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Class: Antimycobacterials, Miscellaneous
ATC Class: J04BA02
VA Class: AM900
Chemical Name: Diaminodiphenylsulfone
Molecular Formula: C12H12N2O2S
CAS Number: 80-08-0

Introduction

Antimycobacterial; antiprotozoal; sulfone.116

Uses for Dapsone

Leprosy

Treatment of leprosy (Hansen's disease) in conjunction with other anti-infectives.105 116 216 217 218

WHO and US National Hansen's Disease Program (NHDP) recommend multidrug therapy (MDT) for treatment of all forms of leprosy, including multibacillary leprosy and paucibacillary leprosy.216 217 218

MDT regimens can rapidly kill Mycobacterium leprae, render patient noninfectious after only a few days of treatment, delay or prevent emergence of resistant M. leprae, and reduce risk of relapse after treatment discontinuance.105 216 MDT regimens do not enhance rate of clearance of dead bacilli from the body;217 such clearance may take years216 and depends largely on individual's immune response, which may be defective in leprosy patients.217 Reactive episodes reported in leprosy patients receiving treatment appear to be due to destruction of M. leprae and immune responses to released bacterial antigens.216 217 (See Leprosy Reactional States under Cautions.)

For treatment of multibacillary leprosy (i.e., ≥6 lesions or skin smear positive) in adults, WHO recommends a 12-month MDT regimen of dapsone (once daily), rifampin (once monthly), and clofazimine (once daily and once monthly).217 218 For treatment of paucibacillary leprosy (i.e., 1–5 lesions) in adults, WHO recommends a 6-month MDT regimen of dapsone (once daily) and rifampin (once monthly).217 218

For US patients, NHDP recommends more prolonged treatment.216 NHDP recommends that adults with multibacillary leprosy (i.e., those who are skin smear positive and/or have biopsy indicating more advanced disease) receive a 24-month MDT regimen of dapsone (once daily), rifampin (once daily), and clofazimine (once daily), and that adults with paucibacillary leprosy (i.e., those who are skin smear negative without evidence of more advanced disease on biopsy) receive a 12-month MDT regimen of dapsone (once daily) and rifampin (once daily).216 Clofazimine (no longer commercially available in US) may be obtained from NHDP under an investigational new drug (IND) protocol for treatment of leprosy.216

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Treatment of leprosy is complicated and should be undertaken in consultation with a specialist familiar with the disease.105 116 In the US, clinicians should contact NHDP at 800-642-2477 on weekdays from 9:00 a.m. to 5:30 p.m. Eastern Standard Time or via email at nhdped@hrsa.gov for assistance with diagnosis or treatment of leprosy or assistance obtaining clofazimine for treatment of leprosy.216

Dermatitis Herpetiformis

Treatment of dermatitis herpetiformis.116 211

Gluten-free diet recommended for all patients with dermatitis herpetiformis; strict adherence to such a diet can result in slow resolution of skin lesions (may take months to years) and improvement in GI symptoms.211 Dapsone, used as an adjunct to gluten-free diet,211 usually results in prompt decrease in pruritus and resolution of skin lesions in responsive patients.116 211 Dapsone has no effect on GI component of dermatitis herpetiformis.116 211

Some patients who adhere to strict gluten-free diet may be able to decrease dapsone dosage or discontinue the drug after several months when skin manifestations have responded; may then reinitiate dapsone for brief periods as needed to control flares.211

Pneumocystis jirovecii Pneumonia

Alternative for treatment and prevention of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) in adults, adolescents, or children.110 134 153 154 155 156 161 174 176 Designated an orphan drug by FDA for treatment and prevention of PCP.185

Co-trimoxazole is drug of choice for treatment of mild, moderate, or severe PCP in adults, adolescents, and children, including HIV-infected individuals.134 155 156

Dapsone in conjunction with trimethoprim is one of several alternatives recommended by CDC, NIH, and IDSA for treatment of mild to moderate PCP in HIV-infected adults and adolescents when co-trimoxazole cannot be used.155 Although efficacy and safety data limited regarding use for treatment of PCP in children,156 some clinicians also recommend dapsone in conjunction with trimethoprim as an alternative for treatment of mild to moderate PCP in children.134 Not included in CDC, NIH, IDSA, and AAP recommendations for treatment of severe PCP.134 155 156

