Weight-loss drugs Xenical and Alli may pose liver failure risk, FDA warns.

AThe U.S. Food and Drug Administration has issued a warning that the popular weight-loss drugs Xenical and Alli may pose a risk of liver failure.

The FDA issued the warning after reviewing 12 cases of severe liver injury reported in people taking Xenical and one case reported with the use of Alli.

Of the 13 cases:

• Twelve were foreign reports of severe liver injury with Xenical.
• One was a U.S. report of severe liver injury with Alli.
• Two patients died from liver failure.
• Three patients required liver transplantation.

The active ingredient in both of these drugs is orlistat. Xenical(orlistat 120 mg) is a prescription drug. Alli (orlistat 60 mg) is sold over-the-counter without a prescription.

The link between taking the drugs and liver failure has not been proven, but the FDA decided to issue the warning because of the seriousness of this possible side-effect, the Agency said in an advisory released today.

“In some of these cases, other factors or drugs may have contributed to the development of severe liver injury,” the Agency said.

Consumers should contact their health care professional immediately if they experience itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools–as these may be signs of liver injury, the FDA advised.

“Talk to your health care professional if you have any concerns about your treatment with Xenical or Alli,” the Agency said.

The full text of the FDA’s Consumer Update is below as is the text of an information sheet prepared by the FDA: Questions and Answers: Orlistat and Severe Liver Injury.

FDA Consumer Update

Date Posted: May 26, 2010

Weight-Loss Drugs and Risk of Liver Failure

There is a potential, rare occurrence of liver failure in people who take the weight-loss medications Xenical or Alli, according to the Food and Drug Administration (FDA).

The active ingredient in both of these drugs is orlistat. Xenical(orlistat 120 mg) is a prescription product. Alli (orlistat 60 mg) is sold over-the-counter without a prescription.

What Consumers Should Do

• Contact your health care professional immediately if you experience itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools. These may be signs of liver injury.

• Talk to your health care professional if you have any concerns about your treatment with Xenical or Alli.

• Report any side effects with Xenical or Alli to FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, by fax, or by phone.
  • Online
  • Regular Mail: Use postage-paid, pre-addressed FDA form 3500
  • Fax: 1-800-FDA-0178
  • Phone: 1-800-332-1088

FDA Actions

FDA has identified and reviewed 12 cases of severe liver injury reported in people taking Xenical and one case reported with the use of Alli. In some of these cases, other factors or drugs may have contributed to the development of severe liver injury.

A cause-and-effect relationship of severe liver injury with orlistat use has not been established; however, because of the seriousness of this possible side effect, FDA has revised the drug labels for Xenical and Alli to include new safety information about the rare occurrence of severe liver injury.

This article appears on FDA’s Consumer Updates page, which features the latest on all FDA-regulated products.

Date Posted: May 26, 2010

Q1. What is FDA announcing today?

A. The U.S. Food and Drug Administration (FDA) has approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication. The agency is also adding a new warning about rare reports of severe liver injury to the OTC Drug Facts label for Alli and is working with the manufacturer to ensure that consumers can understand this new warning.

This new safety information is based on FDA’s completed review of reports of severe liver injury in patients taking orlistat. The potential risk of severe liver injury with orlistat was previously discussed at the Center for Drug Evaluation and Research (CDER) Drug Safety Oversight Board in April 2009, and in an August 2009 Early Communication from the Agency.

Q2. What are Xenical and Alli and what are they used for?

A. Xenical and Alli contain different strengths of the same active ingredient, orlistat.

In 1999, FDA approved Xenical (orlistat 120 mg) as a prescription product for obesity management along with a reduced caloric diet for weight loss and to reduce the risk of regaining weight after prior weight loss.

In 2007, Alli (orlistat 60 mg) was approved to be sold without a prescription for weight loss in overweight adults, 18 years and older, when used along with a reduced-calorie and low-fat diet.

Q3. What information did FDA review before approving orlistat?

A. Before approval, FDA conducts a thorough safety and effectiveness review of a drug. This review includes the evaluation of studies conducted in animals and humans. Orlistat was studied in more than seven clinical trials in thousands of obese patients. After reviewing these data, FDA approved orlistat, determining that the product’s benefits outweighed its risks.

