Agomelatine (Valdoxan): risk of liver toxicity

Reminder to test liver function before and during treatment.

Article date: November 2014

Agomelatine (Valdoxan) is a melatonergic antidepressant used to treat major depression in adults.

Liver toxicity is a side effect of agomelatine (see Drug Safety Update article from October 2012).

A recent European review revealed poor clinical compliance with recommended liver function monitoring. We therefore remind you to test liver function before starting agomelatine and regularly during treatment (see below).

We are working with the licence-holder to produce a booklet for prescribers to give to patients when prescribing agomelatine. This will inform patients of the risk of liver injury, the symptoms and signs to look out for, and the importance of regular blood tests.

We also remind you that the efficacy of agomelatine has not been established in patients over 75 years. Agomelatine is not recommended in this age-group.

Advice for healthcare professionals:

  • Perform baseline liver function tests in every patient before starting treatment with agomelatine.
  • Do not start treatment if serum transaminases exceed three times the upper limit of normal.
  • Monitor liver function at 3, 6, 12, and 24 weeks after starting treatment and regularly thereafter when clinically indicated.
  • Stop treatment immediately if serum transaminases exceed three times the upper limit of normal, or if patients have symptoms or signs of suspected liver injury.
  • Tell patients to watch out for the symptoms and signs of liver injury (eg, jaundice, dark urine, bruising). Explain the importance of regular liver function monitoring.
  • Advise patients to stop taking agomelatine and to get medical help immediately if they have any signs or symptoms of liver injury.

Please report any suspected cases of liver toxicity or other side effects via the Yellow Card Scheme (

Further information

European Medicines Agency press release, September 2014

Article citation: Drug Safety Update volume 8 issue 4, November 2014: A1

Published 11 December 2014