Of the 55 pholcodine-containing products in Australia, 44 products currently have stock on shelves in Australian pharmacies and are therefore are subject to the TGA's recall.
See About pholcodine cough medicines cancelled by the TGA for the full list of these products.
Following an investigation into the safety of pholcodine-containing medicines, the Therapeutic Goods Administration (TGA) has decided to cancel the registration of these medicines in Australia and is recalling them from pharmacies.
Pholcodine has been used in adults and children to treat non-productive (dry) cough and is most commonly used in cough syrups and lozenge products. It has also been used in combination with other active substances in products that treat the symptoms of cold and flu.
The TGA investigation follows a review by the European Medicines Agency (EMA) recommending the withdrawal of marketing authorisations for these products.
The EMA review supports a previously suspected link between pholcodine-containing medicines and a risk of anaphylactic reactions (a sudden, severe and life-threatening allergic reaction) to medicines called neuromuscular blocking agents (NMBAs) which are used as muscle relaxants during general anaesthesia.
What the EMA review evaluated
The EMA review was carried out by the Pharmacovigilance Risk Assessment Committee. During the review, the Committee evaluated all available evidence including the final results of the ALPHO study, post-marketing safety data and information submitted by third parties such as health professionals. The data showed that use of pholcodine in the 12 months before general anaesthesia with NMBAs puts people at risk of developing an anaphylactic reaction to these agents.
What is the TGA doing?
After investigating this safety issue, the registration of all pholcodine-containing medicines in Australia is being cancelled and any pholcodine-containing medicines are being recalled from pharmacy shelves.
We consider that the recommendations by the EMA and the results of the ALPHO study are applicable to the Australian population. This is supported by a Western Australian study which showed that previous pholcodine consumption was a statistically significant risk factor for NMBA anaphylaxis.1
A search of the TGA’s Database of Adverse Event Notifications (DAEN) on 9 February 2023 identified 50 Australian cases of suspected pholcodine-related anaphylactic reactions to NMBAs. This included one fatality. These reports of NMBA anaphylaxis documented either previous pholcodine use or test results indicating increased hypersensitivity to pholcodine. Sixteen of these cases have been published in the medical literature.2-6
Anaphylactic reactions are serious and potentially life-threatening. However, while patients undergoing surgery are typically asked about the prescription medicines they may currently being treated with in preparation for the procedure, hospitals and surgery facilities do not consistently ask about over the counter medicine use such as cough lozenges and syrups, especially if such use was some months earlier.
Given it is difficult to reliably predict who may be at risk of anaphylaxis to NMBAs, and the seriousness of the safety risk for pholcodine-containing medicines, the TGA is cancelling the registration of all pholcodine-containing medicines in Australia and is recalling products from pharmacies.
What should consumers do?
Check if any of your over-the-counter cold and flu medicines contain pholcodine. Pholcodine is particularly used in cough lozenge or syrup products, but can be found in other medicines. If they do, ask your doctor or pharmacist to suggest an alternative treatment.
If you need general anaesthesia and have taken pholcodine in the past 12 months, tell your health professional prior to the procedure. It may help to show this safety alert to your doctor.
What should health professionals do?
Health professionals should advise patients to stop taking pholcodine-containing medicines and consider appropriate alternatives to treat their symptoms.
Health professionals should also check whether patients scheduled to undergo general anaesthesia with NMBAs have used pholcodine in the previous 12 months and should remain aware of the risk of anaphylactic reactions in these patients.
More about pholcodine
Pholcodine is an opioid medicine that works directly in the brain, suppressing 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 and has been available over-the-counter from pharmacies. Cold and flu medicines often contained pholcodine in combination with other substances and were available as oral liquids and lozenges under various trade names and as generics.
- Sadleir PHM, et al. Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study. Br J Anaesth. 2021 126(5):940-948. doi: 10.1016/j.bja.2020.12.018.
- Li J, et al. Integrating basophil activation tests into evaluation of perioperative anaphylaxis to neuromuscular blocking agents. Br J Anaesth. 2019 123(1):135-143. doi: 10.1016/j.bja.2019.02.024.
- Pedersen AF, et al. Failure to investigate anaesthetic anaphylaxis resulting in a preventable second anaphylactic reaction. Anaesth Intensive Care. 2012 Nov;40(6):1053-5. doi: 10.1177/0310057X1204000619.
- Gurunathan U, et al. Coronary vasospasm in the setting of perioperative anaphylaxis: A case report. Anaesth Intensive Care. 2022 50(6):491-494. doi: 10.1177/0310057X221088602.
- Brusch AM, et al. Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis. Br J Clin Pharmacol. 2014 78(1):14-23. doi: 10.1111/bcp.12290.
- Lee J, et al. Pholcodine-associated allergy and cross-reactivity with neuromuscular blocking drugs. Intern Med J. 2016 46(S4):17. doi: 10.1111/imj.40_13197.
Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.
The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.