FDA Adds Risk for Severe Liver Injury to Orlistat Label

In addition, the Drug Facts label for an over-the-counter, 60-mg formulation of orlistat (Alli) will now feature a warning about severe liver injury. Xenical, available only by prescription, is a 120-mg formulation.

Last August, the FDA announced that it was studying a possible link between orlistat and liver injury. Last weeks' announcement is based on a completed FDA review of all available data from preclinical and clinical trials, postmarketing studies, and drug utilization from April 1999 through August 7, 2009.

Signals of significant liver damage did not emerge in preclinical or clinical trials. However, the FDA identified 13 postmarketing cases of severe liver injury -- 12 of them foreign cases involving Xenical and the other a US case involving Alli. Some patients died or needed a liver transplant.

The FDA stated that it has not yet established a causal relationship between orlistat use and severe liver injury and cited 3 factors making this determination difficult:

• The 13 cases of severe liver injury stand alongside an estimated 40 million people who have used some version of orlistat.
• Some of the 13 patients used other drugs or had conditions that might have contributed to severe liver injury.
• Severe liver injury can occur without a distinct reason in people not taking drugs.

The FDA is advising clinicians to instruct orlistat users to report any symptoms of hepatic dysfunction such as anorexia, pruritus, jaundice, dark urine, light-colored stools, or right upper quadrant pain. Patients should discontinue orlistat therapy if liver injury is suspected.

More information on today's FDA announcement is available on the agency's website.