Phenylephrine under FDA scanner; what does it mean for cough syrups?

This decongestant, which comes in various forms including liquids, pills and nasal sprays and is available in India as well, was first approved by the FDA for over-the-counter (OTC) use in the 1970s. If the FDA’s advisory committee that will meet on September 11 and 12, recommends that phenylephrine is ‘useless’ and ineffective, it can mean that the drug which then is not recognised as safe and effective, will eventually be pulled off the store shelves.

Notably, in India, phenylephrine is used commonly in cold and cough formulations in medicines such as Alcold Plus, Alerid-D, Alex Cough syrup, Alex Kid (Paed), Berlin-D, Ceticold, Chericof syrup, Coldrest, Digicof, Drosyn, Ebast-DC, Encold, Hicet, Levocet-D, Maxtra, Macbery-D Cold. In the West, it is commonly found in drugs such as Nyquil, Sudafed, Mucinex, and Benadryl.

What’s the problem with phenylephrine?

Primarily, FDA scientists after assessing data on the drug have found that it just does not work as a nasal decongestant even when given in high doses. It's not about whether the oral nasal decongestant is safe or not, said FDA scientists in their briefing documents that they posted online. 

Medical studies have found that when the oral decongestant is taken orally, a significant portion of phenylephrine gets metabolised in the gut and liver before it reaches the bloodstream. What this means is that a very small amount of the drug actually reaches the nose and eases the congestion.

In a report titled The Uselessness of Phenylephrine in the journal Science last year, the article described the nasal decongestant as a "useless bait-and-switch" on the consumer. Largely because it just does not reach significant levels in the blood and is absolutely worthless as an oral medicine.

The harmful effect

This nasal decongestant can be harmful because besides not just working, the drugs have side effects like headache, insomnia, and nervousness.

Also, keeping oral phenylephrine in over-the-counter drugs is a “disservice to patients”, said reports quoting experts. Primarily because the patients may end up taking higher doses than recommended. It also delays doctor’s visits for more effective prescriptions.

The history

Way back in 2007, the FDA had started probing the efficacy of oral phenylephrine after a group of pharmacists filed a Citizen Petition stating that it is no better than a placebo. The pharmacists quoted studies that showed that very little of phenylephrine gets assimilated in the bloodstream.

An advisory committee meeting was asked to study the issue that same year. A metanalysis report however approved the drug though there were industry presentations of new bioavailability data that showed that it is not effective. But the FDA did not remove it off the shelves at that time and asked for more data.

Later in 2015, based on large clinical trials that had taken place by then, another citizen petition wanted phenylephrine to be reclassified as not generally safe and effective, and demanded that it be taken off the shelves. 

Pro phenylephrine

The Consumer Healthcare Products Association, an industry representative group in the US that represents over-the-counter drug manufacturers, is against removing oral phenylephrine from the market. They feel it is the only widely available over-the-counter oral nasal decongestant and it has clear benefits and a critical role to play in public health. Removing the drug from the market could cause people to delay or forgo treatment, said the association.

They pointed to the "totality of the scientific evidence" with pre-existing studies to support its efficacy. They criticised the more recent clinical studies for having "important limitations (e.g., inadequate blinding and concomitant use of an antihistamine) and were conducted using a study population that is not appropriate to evaluate the efficacy of PE for OTC use."

Big impact

But, the FDA seems to be already leaning towards declaring that phenylephrine doesn't work.

If the FDA goes ahead and terms phenylephrine as 'useless; then every single one of the oral use combination medicines with phenylephrine as a component as a "nasal decongestant", will have to be taken off the shelves and revamped.

In the US, it is so commonly used that it is found in 261 different OTC products. The ramifications in India are bound to be big as well.