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Adverse Events Associated with High-Dose Rifabutin in Macrolide-Containing Regimens for the Treatment of Mycobacterium avium Complex Lung Disease
David E. Griffith, Barbara A. Brown, William M. Girard and Richard J. Wallace, Jr.
Clinical Infectious Diseases
Vol. 21, No. 3 (Sep., 1995), pp. 594-598
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/4458873
Page Count: 5
You can always find the topics here!Topics: Dosage, Lung diseases, Uveitis, Mycobacterium avium complex, Enzymes, Arthralgia, Macrolides, Liver, Toxicity, AIDS
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We initiated a multidrug trial that included high-dose rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Twenty-six patients received rifabutin (600 mg/d) in combination with ethambutol, streptomycin, and either clarithromycin (500 mg b.i.d.; 15 patients) or azithromycin (600 mg/d; 11 patients). Rifabutin-related adverse events occurred in 77% of patients. Fifty-eight percent of patients required a dosage adjustment or discontinuance of rifabutin therapy. The most common adverse event was a reduction in the mean total white blood cell (WBC) count, which decreased from 8,600 ± 2,800/mm³ before treatment to 4,500 ± 2,100/mm³ during treatment (P = .0001). Although all patients had some decrease in WBC count, only three patients (12%) required a dosage adjustment for this reason. Other common adverse events included gastrointestinal symptoms (nausea, vomiting, or diarrhea; 42%) and abnormal liver enzyme levels (12%). Eight of 11 patients (73%) with gastrointestinal symptoms, including one patient with abnormal liver enzyme levels, required a rifabutin-dosage adjustment. The most severe adverse events, always requiring an adjustment of therapy, were a diffuse polyarthralgia syndrome (19%) and anterior uveitis (8%). The latter toxicity has previously been reported to occur only in patients with AIDS and was seen only in patients who also were receiving clarithromycin. On the basis of the current findings, we recommend that rifabutin be used at a dose of 300 mg/d in multidrug regimens that include a macrolide for treatment of MAC lung disease.
Clinical Infectious Diseases © 1995 Oxford University Press