Background

Phenylephrine is an ingredient used in medications intended to clear congestion from a cold, flu, or allergies. Currently, phenylephrine can be found in over 260 oral nose and sinus medications, including versions of Benadryl, Mucinex, and Tylenol, according to a 2020 study published in JAMA Otolaryngology–Head & Neck Surgery.

Many drug manufacturers also use phenylephrine in place of pseudoephedrine, another oral decongestant, after its sales were restricted to prevent it from being used to create illicit methamphetamine.

However, several studies and analyses from scientists suggest that phenylephrine may be ineffective. At least four randomly controlled studies funded by drug manufacturers have found that the ingredient was not more effective at relieving congestion than a placebo.

According to physicians and pharmacists, oral phenylephrine is metabolized in the gut and liver and does not reach the bloodstream in sufficient levels to narrow blood vessels and provide relief from symptoms.

"The evidence is clear that oral phenylephrine does not work," said Randy Hatton, a professor at the University of Florida's school of pharmacy who has evaluated research on phenylephrine drugs. "If it doesn't get into the blood in the first place, it can't go to the nose and cause nasal constriction and therefore relieve your congestion."

Because of the ingredient's potential ineffectiveness, doctors, pharmacists, and industry groups — including the American Academy of Allergy, Asthma and Immunology and the American College of Clinical Pharmacy — have argued the medications with phenylephrine should not be sold.

FDA advisory panel rules common decongestant is ineffective

Earlier this week, FDA's Nonprescription Drugs Advisory Committee unanimously ruled that current evidence does not support the use of phenylephrine in over-the-counter products.

In a scientific review published ahead of the committee's meeting, FDA reviewers found that studies from the 1960s and 1970s that supported phenylephrine's original approval were "extremely small" and used statistical/research techniques that are no longer accepted.

"The bottom line is that none of the original studies stand up to modern standards of study design or conduct," said Peter Starke, FDA's lead medical reviewer.

The committee also evaluated three more recent studies that were conducted by Merck and Johnson & Johnson. The studies enrolled hundreds of patients and found that patients who received drugs with phenylephrine were no better off than those who received a placebo. FDA determined that these studies "confirm that orally administered [phenylephrine] is not effective at any dose that can be developed and still provide a reasonable margin of safety."

"I think we clearly have better options in the over-the-counter space to help our patients, and the studies do not support that this is an effective drug," said Maria Coyle, the committee's chair and an associate professor of pharmacy at Ohio State University.

According to the committee members, having an ineffective ingredient in medications, even if it is largely safe, would not be beneficial for patients. There could also be unnecessary or delayed care visits and risks associated with patients increasing the dose of a medication with phenylephrine beyond the recommended amount in order to get relief.

"I do not believe that the evidence that was presented supports in any way the efficacy of this product remaining on the market," said Diane Ginsburg, a committee member and associate dean for healthcare partnerships at the University of Texas at Austin College of Pharmacy. "We really should not have products on the market that are not effective."

What will happen next?

Based on the advisory committee's decision, FDA could revoke oral phenylephrine's "generally regarded as safe and effective" status due to a lack of efficacy, which would potentially lead to hundreds of products with the ingredient being removed from the market. Although the agency typically follows the recommendations of its advisory committees, it is not required to, and it could be several months before a final decision is reached, the New York Times reports.

Following the committee's decision, the Consumer Healthcare Products Association (CHPA) issued a statement asserting that phenylephrine is both safe and effective. The organization also noted that removing products with the ingredients would have "negative unintended consequences," including some patients visiting doctors unnecessarily or not getting treatment at all.

"Simply put, the burdens created from decreased choice and availability of these products would be placed directly onto consumers and an already-strained U.S. health care system," said Marcia Howard, CHPA's VP of regulatory and scientific affairs.

Separately, Scott Gottlieb, a former FDA commissioner and current Pfizer board member, said the committee's decision was "a shame," and that removing phenylephrine from the market could lead to "even fewer accessible options [for patients], driving up healthcare costs."

If FDA ultimately decides to remove phenylephrine from the market, the committee members said the agency will need to raise awareness of the change and help pharmacists and physicians provide education about safe and effective alternatives for patients.

"This is going to change how the cold and cough aisle looks in the pharmacy," said Susan Blalock, a committee member and professor emeritus at the University of North Carolina at Chapel Hill School of Pharmacy. "FDA really shouldn't underestimate the communication challenges that are going to be associated with this, but that does not suggest in any way that they should not stay the course." (Jewett/Rabin, New York Times, 9/13; Phend, MedPage Today, 9/12; Hopkins, Wall Street Journal, 9/12; Perrone, Associated Press, 9/12; Habeshian, Axios, 9/12; Choi, The Hill, 9/12)

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