Class: Antimycobacterials, Miscellaneous
ATC Class: J04BA02
VA Class: AM900
Chemical Name: Diaminodiphenylsulfone
Molecular Formula: C12H12N2O2S
CAS Number: 80-08-0
Antimycobacterial; antiprotozoal; sulfone.116
Uses for Dapsone
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
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
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
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
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
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
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
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
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
Prevention of Recurrence (Secondary Prophylaxis)†Oral
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.)
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
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.)
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
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
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
Prevention (Primary Prophylaxis)†Oral
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
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
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
Multibacillary or Paucibacillary LeprosyOral
Maximum 100 mg once daily.146
Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia†
Prevention (Primary Prophylaxis)†Oral
Children ≥1 month of age: Maximum 25 mg once daily.173
No special population dosage recommendation at this time.a
Cautions for Dapsone
Hypersensitivity to dapsone and/or dapsone derivatives.116
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
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
A potentially fatal hypersensitivity reaction with symptoms of fever, malaise, jaundice (with hepatic necrosis), exfoliative dermatitis, lymphadenopathy, methemoglobinemia, and hemolytic anemia may occur.a
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
Nervous System Effects
Insomnia, headache, nervousness, vertigo, and psychosis also reported.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
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
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
Common Adverse Effects
Interactions for Dapsone
Drugs Associated with 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.116 a
Possible increased dapsone concentrationsm
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
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
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
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
Distributes into most tissues.a
Crosses the placenta.128
Distributed into human milk.116
Plasma Protein Binding
Hemodialysis enhances elimination of dapsone and its monoacetyl derivative.104
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
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
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.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Dapsone Tablets (scored)
Dapsone Tablets (scored)
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.
100. McConkey B, Davies P, Crockson RA et al. Effects of gold, dapsone, and prednisone on serum C-reactive protein and haptoglobin and the erythrocyte sedimentation rate in rheumatoid arthritis. Ann Rheum Dis. 1979; 38:141-4. [IDIS 123066] [PubMed 109055]
101. Swinson DR, Zlosnick J, Jackson I. Double blind trial of dapsone against placebo in rheumatoid arthritis. Ann Rheum Dis. 1981; 40:235-9. [IDIS 165197] [PubMed 7018409]
102. Fowler PD, Shadforth MF, Crook PR et al. Report on chloroquine and dapsone in the treatment of rheumatoid arthritis: a 6-month comparative study. Ann Rheum Dis. 1984; 43:200-4. [IDIS 184550] [PubMed 6370150]
103. Neuvonen PJ, Elonen E, Mattila MJ. Oral activated charcoal and dapsone elimination. Clin Pharmacol Ther. 1980; 27:823-7. [IDIS 115409] [PubMed 7379451]
104. Neuvonen PJ, Elonen E, Haapanen EJ. Acute dapsone intoxication: clinical findings and effect of oral charcoal and haemodialysis on dapsone elimination. Acta Med Scand. 1983; 214:215-20. [IDIS 179130] [PubMed 6660028]
105. Dworkin MS, Hanson DL, Kaplan JE et al. Risk for preventable opportunistic infections in persons with AIDS after antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis thresholds. J Infect Dis. 2000; 182:611-5. [PubMed 10915098]
106. Mussini C, Pezzotto P, Govoni A et al. Discontinuation of primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficient virus type 1-infected patients: the changes in opportunistic prophylaxis study. J Infect Dis. 2000; 181:1635-42. [IDIS 447385] [PubMed 10823763]
107. Anon. Drugs for parasitic infections. Med Lett Drugs Ther. Aug 2004. From the Medical Letter website ().
108. Lopez Bernaldo de Quiros JC, Miro JM, Pena JM et al. A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection: Grupo de Estudio del SIDA 04/98. N Engl J Med. 2001; 344:159-67. [IDIS 458267] [PubMed 11172138]
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]
113. Johnson DA, Cattau EL, Kuritsky JN et al. Liver involvement in the sulfone syndrome. Arch Intern Med. 1986; 146:875-7. [IDIS 216377] [PubMed 3963977]
114. Jacobson RR. Treatment. In: Hastings RC, ed. Leprosy. New York: Churchill Livingstone; 1985:193-222.
115. Report of a WHO Study Group. Chemotherapy of leprosy for control programmes. Technical Report Series No. 675. Geneva: World Health Organization; 1982:3-33.
