Pharmacists warned on pholcodine cough mixtures

46189991 - cough and cold medicine

Anaesthetists are calling for a ban, or an upschedule to Prescription Only, for cough medicines containing pholcodine

Dr Paul McAleer, a specialist anaesthetist and chair of the multidisciplinary organisation The Australian and New Zealand Anaesthetic Allergy Group, told the AJP that pharmacists may be unaware that the mixtures are believed to be linked to a risk of perioperative anaphylaxis.

Around seven deaths a year are due to allergic reaction to anaesthesia, four of which are likely triggered by a neuromuscular blocking agent.

“In Australia and New Zealand, the majority of anaphylaxis-triggered anaesthesia is due to muscle paralysing drugs, or relaxants as we call them, used in maybe a third of operations,” Dr McAleer said.

“And they have a particular structure which contains one or more quaternary ammonium ions.

“Quaternary ammonium ions are how muscle relaxants in fact work. Pholcodine also has a single quaternary ammonium ion, and we believe the ingestion of pholcodine is making some people allergic to quaternary ammonium ions.

“While they may not react to pholcodine itself – and it’s complicated, but pholcodine only has one of these, so it’s difficult for it to cross-link to IgE in an immune cell – muscle relaxants have two, and can cause an allergic reaction when given intravenously.”

There is “strong and repeated evidence” to support this theory, Dr McAleer said.

In 2017, he and colleagues published an editorial in Anaesthesia and Intensive Care which cited research examining the difference in rates of anaphylaxis to neuromuscular blocking agents (NMBAs) in Norway and Sweden.

Norwegian rates were high, while Swedish rates were low.

These researchers – Florvaag and Johanssen – visited the homes of people in both countries to see if they could find sources of quaternary ammonium ions.

“The predominant difference identified was in the availability and use of the over-the-counter cough suppressant pholcodine (PHO),” Dr McAleer and colleagues wrote at the time.

“PHO was not available in Sweden and was widely used in Norway. It was postulated that the substituted ammonium ion structure of PHO… was resulting in sensitisation and an increased reaction rate to NMBAs observed in Norway relative to Sweden.”

The pholcodine product on the market in Norway was voluntarily withdrawn, and a reduction in NMBA anaphylaxis was then observed over the next three years.

In 2017, Dr McAleer and colleagues wrote that they believed the over-the-counter availability of phocoldine to be an “unacceptable” risk to Australians, with “negligible” benefit.

He has now told the AJP that attempts to engage the TGA over the issue have not met with success.

“The TGA was approached on several occasions and repeatedly declined to make any change to the availability of pholcodine cough syrup,” he said.

“Our requests are to ban it, effectively, but at the least to make it prescription so that it’s more difficult for people to get access to it, even though it has no known benefit.”

Channel Nine has now picked up the story, interviewing a woman named Narelle Campbell who suffered an anaphylactic reaction to the anaesthetic used in surgery to treat an aneurism.

Dr McAleer said that there is little evidence to support the use of pholcodine-containing cough preparations and asked pharmacists to consider discussing their risks with patients.

“Pharmacists probably know that pholcodine has no proven benefit at all – there’s no evidence of efficacy,” he said. “It’s a very, very weak opioid.”

The ingredient was added to a number of cough mixtures some years ago, following concerns about the misuse of codeine in some products, he said.

“If we were to make an approach to pharmacists, it would be that they’re on the front lines of selling these products, and they can advise patients that there are alternatives, as well as that there may be some risks with the ingestion of pholcodine on a regular basis.

“They’re in a perfect position to warn patients that by taking pholcodine, they are not getting a known benefit and they may be exposing themselves to a huge risk.

“There are alternatives which do just as good – or as bad – a job as pholcodine.”

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