Document 0698
 DOCN  M9650698
 TI    Rifabutin-associated uveitis.
 DT    9605
 AU    Tseng AL; Walmsley SL; Wellesley Health Center, University of Toronto,
       Ontario, Canada.
 SO    Ann Pharmacother. 1995 Nov;29(11):1149-55. Unique Identifier : AIDSLINE
       MED/96156289
 AB    OBJECTIVE: To review rifabutin-associated uveitis and discuss the
       mechanism and potential role of drug interactions with clarithromycin
       and fluconazole in contributing to this adverse event. DATA SOURCES: A
       MEDLINE search (1991 through September 1994) of English-language
       literature using the main MeSH headings rifabutin and uveitis and the
       subheadings adverse effects and chemically induced. Relevant articles
       also were selected from references of identified articles. Abstracts
       from recent medical conferences of infectious diseases, pharmacology,
       and HIV were screened for additional data. STUDY SELECTION AND DATA
       EXTRACTION: All articles and abstracts reporting uveitis potentially
       related to rifabutin were considered for inclusion. Fifty-four cases
       were identified. Pertinent information from the case reports, as judged
       by the authors, was selected and synthesized for discussion. DATA
       SYNTHESIS: Rifabutin is being prescribed increasingly for the treatment
       and prophylaxis of Mycobacterium avium complex (MAC) infection in the
       HIV-infected population. Uveitis was initially thought to be a rare,
       dose-limited complication of rifabutin therapy. In an early dose-ranging
       tolerance study, uveitis was associated with daily doses of 1200 mg or
       more. Because this toxicity appeared to be dose-related, lower dosages
       (300-600 mg/d) of rifabutin were selected for study in subsequent
       clinical trials. More recent reports noting the association of uveitis
       with these lower dosages of rifabutin have raised concerns about the
       prevalence of this adverse event. In the 54 identified cases, patients
       presented with symptoms of unilateral or bilateral uveitis from 2 weeks
       to more than 7 months following initiation of rifabutin therapy. In all
       reported cases, patients were receiving concurrent therapy with
       clarithromycin and/or fluconazole, both of which have inhibitory effects
       on rifabutin metabolism. In most cases, uveitis resolved within 1-2
       months following discontinuation of rifabutin with or without
       administration of topical corticosteroids. CONCLUSIONS: Rifabutin is
       prescribed frequently for the prophylaxis and treatment of MAC
       infection, especially in patients with HIV. Uveitis is a rare,
       dose-related toxicity of this therapy. The risk of rifabutin-associated
       uveitis may be increased in patients receiving concurrent therapy with
       clarithromycin or fluconazole because of drug interactions. Patients
       receiving therapy with combinations of any of these agents should be
       warned about signs and symptoms of uveitis and be monitored closely for
       the development of rifabutin toxicity. If uveitis develops, rifabutin
       therapy should be discontinued promptly.
 DE    Antibiotics/*ADVERSE EFFECTS/PHARMACOLOGY  Antibiotics,
       Macrolide/PHARMACOLOGY  Antifungal Agents/PHARMACOLOGY
       Clarithromycin/PHARMACOLOGY  Clinical Trials  Comparative Study  Drug
       Interactions  Fluconazole/PHARMACOLOGY  Human  Mycobacterium
       avium-intracellulare Infection/DRUG THERAPY  Rifabutin/*ADVERSE
       EFFECTS/PHARMACOLOGY  Uveitis/*CHEMICALLY INDUCED  JOURNAL ARTICLE
       REVIEW  REVIEW OF REPORTED CASES

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