FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury
[05-26-2010] 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.
Xenical and Alli are medications used for weight-loss that contain different strengths of the same active ingredient, orlistat. Xenical (orlistat 120 mg) is available by pre******ion and Alli (orlistat 60 mg) is sold over-the-counter without a pre******ion.
This new safety information, originally announced in August 2009, is based on FDA's completed review that identified 13 total reports of severe liver injury with orlistat; 12 foreign reports with Xenical and 1 U.S. report with Alli (see Data Summary).
The following factors make confirming a cause-and-effect relationship between orlistat and severe liver injury difficult:
At this time, 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. The agency is also working with the manufacturer of Alli to ensure that consumers can understand this new warning
- <LI style="MARGIN-LEFT: 20px">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. <LI style="MARGIN-LEFT: 20px">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.
Additional Information for Patients and Consumers
Additional Information for Healthcare Professionals
- Be aware that cases of severe liver injury have been reported rarely in people taking Xenical and Alli.
- Contact your healthcare professional if you develop itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools. These may be signs of liver injury.
- Talk to your healthcare professional about any concerns you have with these medications.
- Report any side effects with Xenical or Alli to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.
- Be aware that postmarketing cases of severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported rarely in people using Xenical and Alli. Some of these cases resulted in liver transplant or death.
- Weigh the benefits of weight-loss with Xenical and Alli against the potential risks when determining if these medications are appropriate for patients.
- Instruct patients to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light colored stools, or right upper quadrant pain) when using these medications.
- If liver injury is suspected, orlistat and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained.
- Report any adverse events with Xenical or Alli to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.
The decision to include information about severe liver injury in the drug label for Xenical and Alli is based on FDA's comprehensive review of all available data (pre-clinical, clinical trial, postmarketing, and drug utilization) on severe liver injury associated with Xenical through August 7, 2009, and a review of postmarket data on Alli through October 1, 2008. There were no signals of significant liver injury in either the pre-clinical studies or clinical trials data.
FDA identified 12 postmarketing cases of severe liver injury reported with the use of 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.
Of the 13 cases:
- <LI style="MARGIN-LEFT: 20px">Twelve were foreign reports of severe liver injury with Xenical. <LI style="MARGIN-LEFT: 20px">One was a U.S. report of severe liver injury with Alli. <LI style="MARGIN-LEFT: 20px">Two patients died from liver failure.
- Three patients required liver transplantation.