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.
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.
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.
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.
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.
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.
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.
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)