August 22, 2012

Two Fluoroquinolone Antibiotics Associated With
Liver Injury in New Study

TorontoTwo commonly used fluoroquinolone antibiotics can increase the risk of severe liver injury when used in older patients, according to a new Canadian study, and the authors are calling for the issuance of more regulatory warnings about the drugs.

That study, published in CMAJ, found an association between the commonly used broad-spectrum antibiotics moxifloxacin and levofloxacin and an increased risk of severe liver injury in patients age 66 years or older. The antibiotics are often prescribed for routine conditions such as respiratory and sinus infections.

Both the European Medicines Agency and Health Canada previously have issued warnings about the risk of liver injury from moxifloxacin.

Moxifloxacin is marketed as Avelox in the U.S. by the Schering Corporation under license from Bayer. Levofloxacin is marketed as Levaquin in the U.S. by Janssen Pharmaceuticals, Inc.

This study used health care data from Ontario from 2002 to 2011, identifying outpatients age 66 years or older who had no history of liver disease but were admitted to a hospital for acute liver injury within 30 days of receiving a prescription for one of five broad-spectrum antibiotics: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil, or clarithromycin. Those individuals were then compared to age- and sex-matched controls who had taken the antibiotics but had not been admitted to the hospital.

Of the 144 patients admitted for acute liver injury, 88 (61.1%) died during that hospital stay.

"Compared with clarithromycin, moxifloxacin was associated with a more than 2-fold increased risk of admission to hospital for acute liver injury," the authors write. "Levofloxacin was also associated with a statistically significant but lower risk of hepatotoxicity than...moxifloxacin."

No such risk was identified with the use of either ciprofloxacin or cefuroxime axetil, they add.

The cases of acute liver injury were serious but also rare, representing about six cases for every 100,000 patients treated with the antibiotics.

The authors note that their findings underscore the need for more studies on the risks of moxifloxacin, pointing out, "Despite recent regulatory warnings regarding the hepatic safety of moxifloxacin, there is a lack of controlled studies supporting the notion that moxifloxacin presents a particular risk relative to other broad-spectrum antibiotic agents and, in particular, to other fluoroquinolones."

In the meantime, they note, "Although our results require confirmation in other settings, the findings suggest that both moxifloxacin and levofloxacin be considered for regulatory warnings regarding acute liver injury."

Fluoroquinolones are known to sometimes cause mild, transient elevations in aminotransferase levels, although acute liver injury rarely occurs.

The authors of an accompanying commentary in CMAJ suggest that, because the absolute risk of severe drug-induced liver injury is very low, clinicians should choose the most efficacious antibiotic rather than try to avoid a very uncommon adverse reaction.

U.S. Pharmacist Social Connect