Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 November - 1 December 2022

EMA recommends withdrawal of pholcodine medicines from EU market

EMA’s safety committee, PRAC, has concluded its review of medicines containing pholcodine, which are used in adults and children to treat non-productive (dry) cough and, in combination with other active substances, for the treatment of symptoms of cold and flu, and has recommended the revocation of the EU marketing authorisations for these medicines.

During the review, the PRAC evaluated all available evidence including the final results of the ALPHO study,¹ post-marketing safety data and information submitted by third parties such as healthcare professionals. The available data showed that use of pholcodine in the 12 months before general anaesthesia with neuromuscular blocking agents (NMBA) is a risk factor for developing an anaphylactic reaction (a sudden, severe and life-threatening allergic reaction) to NMBAs.

As it was not possible to identify effective measures to minimise this risk, nor to identify a patient population for whom the benefits of pholcodine outweigh its risks, pholcodine-containing medicines are being withdrawn from the EU market and will therefore no longer be available by prescription or over the counter.

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

Publication of COVID-19 vaccines safety updates to cease in December 2022

The wide uptake of COVID-19 vaccines has led to a rapid accumulation of extensive safety data from spontaneous reports of suspected side effects.

Since the first vaccines were authorised in December 2020, EMA has regularly provided information on the PRAC’s assessment of these reports, as well as data from other sources, through dedicated monthly safety updates. The majority of the EU population has now received at least one COVID-19 vaccine, and data from clinical trials, other studies and spontaneous reporting have established the safety profile of these vaccines. Therefore, the publication of the monthly updates will cease with the December 2022 issue.

As for all medicines authorised in the EU, emerging safety data will continue to be monitored and assessed.

From January 2023, relevant changes to the product information of COVID-19 vaccines will be communicated via the PRAC highlights. Dedicated public health communications may also be issued, if needed.

Information on the identified side effects for each vaccine is included in the product information, available in all European Union/European Economic Area languages on EMA’s corporate website. High-level information on suspected adverse reaction reports will continue to be updated monthly on EMA’s webpage on COVID-19 vaccines safety. The centralised European database of suspected adverse reactions to medicines - EudraVigilance - will continue to be updated weekly.

New safety information for healthcare professionals

As part of its advice on safety-related aspects to other EMA committees, the PRAC discussed a direct healthcare professional communication (DHPC) containing important information on pholcodine medicines.

Pholcodine medicines no longer available in the EU

This DHPC will inform healthcare professionals of EMA’s recommendation to revoke the EU marketing authorisation for pholcodine-containing medicines.

Healthcare professionals should re-evaluate their patients, consider other treatment alternatives, and advise patients to stop using pholcodine-containing medicinal products.

In case of anaesthesia requiring administration of neuromuscular blocking agents (NMBAs), healthcare professionals should check whether patients have used pholcodine-containing medicinal products in the last 12 months and, if so, maintain awareness of potential anaphylactic reactions to NMBAs.

The DHPC for pholcodine medicines will be forwarded to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). When adopted, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on the ‘Direct healthcare professional communications’ page and in national registers in EU Member States.

¹ Companies marketing pholcodine medicines were requested to conduct the ALPHO study following a previous safety review conducted in 2011.

• 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.