       Document 0484
 DOCN  M9640484
 TI    Adverse events associated with high-dose rifabutin in
       macrolide-containing regimens for the treatment of Mycobacterium avium
       complex lung disease.
 DT    9604
 AU    Griffith DE; Brown BA; Girard WM; Wallace RJ Jr; Department of Medicine,
       University of Texas Health Center, Tyler; 75710, USA.
 SO    Clin Infect Dis. 1995 Sep;21(3):594-8. Unique Identifier : AIDSLINE
       MED/96077379
 AB    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.
 DE    Adult  Aged  Antibiotics, Combined/*ADMINISTRATION & DOSAGE/*ADVERSE
       EFFECTS  Antibiotics, Macrolide/*ADMINISTRATION & DOSAGE/*ADVERSE
       EFFECTS  Arthralgia/CHEMICALLY INDUCED  Drug Interactions  Drug
       Tolerance  Female  Gastrointestinal System/DRUG EFFECTS  Human
       Leukopenia/CHEMICALLY INDUCED  Liver/DRUG EFFECTS/ENZYMOLOGY  Lung
       Diseases/*DRUG THERAPY  Male  Middle Age  Mycobacterium
       avium-intracellulare Infection/*DRUG THERAPY  Rifabutin/*ADMINISTRATION
       & DOSAGE/*ADVERSE EFFECTS  Support, Non-U.S. Gov't  CLINICAL TRIAL
       JOURNAL ARTICLE

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

