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Dapsone (Aczone): Uses

Leprosy

Dapsone is used in rifampin-based multiple-drug regimens for the treatment of multibacillary and paucibacillary leprosy. Although dapsone was used alone in the past for the treatment of leprosy, the World Health Organization (WHO) and most clinicians currently recommend that rifampin-based multiple-drug regimens be used for the treatment of all forms of leprosy.

Leprosy

Multiple-drug regimens may reduce infectiousness of the patient more rapidly as well as delay or prevent the emergence of resistant organisms. Rifampin-based regimens are necessary because of the increasing incidence of dapsone-resistant Mycobacterium leprae, and these regimens are designed to be effective against all strains of M. leprae, regardless of their susceptibility to dapsone.

Because rifampin is bactericidal against M. leprae, once-monthly administration of rifampin is the principal component of the currently recommended multiple-drug regimens; dapsone and clofazimine are included in the regimens to prevent the emergence of rifampin-resistant M. leprae.

Leprosy

For the treatment of multibacillary leprosy (i.e., more than 5 lesions or skin smear positive for acid-fast bacteria), the WHO currently recommends a 12-month multiple-drug regimen that includes rifampin, clofazimine, and dapsone. If a patient receiving this regimen experiences severe adverse effects related to dapsone, the WHO states that dapsone may be discontinued and rifampin and clofazimine continued at usually recommended dosages.

For the treatment of paucibacillary leprosy (i.e., 2-5 lesions), the WHO recommends a 6-month regimen of rifampin and dapsone. If a patient receiving this regimen experiences severe adverse effects related to dapsone, the WHO states that dapsone may be discontinued and clofazimine (given in the usual dosage recommended for multibacillary leprosy) may be substituted.

Dermatitis Herpetiformis

Dapsone is the drug of choice for the treatment of dermatitis herpetiformis.

Most clinicians recommend that sulfapyridine be used in the treatment of dermatitis herpetiformis only when dapsone cannot be used. In responsive patients, initiation of dapsone therapy usually results in a prompt decrease in pruritus and control of skin lesions of dermatitis herpetiformis; however, dapsone has no effect on cutaneous IgA and complement deposition.

Dermatitis Herpetiformis

Discontinuance of dapsone therapy generally results in rapid exacerbation of lesions and severe pruritus. The use of a gluten-free diet in conjunction with dapsone therapy results in improvement of clinical symptoms and lowers dapsone maintenance dosage requirements in approximately 60% of patients.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment

Dapsone is used in conjunction with trimethoprim for the treatment of initial episodes of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) in adults with acquired immunodeficiency syndrome (AIDS); dapsone is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition. A combination regimen of dapsone (100 mg once daily) and trimethoprim (20 mg/kg daily in 4 divided doses) given for 21 days is effective for the treatment of initial episodes of PCP in patients with AIDS, achieving a clinical response rate of 93% in one study in patients with mild to moderately severe initial episodes of the disease.

Most patients exhibit clinical improvement within 6 days, and the combination of drugs generally appears to be well tolerated.

Therapy with dapsone and trimethoprim appears to be as effective as oral co-trimoxazole for the treatment of initial episodes of mild to moderately severe PCP but is better tolerated than co-trimoxazole in AIDS patients.

While co-trimoxazole is the drug of choice for the treatment of PCP, a regimen of dapsone and trimethoprim is one of several alternative regimens that can be used in patients who are intolerant of co-trimoxazole.

Dapsone alone appears to be less effective than currently preferred anti-infective agents (co-trimoxazole) or the combination of dapsone and trimethoprim for the treatment of initial episodes of PCP in patients with AIDS.

Prevention

Dapsone is used alone or in conjunction with pyrimethamine for prophylaxis of PCP in HIV-infected individuals; dapsone is designated an orphan drug by the FDA for use in this condition. Although co-trimoxazole generally is the drug of choice for both primary and secondary prophylaxis of PCP in HIV-infected individuals, the Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) and other clinicians recommend dapsone or dapsone and pyrimethamine (with leucovorin) as alternatives.

Dapsone alone is recommended as an alternative to co-trimoxazole for PCP prophylaxis in pregnant women.

Primary Prophylaxis

The USPHS/IDSA recommends that primary prophylaxis against PCP be initiated in HIV-infected adults and adolescents who have CD4+ T-cell counts less than 200/mm3 or a history of oropharyngeal candidiasis. HIV-infected adults and adolescents with a CD4+ T-cell percentage less than 14% or a history of an AIDS-defining illness who do not otherwise qualify for prophylaxis also should be considered for primary prophylaxis. If CD4+ T-cell counts are monitored less frequently than every 3 months, individuals with CD4+ T-cell counts greater than 200 but less than 250/mm3 also should be considered for primary prophylaxis.

