Valdoxan

agomelatine

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This is a summary of the European public assessment report (EPAR) for Valdoxan. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Valdoxan.

What is Valdoxan?

Valdoxan is a medicine that contains the active substance agomelatine. It is available as tablets (25 mg).

What is Valdoxan used for?

Valdoxan is used to treat major depression in adults below 75 years of age. Major depression is a condition in which patients have mood disturbances that interfere with their everyday life. Symptoms often include deep sadness, feelings of worthlessness, loss of interest in favourite activities, sleep disturbances, a feeling of being slowed down, feelings of anxiety and changes in weight.

The medicine can only be obtained with a prescription.

How is Valdoxan used?

The recommended dose of Valdoxan is one tablet once a day, taken at bedtime. If there is no improvement in symptoms after two weeks, the doctor may increase the dose to two tablets taken together at bedtime. Patients with depression should be treated for at least six months to make sure that they are free of symptoms.

The patient’s liver should be checked with blood tests when treatment starts and when the dose is increased, followed by further tests around three, six, 12 and 24 weeks later. The liver should also be checked if the patient develops symptoms that could indicate liver problems. Treatment should be interrupted in patients with abnormal liver enzyme levels in the blood. Blood tests should then be repeated regularly until the liver enzymes have returned to normal levels.

How does Valdoxan work?

The active substance in Valdoxan, agomelatine, is an antidepressant. It works in two ways, by stimulating the MT1 and MT2 receptors, which are normally activated by melatonin, and also by blocking the 5-HT2C receptors, which are normally activated by the neurotransmitter 5‑hydroxytryptamine (also called serotonin). This is thought to lead to increases in the levels of dopamine and noradrenaline between nerve cells in the areas of the brain that are involved in the control of mood. This is believed to help relieve the symptoms of depression. Valdoxan might also help to normalise the patient’s sleep patterns.

How has Valdoxan been studied?

Valdoxan has been compared with placebo (a dummy treatment) in five main short-term studies involving a total of 1,893 adults with major depression. Three of these studies included some patients treated with other antidepressants, either fluoxetine or paroxetine, as an ‘active comparator’. The active comparator groups were included to check that the study was able to measure the effectiveness of medicines in treating depression. The main measure of effectiveness in these five studies was the change in symptoms after six weeks, as measured on a standard scale for depression called the Hamilton Depression Rating Scale (HAM D). The company also presented the results of a further study comparing Valdoxan with sertraline (another antidepressant).

Two other main studies compared the ability of Valdoxan and placebo to prevent symptoms returning in 706 patients whose depression had already been controlled with Valdoxan. The main measure of effectiveness was the number of patients whose symptoms returned during 24 to 26 weeks of treatment.

What benefit has Valdoxan shown during the studies?

In the short-term studies, Valdoxan was seen to be more effective than placebo in the two studies where no active comparator was used. In the other three studies, which did include an active comparator, there were no differences in scores between the patients taking Valdoxan and those taking placebo. However, no effect of fluoxetine or paroxetine was seen in two of these studies, making the results difficult to interpret. The additional study showed that agomelatine was more effective than sertraline, with a difference in HAM D scores of 1.68 after six weeks.

In the first of the long-term studies, there was no difference between Valdoxan and placebo in preventing symptoms from returning during 26 weeks of treatment. However, the second study showed that symptoms returned in 21% of the patients taking Valdoxan over 24 weeks (34 out of 165), compared with 41% of the patients taking placebo (72 out of 174).

What is the risk associated with Valdoxan?

The most common side effects with Valdoxan (seen in between 1 and 10 patients in 100) are headache, dizziness, somnolence (sleepiness), insomnia (difficulty sleeping), migraine, nausea (feeling sick), diarrhoea, constipation, abdominal pain (stomach ache), vomiting, hyperhidrosis (excessive sweating), back pain, fatigue (tiredness), increases in liver enzymes and anxiety. Most side effects were mild or moderate in intensity, happened within the first two weeks of treatment and were temporary. For the full list of all side effects reported with Valdoxan, see the package leaflet.

