Dapsone Clofazimine

Levamisole has been used experimentally in leprosy, particularly in combination with dapsone. This combination was used in a documented series of Indian patients, some currently lepromatous and others in the course of a leprosy reaction (1). When using doses sufficient to provide as good an effect as that obtained with clofazimine + dapsone in a comparison group, adverse effects were limited to gastrointestinal intolerance (which was usually mild), affecting only five of the 30 patients treated an incidental case developed pyrexia. 

Antimicrobials Ciprofloxacin Clofazimine Dapsone Demeclocycline Doxycycline Enoxacin Rucytosine Griseofulvin Lomefloxacin Minocycline Nahdixic acid Norfloxacin Ofloxacin Oxytetracycline Pyrazinamide Sulfonamides Tetracycline Trimethoprim... 

Leprosy, also referred to as Hansen s disease, is caused by the bacterium Mycobacterium leprae. Although rare in colder climates, this disease may be seen in tropical and subtropical zones. Dapsone and clofazimine (Lamprene) are the two drags currently used to treat leprosy. The leprostatic drugs are listed in the Summaiy Drug Table Leprostatic Dragp. 

Dapsone (diaminodiphenylsulphone Fig. 5.16F) is used specifically in the treatment of leprosy. However, because resistance to dapsone is unfortunately now well known, it is recommended that dapsone be used in conjunction with rifampicin and clofazimine. 

Clofazimine is a substituted iminophenazine that was first proposed for treating leprosy in 1962 however, it entered into medical practice toward the end of the 1980s. The mechanisms of its action is not definitively known, although there is the assumption that it can inhibit the formation of matrixes with DNA, which leads to a delay in the growth of mycobacteria. Clofazimine exhibits a bactericidal effect between that of dapsone and rifampicin. Synonym of this drug is lamprene. 

Clofazimine is a phenazine dye with some my-cobactericidal activity. It is only used in combination with dapsone to reduce the emerging resistance against dapsone. Its efficacy in the management of erythema nodosum leprosum is based on its antiinflammatory activity. 

Dapsone, combined with other antUeprosy agents like rifampin and clofazimine, is used in the treatment of both multibacillary and paucibacillary M. leprae infections. Dapsone is also used in the treatment and prevention of Pneumocystis carinii pneumonia in AIDS patients who are allergic to or intolerant of trimethoprim-sulfamethoxazole. 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

PABA) incorporation into folic acid (inhibition of folate synthesis). In large proportion of Mycobacterium leprae infections e.g. in lepromatous leprosy, resistance can develop, so combination of dapsone, rifampicin and clofazimine is used in initial therapy. 

Clofazimine is phenazine dye and used as alternative to dapsone in dapsone intolerant/resistant cases and in combination with dapsone and rifampicin in the multidrug treatment of leprosy. It s probable mechanism of action is its involvement in DNA binding, it may interfere with template function of DNA. 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Clofazimine is a phenazine dye that can be used as an alternative to dapsone. Its mechanism of action is unknown but may involve DNA binding. 

Leprosy (Hansen s disease) is caused by M- leprae. Bacilli from skin lesions or nasal discharges of infected patients enter susceptible individuals via the skin or respiratory tract. The World Health Organization recommends the triple drug regimen, dapsone, clofazimine, and rifampin (see p. 333) for 6 to 24 months. 

Alycobocteriiim leprae (leprosy) Actinomycetes dapsone + rifampicin clofazimine ethionamide or cycloserine... 

Pyoderma gangrenosum Systemic corticosteroids are usually effective. Immunosuppressives, e.g. ciclosporin may be used for steroid-sparing effect. Some patients respond to dapsone, minocycline or clofazimine. ... 

In 28 patients with lepromatous leprosy, clofazimine did not influence the urinary excretion of dapsone, except in one case (46). 

Grabosz JA, Wheate HW. Effect of clofazimine on the urinary excretion of DDS (dapsone). Int J Lepr Other Mycobact Dis 1975 43(l) 61-2. 

Hepatotoxicity of combined therapy for leprosy has been reported in 39 patients treated with dapsone, pro-tionamide, and rifampicin. There were similar findings in 50 patients treated with dapsone, clofazimine, rifampicin, and protionamide. Deaths probably related to the drngs occurred in both groups after 3-4 months of treatment... 

Clofazimine is used in the treatment of lepromatous leprosy. including dap.sone-resistant forms of the di.sca.se. In sidition to its antibacterial action, the drug appears to possess anti-inflammatory and immune-modulating effects that are of value in controlling neuritic complications and in suppressing erythema nodosum leprosum reactions associated with lepromatous leprosy. It is frequently used in combina-iion with other drugs, such as dapsone or rifampin. 

Dapsone is u.sed in the treatment of both lepromatous and tuberculoid types of lcpro.sy. Dapsone is used widely for all forms of leprosy, often in combination with clofazimine and rifampin. Initial treatment often includes rifampin with dap-.sone. followed by dapsone alone. It is also u.s to prevent the occurrence of multibacillary lcpro.sy when given prophy-lactically. 

Clofazimine, a substituted aminophenazine dye with lepro-static properties (50 to 100 mg p.o. once daily), is indicated in the treatment of dapsone-resistant leprosy and erythema nodosum leprosum. 

Isoniazid is ineffective in the treatment of leprosy or M. avium complex infection. Lepromatous (multibacillary) leprosy is treated with dapsone, clofazimine, and rifampin for a minimum of 2 years, whereas tuberculoid (pauciba-cillary) leprosy is treated with dapsone and rifampin for 6 months. 

M. leprae Dapsone -1- rifampin + clofazimine Minocycline moxifloxacin or gatifloxacin clarithromycin ethionamide... 

The worldwide incidence of leprosy (Hansen s disease) has plummeted by nearly 90% to -534,000. The cornerstone of this global elimination strategy is the provision of effective multidrug chemotherapy, namely dapsone, rifampin, and clofazimine (Table 47-1), to all leprosy patients in the world. The success of the strategy is evident by the end of 2003, over half of the countries considered endemic for leprosy in 1985 had achieved disease elimination (i.e., a prevalence rate of <1 case per 10,000 inhabitants). 

Clofazimine is orally absorbed and accumulates in tissues. Human leprosy from which dap-sone-resistant bacilli have been recovered has been treated with clofazimine with good results. However, unlike dapsone-sensitive microorganisms, in which killing occurs immediately after dapsone is administered, dapsone-resistant strains do not exhibit an appreciable effect until 50 days after initiation of therapy with clofazimine. The daily dose of clofazimine is usually 100 mg. Patients treated with clofazimine may develop red discoloration of the skin. 

The WHO recommends therapy with multiple drugs for all patients with leprosy to reduce the development of resistance, provide adequate therapy when primary resistance already exists, and reduce the duration of therapy. For patients with lepromatous disease, the following regimen is suggested dapsone, 100 mg/day plus clofazimine, 50 mg/day (unsupervised) plus rifampin, 600 mg, and clofazimine, 300 mg, once a month under supervision for 1-5 years. Some prefer to treat lepromatous leprosy with daily dapsone (100 mg) and daily rifampin (450-600 mg). All drugs are given orally. The minimal duration of therapy is 2 years, and treatment should continue until acid-fast bacilli are not detected in lesions. 

B. Other Agents Alternative drugs for leprosy include rifampin (see above) and clofaziinhie. Clofazimine is given in cases of dapsone resistance or intolerance. The drug causes gastrointestinal irritation and marked skin discoloration. 

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