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 in conjunction with other anti-infectives.116 146 193 194 195 196 197 198 199 200 201 l

WHO and others recommend rifampin-based multiple-drug regimens for treatment of all forms of leprosy, including multibacillary leprosy (>5 skin lesions) and paucibacillary leprosy (2–5 lesions).146 193 194 195 196 197 198 199 200 201 l

Because rifampin is bactericidal against Mycobacterium leprae, it is the principal component of multiple-drug leprosy regimens;193 194 195 196 201 l other drugs are included in the regimens to prevent emergence of rifampin-resistant M. leprae.193 195 l

For treatment of multibacillary leprosy, WHO and others recommend a multiple-drug regimen that includes rifampin, dapsone, and clofazimine.115 146 193 194 195 196 197 198 199 200 201 l If severe adverse effects related to dapsone occur, dapsone may be discontinued, and rifampin and clofazimine continued at usually recommended dosages.199 200

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For treatment of paucibacillary leprosy, WHO and others recommend a multiple-drug regimen that includes rifampin and dapsone.146 199 200 l If severe adverse effects related to dapsone occur, dapsone may be discontinued and substituted with clofazimine (no longer commercially available in the US; available by contacting the National Hansen’s Disease Program at 800-642-2477).199 200

Treatment of leprosy is complicated and should be undertaken in consultation with a specialist familiar with the disease (e.g., clinicians from the National Hansen’s Disease Program at 800-642-2477 or ).116 146 k

Dermatitis Herpetiformis

Treatment of dermatitis herpetiformis.116 Used in conjunction with a gluten-free diet.a

Used to control dermatologic symptoms of the disease;116 may decrease pruritus and improve skin lesions,116 but has no effect on the GI component of disease116 or on cutaneous IgA and complement deposition.a Rapid exacerbation of lesions and severe pruritus usually occur when dapsone discontinued.a

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment or prevention of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) alone or in conjunction with other anti-infectives.107 110 146 153 154 161 173 174 176 d f Designated an orphan drug by FDA for treatment or prevention of PCP pneumonia.185

Co-trimoxazole is initial drug of choice for treatment of PCP in most adults, adolescents, and children, including HIV-infected individuals.107 146 174 176 d f Dapsone used in conjunction with trimethoprim is one of several alternatives for treatment of mild to moderate PCP in adults or adolescents when co-trimoxazole cannot be used;107 146 174 176 d not studied for treatment of PCP in children.146 f

Dapsone monotherapy or dapsone used in conjunction with pyrimethamine and leucovorin are alternative regimens for prevention of initial episodes of PCP (primary prophylaxis of PCP) in adults or adolescents at increased risk, including HIV-infected individuals, when co-trimoxazole (the drug of choice) cannot be used.107 146 147 148 149 150 151 152 153 154 155 156 157 158 163 164 165 166 167 168 169 170 171 172 173 177 178 179 180 183 184 Dapsone monotherapy also is an alternative for primary PCP prophylaxis in children,107 146 173 especially children <5 years of age;146 only limited data available on use of dapsone in conjunction with pyrimethamine for such prophylaxis in children.146

Dapsone monotherapy or dapsone used in conjunction with pyrimethamine and leucovorin are alternative regimens that can be used for long-term suppressive or chronic maintenance therapy (secondary prophylaxis of PCP) in adults or adolescents when co-trimoxazole (the drug of choice) cannot be used.107 173 d Dapsone monotherapy also is an alternative for secondary PCP prophylaxis in children,107 146 173 especially children <5 years of age;146 only limited data available on use of dapsone in conjunction with pyrimethamine for such prophylaxis in children.146

Dapsone monotherapy is an alternative for PCP prophylaxis in pregnant women.173

Toxoplasmosis

Prevention of toxoplasmosis caused by Toxoplasma gondii in conjunction with other anti-infectives.146 173 Has been used in conjunction with pyrimethamine and leucovorin for treatment of toxoplasmosis,d but not included in current CDC, NIH, and IDSA recommendations for treatment of the disease.173 d f

Dapsone used in conjunction with pyrimethamine and leucovorin is one of several recommended alternatives for prevention of T. gondii encephalitis (primary prophylaxis) in HIV infected adults, adolescents, and children when the drug of choice (co-trimoxazole) cannot be used.146 173

Dapsone is not included in current CDC, NIH, and IDSA recommendations for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent relapse of toxoplasmosis encephalitis in HIV infected adults, adolescents, or children.d f

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

Manufacturer states dosage in children should be based on usual adult dosage using correspondingly smaller doses.116 (See Adult Dosage under Dosage and Administration.) Some clinicians recommend a pediatric dosage of 1 mg/kg (up to 100 mg) once daily.146

