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FDA panel deems phenylephrine ineffective


America’s most popular oral nasal decongestant, phenylephrine, was deemed ineffective by a Food and Drug Administration panel in a unanimous vote on Sept. 12.

The Nonprescription Drug Advisory Committee discussed the efficacy and pharmacokinetic data for phenylephrine. The committee’s next move is to determine if the drug’s status as Generally Recognized as Safe and Effective should be revoked. This would mean manufacturers would have to come up with new formulations, or products containing the drug would be removed from store shelves. NDAC did not disclose a timeline for assessing GRASE status.

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The vote that formally declared phenylephrine ineffective was in line with a review of pharmacology and clinical data presented by the FDA on Sept. 11, which found that the oral bioavailability of the drug is less than 1%, compared with 38%, a number often cited in the literature and based on outdated technology.

A mechanism potentially responsible for inefficacy may be the half-life of phenylephrine.

“The half-life of the parent phenylephrine is much shorter than that of total phenylephrine, suggesting that the duration of action for active parent phenylephrine is far shorter than the monographed dosing interval of every 4 hours and is therefore open to question,” the review states.

The side effects of phenylephrine include headaches, insomnia, and nervousness. At higher doses, it can increase blood pressure.

The review also found that original studies used to support the efficacy of phenylephrine were inconclusive at best and contained potential methodological, statistical, and data integrity issues.

Pseudoephedrine is the only other nonprescription oral nasal decongestant on the retail market but is only available behind the counter due to its use as a potential narcotic.

Manufacturers have used phenylephrine instead of pseudoephedrine in many products due to this limitation.

Revoking the GRASE status of phenylephrine would leave patients without an over-the-counter option.

According to the FDA review, 242 million packages or bottles of phenylephrine products were sold in 2022, resulting in $1.76 billion in sales. A little over 50 million packages of pseudoephedrine were sold that same year, resulting in $542 million in sales.

“I think there’s a huge potential for consumer concern,” Diane B. Ginsburg, PhD, MS, RPh, the pharmacy practice division associate dean for Healthcare Partnerships at The University of Texas at Austin, said during the panel.

She said patients may be confused and concerned about the panel vote, especially those who feel they have benefitted from phenylephrine products. In the event of GRASE removal, she advised reassuring patients that phenylephrine is being pulled from shelves due to inefficacy rather than immediate health risks.

“The real positive here to me is the opportunity from an educational perspective to show consumers the fact that there are a lot more ways to treat” conditions that present with the symptom of congestion, such as rhinitis.

According to the FDA review, “most consumers may simply need instruction on the alternatives, including how to obtain ‘behind-the-counter’ pseudoephedrine or to use alternative treatments, including intranasal decongestants (including intranasal phenylephrine), intranasal steroids, intranasal antihistamines, or intranasal saline products.”

Despite these complications, “there are a number of potential benefits that would be derived by changing the GRASE status of oral phenylephrine.”

These include avoiding unnecessary costs of taking an ineffective drug, potential allergic reactions and side effects, and the risks of patients taking a higher dosage.

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