The weight loss drug orlistat (known as Alli and Xenical) should be banned because of increasing evidence that it causes liver damage, kidney stones and pancreatitis, says Public Citizen, a US consumer advocacy group.

Public Citizen issued a petition to the US Food and Drug Administration on Thursday, calling for an immediate ban of orlistat, available in the US over the counter as Alli and on prescription as Xenical. This is the second FDA petition from the group in five years.

The Washington DC-based advocacy group told the press that the drugs not only damage the liver, about which the FDA issued a warning in May last year, but also, because of new information from FDA adverse reaction reports, they have also been linked with 47 cases of acute pancreatitis and 73 cases of kidney stones.

The risks of taking orlistat, which is available in a 120 mg dose under prescription as Xenical, and in a 60 mg dose over the counter as Alli, greatly outweigh the benefits, which are themselves questionable, says the consumer group, because neither forms have been shown to be much more effective than diet and exercise.

Director of Public Citizen’s Health Research Group, Dr Sidney Wolfe, told the press that:

“These drugs have the potential to cause significant damage to multiple critical organs, yet they provide meager benefits in reducing weight loss in obese and overweight patients.”

He called for the FDA to tell the manufacturers of the drugs, Hoffman-LaRoche and GlaxoSmithKline, to pull them from the market “immediately”.

Orlistat works by blocking the effect of ezymes that break down fats in the intestines, so they are not converted into free fatty acids for absorption in the body but excreted in undigested form through the feces instead.

The main side effect that users experience when they take the drug is oily and loose stools with excessive wind because of the unabsorbed fat reaching the large intestine. They can also experience fecal incontinence and a frequent, urgent need to empty the bowels. To minimize side effects users are urged to avoid foods with high fat content and follow a low-fat, calorie-reduced diet.

In May 2010 the FDA issued a warning about “severe liver injury” linked to orlistat use, following 12 reports of severe liver toxicity from other countries tied to Xenical and one for Alli in the US. In two cases the patients died of liver failure and in three cases they needed liver transplants. However, the FDA stressed that a “cause and effect relationship of severe liver injury with orlistat use has not been established”.

Public Citizen said they had searched FDA MedWatch adverse reaction reports and found 47 cases of pancreatitis and 73 cases of kidney stones associated with Xenical or Alli. Of the pancreatitis cases, 39 patients required hospitalization and one died, and of the kidney stones cases, 23 of the patients required hospitalization. In one of the reported cases of kidney stones the patient had to have dialysis and subsequently died.

MedWatch is a voluntary reporting system where healthcare professionals, consumers, and patients can inform the FDA any adverse events associated with use of medical products.

Acute pancreatitis may be difficult to diagnose in patients taking orlistat because some symptoms, such as abdominal pain and nausea, are similar to the side effects of the drug.

Public Citizen said they also reviewed the medical literature and found at least three patients taking orlistat developed acute kidney failure because small crystals of calcium developed in their kidneys.

In 2006, the group called for the FDA to ban Xenical because research in rats had shown that orlistat caused pre-cancerous lesions in the colon, but the FDA rejected the petition.

In its latest petition, Public Citizen maintains that the weight lost by users of both the prescription and over the counter forms of orlistat was “minimal” and gave the example that users who took the 60-mg dose for one year in addition to dieting and exercising, only lost 5.6 extra pounds compared to users who just did the dieting and exercise. And those who took the higher 120 mg dose, only lost 7 extra pounds compared to the diet and exercise only users.

“But the biggest problem with the drugs is their potential to cause serious injuries and death,” said a Public Citizen statement, which also refers to other side effects such as “interference with the absorption of fat-soluble vitamins and drugs, fecal urgency, gas with discharge and abdominal pain”.

Prescriptions for Xenical have fallen from 2.6 million in 2000, when it first came out in the US, to 0.11 million in 2009. Sales of Alli have fallen from $145 million in its first year of marketing in the US (mid-2007 to mid-2008) to $84 million in the latest period for which data is available (mid-2009 to mid-2010).

Speculating on how the FDA might react to this latest petition, some experts may suggest the agency will let the markets decide.

Keith Ayoob, director of the nutrition clinic at the Rose R. Kennedy Center at the Albert Einstein College of Medicine in New York told ABC News that the market for Alli has already shrunk “considerably” and the drug will probably just “wither away on its own”.

“It wouldn’t surprise me if the FDA allowed it to continue with restriction without pulling it,” he added.

Meanwhile, GlaxoSmithKline said on Thursday that it plans to sell off Alli along with some other over the counter brands.

Sources: Public Citizen, FDA, ABC News, Wall Street Journal.

Written by: Catharine Paddock, PhD