European Medicines Agency Concerned Over Orlistat Liver Damage; FDA Falls Silent

January 4, 2012, 8:00AM. By Gordon Gibb

Washington, DCIt's been about 18 months now since the US Food and Drug Administration (FDA) articulated its latest cautionary initiative regarding Orlistat, the weight-loss drug that is sourced by prescription but is also available in a different strength over the counter (OTC) as Alli. That's when the FDA approved new safety labeling for both Alli and its big brother Xenical that stemmed from a review of the drug in light of concern over severe liver injury.

There's been nothing forthcoming from the FDA since. However the European Medicines Agency (EMA) announced this past fall that it will be conducting a review of Orlistat due to reports of Orlistat liver damage. According to a September 22, 2011 report carried by Reuters, the EMA said in a statement that the risk to the liver of weight-loss drugs containing Orlistat was "well-known."

While keeping Orlistat under close review for some time, the EMA announced that its updated probe would focus on the strength of evidence relating to severe liver injury.

The Alli diet drug, at 60mg, is manufactured by GlaxoSmithKline and is exactly half the strength of Roche's Xenical, which is only available by prescription. Both drugs have previously come under fire by the consumer advocacy group, Public Citizen. Following the receipt of 32 adverse reaction reports from 1999 to 2008, the FDA announced on August 24, 2009, that it was putting Orlistat under review, pending further study of Orlistat liver damage concerns. Among those reports, are various Alli side effects.

Orlistat was approved by the EMA in January 2009 and is so far available OTC. There is no requirement for a prescription within the European Union.

At the time of its most recent dictum on Alli Orlistat, the FDA noted that there had been one reported case of Alli liver damage in the US, with 12 international cases of Orlistat liver damage involving Xenical over a 10-year period ending in August 2009. The FDA noted that some patients presenting liver issues were also taking other drugs or suffered from conditions that may have contributed to severe liver injury.

Still, advocates like Public Citizen continue to rail against Orlistat. Its first petition seeking to have tetrahydrolipstatin (Orlistat, Alli, Xenical) removed form the market came in 2006, a year before the FDA gave GlaxoSmithKline its blessing to introduce half-strength Orlistat, dubbed Alli, as an OTC weight-loss drug.

With its latest petition filed with the FDA in April of last year, Public Citizen is entering its seventh year railing against Orlistat, imploring the federal regulator to remove it from the marketplace. It is not known if Public Citizen may consider an Orlistat lawsuit or an Alli lawsuit—strategies the advocacy group has used in the past to make its point to regulators.

While the FDA notes that severe liver failure is rare, the agency admits that of the adverse events the FDA reviewed, three patients required liver transplants and two patients died.

Orlistat works by blocking the absorption of fat, and as a weight-loss aid has been deemed effective. The FDA noted both in its printed data and during a brief video summary of the issue dated August 2009 that more than 40 million patients worldwide used Alli and Xenical over a 10-year period with 13 cases of severe liver injury globally.

But that hasn't stopped the EMA from looking into Orlistat, as recently as this past September. The EMA initiative is the latest response to concern over Orlistat, next to the release of Public Citizen's most recent petition in April 2011. The FDA has not been heard from since August 2010.

Symptoms of possible Alli liver damage include itching, yellow eyes or skin, dark urine, light-colored stools and loss of appetite.