Introduction

Antimycobacterial; antiprotozoal; sulfone.

Uses for Dapsone (Systemic)

Leprosy

Treatment of leprosy (Hansen's disease) in conjunction with other anti-infectives.

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.

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. MDT regimens do not enhance rate of clearance of dead bacilli from the body; such clearance may take years and depends largely on individual's immune response, which may be defective in leprosy patients. Reactive episodes reported in leprosy patients receiving treatment appear to be due to destruction of M. leprae and immune responses to released bacterial antigens. (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). 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).

For US patients, NHDP recommends more prolonged treatment. 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). Clofazimine (no longer commercially available in US) may be obtained from NHDP under an investigational new drug (IND) protocol for treatment of leprosy.

Treatment of leprosy is complicated and should be undertaken in consultation with a specialist familiar with the disease. 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 [email protected] for assistance with diagnosis or treatment of leprosy or assistance obtaining clofazimine for treatment of leprosy.

Dermatitis Herpetiformis

Treatment of dermatitis herpetiformis.

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. Dapsone, used as an adjunct to gluten-free diet, usually results in prompt decrease in pruritus and resolution of skin lesions in responsive patients. Dapsone has no effect on GI component of dermatitis herpetiformis.

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.

Pneumocystis jirovecii Pneumonia

Alternative for treatment and prevention of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia^{† [off-label]} (PCP) in adults, adolescents, or children. Designated an orphan drug by FDA for treatment and prevention of PCP.

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

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

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

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

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); used alone for primary and secondary PCP prophylaxis in HIV-infected pediatric patients.

Toxoplasmosis

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

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); used in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in HIV-infected adults and adolescents.

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); used in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in HIV-infected pediatric patients.

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.

Dapsone (Systemic) Dosage and Administration

Administration

Oral Administration

Administer orally.

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.

Dosage

Pediatric Patients

Leprosy

Multibacillary Leprosy

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.

Children <10 years of age: WHO recommends appropriately adjusted dosage based on weight (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).

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.

Paucibacillary Leprosy

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.

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

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.

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.

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

Pneumocystis jirovecii Pneumonia (PCP)†

Treatment of Mild to Moderate PCP†

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).

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).

Prevention of Initial Episode (Primary Prophylaxis) of PCP†

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

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

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.

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

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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

Prevention of Recurrence (Secondary Prophylaxis) of PCP†

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

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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).

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

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.

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. Reinitiate if CD4⁺ T-cell percentage decreases to <15%.

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

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

Adults

Leprosy

Multibacillary Leprosy

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.

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.

Paucibacillary Leprosy

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

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

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.

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

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

Occasional new lesions (3 or 4 per week) may occur during maintenance therapy and generally are not an indication to alter maintenance dosage. Maintenance dosage often can be reduced or the drug discontinued after several months in patients who adhere to a gluten-free diet. 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).

Pneumocystis jirovecii Pneumonia (PCP)†

Treatment of Mild to Moderate PCP†

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

Prevention of Initial Episode (Primary Prophylaxis) of PCP†

100 mg once daily or 50 mg twice daily.

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

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

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

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.

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

Prevention of Recurrence (Secondary Prophylaxis) of PCP†

100 mg once daily or 50 mg twice daily.

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

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

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

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. Reinitiate secondary PCP prophylaxis if CD4⁺ T-cell count decreases to <200/mm³ or PCP recurs when CD4⁺ T-cell count >200/mm³.

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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

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

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

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.

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

Prescribing Limits

Pediatric Patients

Leprosy

Multibacillary or Paucibacillary Leprosy

Maximum 100 mg once daily.

Pneumocystis jirovecii Pneumonia (PCP)†

Prevention of Initial Episode (Primary Prophylaxis) of PCP† or Prevention of Recurrence (Secondary Prophylaxis) of PCP†

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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

Special Populations

No special population dosage recommendation at this time.

Contraindications

• Hypersensitivity to dapsone or dapsone derivatives.

Warnings/Precautions

Warnings

Hematologic Effects

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

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

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

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). Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.

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).

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

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.

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.

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

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

Nervous System Effects

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

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

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

Hepatic Effects

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

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. Liver function test abnormalities occur more frequently when dapsone is used in conjunction with trimethoprim than when dapsone monotherapy is used.

Laboratory Monitoring

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

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

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

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. 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.

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

Reversal reactions (type 1) usually evidenced by edema and erythema of pre-existing lesions; 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. 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.

ENL reactions (type 2) are recurrent immunologically mediated reactions 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. ENL reported less frequently with currently recommended MDT regimens that include clofazimine compared with dapsone monotherapy. These reactions considered to be a manifestation of the disease rather than an adverse reaction to antileprosy regimens.

Treatment of leprosy reactional states depends on severity of manifestations; severe reactions may require hospitalization. Antileprosy regimen usually continued despite occurrence of a leprosy reactional state and, if nerve injury or skin ulceration threatened, corticosteroids are administered.

Reversal reactions that include neuritis or ulceration always require corticosteroid treatment (e.g., prednisone 1 mg/kg daily); 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. 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. Thalidomide and clofazimine also effective for treatment of ENL reactions.

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

Therapy for leprosy and leprosy reactional states should be undertaken in consultation with an expert in the treatment of leprosy. 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 [email protected] for information on management of leprosy reactional states.

Specific Populations

Pregnancy

Category C.

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

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

Lactation

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

Pediatric Use

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

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). 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).

Common Adverse Effects

Dose-related hemolytic anemia and methemoglobinemia.

Administration

Oral Administration

Administer orally.

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.

Dosage

Pediatric Patients

Leprosy

Multibacillary Leprosy

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.

Children <10 years of age: WHO recommends appropriately adjusted dosage based on weight (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).

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.

Paucibacillary Leprosy

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.

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

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.

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.

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

Pneumocystis jirovecii Pneumonia (PCP)†

Treatment of Mild to Moderate PCP†

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).

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).

Prevention of Initial Episode (Primary Prophylaxis) of PCP†

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

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

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.

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

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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

Prevention of Recurrence (Secondary Prophylaxis) of PCP†

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

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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).

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

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.

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. Reinitiate if CD4⁺ T-cell percentage decreases to <15%.

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

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

Adults

Leprosy

Multibacillary Leprosy

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.

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.

Paucibacillary Leprosy

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

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

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.

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

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

Occasional new lesions (3 or 4 per week) may occur during maintenance therapy and generally are not an indication to alter maintenance dosage. Maintenance dosage often can be reduced or the drug discontinued after several months in patients who adhere to a gluten-free diet. 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).

Pneumocystis jirovecii Pneumonia (PCP)†

Treatment of Mild to Moderate PCP†

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

Prevention of Initial Episode (Primary Prophylaxis) of PCP†

100 mg once daily or 50 mg twice daily.

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

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

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

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.

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

Prevention of Recurrence (Secondary Prophylaxis) of PCP†

100 mg once daily or 50 mg twice daily.

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

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

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

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. Reinitiate secondary PCP prophylaxis if CD4⁺ T-cell count decreases to <200/mm³ or PCP recurs when CD4⁺ T-cell count >200/mm³.

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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

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

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

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.

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

Prescribing Limits

Pediatric Patients

Leprosy

Multibacillary or Paucibacillary Leprosy

Maximum 100 mg once daily.

Pneumocystis jirovecii Pneumonia (PCP)†

Prevention of Initial Episode (Primary Prophylaxis) of PCP† or Prevention of Recurrence (Secondary Prophylaxis) of PCP†

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

Toxoplasmosis†

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis†

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

Special Populations

No special population dosage recommendation at this time.

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.

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.

Specific Drugs