Recommended by CDC, NIH, and IDSA as alternative for prevention of initial episode of PCP (primary prophylaxis) in HIV-infected adults and adolescents who cannot tolerate drug of choice (co-trimoxazole);155 used alone or in conjunction with pyrimethamine (and leucovorin) for primary PCP prophylaxis in HIV-infected adults and adolescents.155

Recommended by CDC, NIH, and IDSA as alternative for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of PCP in HIV-infected adults and adolescents who cannot tolerate drug of choice (co-trimoxazole);155 used alone or in conjunction with pyrimethamine (and leucovorin) for secondary PCP prophylaxis in HIV-infected adults and adolescents.155

Recommended by CDC, NIH, IDSA, and AAP as alternative for primary and secondary PCP prophylaxis in HIV-infected children and infants ≥1 month of age who cannot tolerate drug of choice (co-trimoxazole);156 used alone for primary and secondary PCP prophylaxis in HIV-infected pediatric patients.156

Toxoplasmosis

Alternative for primary prophylaxis to prevent initial episode of toxoplasmosis caused by Toxoplasma gondii in HIV-infected adults, adolescents, and children.134 155 156 Designated an orphan drug by FDA for toxoplasmosis prophylaxis in severely immunocompromised individuals with CD4+ T-cell counts <100/mm3.185

Recommended by CDC, NIH, and IDSA as preferred alternative for prevention of initial episodes of toxoplasmosis (primary prophylaxis) in HIV-infected adults and adolescents who cannot tolerate drug of choice (co-trimoxazole);155 used in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in HIV-infected adults and adolescents.155

Recommended by CDC, NIH, IDSA, and AAP as preferred alternative for primary toxoplasmosis prophylaxis in HIV-infected children and infants ≥1 month of age who cannot tolerate drug of choice (co-trimoxazole);156 used in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in HIV-infected pediatric patients.156

Not included in CDC, NIH, IDSA, and AAP recommendations for treatment of toxoplasmosis or chronic maintenance therapy to prevent relapse of toxoplasmosis (secondary prophylaxis) in HIV-infected adults, adolescents, and children.155 156

Dapsone Dosage and Administration

Administration

Oral Administration

Administer orally.116

For those unable to swallow tablets whole, the tablets have been crushed and dissolved in strawberry syrup; bioavailability of such preparations not evaluated to date.a

Dosage

Pediatric Patients

Leprosy
Multibacillary Leprosy
Oral

Children 10–14 years of age: WHO recommends 50 mg once daily in conjunction with oral rifampin (450 mg once monthly) and oral clofazimine (50 mg once every other day and 150 mg once monthly) given for 12 months.217

Children <10 years of age: WHO recommends appropriately adjusted dosage based on weight217 218 (e.g., dapsone 2 mg/kg once daily in conjunction with rifampin [10 mg/kg once monthly] and clofazimine [1 mg/kg once every other day] given for 12 months).218

US children: NHDP recommends 1 mg/kg once daily in conjunction with oral rifampin (10–20 mg/kg [up to 600 mg] once daily) and oral clofazimine (1 mg/kg once daily or 2 mg/kg once every other day) given for 24 months.216

Paucibacillary Leprosy
Oral

Children 10–14 years of age: WHO recommends 50 mg once daily in conjunction with oral rifampin (450 mg once monthly) given for 6 months.217

Children <10 years of age: WHO recommends appropriately adjusted dosage based on weight217 218 (e.g., dapsone 2 mg/kg once daily in conjunction with rifampin [10 mg/kg once monthly] given for 6 months).218

US children: NHDP recommends 1 mg/kg once daily in conjunction with oral rifampin (10–20 mg/kg [up to 600 mg] once daily) given for 12 months.216

Dermatitis Herpetiformis
Oral

Individually titrate dosage to find daily dosage that most effectively controls pruritus and lesions; daily dosage should then be reduced to a minimum maintenance dosage as soon as possible.116

Manufacturer states dosage in children should be based on usual adult dosage using correspondingly smaller doses.116 (See Adult Dosage under Dosage and Administration).

