Xenical and Alli Liver Damage Reports Reviewed by FDA

The FDA appears to be reviewing a possible connection between reports of liver damage and orlistat, which is a weight-loss drug contained in the prescription Xenical and the over-the-counter Alli.

According to a report by Scrips News, the FDA discussed orlistat’s potential link to hepatoxicity at an April 16 meeting of its Drug Safety Oversight Board (DSB), and the agency is continuing to review whether there is any connection between the drug and reports of liver damage.

The FDA is looking at both the prescription and non-prescription versions of the drug and said that any action taken would depend on the outcome of its analysis. The FDA would not state how many post-marketing liver damage reports it was investigating.

Orlistat is the active pharmaceutical ingredient in Roche’s Xenical, which was approved as a prescription medication in 1999. Last year, GlaxoSmithKline’s Alli, a lower dose version of the drug, was approved for over-the-counter use.

The medications are intended for use together with a reduced-calorie diet, and work by preventing the absorption of fats, thereby reducing caloric intake.

In 2008, Xenical generated sales of $30 million and Alli generated sales of $131 million during its first full year on the market.

Hepatoxicity is chemical damage to the liver, usually caused by drugs. The liver is the body’s main mechanism for metabolizing drugs, making it susceptible to chemical damage. Hepatoxicity can manifest in a variety of ways, including:

• Necrosis of the liver, a form of hepatitis
• Inflammation of the liver
• Vascular lesions
• Acute liver failure

Xenical’s labeling already lists liver injury as a potential side effect, stating that “exceptional cases of hepatitis that may be serious have been reported.” However, the label points out that that no direct relationship has been established between hepatitis and orlistat therapy.

Obesity itself is often linked to liver injury, and the fact that the FDA is reviewing adverse event reports associated with the use of Xenical and Alli does not mean that there is any cause and effect relationship.

The primary known side effects of Xenical and Alli include oily and loose stools, fecal incontinence, frequent or urgent bowel movements and flatulence, which tend to be most severe when the treatment is started and may decrease with time.

The FDA put orlistat on a list of drugs linked to new safety risks earlier this year after examining reports of Xenical’s possible links to rectal bleeding, however the agency determined that no action was needed.

It has also been suggested that Orlistat side effects may increase the risk of colon cancer and breast cancer, leading the consumer advocacy group Public Citizen to call for an Xenical recall in 2006.