Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2019

News 17/05/2019

Restrictions in use of Xeljanz while PRAC reviews risk of blood clots in lungs

EMA’s safety committee (PRAC) has started a new review of Xeljanz (tofacitinib) and has recommended, as a temporary measure during the review, that doctors must not prescribe the 10 mg twice-daily dose of this medicine in patients who are at high risk of blood clots in the lungs. These include patients who have heart failure, cancer, inherited blood clotting disorders or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy or are undergoing major surgery.

The PRAC’s recommendation follows results from an ongoing study in patients with rheumatoid arthritis, which showed an increased risk of blood clots in the lungs and death when the 10 mg twice daily dose was used.

The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded.

More information is available below.

PRAC recommends withdrawal of marketing authorisations for fenspiride medicines

The PRAC has recommended that the marketing authorisations for cough medicines containing fenspiride be revoked, so they can no longer be marketed in the European Union. This follows a review that has confirmed that fenspiride medicines could cause heart rhythm problems.

In its review, the PRAC considered all the available evidence, such as cases of QT prolongation and torsades de pointes (abnormalities of the heart’s electrical activity that may lead to heart rhythm disturbances) in patients using these medicines, results of laboratory studies, data from published literature and stakeholder input.

Healthcare professionals should no longer prescribe fenspiride medicines and should advise their patients to stop taking them. Patients are advised to stop taking these medicines and contact their doctor or pharmacist for advice on alternative treatments, if needed.  

More information is available below.

Monthly statistical overview of PRAC activity to be published on EMA’s website

From now onwards, a monthly infographic of PRAC’s activity will be published on EMA’s website. The infographic presents the total number of procedures discussed during each PRAC meeting, as captured and detailed in the meeting agenda. The PRAC’s broad range of responsibilities cover all aspects of the risk management of medicines throughout their lifecycle: assessment of signals, periodic safety update reports, risk management plans, post-authorisation safety studies and referrals. These terms are explained below:

  • Safety signal assessments. A safety signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under 'Signal management'.
  • Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances, but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under 'Periodic safety update reports: questions and answers'.
  • Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under 'Risk-management plans'.
  • Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under 'Post-authorisation safety studies'.
  • Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under referral procedures.

Over 1,500 studies now recorded in EU register of post-authorisation studies

The 1,500th study has been uploaded in the EU electronic Register of Post-Authorisation Studies (EU PAS Register).

The EU PAS Register provides a wealth of information on the safety and effectiveness of authorised medicines. It is an openly accessible platform with information on post authorisation research in medicines already marketed in Europe and includes study protocols, study results, related publications and other relevant information.

The information in the EU PAS Register helps to reduce publication bias (when a study outcome influences the decision whether to publish or otherwise distribute it) through increased transparency of medicines research, improves the quality of post-authorisation studies by facilitating peer-review of protocols and results, facilitates collaboration among stakeholders, and ensures compliance with EU pharmacovigilance legislation requirements.

The EU PAS Register was developed through the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), which is coordinated by EMA to support research in pharmacoepidemiology and pharmacovigilance.

PRAC statistics: May 2019

PRAC highlights May figures

Start of referral - Article 31 referral

Ongoing referrals




Article-31 procedure: Estradiol-containing (0.01% w/w) medicinal products for topical use

Under evaluation

PRAC continued its assessment

Article-31 procedure: Fluorouracil and fluorouracil related substances (capecitabine, tegafur and flucytosine) containing medicinal products

Under evaluation

PRAC continued its assessment

Article-20 procedure: Lemtrada

Under evaluation

PRAC continued its assessment

Article-31 procedure: Methotrexate containing medicinal products

Under evaluation

PRAC adopted a list of outstanding issues

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