Q4. Were there any potential safety signals for severe liver injury with orlistat use during clinical trials?

A. No safety concerns for severe liver injury were identified in the clinical trials submitted for the Xenical approval. There were seven clinical studies that involved approximately 2,847 subjects. Of these subjects, 2,153 received at least one year of orlistat treatment and 884 received at least two years of orlistat treatment.

Monitoring for liver injury was routinely performed in all seven clinical trials. No significant increases in liver enzymes (a sign of potential severe liver injury) were observed in patients who were taking orlistat compared to those taking a placebo.

Q5. How did FDA learn about the risk of severe liver injury?

A. During routine monitoring of post-marketing adverse events submitted to the FDA from U.S. and foreign sources, the agency identified severe liver injury as a potential safety concern with orlistat use. Based on these initial findings, FDA issued an August 2009 Early Communication to inform the public about its ongoing review of this safety issue.

During the agency’s initial review, 32 reports of serious liver injury, including 6 cases of liver failure were identified. The agency then conducted a comprehensive review of available data on severe liver injury associated with Xenical through August 7, 2009, and a review of post marketing data on Alli from 2007 through October 1, 2008. This final review identified 13 cases of severe liver injury.

Of the 13 cases of severe liver injury, 12 were reported with the use of Xenical and one was reported with the use of Alli. In some of these cases, other factors or drugs may have contributed to the development of severe liver injury.

Of the 13 cases:

• Twelve were foreign reports of severe liver injury with Xenical.
• One was a U.S. report of severe liver injury with Alli.
• Two patients died from liver failure.
• Three patients required liver transplantation.

The agency also noted the following factors that make confirming a cause-and-effect relationship between orlistat and severe liver injury difficult:

• One U.S. case with Alli and 12 foreign cases with Xenical reported between April 1999 and August 2009 out of an estimated 40 million people worldwide who have used Xenical or Alli.
• Some patients in the reported cases also used other drugs or had other conditions that may have contributed to the development of severe liver injury.
• Severe liver injury can occur in people not taking drugs and without a distinct cause.

Q6. If a cause and effect relationship has not been established, why is FDA changing the label?

A. Although a cause and effect relationship of severe liver injury with orlistat use has not been established, because of the seriousness of severe liver injury, FDA has added information about reported cases of severe liver injury to the label of Xenical and Alli to educate the public about the signs and symptoms of liver injury and the need to see a physician promptly should they occur.

Q7. How can people identify the signs and symptoms of severe liver injury?

A. The signs and symptoms of severe liver injury include itching, yellow eyes or skin, fever, weakness, vomiting, fatigue, dark urine, light-colored stools, or loss of appetite. People who experience these signs and symptoms should contact their healthcare professional immediately.

A. FDA advises patients who are concerned about their use of prescription or over-the-counter orlistat to discuss those concerns with their healthcare professionals. People should continue to take Xenical as directed on the prescription label, and follow the directions for use on the Drug Facts box for Alli. In addition, they should stop use of orlistat and contact their healthcare professional if they develop itching, yellow eyes or skin, dark urine, light-colored stools, or loss of appetite.  These may be signs of a serious condition such as liver injury.

Q9. What does FDA advise healthcare professionals do if they have patients taking orlistat?

A. Healthcare professionals should be aware that postmarketing cases of severe liver injury have been reported rarely with the use of orlistat. They should weigh the benefits of weight-loss with the potential risks associated with Xenical and Alli before prescribing or recommending these medications to their patients.

Healthcare professionals should also educate their patients to identify the signs and symptoms of liver injury.

Q10. How can I report a side effect with Xenical or Alli to the FDA?

A. You can report side effects to the FDA in the following ways:

• Visit www.fda.gov/medwatch and click on “How to Report”
• Call – 800-FDA-1088
• Regular Mail or Fax – 800-FDA-0178 postage-paid Form FDA 3500 (PDF – 1MB)

Tags: Alli, FDA, Orlistat, Xenical

Category: Drugs & Medicines, FDA Advice, News