Valdoxan must not be used in patients who have problems with their liver, such as cirrhosis (scarring of the liver) or active liver disease, nor in patients whose level of transaminases (liver enzymes) in the blood is more than three times the normal level. It must also not be used in patients who are taking medicines that slow down the breakdown of Valdoxan in the body, such as fluvoxamine (another antidepressant) and ciprofloxacin (an antibiotic). For the full list of restrictions, see the package leaflet.

Why has Valdoxan been approved?

The CHMP noted that Valdoxan’s benefits in terms of treating depression might be lower than seen with other antidepressants. However, since the medicine has a different mode of action, few side effects and a different safety profile to existing antidepressants, the Committee concluded that Valdoxan could be a valuable treatment for some patients as long as their liver function is tested frequently. Therefore, the CHMP decided that Valdoxan’s benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe use of Valdoxan?

A risk management plan has been developed to ensure that Valdoxan is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Valdoxan, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that makes Valdoxan will supply educational material for doctors prescribing Valdoxan. This material explains the safety of the medicine, its interactions with other medicines, and includes guidance on the monitoring of liver function and management of possible symptoms of liver problems.

Other information about Valdoxan

The European Commission granted a marketing authorisation valid throughout the European Union for Valdoxan on 19 February 2009.

For more information about treatment with Valdoxan read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Name Language First published Last updated
Valdoxan : EPAR - Summary for the public BG = bălgarski 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public ES = español 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public CS = čeština 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public DA = dansk 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public DE = Deutsch 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public ET = eesti keel 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public EL = elliniká 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public EN = English 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public FR = français 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public IT = italiano 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public LV = latviešu valoda 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public LT = lietuvių kalba 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public HU = magyar 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public MT = Malti 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public NL = Nederlands 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public PL = polski 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public PT = português 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public RO = română 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public SK = slovenčina 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public SL = slovenščina 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public FI = suomi 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public SV = svenska 17/03/2009 10/12/2013
Valdoxan : EPAR - Summary for the public HR = Hrvatski 17/03/2009 10/12/2013

This EPAR was last updated on 10/12/2013 .

Authorisation details

Product details

Product details for Valdoxan
NameValdoxan
Agency product numberEMEA/H/C/000915
Active substance

agomelatine

International non-proprietary name (INN) or common name

agomelatine

Therapeutic area Depressive Disorder, Major
Anatomical therapeutic chemical (ATC) code N06AX22

Publication details

Publication details for Valdoxan
Marketing-authorisation holder

Les Laboratoires Servier

Revision11
Date of issue of marketing authorisation valid throughout the European Union19/02/2009

Contact address:

Les Laboratoires Servier
50, rue Carnot
F-92284 Suresnes Cedex
France

Product information

Product information

13/11/2013  Valdoxan -EMEA/H/C/000915 -R/0017

Name Language First published Last updated
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013
Valdoxan : EPAR - Product Information HR = Hrvatski 17/03/2009 10/12/2013

Contents

  • Annex I - Summary of product characteristics
  • Annex IIA - Manufacturing-authorisation holder responsible for batch release
  • Annex IIB - Conditions of the marketing authorisation
  • Annex IIIA - Labelling
  • Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.


Name Language First published Last updated
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  
Valdoxan : EPAR - All Authorised presentations HR = Hrvatski 17/03/2009  

Pharmacotherapeutic group

Psychoanaleptics

Therapeutic indication

Treatment of major depressive episodes in adults.

Assessment History

Changes since initial authorisation of medicine

Initial marketing-authorisation documents

Name Language First published Last updated
Valdoxan : EPAR - Public assessment report HR = Hrvatski 17/03/2009  
Committee for medicinal products for human use, summary of positive opinion for Valdoxan HR = Hrvatski 20/11/2008  

Authorised

This medicine is approved for use in the European Union