Children <10 years of age: 25 mg once daily in conjunction with rifampin (300 mg once monthly) and clofazimine (50 mg twice weekly and 100 mg once monthly) recommended by WHO.198

Children 10–14 years of age: 50 mg once daily in conjunction with rifampin (450 mg once monthly) and clofazimine (50 mg every other day and 150 mg once monthly).198

Usual duration of treatment is 12 months.198 l An additional 12 months of treatment may be necessary in some patients (e.g., those with a high baseline bacterial index who have no evidence of improvement or have evidence of deterioration after the initial 12 months of treatment).200 l

Paucibacillary Leprosy
Oral

Manufacturer states dosage in children should be based on usual adult dosage using correspondingly smaller doses.116 (See Adult Dosage under Dosage and Administration.) Some clinicians recommend a pediatric dosage of 1–2 mg/kg (up to 100 mg) once daily.146

Children <10 years of age: 25 mg once daily in conjunction with rifampin (300 mg once monthly).198

Children 10–14 years of age: 50 mg once daily in conjunction with rifampin (450 mg once monthly).198

Usual duration of treatment is 6 months.198 l

Dermatitis Herpetiformis
Oral

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

Titrate individual dose to find the daily dosage that most effectively controls pruritus and lesions; daily dosage should then be reduced as soon as possible to a minimum maintenance level.116

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia
Prevention (Primary Prophylaxis)
Oral

Children ≥1 month of age: 2 mg/kg (up to 100 mg) once daily107 146 173 or 4 mg/kg (up to 200 mg) once weekly.107 146 173

Adolescents: 50 mg twice daily or 100 mg once daily.107 173 Alternatively, 50 mg once daily or 200 mg once weekly in conjunction with oral pyrimethamine (50 mg or 75 mg once weekly) and oral leucovorin (25 mg once weekly).107 173

Primary prophylaxis against PCP should be initiated at 4–6 weeks of age in children born to HIV-infected mothers; discontinue prophylaxis in those subsequently found not to be infected with HIV, but continue prophylaxis for the first year of life in those whose HIV status remains unknown.146 173

In HIV-infected children 1–5 years of age, primary prophylaxis should be initiated if CD4+ T-cell counts are <500/mm3 or CD4+ percentage is <15%.173 In HIV-infected children 6–12 years of age, primary prophylaxis should be initiated if CD4+ T-cell counts are <200/mm3 or CD4+ percentage is <15%.173

The safety of discontinuing primary prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.146 173 Based on experience discontinuing primary PCP prophylaxis in adults and adolescents who have adequate CD4+ T-cell count, AAP states that discontinuing such prophylaxis should be considered for children who have adequate CD4+ T-cell counts.146

Criteria for initiating or discontinuing primary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.173 d (See Adult Dosage under Dosage and Administration.)

Prevention of Recurrence (Secondary Prophylaxis)
Oral

Children ≥1 month of age: 2 mg/kg (up to 100 mg) once daily107 146 173 or 4 mg/kg (up to 200 mg) once weekly.107 146 173

Adolescents: 50 mg twice daily or 100 mg once daily.107 173 d Alternatively, 50 mg once daily or 200 mg once weekly in conjunction with oral pyrimethamine (50 mg or 75 mg once weekly, respectively) and oral leucovorin (25 mg once weekly).107 173 d

The safety of discontinuing secondary prophylaxis against PCP in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.146 173 f Children who have a history of PCP should receive life-long suppressive therapy to prevent recurrence.146 173 f

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

Toxoplasmosis
Prevention (Primary Prophylaxis)
Oral

Children ≥1 month of age: 2 mg/kg or 15 mg/m2 (maximum 25 mg) once daily in conjunction with oral pyrimethamine (1 mg/kg once daily) and oral leucovorin (5 mg once every 3 days).173

Adolescents: 50 mg once daily with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).173 Alternatively, 200 mg once weekly with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).173

Primary prophylaxis against T. gondii encephalitis should be initiated in all HIV-infected infants and children with severe immunosuppression who are seropositive for Toxoplasma IgG antibody.146 173

The safety of discontinuing primary toxoplasmosis prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied to date.173

Criteria for initiating or discontinuing primary prophylaxis against toxoplasmosis in adolescents are the same as those recommended for adults.173 (See Adult Dosage under Dosage and Administration.)