Pneumocystis jirovecii Pneumonia (PCP)
Treatment of Mild to Moderate PCP
Oral

Children: 2 mg/kg (up to 100 mg) once daily for 21 days in conjunction with oral trimethoprim (5 mg/kg 3 times daily for 21 days).134 156

Adolescents ≥13 years of age: 100 mg once daily for 21 days in conjunction with oral trimethoprim (5 mg/kg 3 times daily for 21 days).134 155

Prevention of Initial Episode (Primary Prophylaxis) of PCP
Oral

Children ≥1 month of age: 2 mg/kg (up to 100 mg) once daily or 4 mg/kg (up to 200 mg) once weekly.134 156

Adolescents ≥13 years of age: 100 mg once daily or 50 mg twice daily.134 155 Alternatively, 50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).155 Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).155

Infants born to HIV-infected mothers: Initiate primary PCP prophylaxis at 4–6 weeks of age and continue until infant found to be non-HIV-infected or presumptively non-HIV-infected.156

HIV-infected infants <1 year of age: Initiate primary PCP prophylaxis regardless of CD4+ T-cell count or CD4+ percentage;156 at minimum, continue throughout first year of life.156

HIV-infected children 1 to <6 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <500/mm3 or CD4+ percentage <15%.156

HIV-infected children 6–12 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <200/mm3 or CD4+ percentage <15%.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing primary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Prevention of Recurrence (Secondary Prophylaxis) of PCP
Oral

Children ≥1 month of age: 2 mg/kg (up to 100 mg) once daily or 4 mg/kg (up to 200 mg) once weekly.134 156

Adolescents ≥13 years of age: 100 mg once daily or 50 mg twice daily.134 155 Alternatively, 50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).155 Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).155

Initiate secondary PCP prophylaxis in all HIV-infected infants and children with a history of PCP.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing secondary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Toxoplasmosis
Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis
Oral

Children ≥1 month of age: 2 mg/kg or 15 mg/m2 (up to 25 mg) once daily in conjunction with oral pyrimethamine (1 mg/kg [up to 25 mg] once daily) and oral leucovorin (5 mg once every 3 days).156

Adolescents: 50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).155 Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).155

HIV-infected children seropositive for T. gondii: Initiate primary toxoplasmosis prophylaxis in those <6 years of age if CD4+ T-cell percentage <15% and in those ≥6 years of age if CD4+ T-cell count <100/mm3.156

Consider discontinuing primary toxoplasmosis prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell percentages that have remained ≥15% for >3 months.156 Reinitiate if CD4+ T-cell percentage decreases to <15%.156

Consider discontinuing primary toxoplasmosis prophylaxis in HIV-infected children ≥6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained >200/mm3 for >3 months.156 Reinitiate if CD4+ T-cell count decreases to <100–200/mm3.156

Criteria for initiating or discontinuing primary toxoplasmosis prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Adults

Leprosy
Multibacillary Leprosy
Oral

WHO recommends 100 mg once daily in conjunction with oral rifampin (600 mg once monthly) and oral clofazimine (50 mg once daily and 300 mg once monthly) given for 12 months.217 218

US adults: NHDP recommends 100 mg once daily in conjunction with oral rifampin (600 mg once daily) and oral clofazimine (50 mg once daily) given for 24 months.216

Paucibacillary Leprosy
Oral

WHO recommends 100 mg once daily in conjunction with oral rifampin (600 mg once monthly) given for 6 months.217 218

US adults: NHDP recommends 100 mg once daily in conjunction with oral rifampin (600 mg once daily) given for 12 months.216

Dermatitis Herpetiformis
Oral

Individually titrate dosage to find daily dosage that most effectively controls pruritus and lesions; daily dosage should then be reduced to a minimum maintenance dosage as soon as possible.116

Manufacturer recommends 50 mg daily initially;116 if full control not achieved within the range of 50–300 mg daily, higher dosage may be tried.116

Some clinicians state that dosages of 25–100 mg daily usually control symptoms.211