The USPHS/IDSA currently recommends that children born to HIV-infected mothers receive primary prophylaxis against PCP beginning at 4-6 weeks of age; prophylaxis can be discontinued in children subsequently found not to be infected with HIV, but those whose HIV status remains unknown should continue to receive PCP primary prophylaxis for the first year of life.

The need for subsequent prophylaxis in children should be based on age-specific CD4+ T-cell count thresholds. The USPHS/IDSA and other clinicians recommend oral co-trimoxazole as the drug of choice for primary PCP prophylaxis in HIV-infected adults, adolescents, infants, and children.

For individuals who experience an adverse reaction to co-trimoxazole that is not life-threatening, the USPHS/IDSA recommends that the drug be continued if feasible; for individuals who have discontinued co-trimoxazole because of an adverse effect, reinstitution of co-trimoxazole should be considered once the adverse effect has resolved.

Alternative regimens recommended by the USPHS/IDSA and other clinicians for primary prophylaxis against PCP in HIV-infected adults and adolescents who cannot tolerate co-trimoxazole include dapsone, dapsone and pyrimethamine (with leucovorin), aerosolized pentamidine, or atovaquone.

Alternative regimens recommended for primary PCP prophylaxis in HIV-infected infants and children include dapsone, aerosolized pentamidine, or atovaquone. Current evidence indicates that primary prophylaxis against PCP can be discontinued in HIV-infected adults and adolescents responding to potent antiretroviral therapy who have a sustained (3 months or longer) increase in CD4+ T-cell counts from less than 200/mm3 to greater than 200/mm3.

Patients included in studies evaluating discontinuance of primary prophylaxis generally were receiving antiretroviral regimens that included HIV protease inhibitors; median follow-up ranged from 6-16 months and median CD4+ T-cell count at the time prophylaxis was discontinued was greater than 300/mm3. In addition, at the time prophylaxis was discontinued, most patients had CD4+ T-cell counts exceeding 200/mm3 for at least 3 months and many patients had sustained plasma HIV-1 RNA levels below the detection limits of available assays.

The USPHS/IDSA states that discontinuance of primary PCP prophylaxis is recommended in HIV-infected adults and adolescents who have sustained a CD4+ T-cell count exceeding 200/mm3 for at least 3 because such prophylaxis appears to add little benefit in terms of disease prevention (PCP, toxoplasmosis, bacterial infections) and discontinuance reduces the medication burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.

However, the USPHS/IDSA states that primary PCP prophylaxis should be restarted if the CD4+ T-cell count decreases to less than 200/mm3. The safety of discontinuing primary PCP prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.

Prevention of Recurrence

The USPHS/IDSA currently recommends that HIV-infected individuals who have a history of PCP receive long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence.

The same regimens recommended for primary PCP prophylaxis are used for secondary prophylaxis.

Secondary prophylaxis generally is administered for life, unless immune recovery has occurred as the result of potent antiretroviral therapy.

Current evidence indicates that secondary prophylaxis against PCP can be discontinued in HIV-infected adults and adolescents responding to potent antiretroviral therapy who have a sustained (3 months or longer) increase in CD4+ T-cell counts from less than 200/mm3 to greater than 200/mm3.

Patients in studies evaluating discontinuance of secondary PCP prophylaxis had responded to potent antiretroviral therapy with an increase in CD4+ T-cell counts to greater than 200/mm3 for at least 3 months.

Most patients were receiving a antiretroviral regimen that included a HIV protease inhibitor; the median CD4+ T-cell count at the time prophylaxis was discontinued was greater than 300/mm3 and most patients had sustained plasma HIV-1 RNA levels below the detection limits of the available assays.

The longest follow-up was 13 months. The USPHS/IDSA states that discontinuance of secondary PCP prophylaxis in adults and adolescents who have a sustained (3 months or longer) increase in CD4+ T-cell counts to greater than 200/mm3 is recommended because such prophylaxis appears to add little benefit in terms of disease prevention (PCP, toxoplasmosis, bacterial infections) and discontinuance reduces the medication burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.

However, in patients who had PCP episodes when they had CD4+ T-cell counts greater than 200/mm3, it probably is prudent to continue secondary PCP prophylaxis for life regardless of how high the CD4+ T-cell count increases in response to potent antiretroviral therapy. If secondary PCP prophylaxis is discontinued in HIV-infected adults or adolescents meeting the recommended criteria, the USPHS/IDSA recommends that it be restarted if the CD4+ T-cell count decreases to less than 200/mm3 or if PCP recurs at a CD4+ T-cell count greater than 200/mm3.

The USPHS/IDSA states that children who have a history of PCP should receive lifelong suppressive therapy to prevent recurrence. The safety of discontinuing secondary PCP prophylaxis in HIV-infected children has not been extensively studied.

