:
    • Combining daily doses of 50 mg and weekly doses of pyrimethamine and leucovorin, or daily doses of 200 mg and weekly doses of both, is recommended.

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:

• Intolerance to any ingredient in the formulation or to 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

  • Overuse diseases from bacteria or fungi, like pseudomembranous diarrhoea and diarrhoea linked to C. difficile, can result from prolonged use. More than two months after receiving antibiotics, CDAD has been observed.

• 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 para-aminobenzoic (PABA) competitive antagonist that blocks normal bacterial usage of PABA for folic acid production.

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: