Document 0782
 DOCN  M9550782
 TI    Clinically significant drug interactions with antituberculosis agents.
 DT    9505
 AU    Grange JM; Winstanley PA; Davies PD; Department of Microbiology,
       National Heart and Lung Institute,; London, England.
 SO    Drug Saf. 1994 Oct;11(4):242-51. Unique Identifier : AIDSLINE
       MED/95151177
 AB    Standard short-course regimens for tuberculosis are used worldwide with
       very few problems. Unfortunately, the emergence of multiple
       drug-resistant tuberculosis in many parts of the world is leading to a
       diversification 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
       treatment of HIV/AIDS patients with tuberculosis or disease due to
       Mycobacterium avium-intracellulare complex (MAC) infection with new
       drugs and multidrug regimens has added to the problem of drug
       interactions, especially as such patients may often be receiving
       concomitant treatment for a range of bacterial, fungal and viral
       infections. In general, there are very few clinically significant
       interactions between the first-line antituberculosis drugs themselves,
       although problems of bioavailability, notably of rifampicin (rifampin),
       have been encountered in the manufacture of combination tablets. Of the
       first-line drugs used to treat tuberculosis, i.e. rifampicin, isoniazid
       and pyrazinamide, rifampicin is particularly likely to cause clinically
       significant drug interactions 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 cyclosproin. The use of quinolones to treat multiple
       drug-resistant tuberculosis and AIDS-related MAC disease raises further
       problems of drug interactions as, in contrast to rifampicin, these drugs
       inhibit some cytochrome isoenzymes, leading to reduced metabolism of
       certain drugs.
 DE    Absorption/DRUG EFFECTS  Antitubercular
       Agents/*PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC  USE
       Biotransformation/DRUG EFFECTS  Cytochrome P-450/METABOLISM  Drug
       Interactions  Drug Therapy, Combination  Enzyme Induction/DRUG EFFECTS
       Human  Isoenzymes/METABOLISM
       Isoniazid/*PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC USE
       Quinolones/*PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC USE
       Rifabutin/*PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC USE
       Rifampin/*PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC USE  Tissue
       Distribution/DRUG EFFECTS  Tuberculosis/DRUG THERAPY  CLINICAL TRIAL
       JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).