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Fixed-Dose Combinations of Antituberculous Medications To Prevent Drug Resistance

Thomas Moulding, MD; Asim K. Dutt, MD; and Lee B. Reichman, MD, MPH
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From Harbor-University of California, Los Angeles, Medical Center, Torrance, California. Alvin C. York Veterans Administration Medical Center, Murfreesboro, Tennessee. New Jersey Medical School, Newark, New Jersey. Requests for Reprints: Thomas S. Moulding, MD, Division of Respiratory and Critical Care Physiology and Medicine, Harbor-University of California, Los Angeles, Medical Center, Torrance, CA 90501. Grant Support: By Cooperative Agreement 200-93-0636 from the Centers for Disease Control and Prevention; Tuberculosis Career Academic Award K07-h103015-01 from the Division of Lung Disease of the National Heart, Lung, and Blood Institute; and Research Consortium Grant 200-93-0690 from the Centers for Disease Control and Prevention.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(12):951-954. doi:10.7326/0003-4819-122-12-199506150-00010
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The treatment of tuberculosis requires at least two drugs to retard the development of drug resistance. Unfortunately, patients may take only one drug (monotherapy) when more than one is prescribed. Fixed-dose combinations with two or more antituberculous drugs in one capsule or tablet are available to prevent this. In the United States, these drugs are Rifamate (Marion Merrell Dow), which contains isoniazid plus rifampin, and Rifater (Marion Merrell Dow), which contains isoniazid plus rifampin and pyrazinamide. Because these preparations make monotherapy impossible, they are clearly preferable to individual drugs. In the United States in 1993, however, only 15% to 18% of rifampin was sold in the form of fixed-dose combinations. To correct this deficiency, fixed-dose combinations should be widely promoted and accepted as a primary way to prevent drug-resistant tuberculosis. There are two caveats regarding these preparations. First, many fixed-dose combinations, especially those in developing countries, achieve inadequate blood levels of one or more of the component drugs, especially rifampin. Our recommendations apply only to preparations with proven bioavailability. Second, because the name Rifamate is similar to the name rifampin, mistakes in prescribing and dispensing can result in the patient receiving rifampin alone when Rifamate is intended. A name change from Rifamate to a highly distinctive name such as Rif-Isoniazid is needed to prevent such occurrences.





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