Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 29 August – 1 September 2022

News 02/09/2022

PRAC starts review of topiramate use in pregnancy and women of childbearing potential

EMA’s safety committee (PRAC) has started a review of topiramate and the risk of neurodevelopmental disorders in children whose mothers were taking topiramate during pregnancy.

Topiramate is a medicine used in the European Union (EU) for the treatment of epilepsy, prevention of migraine and, in some countries, in combination with phentermine for body weight reduction.

Use of topiramate in pregnant women is known to increase the risk of birth defects. Women with epilepsy who are being treated with topiramate for their seizures are advised to avoid becoming pregnant, and to consult their doctor for advice if they wish to become pregnant. Topiramate must not be used to prevent migraine or control body weight in pregnant women and in women of childbearing potential (women able to have children) who are not using highly effective birth control methods (contraception).

The review was triggered by a recent study1 which suggested a possible increase in the risk of neurodevelopmental disorders, in particular autism spectrum disorders and intellectual disability, in children whose mothers were taking topiramate during pregnancy.  

The PRAC started reviewing the study results as part of a safety signal assessment in July 2022. The committee will now conduct an in-depth review of the available data on the benefits and risks of topiramate use in pregnant women and women of childbearing potential in the approved indications. The committee will look in particular at the current risk minimisation measures and consider the need for additional measures to minimise the risks of topiramate use in these women.

While the review is ongoing, topiramate should continue to be used according to the authorised product information. Women should discuss any questions or concerns about their topiramate treatment with their doctor or pharmacist. Patients should not stop antiepileptic treatment before speaking with their doctor.

EMA will communicate the PRAC’s recommendation once the review has concluded.

More information is available in EMA’s public health communication.


PRAC: Review of pholcodine medicines started

EMA has started a review of medicines that contain pholcodine following concerns that their use may put people at risk of developing anaphylactic reactions (a sudden, severe and life-threatening allergic reaction) to certain medicines called neuromuscular blocking agents (NMBA).

Pholcodine is used to treat non-productive (dry) cough in adults and children and NMBAs are used in general anaesthesia to prevent spontaneous muscle movements to improve operating conditions.

The review was requested by the French medicines agency (ANSM) following preliminary results of a study carried out in France2. The results of the study suggested that taking pholcodine up to 12 months before general anaesthesia may increase the risk of having an NMBA-related anaphylactic reaction. Based on these results ANSM is considering, as a precautionary measure, to suspend the use of pholcodine-containing medicines in France.

The PRAC will now review the results of the ALPHO study together with all available data and assess their impact on the benefit-risk balance of pholcodine-containing medicines and issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.

More information is available in EMA’s public health communication.

1 Bjørk M, Zoega H, Leinonen MK, et al. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA Neurol. Published online May 31, 2022. doi:10.1001/jamaneurol.2022.1269.

2 Allergy to Neuromuscular Blocking Agents and Pholcodine Exposure (ALPHO)

PRAC statistics: September 2022

PRAC statistics: June 2022


  • Safety signal assessments. A safety signal is information which suggests a new potentially causal association, or a new aspect of a known association between a medicine and an adverse event that warrants further investigation. Safety 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.
  • Summary safety reports have been introduced as part of the enhanced safety monitoring of COVID-19 vaccines. Marketing authorisation holders are required to submit these reports to EMA, starting on a monthly basis. Their submission complements the submission of PSURs. For more information see EMA’s pharmacovigilance plan for COVID-19 vaccines

Ongoing referrals




Janus Kinase inhibitors (JAKi) – Article 20 ReferralUnder evaluationPRAC continued its assessment
Terlipressin-containing medicinal productsUnder evaluationPRAC continued its assessment
Amfepramone-containing medicinal productsUnder re-evaluationPRAC started re-examination

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