Adults

Leprosy
Multibacillary Leprosy
Oral

100 mg once daily in conjunction with rifampin (600 mg once monthly) and clofazimine (50 mg once daily and 300 mg once monthly).193 198 200 201

Usual duration of therapy is 12 months.193 198 200 201 l An additional 12 months of treatment may be necessary in some patients (e.g., those with a high baseline bacterial index who have no evidence of improvement or have evidence of deterioration after the initial 12 months of treatment).200 l

Paucibacillary Leprosy
Oral

100 mg once daily with rifampin (600 mg once monthly).193 198 199 200

Usual duration of treatment is 6 months.198 l

Dermatitis Herpetiformis
Oral

50 mg daily initially, then titrate individual dose to find the daily dosage that most effectively controls pruritus and lesions.116 If full control is not achieved within the range of 50–300 mg daily, higher dosage may be tried.116

As soon as possible, reduce daily dosage to a minimum maintenance dosage.116 Maintenance dosage generally ranges from 25–400 mg daily.a

Occasional new lesions (3 or 4 per week) may occur during maintenance therapy and generally are not an indication for altering maintenance dosage.a Maintenance dosage often can be reduced in patients who adhere to a gluten-free diet for ≥6 months.a The 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 jiroveci (Pneumocystis carinii) Pneumonia
Treatment of Mild to Moderate Infections
Oral

100 mg once daily in conjunction with oral trimethoprim (5 mg/kg 3 times daily) for 21 days.107 176 d

Prevention (Primary Prophylaxis)
Oral

50 mg twice daily or 100 mg once daily.107 173

Alternatively, 50 mg once daily or 200 mg once weekly in conjunction with oral pyrimethamine (50 mg or 75 mg once weekly, respectively) and oral leucovorin (25 mg once weekly).107 173

Initiate primary prophylaxis against PCP in HIV-infected adults and adolescents with CD4+ T-cell counts <200/mm3 or a history of oropharyngeal candidiasis.173 Also consider primary prophylaxis if CD4+ T-cell percentage is <14% or there is a history of an AIDS-defining illness.173

Primary prophylaxis can be discontinued in adults and adolescents responding to potent antiretroviral therapy who have a sustained (3 months or longer) increase in CD4+ T-cell counts from <200/mm3 to >200/mm3.173

Reinitiate primary prophylaxis if CD4+ T-cell count decreases to <200/mm3.173

Prevention of Recurrence (Secondary Prophylaxis)
Oral

50 mg twice daily or 100 mg once daily.107 173 d

Alternatively, 50 mg once daily or 200 mg once weekly in conjunction with oral pyrimethamine (50 mg or 75 mg once weekly, respectively) and oral leucovorin (25 mg once weekly).107 173 d

Initiate long-term suppressive therapy or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence in those with a history of PCP.173 d

Discontinuance of secondary prophylaxis is recommended in those who have a sustained (3 months or longer) increase in CD4+ T-cell counts to >200/mm3173 d since such prophylaxis appears to add little benefit in terms of disease prevention and discontinuance reduces medication burden, potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.173

Reinitiate secondary prophylaxis if CD4+ T-cell count decreases to <200/mm3 or if PCP recurs at a CD4+ T-cell count >200/mm3.173 d It probably is prudent to continue secondary prophylaxis for life in those who had PCP episodes when they had CD4+ T-cell counts >200/mm3.173

Toxoplasmosis
Prevention (Primary Prophylaxis)
Oral

50 mg once daily with oral pyrimethamine (50 mg once weekly) and oral leucovorin (25 mg once weekly).173

Alternatively, 200 mg once weekly with oral pyrimethamine (75 mg once weekly) and oral leucovorin (25 mg once weekly).173

Discontinuance of primary toxoplasmosis prophylaxis is recommended in HIV-infected adults and adolescents who have a sustained (3 months or longer) increase in CD4+ T-cell counts to >200/mm3 since such prophylaxis appears to add little benefit in terms of disease prevention and discontinuance reduces medication burden, potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.173

Reinitiate primary prophylaxis if CD4+ T-cell count decreases to <100–200/mm3.173

Prescribing Limits

Pediatric Patients

Leprosy
Multibacillary or Paucibacillary Leprosy
Oral

Maximum 100 mg once daily.146

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia
Prevention (Primary Prophylaxis) or Prevention of Recurrence (Secondary Prophylaxis)
Oral

Children ≥1 month of age: Maximum 100 mg once daily107 146 173 or maximum 200 mg once weekly.107 146 173

Toxoplasmosis
Prevention (Primary Prophylaxis)
Oral

Children ≥1 month of age: Maximum 25 mg once daily.173

Special Populations

No special population dosage recommendation at this time.a

Cautions for Dapsone

Contraindications

  • Hypersensitivity to dapsone and/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.161 162 163 164