Occasional new lesions (3 or 4 per week) may occur during maintenance therapy and generally are not an indication to alter maintenance dosage.a Maintenance dosage often can be reduced or the drug discontinued after several months in patients who adhere to a gluten-free diet.211 Manufacturer states that average time for dosage reduction is 8 months (range 4 months to 2.5 years) and average time before discontinuance is 29 months (range 6 months to 9 years).116

Pneumocystis jirovecii Pneumonia (PCP)
Treatment of Mild to Moderate PCP
Oral

100 mg once daily in conjunction with oral trimethoprim (5 mg/kg 3 times daily) for 21 days.134 155

Prevention of Initial Episode (Primary Prophylaxis) of PCP
Oral

100 mg once daily or 50 mg twice daily.134 155

Alternatively, 50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).134 155

Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).134 155

Initiate primary PCP prophylaxis in HIV-infected adults with CD4+ T-cell counts <200/mm3 or a history of oropharyngeal candidiasis.155 Also consider primary PCP prophylaxis if CD4+ T-cell percentage <14% or there is a history of an AIDS-defining illness.155 Also consider in those with CD4+ T-cell counts >200/mm3 but <250/mm3 if frequent monitoring (e.g., every 3 months) not possible.155

Discontinue primary PCP prophylaxis in HIV-infected adults responding to antiretroviral therapy who have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155

Reinitiate primary PCP prophylaxis if CD4+ T-cell count decreases to <200/mm3.155

Prevention of Recurrence (Secondary Prophylaxis) of PCP
Oral

100 mg once daily or 50 mg twice daily.134 155

Alternatively, 50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).134 155

Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).134 155

Initiate secondary PCP prophylaxis in all HIV-infected adults with a history of PCP.155

Consider discontinuing secondary PCP prophylaxis in HIV-infected adults who have responded to antiretroviral therapy and have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155 Reinitiate secondary PCP prophylaxis if CD4+ T-cell count decreases to <200/mm3 or PCP recurs when CD4+ T-cell count >200/mm3.155

Consider continuing secondary prophylaxis for life (regardless of CD4+ T-cell count) if PCP occurred or recurred when CD4+ T-cell count >200/mm3.155

Toxoplasmosis
Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis
Oral

50 mg once daily in conjunction with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).155

Alternatively, 200 mg once weekly in conjunction with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).155

Initiate primary toxoplasmosis prophylaxis in all HIV-infected adults seropositive for Toxoplasma IgG antibody who have CD4+ T-cell counts <100/mm3.155

Discontinue primary toxoplasmosis prophylaxis in HIV-infected adults responding to antiretroviral therapy who have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155

Reinitiate primary toxoplasmosis prophylaxis if CD4+ T-cell count decreases to <100–200/mm3.155

Prescribing Limits

Pediatric Patients

Leprosy
Multibacillary or Paucibacillary Leprosy
Oral

Maximum 100 mg once daily.105

Pneumocystis jirovecii Pneumonia (PCP)
Prevention of Initial Episode (Primary Prophylaxis) of PCP or Prevention of Recurrence (Secondary Prophylaxis) of PCP
Oral

Children ≥1 month of age: Maximum 100 mg once daily134 156 or maximum 200 mg once weekly.134 156

Toxoplasmosis
Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis
Oral

Children ≥1 month of age: Maximum 25 mg once daily.156

Special Populations

No special population dosage recommendation at this time.a

Cautions for Dapsone

Contraindications

  • Hypersensitivity to dapsone or dapsone derivatives.116

Warnings/Precautions

Warnings

Hematologic Effects

Agranulocytosis, aplastic anemia, and other blood dyscrasias reported; fatalities have occurred.116

Patients with severe anemia should be treated for anemia before dapsone is initiated; monitor hemoglobin.116

Hemolysis and Heinz body formation may be exaggerated in individuals with glucose-6-dehydrogenase (G-6-PD) deficiency, methemoglobin reductase deficiency, or hemoglobin M.116 Use with caution in such patients.116 Some clinicians recommend screening for G-6-PD deficiency prior to initiating dapsone, especially in HIV-infected individuals.160 161 162 164

Use with caution in patients who are exposed to other drugs or agents that are capable of inducing hemolysis (see Interactions) and in patients with conditions associated with hemolysis (e.g., certain infections, diabetic ketosis).116 Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.116

