FDA Should Remove Weight-Loss Drugs ALLI and XENICAL From the Market

The over-the-counter (ALLI) and prescription forms (XENICAL) of weight-loss drug orlistat should be removed from the market immediately because they not only can damage the liver, but also, based on new information obtained from Food and Drug Administration (FDA) adverse reaction files, have been associated with 47 cases of acute pancreatitis and 73 cases of kidney stones. On April 14, 2011, Public Citizen petitioned the FDA to immediately ban both ALLI and XENICAL.

XENICAL has 120 milligrams (mgs) of orlistat and ALLI has 60 mgs. Their serious risks greatly outweigh their benefits, which are questionable, because neither has been shown to be much more effective than diet and exercise.

The most serious risks associated with XENICAL and ALLI include severe liver injury, acute pancreatitis and acute renal failure. Any one of these alone would be sufficient basis for banning these drugs. Orlistat has the potential to cause significant damage to multiple critical organs, yet it provides meager benefits in reducing weight in obese and overweight patients. For this reason, the FDA should tell the manufacturers of these drugs, Hoffmann-La Roche and GlaxoSmithKline, to pull XENICAL and ALLI, respectively, from the market immediately.

The 2011 petition is our second appeal to have XENICAL taken off pharmacy shelves. In April 2006, we urged a ban of XENICAL because research in rats had demonstrated that orlistat caused the formation of precancerous lesions in the colon. The FDA rejected that petition.

Decrease in orlistat use

U.S. physicians have been writing fewer prescriptions for XENICAL, long before over-the-counter ALLI was available, because of its serious risks and marginal effectiveness. Prescriptions for XENICAL in the U.S. declined 81 percent, from 2.6 million in 2000, when XENICAL first became available in the U.S., to just 490,000 in 2007. By 2009, the number of XENICAL prescriptions in the U.S. further decreased to 110,000 prescriptions, representing only 4 percent of its peak in 2000 but still exposing tens of thousands of patients to a drug with serious risks that greatly outweigh its spare benefits.

Meanwhile, sales of ALLI plummeted from $145 million in the first year of marketing (mid-2007 to mid-2008) to $84 million between mid-2009 and mid-2010, the latest years for which data are available.

Public Citizen concerns

The Public Citizen petition states that the weight lost by users of both prescription- and over-the-counter-strength orlistat was minimal. For example, people taking XENICAL while dieting and exercising for one year lost only 5.6 additional pounds from the 60-mg dose and seven additional pounds from the 120-mg dose compared to the group that engaged only in diet and exercise. Similarly, those in a four-month study of ALLI lost only two to four more pounds than those who solely changed their diet and exercise routines.

But the biggest problem with the drugs is their potential to cause serious injuries and death.

On May 26, 2010, the FDA issued a warning about “severe liver injury” resulting from using orlistat. The agency identified 12 foreign reports of severe liver toxicity associated with XENICAL and one domestic case for ALLI. Two of the patients died of liver failure and three required liver transplants.

Another serious adverse effect of taking XENICAL or ALLI is acute pancreatitis, which may be especially difficult to diagnose since orlistat’s most common side effects, including abdominal pain and nausea, are also typically symptoms of pancreatitis. Our research of FDA’s MedWatch adverse reaction reports found 47 cases of pancreatitis associated with XENICAL or ALLI. Thirty-nine of those patients required hospitalization and one died.

Our analysis of FDA’s MedWatch reports also identified 73 cases of kidney stones associated with XENICAL or ALLI use, of which 23 required hospitalization. In a review of the medical literature, we also identified at least three patients who were taking orlistat and developed acute kidney failure because tiny calcium salt crystals formed throughout the kidneys. In one reported case, the patient required dialysis and ultimately died.

Additional risks of these drugs include interference with the absorption of fat-soluble vitamins and other drugs, fecal urgency, gas with discharge and abdominal pain.

What You Can Do

Consumers may report serious adverse events with drugs or product quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

• Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
• Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: (800) FDA-0178
• Phone: (800) FDA-1088