Ethambutol Ciclosporin

Enhanced hepatotoxicity of conventional antituberculosis regimens has been reported in recipients of orthotopic hver transplants, which is not unexpected, because of bouts of organ rejection (25). The authors recommended ofloxacin for these patients on the basis of favorable outcome in six cases. A conventional antituberculosis induction regimen was used initially until hepatotoxicity developed in all six patients. Thereafter they were treated with a combination of ofloxacin and ethambutol, with apparent cure in all. It should be noted that most of the patients took isoniazid + rifampicin for almost 2 months, which is the usual period when hepatotoxic reactions occur. Perhaps one should evaluate substitution of rifampicin with ofloxacin from the very beginning in order to minimize hepatotoxicity, as well as interference with ciclosporin leading to graft rejection noted in an earlier study (26). 

Ciclosporin serum levels are markedly reduced by rifampicin and transplant rejection can rapidly develop. Rifamycin seems to interact similarly, but limited evidence suggests that rifabutin interacts to a lesser extent. Ethambutol and isoniazid do not generally appear to interact with ciclosporin although case reports have described alterations in ciclosporin 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. ... 

Isonlazld and ethambutol do not normally interact with ciclosporin. However, there is one case report describing a patient who had a gradual rise in serum ciclosporin levels when isoniazid and ethambutol were stopped, and another which attributed a marked rise in ciclosporin levels to the use of isoniazid." There have been several other case reports of successful treatment of tuberculosis in heart and kidney transplant patients using isoniazid, ethambutoi, pyrazinamide with ofloxacin, or streptomycin.Consider also pyrazinamide , (p.l044), and quinolones , (p.1018). 

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See also in sourсe #XX -- [ ]

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