Serious Liver Injury

By Meadows, Michelle | FDA Consumer, May 2001 | Go to article overview

Serious Liver Injury


Meadows, Michelle, FDA Consumer


Leading Reason For Drug Removals, Restrictions

People who experience acute liver failure become critically ill in a matter of days, with most cases resulting in the need for a liver transplant or even death Drug-induced liver injury has become the number one cause of this rare syndrome. It's also the leading reason that drugs are removed from the market or require restricted use and special monitoring of patients.

During a drug's development, manufacturers conduct animal tests that include an assessment of potential toxic effects of the new drug on the liver. Additionally, liver function testing is conducted on humans to detect adverse reactions--some of which may keep the drug from making it to the market. But acute liver failure due to a new drug is a very rare event, and may show up only after a drug has been approved.

Because clinical trials typically involve several thousand subjects, they pick up common problems--affecting 1 person in 500 or 1 in 1,000, says Peter Honig, M.D., director of the Food and Drug Administration's office of postmarketing drug risk assessment. "But they aren't designed to pick up rare adverse events, occurring at a rate of 1 per 50,000 exposures," such as acute liver failure, he says. Liver injury can also be hard to predict because genetics may make one patient more susceptible to liver problems than others. Or, a drug may have toxic effects when used with other substances or when used too long.

Because liver failure also can occur rarely in people not exposed to drugs, it is often hard to know if early cases reported for a new drug were actually caused by the drug. When cases of liver injury are caused by a drug, whether before drug marketing or after, experts weigh the risk against the value of the drug. "Unless the drug is treating a life-threatening illness, a significant rate of severe injury (greater than 1 in 50,000 exposures) will lead to limiting the drug's use or withdrawing it from the market," Honig explains.

Most recently, the FDA asked Parke Davis/Warner Lambert to voluntarily withdraw the diabetes drug Rezulin (troglitazone) from the market in March 2000. FDA officials had reviewed safety data showing that Rezulin is more toxic to the liver than two newer, similar drugs on the market, Avandia (rosiglitazone) and Actos (pioglitazone). And in 1998, the FDA asked Wyeth-Ayerst Laboratories to voluntarily remove the pain medication Duract (bromfenac) from the market. The FDA had received reports of liver failure associated with the drug when it was used for longer periods than the 10 days specified in the labeling.

Trovan (trovafloxacin/alatrofloxacin) is an example of a drug with significant limitations of use because of the potential for serious liver injury. The antimicrobial therapy treats a variety of infections, from mild to life threatening. Though no cases of liver failure, liver transplant, or death were reported in the 7,000 patients who took part in premarketing clinical trials for Trovan, the FDA began receiving reports of liver failure after Pfizer began marketing the drug in 1998. As a result, the FDA and Pfizer agreed to restrictions, which include limiting distribution of Trovan to inpatient facilities (hospitals, nursing homes) so doctors can closely monitor patients taking the drug. Trovan use was also limited to the treatment of patients with serious, life- or limb-threatening infections.

The FDA is working with other organizations to identify potential liver problems before drugs have been approved. And when that's not possible, experts want to spot problems quickly after marketing through spontaneous adverse event reporting. In February 2000, representatives from pharmaceutical companies, universities, and the FDA met in Chantilly, Va. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Serious Liver Injury
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

Cited passage

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited passage

Welcome to the new Questia Reader

The Questia Reader has been updated to provide you with an even better online reading experience.  It is now 100% Responsive, which means you can read our books and articles on any sized device you wish.  All of your favorite tools like notes, highlights, and citations are still here, but the way you select text has been updated to be easier to use, especially on touchscreen devices.  Here's how:

1. Click or tap the first word you want to select.
2. Click or tap the last word you want to select.

OK, got it!

Thanks for trying Questia!

Please continue trying out our research tools, but please note, full functionality is available only to our active members.

Your work will be lost once you leave this Web page.

For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

Already a member? Log in now.