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity to dapsone may rarely result in serious cutaneous reactions (e.g., bullous reactions, exfoliative dermatitis, toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria, erythema nodosum).116

If new or toxic dermatologic reactions occur, promptly discontinue dapsone and institute appropriate therapy.116

Sulfone Syndrome

A potentially fatal hypersensitivity reaction with symptoms of fever, malaise, jaundice (with hepatic necrosis), exfoliative dermatitis, lymphadenopathy, methemoglobinemia, and hemolytic anemia may occur.a

General Precautions

Dermatologic Reactions

Adverse cutaneous effects may occur, including exfoliative dermatitis, toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform eruptions, urticaria, and erythema nodosum.116 a

If new or toxic dermatologic reactions occur, discontinue dapsone and initiate appropriate therapy.116

Rash occurs in about 30–40% of AIDS patients receiving dapsone in conjunction with trimethoprim,161 162 but occurs less frequently in those receiving dapsone monotherapy.162

Nervous System Effects

Peripheral neuropathy with motor loss reported rarely with high dapsone dosage (200–500 mg daily).116 a

If muscle weakness occurs, discontinue dapsone.116 Complete recovery may occur if the drug is withdrawn, but may take many months to several years.116 a

Insomnia, headache, nervousness, vertigo, and psychosis also reported.116

Hepatic Effects

Toxic hepatitis and cholestatic jaundice reported.116 Cholestatic jaundice may be a hypersensitivity reaction and generally appears to be reversible following discontinuance of dapsone.a

Adverse hepatic effects reported shortly after initiation of dapsone therapy and may be manifested by increased serum concentrations of alkaline phosphatase, AST, bilirubin, and LDH.113 Liver function test abnormalities occur more frequently when dapsone is used in conjunction with trimethoprim than when dapsone monotherapy is used.162

Laboratory Monitoring

Monitor hemoglobin, hematocrit, and methemoglobin concentrations periodically, particularly in HIV-infected individuals receiving dapsone in conjunction with trimethoprim.160 161 162 164 (See Specific Drugs under Interactions.)

Perform CBCs frequently.116 When feasible, perform CBCs once weekly during first month of therapy, once monthly for the next 6 months, and once every 6 months thereafter.116 If a substantial reduction in leukocytes, platelets, or hematopoiesis is evident, discontinue dapsone and monitor patient closely.116

When feasible, perform baseline liver function tests and monitor during therapy.116 If any abnormality in liver function is evident, discontinue dapsone until the source of the abnormality is established.116

Leprosy Reactional States

In patients with leprosy, effective treatment with dapsone or other antileprosy agents generally results in abrupt changes in clinical and immune state and many patients have reactive episodes (reactions) that may be mild to severe.105 116 216 Leprosy reactive episodes can occur before, during, or after treatment is completed and apparently result from destruction of M. leprae and immune response to released bacterial antigens.216 217

Reactive episodes are classified into 2 types: reversal reactions (type 1) and erythema nodosum leprosum (ENL) reactions (type 2).116 Other reactions (e.g., neuritis or silent neuropathies, iridocyclitis, orchitis) also can occur independently of reactive episodes.216

Reversal reactions (type 1) usually evidenced by edema and erythema of pre-existing lesions;216 presumably occur because `patient is able to mount an enhanced delayed hypersensitivity response to residual infection leading to swelling of existing skin and nerve lesions.116 Existing lesions become erythematous and edematous and may ulcerate; fever and increased WBC count occur frequently; acute neuritis and loss of nerve function may develop.116 a

ENL reactions (type 2) are recurrent immunologically mediated reactions203 205 206 and usually manifest with fever and painful erythematous nodules; peripheral neuritis, orchitis, lymphadenitis, iridocyclitis, nephritis, periostitis, arthralgia, malaise, albuminuria, epistaxis, or depression may also occur.116 216 ENL reported less frequently with currently recommended MDT regimens that include clofazimine compared with dapsone monotherapy.204 208 These reactions considered to be a manifestation of the disease rather than an adverse reaction to antileprosy regimens.116 206 207 208

