WASHINGTON—
The main decongestant used by millions of people seeking relief from nasal congestion is no better than a placebo, according to government experts who reviewed the latest study on the ingredient in question.
Advisers to the US Food and Drug Administration (FDA) voted unanimously against the effectiveness of the key drug, which is found in popular versions of Sudafed, Dayquil and other medications available on store shelves.
“Modern studies, when well conducted, show no improvement in congestion with phenylephrine,” said Dr. Mark Dykewicz, an allergist at Saint Louis University School of Medicine.
The FDA brought together its outside advisers to take another look at phenylephrine, which became the leading over-the-counter decongestant drug when drugs with an older ingredient – pseudoephedrine – were sold only by prescription. A 2006 law required this because pseudoephedrine can be illegally converted into methamphetamine.
These original versions of Sudafed and other drugs are still available without a prescription, but they are less popular and account for about a fifth of the $2.2 billion oral decongestant market. Versions with phenylephrine make up the rest, some of which are marked with “PE” on the packaging.
If the FDA follows the panel’s recommendations, Johnson & Johnson, Bayer and other manufacturers could be forced to remove oral medications containing phenylephrine from shelves. This would force consumers to resort to over-the-counter products containing pseudoephedrine or sprays and nasal drops containing phenylephrine.
In that case, the FDA would need to work with pharmacies, pharmacists and other health professionals to inform consumers about remaining options for treating congestion, group members said Tuesday.
The group also told the FDA that studying higher doses of phenylephrine is not an option because it can raise blood pressure to potentially dangerous levels.
“I think there is a safety issue,” said Dr. Paul Pisaric of Archwell Health in Oklahoma. “I think the case is closed for me. It doesn’t work.”
This week’s two-day meeting was inspired by researchers at the University of Florida, who called on the FDA to recall most phenylephrine products based on recent studies that showed they were no better than placebo pills in patients with colds and allergies. The same researchers also questioned the drug’s effectiveness in 2007, but the FDA allowed the products to remain on the market pending further study.
That was also the recommendation of the FDA’s external experts at the time, who held a similar meeting about the drug in 2007.
This time, all 16 members of the FDA panel agreed that the current evidence does not support the drug’s benefit.
“I think this drug at its oral dosage should have been removed from the market a long time ago,” said Jennifer Schwartzott, a patient representative on the panel. “Patients need and deserve medications that safely and effectively treat their symptoms, and I don’t believe this medication will do that.”
The advisers essentially supported the conclusions of an FDA scientific review released before this week’s meeting, which found numerous deficiencies in studies from the 1960s and 1970s that supported the original approval of phenylephrine. The studies were “extremely small” and used statistical and research techniques that regulators said the agency no longer accepts.
“The bottom line is that none of the original studies stand up to modern standards of study design or conduct,” said Dr. Peter Starke, the agency’s chief medical examiner.
Additionally, three larger, more rigorous studies published since 2016 showed no difference between phenylephrine medications and placebos in relieving congestion. These studies were conducted by Merck and Johnson & Johnson and included hundreds of patients.
A trade group representing over-the-counter drug makers, the Consumer Healthcare Products Association, argued that the new studies had limitations and that consumers should continue to have “easy access” to phenylephrine.
Like many other over-the-counter ingredients, phenylephrine was approved as part of a comprehensive FDA review that began in 1972. It was sold in various forms for more than 75 years before the agency’s own regulations on drug effectiveness took effect.
“When a product has been on the market for so long, it is human nature to make assumptions about what we think we know about the product,” said Dr. Theresa Michele, head of the FDA’s Division of Non-Prescription Drugs.
But FDA reviewers said their latest assessment reflects new findings from tests on how quickly phenylephrine is metabolized when taken orally, leaving only trace amounts in the nasal passages to relieve congestion. The medication appears to be most effective when applied directly to the nose, in the form of sprays or drops, and these products are not reviewed.
The non-binding vote on Tuesday is unlikely to have any immediate consequences.
The group’s negative opinion opens the door for the FDA to remove phenylephrine from a federal list of decongestants considered effective for over-the-counter pills and liquids. The FDA said recalling the products would avoid “unnecessary costs and delays in treatment caused by taking a drug that provides no benefit.”
The FDA’s list of nasal decongestants or monograph has not been updated since 1995. The process of amending a monograph has traditionally taken years or decades and required multiple rounds of review and public comment. But a law passed by Congress in 2020 streamlines the process and is intended to allow the FDA to expedite the release of new rules for over-the-counter ingredients.
