Dear Healthcare professional Letter about the new contraindication and reminder for monitoring liver function when using agomelatine (Valdoxan/Thymanax 25 mg film-coated tablets
Servier Pharma d.o.o., the marketing authorisation holder for medicinal products Valdoxan 25 mg film-coated tablets and Thymanex 25 mg film-coated tablets (agomelatine) is, in collaboration with the Agency for Medicinal Products and Medical Devices (HALMED) sending a letter to healthcare professionals to inform them about the introduction of a new contraindication and to remind them for a need for liver function monitoring with the use of agomelatine.
- Liver injuries, including hepatic failure resulting in death or liver transplantation in agomelatine-treated patients with hepatic risk factors.
- Agomelatine is contraindicated in in patients with transaminase levels > 3 times the upper limit of normal.
- Prescribers are reminded to perform liver function tests in all patients receiving agomelatine and to discontinue the agomelatine treatment if a patient has symptoms or signs of liver injury.
- Patients must be informed about the symptoms of liver injury and advised to stop taking agomelatine immediately and seek urgent medical advice if these symptoms appear.
- Efficacy and safety of agomelatine (25-50 mg/day) are confirmed in elderly patients with depression (< 75 years). In patients ≥ 75 years there is no confirmed significant impact and agomelatine should not be used in patients ≥ 75 years.
Liver function tests
Prescribers are reminded to perform liver function tests in all patients receiving agomelatine:
- at start of treatment
- periodically after 3 weeks and 6 weeks (end of acute phase), and after 12 weeks and 24 weeks (end of maintenance phase)
- at the same time intervals as above when increasing the dose of agomelatine, as well as when introducing the medicine
- whenever clinically indicated
In any patient who develops increased serum transaminase levels liver function tests must be repeated within 48 hours. Prescribers are also reminded that the use of agomelatine is contraindicated in patients with liver injury (cirrhosis or active liver disease).
The use of agomelatine is indicated in the treatment of large depressive episodes in adults. The risk of increased transaminase level in patients using agomelatine has been known from the approval of the medicine in Europe in 2009. Information about the hepatotoxic effects of agomelatine are included in the summary of product characteristics and package leaflet. The marketing authorisation holder sent a letter in January this year to healthcare professionals in cases of severe liver injuries associated with use of agomelatine and the importance of liver function monitoring was emphasised during agomelatine treatment, which you can read about here.
The European Medicines Agency (EMA) has estimated that in the EU Member States the recommendations indicated in the summary of product information and package leaflet (liver function monitoring, risk factors leading to liver injuries) were not strictly taken into consideration, due to which EMA concludes that the benefits of agomelatine outweigh the risks if additional measures of risk minimisation are introduced (introduction of the above new contraindication and Dear Healthcare Professional Letter).
Here you can view the Dear Healthcare Professional Letter (in Croatian).
HALMED has not received any adverse reaction report to agomelatine associated with a liver side-effect. HALMED will continue to monitor the safe use of these medicines and inform the public promptly about any new information.
We remind healthcare professionals that they should report any adverse reaction to HALMED, as well as quality defect. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult with their doctor or pharmacist about the continuation of their therapy.