Toxoplasmosis

Prevention

Although dapsone is not used for the treatment of toxoplasmosis, a 2-drug regimen of dapsone and pyrimethamine is recommended as an alternative to co-trimoxazole for primary or secondary prophylaxis of Toxoplasma gondii encephalitis and dapsone alone is recommended as an alternative to co-trimoxazole for secondary toxoplasmosis prophylaxis.

Primary Prophylaxis

The USPHS/IDSA currently recommends primary prophylaxis against T. gondii encephalitis for all HIV-infected adults and adolescents who are seropositive for Toxoplasma IgG antibody and have CD4+ T-cell counts less than 100/mm3. HIV-infected infants and children with severe immunosuppression who are seropositive for Toxoplasma IgG antibody also should receive primary prophylaxis against T. gondii encephalitis. The USPHS/IDSA recommends co-trimoxazole as the drug of choice for primary prophylaxis against toxoplasmosis in HIV-infected adults, adolescents, and children.

A regimen of dapsone and pyrimethamine (with leucovorin) is the recommended alternative for primary prophylaxis against toxoplasmosis in patients who cannot tolerate co-trimoxazole.

A regimen of atovaquone with or without pyrimethamine and leucovorin also may be considered an alternative regimen in patients who cannot tolerate co-trimoxazole. Alternative regimens for primary prophylaxis against T. gondii in HIV-infected infants and children who cannot receive co-trimoxazole are dapsone with pyrimethamine (with leucovorin) or atovaquone.

Toxoplasmosis

Current evidence indicates that primary toxoplasmosis prophylaxis can be discontinued with minimal risk of developing toxoplasmic encephalitis in adults and adolescents responding to potent antiretroviral therapy who have a sustained (3 months or longer) increase in CD4+ T-cell counts from less than 200/mm3 to greater than 200/mm3.

Patients included in these studies generally were receiving primary prophylaxis and antiretroviral regimens that included HIV-protease inhibitors; median follow-up ranged from 7-22 months and median CD4+ T-cell count at the time prophylaxis was discontinued exceeded 300/mm3. At the time prophylaxis was discontinued, many patients had sustained plasma HIV-1 RNA levels below the detection limits of the available assays.

While patients with CD4+ T-cell counts below 100/mm3 are at greatest risk for toxoplasmic encephalitis, the risk in patients whose CD4+ T-cell counts have increased to 100-200/mm3 has not been studied as extensively as in those whose CD4+ T-cell counts have increased to greater than 200/mm3. Therefore, the recommendation to discontinue primary toxoplasmosis prophylaxis specifies that prophylaxis can be discontinued when the CD4+ T-cell count exceeds 200/mm3.

The USPHS/IDSA states that 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 greater than 200/mm3 because prophylaxis appears to add little benefit in terms of disease prevention for toxoplasmosis, and discontinuance reduces the medication burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.

If primary toxoplasmosis prophylaxis is discontinued in adults and adolescents meeting the recommended criteria, the USPHS/IDSA states that it should be restarted if the CD4+ T-cell count decreases to less than 100-200/mm3.

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

Prevention of Recurrence

The USPHS/IDSA recommends that HIV-infected individuals who have had toxoplasmic encephalitis receive long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent relapse. Secondary toxoplasmosis prophylaxis generally is administered for life, unless immune recovery has occurred as a result of potent antiretroviral therapy.

The USPHS/IDSA states that the regimen of choice for secondary prophylaxis to prevent relapse of toxoplasmosis in HIV-infected adults, adolescents, infants, and children is a regimen of sulfadiazine and pyrimethamine (with leucovorin). In patients who cannot tolerate sulfonamides, a regimen of clindamycin and pyrimethamine (with leucovorin) is recommended; a regimen of atovaquone with or without pyrimethamine (with leucovorin) also is an alternative in adults and adolescents.

Dapsone is not recommended for secondary toxoplasmosis prophylaxis.

Other Uses

Dapsone has been effective in the treatment of bullous eruptions or mucocutaneous lesions in patients with systemic lupus erythematosus and discoid lupus erythematosus resistant to conventional antimalarial or corticosteroid therapy.

Dapsone has also been used with some success in the treatment of other diseases characterized by bullous eruptions such as bullous pemphigoid, pemphigus vulgaris, and Hailey-Hailey disease.

Dapsone has been used in a limited number of patients in the treatment of several inflammatory dermatoses (e.g., pyoderma gangrenosum, erythema elevatum diutinum, Weber-Christian disease, Sweet's syndrome, polyarteritis nodosa, granuloma faciale) and pustular dermatoses (e.g., herpes gestationis, impetigo herpetiformis, pustular psoriasis, follicular mucinosa). Dapsone has been used with some success in the treatment of rheumatoid arthritis, relapsing polychondritis, and allergic vasculitis.

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