CLINICALLY SIGNIFICANT DRUG-INTERACTIONS WITH ANTITUBERCULOSIS AGENTS

Standard short-course regimens for tuberculosis are used worldwide wit h very few problems. Unfortunately, the emergence of multiple drug-res istance tuberculosis in many parts of the world is leading to a divers ification of drug regimens and to the use of drugs that are more toxic per se and more likely to interact with others. In addition, the trea tment of HIV/AIDS patients with tuberculosis or disease due to Mycobac terium avium-intracellulare complex (MAC) infection with new drugs and multidrug regimens has added to the problem of drug interactions, esp ecially as such patients may often be receiving concomitant treatment for a range of bacterial, fungal and viral infections. In general, the re are very few clinically significant interactions between the first- line antituberculosis drugs themselves, although problems of bioavaila bility, notably of rifampicin (rifampin), have been encountered in the manufacture of combination tablets. Of the first-line drugs used to t reat tuberculosis, i.e. rifampicin, isoniazid and pyrazinamide, rifamp icin is particularly likely to cause clinically significant drug inter actions as it is a potent inducer of the cytochrome P450 enzyme group, which is involved in the metabolism of many drugs, in particular oral contraceptives, corticosteroids, oral anticoagulants and cyclosporin. The use of quinolones to treat multiple drug-resistant tuberculosis a nd AIDS-related MAC disease raises further problems of drug interactio ns as, in contrast to rifampicin, these drugs inhibit some cytochrome isoenzymes, leading to reduced metabolism of certain drugs.