116. Jacobus Pharmaceutical Company Inc. Dapsone tablets USP prescribing information. Princeton, NJ; 1997 Jun.
117. Kar HK, Bhatia VN, Harikrishnam S. Combined clofazimine- and dapsone-resistant leprosy: a case report. Int J Lepr Other Mycobact Dis. 1986; 54:389-91. [PubMed 3528345]
118. Geigy Pharmaceuticals. Lamprene (clofazimine) prescribing information. Ardsley, NY; 1986 Dec.
119. Venkatesan K, Mathur A, Girdhar BK et al. The effect of clofazimine on the pharmacokinetics of rifampicin and dapsone in leprosy. J Antimicrob Chemother. 1986; 18:715-8. [PubMed 3818497]
120. Venkatesan K, Bharadwaj VP, Ramu G et al. Study on drug interactions. Lepr Ind. 1980; 52:229-35.
121. van Rensburg CEJ, Gatner EMS, Imkamp FMJH et al. Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. Antimicrob Agents Chemother. 1982; 21:693-7. [IDIS 150485] [PubMed 7049077]
122. Anderson R. Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro. Antimicrob Agents Chemother. 1985; 27:257-62. [PubMed 3857019]
123. Anderson R, Lukey P, van Rensburg C et al. Clofazimine-mediated regulation of human polymorphonuclear leukocyte migration by pro-oxidative inactivation of both leukoattractants and cellular migratory responsiveness. Int J Immunopharmacol. 1986; 8:605-19. [PubMed 3793326]
124. Grabosz JAJ, Wheate HW. Effect of clofazimine on the urinary excretion of DDS (dapsone). Int J Lepr Other Mycobact Dis. 1975; 43:61-2. [PubMed 1171834]
125. Balakrishnan S, Seshadri PS. Drug interactions: the influence of rifampicin and clofazimine on the urinary excretion of DDS. Lepr Ind. 1981; 53:17-22.
126. Imkamp FMJH, Anderson R, Gatner EMS. Possible incompatibility of dapsone with clofazimine in the treatment of patients with erythema nodosum leprosum. Lepr Rev. 1982; 53:148-53. [PubMed 7098753]
127. Pruzanski W, Saito S. Influence of agents with immunomodulating activity on phagocytosis and bactericidal function of human polymorphonuclear cells. J Rheumatol. 1983; 10:688-93. [PubMed 6417331]
128. Zuidema J, Hilbers-Modderman ESM, Merkus FWHM. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet. 1986; 11:299-315. [IDIS 220844] [PubMed 3530584]
129. Jolliffe DS. Leprosy reactional states and their treatment. Br J Dermatol. 1977; 97:345-51. [PubMed 336075]
130. Beeching NJ, Ellis CJ. Leprosy and its chemotherapy. J Antimicrob Chemother. 1982; 10:81-7. [PubMed 6749788]
131. Morgan J. Management of steroid-dependency with clofazimine [Lamprene or B 663 (Geigy)]. Lepr Rev. 1970; 41:229-32. [PubMed 5515679]
132. Yawalkar SJ, Vischer W. Lamprene (clofazimine) in leprosy. Lepr Rev. 1979; 50:135-44. [PubMed 396428]
133. Food and Drug Administration. Recent drug approvals. FDA Drug Bull. 1987; 17:8-10.
134. 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.
135. Ahmad RA, Rogers HJ. Pharmacokinetics and protein binding interactions of dapsone and pyrimethamine. Br J Clin Pharmacol. 1980; 10:519-24. [IDIS 128208] [PubMed 7437265]
136. Peters JH, Murray JF Jr, Gordon GR et al. Dapsone in saliva and plasma of man. Pharmacology. 1981; 22:162-71. [PubMed 7208598]
137. Katz SI, Hall RP III, Lawley TJ et al. Dermatitis herpetiformis: the skin and the gut. Ann Intern Med. 1980; 93:857-74. [IDIS 125292] [PubMed 7447195]
138. Glader BE, Conrad ME. Hemolysis by diphenylsulfones: comparative effects of DDS and hydroxylamine-DDS. J Lab Clin Med. 1973; 81:267-72. [PubMed 4683425]
139. Kramer PA, Glader BE, Li TK. Mechanism of methemoglobin formation by diphenylsulfones: effect of 4-amino-4-hydroxy amino diphenylsulfone and other p-substituted derivatives. Biochem Pharmacol. 1972; 21:1265-74. [PubMed 5038672]
140. Schneider MME, Borleffs JCC, Stolk RP et al. Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1 infected patients treated with highly active antiretroviral therapy. Lancet. 1999; 353:201-3. [IDIS 418064] [PubMed 9923876]
141. Furrer H, Egger M, Opravil M et al. Discontinuation of primary prophylaxis against Penumocystis carinii pneumonia in HIV-1 infected adults treated with combination antiretroviral therapy. N Engl J Med. 1999; 340:1301-6. [IDIS 425566] [PubMed 10219064]
142. Reiter WM, Cimoch PJ. Dapsone-induced methemoglobinemia in a patient with P. carinii pneumonia and AIDS. N Engl J Med. 1987; 317:1740-1. [IDIS 236269] [PubMed 3501070]
143. Vischer WA. The experimental properties of G 30 320 (B 663)—a new anti-leprotic agent. Lepr Rev. 1969; 40:107-110. [PubMed 5792376]
144. Vischer WA. Antimicrobial activity of the leprostatic drug 3-(p-chloranilino)-10-(p-chlorphenyl)-2, 10-dihydro-2-(isopropylimino)-phenazine (G 30 320). Arzneimittelforschung. 1968; 8:1529-35.
