The primary decongestant that millions of Americans use in search of relief from nasal congestion is no better than a dummy pill, according to government experts who reviewed the latest research on the long-controversial active ingredient.
Food and Drug Administration advisers voted unanimously Tuesday against the effectiveness of the key drug found in popular versions of Sudafed, Dayquil and other commercially available medications.
“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 has called in its outside advisers to take a fresh look at phenylephrine, which became the leading drug among over-the-counter decongestants when drugs containing an older ingredient, pseudoephedrine, made their way behind pharmacy counters. A 2006 law forced the measure because pseudoephedrine can be illegally processed 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. Phenylephrine versions, sometimes marked “PE” on the packaging, make up the rest.
If the FDA follows the panel’s recommendations, Johnson & Johnson, Bayer and other drugmakers could be required to remove their oral medications that contain phenylephrine from store shelves. This would likely force consumers to switch to over-the-counter pseudoephedrine products or phenylephrine-based nasal sprays and drops.
In that scenario, the FDA would need to work with pharmacies, pharmacists and other health care providers to educate consumers about remaining options for treating congestion, panelists said Tuesday.
The group also told the FDA that studying phenylephrine at higher doses 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 it’s a done deal for me. It doesn’t work.”
This week’s two-day meeting was launched by researchers at the University of Florida, who called on the FDA to remove most phenylephrine products based on recent studies that showed they did not work better in patients with colds and allergic congestion Had placebo pills. 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 met for a similar meeting about the drug in 2007.
This time, all 16 FDA panel members agreed that the current evidence does not show a benefit for the drug.
“I think this drug at this oral dose 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 were no longer accepted by the agency, regulators said.
“The bottom line is that none of the original studies meet modern standards of study design or conduct,” said Dr. Peter Starke, the agency’s chief medical examiner.
Additionally, three larger, rigorously conducted studies published since 2016 showed no difference between phenylephrine medication and placebo for congestion relief. 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 essentially 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 issued its own regulations on drug effectiveness.
“Any time a product has been on the market for this long, it is human nature to make assumptions about what we think we know about the product,” said Dr. Theresa Michele, who heads the FDA’s Office of Non-Prescription Drugs.
But FDA reviewers said their latest review reflects new insights from evidence about 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 tested.
The committee’s non-binding vote on Tuesday is unlikely to have any immediate impact.
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 removing the products would avoid “unnecessary costs and delays in taking a drug that has 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 standards for over-the-counter ingredients.
