0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Fatal and Nonfatal Hepatotoxicity Associated with Flutamide

Diane K. Wysowski, PhD; Joel P. Freiman, MD, MPH; John B. Tourtelot, MD; and Marshall L. Horton, MD
[+] Article and Author Information

From the Food and Drug Administration, Rockville, Maryland; Oakland Naval Hospital, Oakland, California. Requests for Reprints: Reprints will not be available. Acknowledgments: The authors thank the physicians and pharmacists who reported cases and additional information to the FDA and thank Traci Tate for secretarial assistance.


Copyright 2004 by the American College of Physicians


Ann Intern Med. 1993;118(11):860-864. doi:10.7326/0003-4819-118-11-199306010-00006
Text Size: A A A

Objective: To identify and describe patients with hepatotoxicity possibly caused by flutamide, an antiandrogen drug.

Design: Case series of reports, submitted to the Adverse Drug Event Reporting System of the Food and Drug Administration.

Setting: Outpatient clinics and physicians' offices in the United States.

Patients: Nineteen patients treated with flutamide for prostate cancer or benign prostatic hypertrophy (for Investigation of a New Drug or off-label use).

Measurements: Evidence of increased liver enzyme levels, hyperbilirubinemia, associated clinical symptoms, and diagnoses of cholestatic hepatitis. Autopsy reports were used when available.

Results: From the time of marketing of flutamide in February 1989 through March 1991, the Food and Drug Administration received reports of 19 patients in the United States who developed serious hepatotoxicity while using flutamide. Fourteen patients had resolution of abnormal liver function test results after discontinuing or decreasing the dose of flutamide, but five patients died of progressive liver disease. Autopsy reports from three patients and abnormal pathologic results from three other patients (reported to the Food and Drug Administration or in the medical literature) showed hepatocellular necrosis and possibly cholestasis. Thorough work-ups excluded other possible causes than flutamide.

Conclusions: Flutamide appears to cause hepatotoxic effects in certain patients. Physicians should tell patients to immediately report to physicians nausea, vomiting, fatigue, jaundice, and other signs and symptoms of liver injury.

Figures

Grahic Jump Location
Figure 1.
Histologic findings in the liver.

Massive liver necrosis with bile duct proliferation and focal macrovesicular steatosis. (Hematoxylin and eosin stain; original magnification, 40).

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)