145. Mills J, Leoung G, Medina I et al. Dapsone treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Antimicrob Agents Chemother. 1988; 32:1057-60. [IDIS 244090] [PubMed 3263834]
146. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.
147. Anon. Prevention of Pneumocystis carinii pneumonia. Med Lett Drugs Ther. 1988; 30:94-5. [PubMed 3050408]
148. Hughes WT, Kennedy W, Dugdale M et al. Prevention of Pneumocystis carinii pneumonitis in AIDS patients with weekly dapsone. Lancet. 1990; 336:1066. [IDIS 273184] [PubMed 1977035]
149. Working Group on PCP prophylaxis in children. Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR Recomm Rep. 1991; 40(RR-2):1-13.
150. Mallolas J, Zamora L, Gtell JM et al. Low-dose co-trimoxazole, aerosolised pentamidine, or dapsone plus pyrimethamine for prevention of Pneumocystis carinii pneumonia. Lancet. 1991; 337:1162-3.
151. Anon. Guidelines established for PCP prophylaxis in infants and children infected with HIV. NIAID AIDS Agenda. 1991; (Mar/Apr):6.
152. National Institute of Allergy and Infectious Diseases backgrounder: questions and answers about ACTG protocol 021 and PCP prevention. Bethesda, MD: National Institutes of Health Office of Communications; 1991 Sep 6.
153. Davey RT, Masur H. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990; 34:499-504. [IDIS 264893] [PubMed 2140495]
154. Masur H, Lane C, Kovacs JA et al. Pneumocystis pneumonia: from bench to clinic. Ann Intern Med. 1989; 111:813-26. [IDIS 261003] [PubMed 2683916]
155. Centers for Disease Control. Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. MMWR Recomm Rep. 1989; 38(S-5):1-9.
156. Freedberg KA, Tosteson ANA, Cohen CJ et al. Inhaled pentamidine and prevention of pneumocystis pneumonia. N Engl J Med. 1991; 325:735. [IDIS 284642] [PubMed 1908059]
157. Bender BS. Inhaled pentamidine and prevention of pneumocystis pneumonia. N Engl J Med. 1991; 325:735-7. [IDIS 284642] [PubMed 1908059]
158. Falloon J, Masur H. The era of pentamidine prophylaxis: the beginning of the end? Am J Med. 1991; 90:415-7. Editorial.
159. Metroka CE, McMechan MF, Laubenstein LJ et al. Failure of prophylaxis with dapsone in patients taking dideoxyinosine. N Engl J Med. 1991; 325:737. [IDIS 284646] [PubMed 1908060]
160. Jacobus Pharmaceutical Company, Princeton, NJ: Personal communication.
161. Medina I, Mills J, Leoung G et al. Oral therapy for Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome: a controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990; 323:776-82. [IDIS 270540] [PubMed 2392131]
162. Lee BL, Medina I, Benowitz NL et al. Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS): evidence of drug interactions. Ann Intern Med. 1989; 110:606-11. [IDIS 253259] [PubMed 2784648]
163. Reviewers’ comments (personal observations).
164. Cox G, Roberts MS. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. 1991; 324:1742-3.
165. Clotet B, Sirera G, Romeu J et al. Twice weekly dapsone-pyrimethamine for preventing P. carinii pneumonia relapses in HIV infected patients. Int Conf AIDS. 1990; 6:225.
166. Clotet B, Sirera G, Romeu J et al. Twice weekly dapsone-pyrimethamine for preventing primary and secondary Pneumocystis carinii pneumonia (PCP): its role in the prevention of cerebral toxoplasmosis. Int Conf AIDS. 1991; 7:228.