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.a

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.149 162

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.a

Hepatic Effects

Toxic hepatitis and cholestatic jaundice reported.a 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.161 162 163 164 (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 the clinical state of the patient.116 These changes have been termed leprosy reactional states and can be classified into 2 types: reversal reactions (type 1) and erythema nodosum leprosum (ENL) reactions (type 2).116

Reversal reactions (type 1) presumably occur because the patient is able to mount an enhanced delayed hypersensitivity response to the residual infection and this leads to swelling of existing skin and nerve lesions.116 Existing lesions become erythematous and edematous and may ulcerate; fever and an increased leukocyte count occur frequently; acute neuritis and loss of nerve function may develop.116 a

ENL is a recurrent immunologically mediated syndrome.193 203 205 206 ENL is reported less frequently in patients receiving currently recommended multiple-drug regimens that include clofazimine than in patients who received dapsone monotherapy.193 204 208 These reactions are 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 the severity of manifestations;114 116 129 132 193 195 207 209 severe reactions generally require hospitalization.116 132 The antileprosy regimen usually is continued despite the occurrence of a leprosy reactional state116 129 130 132 and, if nerve injury or skin ulceration is threatened, corticosteroids are administered.129 Analgesics, corticosteroids, or surgical decompression of swollen nerve trunks generally are used to suppress reversal reactions.116 ENL reactions generally are treated using analgesics, corticosteroids, and/or thalidomide; clofazimine also has anti-inflammatory effects and is beneficial in the treatment of ENL reactions.114 116 129 130 132 192 193 195 204 207 l

Early diagnosis and treatment of leprosy reactional states is important since these reactions are associated with considerable morbidity, especially if chronic, recurrent ENL occurs.193 195 196 203 204 l

Therapy for leprosy and leprosy reactional states should be undertaken in consultation with an expert in the treatment of leprosy.191 203 l For information on treatment of leprosy reactional states, consult the National Hansen’s Disease Program at 800-642-2477 or .116 191 k

Specific Populations

Pregnancy

Category C.116

In patients with leprosy, some clinicians state that the benefits of maintaining dapsone treatment during pregnancy outweigh the potential risks to the fetus.a

Infertility has been reported in males receiving dapsone; 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 or treatment of dermatitis herpetiformis in children.116 Generally considered to have no effect on growth, development, and functional development of children.116

Has been used in a limited number of children for treatment of mild to moderate PCP,173 but safety and efficacy data not available.f

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 erythema nodosum leprosum (ENL) reactions121 122 123 126

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

Delavirdine

Possible increased dapsone concentrationsm

Didanosine

Studies using buffered didanosine indicate no clinically important effect on pharmacokinetics of a single dose of dapsoneg

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

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 AUCj

Rifampin or rifapentine: Potential increased metabolism and decreased plasma concentrations of dapsone 114 116 h i

Rifampin or rifapentine: Dosage adjustment of dapsone may be neededh i

Dapsone dosage used in rifampin-based multiple-drug regimens for treatment of leprosy is well established;193 195 198 200 201 change in dapsone dosage in these regimens not required114 116

Trimethoprim

Possible increased plasma dapsone concentrations;116 161 162 possible improved efficacy for treatment of PCP compared with dapsone alone;111 145 153 161 162 possible increased risk of adverse effects (e.g., methemoglobinemia, rash, abnormal liver function tests)161 162

Possible increased plasma trimethoprim concentrations116 162

Monitor periodically for potential toxicity (e.g., methemoglobinemia)161 162 163

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

  • Bactericidal and bacteriostatic against Mycobacterium leprae.116

  • Antibacterial activity of dapsone is inhibited by p-aminobenzoic acid (PABA). 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 jiroveci (formerly Pneumocystis carinii)110 111 112 and Plasmodium.a

  • Resistance to dapsone may occur in M. leprae.116

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 patients regarding the signs and symptoms of neuritis and the importance of immediately reporting such signs or symptoms to a clinician.146

  • 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.

Dapsone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg

Dapsone Tablets (scored)

Jacobus

100 mg

Dapsone Tablets (scored)

Jacobus

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. 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 March 1, 2008. 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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109. Furrer H, Opravil M, Rossi M et al. Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study. AIDS. 2001; 15:501-7. [PubMed 11242147]

110. Leoung GS, Mills J, Hopewell PC et al. Dapsone-trimethoprim for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med. 1986; 105:45-8. [IDIS 217842] [PubMed 2940954]

111. Mills J, Leoung G, Medina I et al. Dapsone is ineffective therapy for pneumocystis pneumonia in patients with AIDS. Clin Res. 1986; 34:101A.

112. Hughes WT, Smith BL. Efficacy of diaminodiphenylsulfone and other drugs in murine Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1984; 26:436-40. [PubMed 6335017]

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