2001-74
July 9, 2001

Advisory
Risk of severe liver injury associated with use of the antidepressant Nefazodone

OTTAWA - Health Canada is advising consumers to be aware of new safety information concerning nefazodone, a medication sold in Canada under the following trade names: SERZONE®, LIN-NEFAZODONE® and APO-NEFAZODONE®. Nefazodone is one of a large group of medications prescribed for the treatment of depression.

Nefazodone has been available in Canada since 1994. Over the course of worldwide post-marketing drug use, nefazodone has been associated with case reports of jaundice (yellow discoloration of the skin or eyes), hepatitis (inflammation of the liver), and liver failure which have, on occasion, resulted in hospitalization, liver transplantation or death.

Nefazodone was not associated with liver failure, liver transplant, or death due to possible hepatic problems in the clinical trials which formed the basis for approval of this product. To date, of the estimated 650,000 patients treated with nefazodone in Canada, four cases of liver failure have been reported to Health Canada, of which two required liver transplantation. Health Canada is not aware of any fatal events of liver failure associated with the use of this drug in Canada.

It is not possible to predict which patients will experience these liver complications. Patients receiving nefazodone are encouraged to contact their physicians to discuss the signs and symptoms of possible liver dysfunction. Patients may also wish to discuss with their physicians the possible need for laboratory tests for monitoring liver function.

A health care professional letter has been sent by the drug manufacturers to Canadian physicians and pharmacists to inform them of this new safety information and enable them to counsel patients.

Patients are advised to contact their physicians before discontinuing any medication. However, patients should stop taking nefazodone and seek immediate medical attention if they develop the following signs:

• jaundice (yellowing of the skin or whites of the eye), or
• brown urine.

Patients taking nefazodone who are experiencing symptoms suggesting possible liver damage should contact a physician right away. Such symptoms include:

• nausea
• vomiting
• unusual tiredness
• weakness
• stomach or abdominal pain, and /or
• loss of appetite.