167. Lavelle J, Falloon J, Morgan A et al. Weekly dapsone/pyrimethamine for PCP prophylaxis. Int Conf AIDS. 1991; 7:233.
168. Girard PM, Landman R, Gaudebout C et al. Dapsone-pyrimethamine (D/P) vs aerosolized pentamidine (AP) for primary prophylaxis of pneumocystis (PCP) and neurotoxoplasmosis: the PRIO group. Int Conf AIDS. 1992; 8:We48.
169. Antinori A, Murri R, Ammassari A et al. Primary prevention of Pneumocystis carinii pneumonia: an open controlled study on three different regimens. Int Conf AIDS. 1992; 8:B134.
170. Opravil M, Heald A, Lazzarin A et al. Combined prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis: prospective, randomized trial of dapsone + pyrimethamine vs. aerosolized pentamidine. The Swiss Group for Clinical Studies on AIDS. Int Conf AIDS. 1992; 8:B139.
171. Ogata-Arakaki D, Falloon J, Lavelle J et al. The safety of weekly dapsone and weekly dapsone + pyrimethamine as pneumocystis prophylaxis. Int Conf AIDS. 1990; 6:224.
172. Pont M, Clotet B, Sirera G et al. Dapsone + pyrimethamine twice weekly (group A) versus once weekly associated with aerosolized pentamidine once monthly (group B) to prevent P. carinii pneumonia events in AIDS. Int Conf AIDS. 1992; 8:123.
173. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons with human immunodeficiency virus. From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().
174. Hughes WT. Use of dapsone in the prevention and treatment of Pneumocystis carinii pneumonia: a review. Clin Infect Dis. 1998; 27:191-204. [IDIS 410576] [PubMed 9675476]
175. Weverling GJ, Mocroft A, Ledergerber B et al. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection: EuroSIDA study group. Lancet. 1999; 353:1293-8. [PubMed 10218526]
176. Fishman JA. Treatment of infection due to Pneumocystis carinii. Antimicrob Agents Chemother. 1998; 42:1309-14. [IDIS 408066] [PubMed 9624465]
177. Stavola JJ, Noel GJ. Efficacy and safety of dapsone prophylaxis against Pneumocystis carinii pneumonia in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 1993; 12:644-7. [PubMed 8414776]
178. Girard PM, Landman R, Gaudebout C et al. Dapsone–pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. N Engl J Med. 1993; 328:1514-20. [IDIS 314637] [PubMed 8479488]
179. Martin MA, Cox PH, Beck K et al. A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus–infected patients. Arch Intern Med. 1992; 152:523-8. [IDIS 292784] [PubMed 1546914]
180. Blum RN, Miller LA, Gaggini LC et al. Comparative trial of dapsone versus trimethoprim/sulfamethoxazole for primary prophylaxis of Pneumocystis carinii pneumonia. J Acquir Immune Defic Syndr. 1992; 5:341-7. [PubMed 1548570]
181. Smith GH. Treatment of infections in the patient with acquired immunodeficiency syndrome. Arch Intern Med. 1994; 154:959-73.
182. National Institutes of Health Combined Clinical Staff Conference. Consensus conference: recent advances in the management of AIDS-related opportunistic infections. Ann Intern Med. 1994; 120:945-55. [IDIS 330618] [PubMed 7909657]
183. Gallant JE, Moore RD, Chaisson RE. Prophylaxis for opportunistic infections in patients with HIV infection. Ann Intern Med. 1994; 120:932-44. [IDIS 330617] [PubMed 8172439]
184. Torres RA, Barr M, Thorn M et al. Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. Am J Med. 1993; 95:573-83. [IDIS 323423] [PubMed 8018144]
185. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.
186. Yawalkar SJ, Vischer W. Lamprene (clofazimine) in leprosy. Lepr Rev. 1979; 50:135-44. [PubMed 396428]
187. Farb H, West DP, Pedvis-Leftick A. Clofazimine in pregnancy complicated by leprosy. Obstet Gynecol. 1982; 59:122-3. [IDIS 145212] [PubMed 7078842]
188. Duncan ME, Pearson JM. The association of pregnancy and leprosy—erythema nodosum leprosum in pregnancy and lactation. Lepr Rev. 1984; 55:129-42. [PubMed 6748844]
189. Ciba-Geigy Corporation, Summit, NJ: Personal communication.
190. Reviewers’ comments (personal observations) on Clofazimine 8:16.92.
191. Centers for Disease Control and Prevention. Tuberculosis/Mycobacteriology Branch; 1998 Nov 6. From CDC web site ().
192. Celgene, Warren, NJ: Personal communication.
193. WHO Expert Committee on Leprosy. Seventh Report. WHO Technical Report Series No. 874. Geneva: World Health Organization; 1998:1-43.
