An over-the-counter pharmaceutical icon just took a hit. Last month, the Food and Drug Administration's Nonprescription Drugs Advisory Committee discussed the efficacy of phenylephrine, the nation's most popular oral nasal decongestant. Used for the temporary relief of stuffy nose, sinus, and ear symptoms caused by the common cold, flu, and allergies, it is the active ingredient in products such as Sudafed PE (but not "regular" Sudafed) and some versions of Mucinex, DayQuil, Tylenol sinus, and Advil sinus congestion, as well as store brands based on the same formulations.
On Sept. 12, the committee voted unanimously that phenylephrine is not effective. The vote was largely inevitable in view of the findings of a briefing document prepared for the committee by the FDA and released a day earlier, which found that the oral bioavailability (the extent to which a medication can be used by the body) of the drug is less than 1%, not the 38% often cited in the literature (based on outdated technology).
The review also found that the original studies that purportedly supported the efficacy of phenylephrine contained methodological, statistical, and data integrity flaws.
Moreover, the drug is not without significant side effects, including mild upset stomach, trouble sleeping, dizziness, lightheadedness, headache, nervousness, shaking, and rapid heartbeat. At higher doses, it can increase blood pressure.
The NDAC verdict is a blockbuster finding because of the popularity of phenylephrine-containing products. According to the FDA briefing document, 242 million packages or bottles of phenylephrine products were sold in 2022, which resulted in $1.76 billion in sales.
Presumably, many of those purchases were by repeat users who thought that the products offered relief from their symptoms, so what's going on here?
Well, there are two phenomena that are well known by physicians that can explain this.
The first is the placebo effect, the ability of an inactive treatment, such as the proverbial "sugar pill," to alleviate a sign or symptom of illness. A placebo can induce measurable physiological changes similar to those observed in subjects taking effective medications. Physical signs that have been shown to improve after "treatment" with a placebo include changes in blood pressure, heart rate, and even various blood test results. Symptoms especially amenable to improvement with a placebo include pain management, stress-related insomnia, and fatigue and nausea from cancer treatment.
Thus, the theory would be that you take a phenylephrine pill, which is no more than a placebo, and that seems to make your symptoms improve.
The second possible explanation has a more complicated name but is a simple phenomenon. It's called the post hoc, ergo propter hoc ("after this, therefore because of this") fallacy, which mistakenly links two events as cause and effect because one happens after the other. So, let us posit, as the FDA and its advisory committee did, that phenylephrine is inactive, but patients with congestion take it several times a day for a couple of days and then feel better. Inasmuch as it's used to treat symptoms caused by illnesses such as colds, flu, and allergies that resolve on their own without treatment, it's not surprising that people think, "I took the drug and felt better. The drug worked."
The phenylephrine saga is a good example of why we do (or should do!) rigorous clinical trials to test the safety and efficacy of new drugs. Had such studies been done properly in the first place with phenylephrine, people would have avoided a few side effects and saved lots of money.
Henry I. Miller, a physician and molecular biologist, is the Glenn Swogger distinguished fellow at the American Council on Science and Health. He was the founding director of the FDA's Office of Biotechnology.