1 February 2024

Why is oral phenylephrine still clogging pharmacy shelves?

Pharmaceuticals Political

Last year an advisory committee to the US FDA concluded oral phenylephrine was ineffective as a nasal decongestant.  

The announcement followed decades of growing evidence suggesting the popular cold and flu medicine simply didn’t work.  

So why does an ineffective medicine still dominate our pharmacy shelves? And what is Australia’s regulator, the TGA, doing about it?  

Phenylephrine is an old drug. First patented nearly a century ago, it has been safely deployed in a variety of uses from eye drops that help dilate the pupil to intravenous administration helping increase blood pressure in hypotensive patients.  

In the 1970s, when the FDA first established its influential monograph for over-the-counter medicines, phenylephrine was listed as one of three medicines thought to be safe and effective as oral decongestants. The other two drugs in the monograph were phenylpropanolamine and pseudoephedrine. 

Of the three drugs, phenylephrine had perhaps the weakest supporting body of evidence and subsequently was only infrequently used in oral formulations. Safety issues quickly emerged for phenylpropanolamine: evidence in the 1980s revealed its use was associated with an increased risk of stroke, and by the end of the 1990s it had been mostly removed from the market. 

Pseudoephedrine, a very effective decongestant, faced its own set of challenges at the turn of the 21st century. It was increasingly used in illicit methamphetamine production, so across the early 2000s many countries around the world, including Australia and the US, began to restrict its availability. It moved behind the counter and became difficult to access. 

At the same time pharmaceutical companies looked to the last drug standing in regards to authorised over-the-counter oral decongestants: phenylephrine. The drug suddenly went from rarely used to everywhere as new “PE” formulations dominated pharmacy shelves. But pretty quickly consumers started to notice these new PE cold and flu medicines didn’t work as well as the older ones.  

In the mid-2000s a pharmacology researcher in the US named Randy Hatton started digging into the literature and discovered the evidence for phenylephrine’s efficacy as an oral decongestant was thin.  

A robust 2015 clinical trial found the drug no better than placebo in treating nasal congestion and further research revealed the reason behind oral phenylephrine’s lack of efficacy. It turns out the drug is powerfully metabolised by the gut, with less than 1% of an oral dose thought to reach the bloodstream and ultimately get to nasal cells. When used as a topical nasal spray phenylephrine can work well, but it does nothing useful when swallowed in a pill. 

More than 15 years later, Hatton’s persistent campaigning ultimately led to an advisory committee to the FDA indicating the evidence simply wasn’t there for phenylephrine’s efficacy. Yet the FDA still hasn’t made any formal decision on whether phenylephrine should be removed from American pharmacy shelves.  

A TGA statement to Rheumatology Republic acknowledges the committee’s finding but makes clear the Australian regulator won’t pre-empt the FDA: “The TGA is constantly monitoring actions taken by, and communicating with, comparable overseas regulators and will take action as required. As new scientific information becomes available ingredients may undergo further evaluation to consider the risk benefit profile. At this time, TGA has no plans to conduct a review of the effectiveness of oral phenylephrine but will continue to monitor the outcomes of the FDA’s review.” 

Professor Andrew McLachlan, Dean of Pharmacy at the Sydney Pharmacy School, says regulators often have limited resources and that safety trumps efficacy as a regulatory priority. 

“Out of all the priorities that TGA have – safety of vaccines, safety of devices through to prescription medicines – they would probably see this as low priority,” Professor McLachlan says. “That’s probably why they haven’t taken anything off the market, because it’s not dangerous. It just might not be effective.” 

Consumer Health Products Australia told Rheumatology Republic: “Experts in the US have advised the public that there is no cause for concern. CHP Australia will continue to monitor the situation and collaborate with the TGA to ensure public health and safety.” 

The Pharmaceutical Society of Australia said the updated Australian Pharmaceutical Formulary was due for launch next month and was expected to include new guidance on phenylephrine, but did not give details.  

McLachlan says healthcare professionals have an ethical responsibility to offer evidence-based advice. But due to the self-limiting nature of colds and flu, many consumers are likely to continue to buy these medicines and think they are helping.  

“Until the companies or the TGA Act, there will be a demand for these products,” McLachlan says. And he suggests pharmacists shouldn’t make claims that are unsupported such as saying these products will definitely help consumers. Instead, there are lots of other options with good evidence of efficacy that consumers can explore, from nasal sprays to the pseudoephedrine behind the counter.