194. Whitty CJ, Lockwood DN. Leprosy—new perspectives on an old disease. J Infect. 1999; 38:2-5. [IDIS 424615] [PubMed 10090496]
195. Jacobson RR, Krahenbuhl JL. Leprosy. Lancet. 1999; 353:655-60. [IDIS 421539] [PubMed 10030346]
196. MacDougall AC, Ulrich MI. Mycobacterial Disease: Leprosy. In: Fitzpatrick TB, Eisen AZ, Wolff K et al, eds. Dermatology in General Medicine, 4th ed. New York, NY: McGraw -Hill Inc; 1993:2395-2410.
197. Panda S. Let’s learn some clinical facts on leprosy - before it is eradicated. Bull on Drug Health Information (India). 1998; 5:5-12.
198. Anon. Essential Drugs. WHO Model Formulary. Antibacterials. Antileprosy Drugs. WHO Drug Information. 1997; 11:253-7.
199. WHO Study Group on Chemotherapy of Leprosy. Seventh Report. WHO Technical Report Series No. 847. Geneva: World Health Organization; 1994:1-24.
200. WHO. Action programme for the elimination of leprosy (LEP). From WHO Website () 1999 Sept 23.
201. WHO. Reports on individual drugs. Simplified treatment for leprosy. WHO Drug Information. 1997; 11:131.
203. Gelber RH. Leprosy (Hansen’s disease). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 4th ed. New York, NY: Churchill Livingstone; 1995:2243-50.
204. Lockwood DNJ. The management of erythema nodosum leprosum: current and future options. Lepr Rev. 1996; 67:253-9. [PubMed 9033196]
205. Schreuder PAM. The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in Northeastern Thailand, 1978–1995. II. Reactions. Int J Lepr Other Mycobact Dis. 1998; 66:159-69. [PubMed 9728448]
206. Bhargava P, Mal Kuldeep C, Mathur NK. Erythema nodosum leprosum in subgroups of lepromatous leprosy. Lepr Rev. 1998; 68:373-85.
207. Meyerson MS. Erythema nodosum leprosum. Int J Dermatol. 1996; 35:389-92. [PubMed 8737869]
208. Willcox ML. The impact of multiple drug therapy on leprosy disabilities. Lepr Rev. 1997; 68:350-66. [PubMed 9503872]
209. Kirk O, Lundgren JD, Pedersen C et al. Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy? AIDS. 1999; 13:1647-51.
210. Soriano V, Dona C, Rodriguez-Rosado R et al. Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy. AIDS. 2000; 14:383-6. [PubMed 10770540]
211. Ledergerber B, Mocroft A, Reiss P et al. Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. N Engl J Med. 2001; 344:168-74. [IDIS 458268] [PubMed 11188837]
212. Furrer H, Opravil M, Bernasconi E et al. Stopping primary prophylaxis in HIV-1-infected patients at high risk of toxoplasma encephalitis: Swiss HIV cohort study. Lancet. 2000; 355:2217-8. [IDIS 448523] [PubMed 10881897]
a. AHFS drug information 2007. McEvoy GK, ed. Dapsone. Bethesda, MD: American Society of Health-System Pharmacists; 2007:579-83.
d. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-15):1-112.
f. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-14):1-92.
g. Bristol-Myers Squibb. Videx EC (didanosine) delayed-release capsules enteric-coated beadlets prescribing information. Princeton, NJ; 2006 Jul.
h. Sanofi-Aventis. Rifadin (rifampin capsules) and Rifadin I (rifampin for injection) prescribing information. Bridgewater, NJ; 2007 Mar.
i. Sanofi-Aventis. Priftin (rifapentine) 150 mg tablets prescribing information. Bridgewater, NJ; 2006 Dec.
j. Pfizer. Mycobutin (rifabutin) capsules USP prescribing information. New York, NY; 2006 Feb.
k. National Hansen’s Disease (Leprosy) Program. From the US Department of Health and Human Services website (). Accessed 2008 Jan 7.
l. World Health Organization. WHO recommended multidrug therapy (MDT) regimens. From the WHO website (). Accessed 2008 Jan 7.
m. Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (December 1, 2007). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().