Doctors advised to check if patients undergoing general anaesthesia have used pholcodine in the previous 12 months

Medicines containing pholcodine are being recalled from pharmacies due to the risk of anaphylactic reactions to neuromuscular blocking agents given during general anaesthesia.

The TGA has cancelled the registration of 55 products that contain pholcodine, 44 of which are currently in stock in pharmacies and are subject to the recall.

Pholcodine is commonly found in over-the-counter medicines to relieve non-productive cough—including many cough syrups and lozenges and in combination with other active ingredients for cold and flu symptom relief.

Pholcodine works by binding to opioid receptors in a part of the brain that triggers the cough reflex.

The TGA made the changes after a safety investigation which followed a review by the European Medicines Agency (EMA) in December that recommended withdrawing pholcodine from the market.

The EMA review reported that pholcodine use in the 12 months before general anaesthesia with neuromuscular blocking agents was a risk factor for anaphylaxis.

According to the TGA, there have been 50 reports of suspected pholcodine-related anaphylactic reactions to neuromuscular blockers in Australia, including one fatality.

But safety concerns with pholcodine have been discussed for years.

In 2005 researchers identified that anaphylactic reactions to NMBA were six times more common in Norway than Sweden, “but the only difference between Norway and Sweden was cough mixtures containing pholcodine.”

Norway withdrew pholcodine from the market in 2007, and within three years, incidence of NBMA-suspected anaphylaxis had dropped significantly.

Other studies in Australia and overseas have had similar findings, as summarised by University of Sydney pharmacology Associate Professors Nial Wheate and Tina Hinton here.
“This type of anaphylaxis can occur in people who have had a muscle relaxant before and been previously fine, or in people who receive a muscle relaxant drug for the first time,” Associate Professors Wheate and Hinton wrote.

This difficulty in predicting who will experience a reaction was cited by both the TGA and EMA in their recommendations to withdraw pholcodine.

An editorial published in Australian Prescriber in 2014 outlined the evidence for the link between pholcodine and anaphylaxis when muscle relaxants are used, as well as citing a lack of compelling evidence for the effectiveness of pholcodine for acute cough—but at the time both the TGA and EMA called the evidence of increased risk of anaphylaxis circumstantial and said more data were needed.

Brands that contain pholcodine include Benadryl, Codral, Bisolvon, Difflam, and Duro-Tuss, and many generic versions.

A complete list of the recalled medicines can be found here.