Treatment of leprosy reactional states depends on severity of manifestations;105 114 116 129 132 195 207 209 216 severe reactions may require hospitalization.116 132 Antileprosy regimen usually continued despite occurrence of a leprosy reactional state116 129 130 132 216 and, if nerve injury or skin ulceration threatened, corticosteroids are administered.129

Reversal reactions that include neuritis or ulceration always require corticosteroid treatment (e.g., prednisone 1 mg/kg daily);116 216 only short course of corticosteroid treatment may be needed if patient has only minimally active disease and no neuritis, but prolonged treatment (4–6 months) may be required in those with neuritis.216 Mild ENL reactions may require no treatment or only symptomatic measures (e.g., analgesics); corticosteroid treatment generally effective and always indicated in those with acute neuritis to prevent permanent nerve injury.216 Thalidomide and clofazimine also effective for treatment of ENL reactions.114 116 129 130 132 192 195 204 207 216

Early diagnosis and treatment of leprosy reactional states is important since these reactions are associated with considerable morbidity, especially if chronic recurrent ENL occurs.105 195 196 203 204

Therapy for leprosy and leprosy reactional states should be undertaken in consultation with an expert in the treatment of leprosy.203 In the US, clinicians should consult NHDP at 800-642-2477 on weekdays from 9:00 a.m. to 5:30 p.m. Eastern Standard Time or via email at nhdped@hrsa.gov for information on management of leprosy reactional states.116 216 216

Specific Populations

Pregnancy

Category C.116

In patients with leprosy, some clinicians recommend maintaining dapsone treatment during pregnancy.116 In addition, dapsone has been important for management of dermatitis herpetiformis in some pregnant women.116

Infertility has been reported in some males receiving dapsone;116 fertility may be restored following discontinuance of the drug.a

Lactation

Distributed into milk;116 hemolytic reactions can occur in neonates.116 Discontinue nursing or the drug, taking into account the importance of the drug to the woman.116

Pediatric Use

Labeled for treatment of leprosy and for treatment of dermatitis herpetiformis in children.116 Generally considered to have no effect on growth, development, and functional development of children.116

Although data limited regarding efficacy and safety in children, dapsone in conjunction with trimethoprim recommended as alternative for treatment of mild to moderate PCP in children and dapsone monotherapy recommended as alternative for primary and secondary PCP prophylaxis in HIV-infected children ≥1 month of age (see Pneumocystis jirovecii Pneumonia under Uses).156 Dapsone in conjunction with pyrimethamine (and leucovorin) recommended as alternative for primary prophylaxis of toxoplasmosis in HIV-infected children ≥1 month of age (see Toxoplasmosis under Uses).156

Common Adverse Effects

Dose-related hemolytic anemia and methemoglobinemia.116 a

Interactions for Dapsone

Drugs Associated with Adverse Hematologic Effects

Increased risk of adverse hematologic effects if used with folic acid antagonists (e.g., pyrimethamine); monitor more frequently than usual for adverse hematologic effects.116 a

Increased risk of hemolysis in patients with G-6-PD deficiency if used with other drugs or agents capable of inducing hemolysis in these individuals (e.g., nitrite, aniline, phenylhydrazine, naphthalene, niridazole, nitrofurantoin, primaquine); use caution.116 a

Specific Drugs

Drug

Interaction

Comments

Clofazimine

Dapsone may interfere with some anti-inflammatory effects of clofazimine in patients with ENL reactions121 122 123 126

Higher clofazimine dosage may be needed to control ENL reactions121 122 123 126

Didanosine

Possible decreased GI absorption of dapsone and decreased dapsone efficacy for PCP prophylaxis (greater relapse rate) reported in some HIV-infected patients receiving didanosine159

Studies using buffered didanosine indicate no clinically important effect on dapsone peak concentrations or AUC183

Some clinicians suggest that dapsone and buffered didanosine doses be administered at least 2 hours apart159

Pyrimethamine

Additive adverse hematologic effects; increased risk of agranulocytosis116

Monitor more frequently than usual for adverse hematologic effects116

Rifamycins (rifabutin, rifampin, rifapentine)

