EMA recommends withdrawal of pholcodine medicines from EU market
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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a patient population for whom the benefits of pholcodine outweigh its risks, pholcodine-containing medicines are being withdrawn from the EU market and will therefore no longer be available by prescription or over-the-counter.
Healthcare professionals should consider appropriate treatment alternatives and advise patients to stop taking pholcodine-containing medicines. Healthcare professionals should also check whether patients scheduled to undergo general anaesthesia with NMBAs have used pholcodine in the previous 12 months, and remain aware of the risk of anaphylactic reactions in these patients.
The PRAC recommendations will now be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)2 for consideration at its next meeting in December 2022.
A direct healthcare professional communication (DHPC) including the above recommendations will be sent in due course to healthcare professionals prescribing, dispensing or administering these medicines. The DHPC will also be published on a dedicated page on the EMA website.
Pholcodine is an opioid medicine that is used in adults and children for the treatment of non-productive (dry) cough and, in combination with other active substances, for the treatment of symptoms of cold and flu. It works directly in the brain, depressing the cough reflex by reducing the nerve signals that are sent to the muscles involved in coughing.
Pholcodine has been used as a cough suppressant since the 1950s. In the EU, pholcodine-containing medicines are currently authorised in Belgium, Croatia, France, Ireland, Lithuania, Luxembourg and Slovenia, either subject to medical prescription or as over-the-counter medicines. They often contain pholcodine in combination with other substances and are available as syrups, oral solutions, and capsules under various trade names and as generics. Pholcodine is marketed under various names including Dimetane, Biocalyptol and Broncalene.
The review of pholcodine was initiated on 1 September 2022 at the request of France, under Article 107i of Directive 2001/83/EC.
The review has been carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which has made a set of recommendations. The PRAC recommendations will now be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.
1 Companies marketing pholcodine medicines were requested to conduct the ALPHO study following a previous safety review conducted in 2011.
2 The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.