Rifampicin Clofazimine

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... 

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. 

Others (against mycobacteria) Clofazimine, ethionamide, and rifampicin Gram-positive and mycobacteria... 

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. 

Agents used for the management of leprosy are dap-sone, rifampicin, clofazimine and recently thalido-... 

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. 

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

Balakrishnan, Seshadri PS. Drug interactions—the influence of rifampicin and clofazimine on the urinary excretion of DDS. Lepr India 1981 53(l) 17-22. 

The occurence of drug interactions involving clofazimine have also been investigated. Most of the studies show that clofazimine does not exert any effect on dapsone excretion in leprosy patients (Balakrishnan and Seshadri, 1981 Zuidema et al., 1986). Clofazimine has been shown to significantly reduce the absorption of simultaneously administered rifampicin, resulting in delayed time to reach peak serum concentration and increased t j. No significant changes were seen in Cmax or AUC (Mehta et al., 1986). 

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

Pieters FAJM, Woonink F, Zuidema J. Influence of once-monthly rifampicin and daily clofazimine on the pharmacokinetics of dapsone in leprosy patients in Nigeria. EurJ CUn Pharmacol (1988) 34,73-6. 

Clofazimine 100 mg daily, given to 15 patients with leprosy taking ri-fampiein 600 mg daily and dapsone 100 mg daily, had no effect on the pharmaeokineties of rifampiein. A single-dose study similarly found that the bioavailability of elofazimine remained unaltered when rifampicin was given, although a reduction in the rate of absorption was seen4 No special precautions would seem to be necessary on concurrent use. 

Venkatesan K, Mathur Girdhar BK, Bharadwaj VP. The effect of clofazimine on the pharmacokinetics of rifampicin and dapsone in leprosy. JAntimicrob Chemother (1986) 18, 715-18. 

Mehta J, Gandhi IS, Sane SB, Wamburkar MN. Effect of clofazimine and dapsone on rifampicin (Lositril) pharmacokinetics inmultibacillary andpaucibacillary leprosy cases. Indian JLepr( 9S5)57, 297-310. 

Serum phenytoin levels are markedly reduced by rifampicin, but can be raised by isoniazid. Those who are slow acetylators (slow metabolisers) of isoniazid may develop phenytoin toxicity if the dosage of phenytoin is not reduced appropriately. If rifampicin and isoniazid are given together, serum phenytoin levels may fall in patients who are fast acetylators of isoniazid, but may occasionally rise in those who are slow acetylators. Clofazimine may reduce serum phenytoin levels. 

The clearance of ciclosporin in a patient with a kidney transplant doubled when isoniazid, ethambutol, pyridoxine and rifampicin 600 mg daily were given. When these drugs were replaced by rifabutin 150 mg and clofazimine 100 mg daily the ciclosporin clearance fell to about its former levels, but after about 3 weeks the clearance was about 20% greater than before the antimycobacterial drugs were given. ... 

Goulart IM, Reis AC, De Rezende TM, Borges AS, Ferreira MS, Nishioka SA. Aplastic anaemia associated with multidrug therapy (dapsone, rifampicin and clofazimine) in a patient with lepromatous leprosy. Lepr Rev 2005 76 167-9. 

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