Rifabutin: Decreased dapsone AUC215

Rifampin: May accelerate dapsone metabolism;213 decreased dapsone concentrations reported114 116

Rifapentine: May accelerate dapsone metabolism214

Rifampin: Dosage adjustments may be needed;213 dosage adjustments not needed when used with dapsone for treatment of leprosy114 116

Rifapentine: Dosage adjustments may be needed214

Trimethoprim

Increased dapsone concentrations116 161 162 and increased risk of dapsone-associated adverse effects (e.g., methemoglobinemia);162 possible increased trimethoprim concentrations,116 162 but no evidence of increased risk of trimethoprim-associated adverse effects162

Monitor periodically for potential toxicity (e.g., methemoglobinemia)160 162

Dapsone Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract.116 Peak serum concentrations attained within 2–8 hours.116

At least 8 days of daily administration is necessary to attain steady-state concentrations; steady-state serum concentrations average 2.3 mcg/mL (range 0.1–7 mcg/mL) with an oral dosage of 200 mg daily.116

Distribution

Extent

Distributes into most tissues.a

Crosses the placenta.128

Distributed into human milk.116

Plasma Protein Binding

50–90% bound to plasma proteins.128 135 136

Monoacetyldapsone (the major metabolite) is almost completely bound to plasma proteins.128 135 136

Elimination

Metabolism

Metabolized by acetylation in the liver to monoacetyl and diacetyl derivatives.128 a Rate of acetylation is genetically determined.a

Elimination Route

20% of dose excreted in urine as unchanged drug;a 70–85% excreted in urine as water-soluble metabolites;116 a small amount excreted in feces.a

Hemodialysis enhances elimination of dapsone and its monoacetyl derivative.104

Half-life

Average 20–30 hours (range 10–83 hours).116 a Large interindividual variation.116 a

Stability

Storage

Oral

Tablets

20–25°C.116 Protect from light.116

Actions and Spectrum

  • Bacteriostatic and weakly bactericidal against Mycobacterium leprae.116 216 217

  • Antibacterial activity of dapsone is inhibited by p-aminobenzoic acid (PABA).a Therefore, it probably has a mechanism of action similar to that of sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms.a

  • May inhibit alternate pathway of complement activation and interfere with the myeloperoxidase-H2O2-halide-mediated cytotoxic system within neutrophils.126 127

  • Stimulates neutrophil motility and121 126 inhibits spontaneous and induced synthesis of prostaglandin E2 by polymorphonuclear leukocytes obtained from healthy individuals or patients with leprosy.122 123

  • Mechanism of action in treatment of dermatitis herpetiformis unknown.116 Dapsone only suppresses the disease; cutaneous IgA and complement deposition not affected by the drug.a May act as an immunomodulator when used in the treatment of this and other dermatologic diseases.a

  • Active against M. leprae,116 a M. tuberculosis,a and some other mycobacteria.a Has some activity against Pneumocystis jirovecii (formerly Pneumocystis carinii)110 111 112 and Plasmodium.a

  • Resistance to dapsone may occur in M. leprae;116 strains resistant to both dapsone and clofazimine, but susceptible to rifampin, reported rarely.117

Advice to Patients

  • Importance of completing full course of therapy, even if feeling better after a few days.116

  • Importance of discontinuing drug and informing clinician if rash or any sign of adverse reaction (sore throat, fever, pallor, purpura, jaundice, muscle weakness) occurs.116

  • Advise leprosy patients regarding the signs and symptoms of neuritis and the importance of immediately reporting such signs or symptoms to a clinician.105 (See Leprosy Reactional States under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.116

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.116

  • Importance of informing patients of other important precautionary information.116 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Dapsone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Dapsone Tablets (scored)

100 mg*

Dapsone Tablets (scored)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Dapsone 100MG Tablets (JACOBUS): 30/$42.99 or 90/$119.97

Dapsone 25MG Tablets (JACOBUS): 30/$36.99 or 90/$89.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 29, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

107. Berlin G, Brodin B, Hilden JO et al. Acute dapsone intoxication: a case treated with continuous infusion of methylene blue, forced diuresis and plasma exchange. J Toxicol Clin Toxicol. 1984-5; 22:537-48.

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