EMA Decides Not To Recall Xenical and Alli, Despite Liver Injury Concerns

European health regulators have decided to allow the prescription weight loss drug Xenical and the lower-dose over-the-counter version sold as Alli to remain on the market, indicating that the health benefits outweigh the potential risk of liver injury. 

The European Medicines Agency (EMA) reported on February 16 that it had determined that drugs containing the pharmaceutical ingredient orlistat, including Xenical and Alli, have a positive benefit-risk balance, meaning they do more harm than good.

The orlistat safety review findings mean there is unlikely to be a recall of Xenical or Alli recall in Europe.

The EMA began a Xenical and Alli safety review late last summer to weigh the risk of liver damage from the weight-loss drugs.

The risk of liver injury from Alli and Xenical has been considered well known by most experts, with most known cases being attributed to the more powerful prescription strength version sold as Xenical. However, the EMA wanted to determine whether the most severe cases of liver damage affect the drugs’ benefit-risk profile.

The EMA found 21 cases of hepatic events linked to Xenical between August 8, 2009, and January 31, 2011. Four of those cases were severe instances of liver toxicity that included one death from liver failure.

From May 2007 to January 2011, there were nine cases of suspected severe liver injury linked to Alli. However, the EMA warns that some of those cases could have other causes and noted some cases did not come with sufficient information to make a proper determination.

The EMA estimates that Xenical has been used by 38 million patients worldwide, and Alli has been used by about 11 million patients. Combined, the drugs account for 74% of weight loss drugs prescribed in England in 2009.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) says it found no strong evidence that Xenical or Alli increased the risk of liver injury and that there was no known mechanism for it to do so. The CHMP could find no pattern to the liver problems that were reported and that there were other factors likely to increase the risk of liver injuries in most cases. However, while CHMP said there was no established causal link between Xenical and liver damage, it could not exclude the possibility that the weight loss drug was responsible for some of the more serious and rare cases of liver injury reported.

In the United States, the FDA issued a liver injury warning concerning the drugs in May 2010. Despite the warning, in April of this year, a consumer watchdog group petitioned the FDA to recall Alli and Xenical from the market.

Xenical (orlistat 120mg) is a prescription medication that was approved by the FDA in 1999. The lower dose Alli (orlistat 60mg) is an over-the-counter weight-loss drug that was approved in 2007. Both drugs are marketed by GlaxoSmithKline, PLC, though Xenical is manufactured by Roche.