The UK Medicines and Healthcare products Regulatory Agency (MHRA) has announced the withdrawal of pholcodine-containing cough and cold medicines from the UK market as a precautionary measure.
Dr Fiona Donald, President of the Royal College of Anaesthetists, said:
“Our National Audit Project has previously highlighted the possible link between pholcodine and severe allergic reactions (anaphylaxis) to some drugs used in anaesthesia.
“The MHRA has now reviewed the evidence and concluded that patients who have recently taken medicines containing pholcodine have a slightly increased risk of anaphylaxis when receiving neuromuscular blocking agents, commonly used in anaesthesia. As a result, the MHRA has taken the precautionary measure of withdrawing ‘over the counter’ cough medicines containing pholcodine.
“While we fully support this precautionary measure, it is also important to reassure patients that the risk of anaphylaxis when having any type of anaesthetic is very low – around 1 in every 10,000 cases1. Patients should tell their anaesthetist before they have surgery if they have taken medicines containing pholcodine, but should not worry if they can’t remember, or are unsure.”
1 The RCoA National Audit Project (2018) we reference is useful context and it’s where the 1 in 10,000 figure comes from: https://www.niaa.org.uk/NAP6Report?newsid=1914#pt. That figure is for any type of anaphylaxis – not those linked to pholcodine.
Prof Penny Ward, independent pharmaceutical physician, and Visiting Professor in Pharmaceutical Medicine at King’s College London, said:
“MHRA have today advised that cough medicines containing pholcodine should be taken off the market due to a very small (<1:10,000) but clear risk that people that have taken cough medicines containing this medicine might suffer a serious allergic reaction (anaphylaxis) if they need to have a general anaesthetic including a muscle relaxant within 12 months of having taken the cough medicine.
“The decision to withdraw these medicines was taken following the release of data from the ALPHO study, a case control study which conducted in France. This study found that people that had taken a pholcodine containing medicine within 12 months prior to a general anaesthetic including a muscle relaxant were 4 times more likely to experience a serious allergic reaction to the muscle relaxant used than people that had not taken a medicine containing pholcodine (pre-publication Pholcodine consumption increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study | medRxiv).
“MHRA have come to this decision because there is no clear method which can be used to decrease the very small – but potentially life threatening – risk of serious allergic reactions among patients receiving a muscle relaxing treatment during a general anaesthetic other than by removing the medicine from the market. Although pholcodine is effective in suppressing cough, most illnesses causing coughs will recover, even if not treated, within 1-2 weeks and other medicines which can sooth cough are available if needed. Coughs and colds are common illnesses and although people who know they might need a general anaesthetic for a planned surgical procedure could avoid using pholcodine containing medicines, because the risk lasts for a very long time – 12 to 36 months after exposure – and also because surgery requiring use of a muscle relaxant might be needed in an emergency – appendicitis for example – it is not easy to reduce this risk simply by warning people about it. Indeed, the risk has been known about and information has been included in the prescribing information for more than 10 years. Following pholcodine containing medicines being removed from the market in Norway the risk of serious allergic reactions to muscle relaxants given during a general anaesthetic fell very markedly (Florvaag et al. Allergy. 2011; 66: 955-60. doi: 10.1111/j.1398-9995.2010.02518.x.).
“For all these reasons, MHRA has decided that taking these medicines off the market completely is preferable.
“It should be emphasized that this risk is very small – less than 1/10,000 people given a muscle relaxant during a general anesthetic would experience the reaction – but it can be life threatening if it occurs.
“Pholcodine containing medicines are otherwise well tolerated by the many thousands of adults and children that have taken them.
“Anyone that has any cough or cold remedies in their medicine cupboard should check to see if any contain pholcodine and if so get rid of them. Anyone that has taken a cough or cold remedy recently and is going to have a general anaesthetic should tell the doctor/nurse that they might have taken pholcodine – this also applies if the cough medicine was taken anytime within 12 months prior to an anaesthetic procedure in the future.”
Prof Claire Anderson, President of the Royal Pharmaceutical Society (RPS), said:
“All products containing the cough suppressant pholcodine have been withdrawn due to concerns of its potential to cause a severe allergic reaction in some people having general anaesthesia for surgery.
“If you are taking a cough medicine (including tablets and syrups), check the packaging, label or Patient Information Leaflet to see if pholcodine is a listed ingredient – if it is, and you have any questions, you can talk to your pharmacist who can suggest a different medicine suitable for you.
“The risk to patients who have used pholcodine is very small. If you are due to have surgery, please speak to your pharmacist or medical team for advice.
“A cough usually clears up within 3-4 weeks. You can treat it with other cough medicines or hot lemon and honey (not suitable for babies under 1 year old). Rest up if possible and you can try paracetamol or ibuprofen, if suitable, to treat any pain. If your cough persists for longer than 3-4 weeks seek advice from a healthcare professional.
“This withdrawal is needed as safety of patients is paramount and we support efforts to ensure that all medicines on the market are safe and effective.”
Dr Fiona Donald has no conflicts of interest. Her only registered interests are that in addition to being RCoA President she is also Vice-Chair of the Academy of Medical Royal Colleges and a member of the BMA. We have a bio on our website.
Prof Penny Ward: “No COIs of which I am aware.”
Prof Claire Anderson has no declaration of interest to make.