The Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its regular benefit-risk assessment (known as a periodic safety update report or PSUR) of Valdoxan/Thymanax (agomelatine), two identical medicines used to treat major depression in adults.

As part of this assessment, the PRAC looked at cumulative data on severe side effects on the liver with Valdoxan/Thymanax and recommended further measures to minimise this risk, particularly in vulnerable populations.

The PRAC recommended that the warnings in the product information regarding liver injury be strengthened to further clarify that liver function tests should be performed before and regularly during treatment. As patients aged 75 years and above may be at an increased risk of severe side effects on the liver and beneficial effects have not been documented in these patients, the Committee recommended that Valdoxan/Thymanax should now be contraindicated in patients aged 75 and above. The Committee further recommended that a letter be sent to healthcare professionals to inform them of these changes.

The PRAC recommendations will now be forwarded to the Committee for Medicinal Products for Human Use (CHMP) which will issue the Agency’s final opinion with clear guidance to patients and healthcare professionals at its next meeting of 22-25 September 2014.

The PRAC was established in July 2012. Over its first two years the Committee’s central role in patient safety has been demonstrated.

Proactivity in pharmacovigilance is key, and as such, risk management planning constitutes an important part of the PRAC’s work. The Committee assesses risk-management plans (RMPs), submitted by companies before a medicine can be authorised. These include measures to be taken in order to prevent or minimise the medicine's risks in patients and are regularly updated as new information becomes available. It also looks at the design and results of post-authorisation safety studies of authorised medicines, which are carried out to obtain further information on their safety. In its first two years the Committee conducted more than 600 reviews of risk management plans and 150 reviews of protocols for post-authorisation safety studies.

Overseeing the safety of a medicine once it is used to treat patients in the European Union (EU)  is a core task of the PRAC. The Committee evaluates periodic safety update reports (PSURs) to re-assess the benefit-risk balance of a medicine throughout its lifecycle on the basis of new data collected. More than 650 PSUR reviews have been carried out by the PRAC since it was established.

Another important part of the PRAC’s work is the Committee’s involvement in referral procedures. Referrals are started because of concerns over the safety or the benefit-risk balance of a medicine or a class of medicines. In such procedures, the PRAC evaluates all available data to make a recommendation for a harmonised position across the EU on whether marketing authorisations should be maintained, varied, suspended or withdrawn. Over the last two years, following triggers from Member States and the European Commission, the Committee has started 31 referrals to assess safety concerns of medicines, and issued 23 recommendations on their safe and effective use.

The assessment and management of safety signals is also a key pharmacovigilance function performed by the PRAC. A safety signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. In its first two years of operation, 163 signals have been managed by the Committee, the majority resulting in recommendations for changes to product information for patients and healthcare professionals.

The EMA has launched a public consultation on draft rules of procedures for public hearings to be held by the PRAC. Comments are invited until 15 October 2014 and should be sent to public-hearings@ema.europa.eu using the comments submission form.

The rules of procedures describe the process and practical arrangements for the preparation, conduct and follow-up of public hearings.

Public hearings are a new tool for the EMA to engage EU citizens in the regulatory process of the supervision of medicines and to listen to their views and experiences. The contributions made by the public during a public hearing will be considered by the PRAC and inform the Committee’s decision-making.