Clofazimine Rifampin

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. 

Use in conjunction with either rifampin or clofazimine to prevent development of drug resistance and reduce infectiousness of patient with leprosy more quickly... 

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. 

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. 

Lalonde RG, Fanning MM, Tsoukas CM. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group. N Engl J Med 1996 335(6) 377-83. 

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. 

It has been e.stimatcd that there arc. about 11 million ca.scs of leprosy in the world, of which about 60% are in Asia (with 3.5 million in India alone). The first reports of dapsonc resi.stancc prompted the use of multidrug therapy with dap-.sonc, rifampin, and clofazimine combinations in some geographic iucas. ... 

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. 

Unfortunately, MAC is resistant to the standard drugs used for tuberculosis, such as isoniazid and pyrazinamide. Multiple agents such as rifampin, rifabutin (ansamycin), clofazimine, imipenem, amikacin, ethambutol, ciprofloxacin, clarithromycin, and azithromycin have varying degrees of in vitro anti-MAC activity. Controversy formerly existed as to whether treatment for MAC is beneficial, but data indicate that an aggressive therapeutic approach decreases symptoms... 

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. tuberculosis Isoniazid -1- rifampin - -pyrazinamide -1- ethambutol or streptomycin Moxifloxacin or gatifloxacin cycloserine capreomycin kanamycin amikacin ethionamide clofazimine aminosalicylic acid... 

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). 

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. 

Monthly doses of rifampin delay the emergence of resistance to dapsone Clofazimine should not be given to patients who are intolerant of dapsone or who fail to improve during treatment with dapsone Clofazimine may cause changes in skin color... 

Its mechanism of action is very much similar to that of sulphanilamide. It is employed profusely in the treatment of both lepromatous and tuberculoid types of leprosy. However, in combination with rifampin, it is regarded as the drug of choice in the chemotherapy of leprosy. Besides, the combination with clofazimine affords a similar therapeutic effect. The drug is the most preferred sulfone because of the two cardinal facts, such as (a) cost-effective and b) equally efficacious to other sulfones. 

Antimycobacterials and related drugs Aminosalicylic acid (PAS), Capreomycin, Clofazimine, Cycloserine, Dapsone, Ethambutol, Ethionamide, Isoniazid, Methaniazide, Protionamide, Pyrazinamide, Rifabutin, Rifampicin (Rifampin), Rifamycin, Rihipentine, Rihiximin... 

Pessayre D, Bentata M, Degott C, Nouel O, Miguet JP, Rueff B, Benhamou JP (1977) Iso-niazid-Rifampin fulminant hepatitis. A possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction. Gastroenterology 72 284 Pettit JH (1978) Clofazimine pigmentation. Int J Lepr 46 227... 

Mycobacterium tuberculosis (extensively drug-resistant) Lung Drug combinations (strepto-mycin/isonicotinyl/ hydrazine/rifampin/ ethambutol/pyrazinamide/ moxifloxacine/cycloser-ine/imipenem/co-amoxi-clav/clofazimine/ prochlorperazine/ metronidazole), PA-824 and R207910... 

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