The MHRA has withdrawn pholcodine-containing cough and cold medicines from the UK market as a precautionary measure due to concerns of the potential to cause a severe allergic reaction in some people having general anaesthesia for surgery.
Pholcodine is an opioid medicine approved in adults and children older than 6 years of age to treat non-productive cough and, in combination with other active substances, for the treatment of symptoms of cold and influenza. It has been used as a cough suppressant since the 1950s. Pholcodine-containing products had only been available in the UK for purchase in a pharmacy.
The Medicines and Healthcare products Regulatory Agency (MHRA) said that previous reviews had examined the link between prior use of pholcodine and an "increased risk of anaphylaxis" during general anaesthesia involving neuromuscular blocking agents. "The potential for cross-reactivity between pholcodine and neuromuscular blocking agents was added to the product information for pholcodine-containing medicines in January 2022," the agency said.
A spokesperson for the PAGB commented that: "The link between pholcodine-containing medicinal products and neuromuscular blocking agents has been under investigation for a number of years − it is a known risk."
In their latest review the MHRA considered the cumulative safety information, including the results from a recent study which showed that use of pholcodine during the twelve months preceding anaesthesia was significantly associated with an increased risk (adjusted odds ratio of 4.2) of peri-anaesthetic anaphylaxis to neuromuscular blocking agents.
Risk is Extremely Small
The Commission on Human Medicines (CHM) advised that there is "sufficient overall evidence" for an association with pholcodine, but emphasised that "the absolute risk of anaphylaxis remains very small in patients who have taken pholcodine".
The MHRA pointed out that incidence of anaphylaxis following use of neuromuscular blocking agents was estimated as being "fewer than 1 case per 10,000 procedures".
However, given the advice of the CHM, and the lack of identifiable effective measures to minimise the increased risk of anaphylactic reactions to neuromuscular blocking agents, “pholcodine-containing products are being withdrawn from the market as a precaution”, an MHRA spokesperson said.
Asked to comment for Medscape News UK, PAGB chief executive, Michelle Riddalls, said: "The risk in people who have used pholcodine is extremely small and the MHRA has taken this decision as a precaution."
The MHRA scientific review took place alongside a review conducted by the European Medicines Agency (EMA), which also concluded, in December 2022, that the benefits did not outweigh the risks and recommended the "revocation of the EU marketing authorisations for these medicines".
Robust Safety Measures
The MHRA advised healthcare professionals to ask patients scheduled to undergo general anaesthesia involving neuromuscular blocking agents whether they had used pholcodine-containing medicines - particularly in the past 12 months - and to maintain awareness about the potential for peri-anaesthetic anaphylaxis related to neuromuscular blocking agents.
Dr Fiona Donald, president of the Royal College of Anaesthetists, advised that "patients should tell their anaesthetist before they have surgery if they have taken medicines containing pholcodine," but reassured that patients "should not worry if
they can't remember, or are unsure".
Healthcare professionals were also advised not to dispense or sell pholcodine-containing medicines, and to consider appropriate treatment alternatives for patients who presented with a new dry cough or who were currently taking pholcodine.
Dr Leyla Hannbeck, from the Association of Independent Multiple Pharmacies, told the BBC that it was a "big operation" to remove the products from pharmacy shelves, and advised patients with coughs and colds to contact their local pharmacy for advice.
"The risk to patients who have used pholcodine is very small," reiterated Royal Pharmaceutical Society President Professor Claire Anderson, She added that those due to have surgery should seek advice from their pharmacist or medical team.
Ms Riddalls trumpeted that the precautionary measure was an example of the "robust safety measures that we have in place in the UK working effectively".