On November 7, the US Food and Drug Administration (FDA) proposed removing oral phenylephrine as an active ingredient in over-the-counter (OTC) drug products. Phenylephrine is a nasal decongestant available as a single active ingredient and combined with other active ingredients (eg, acetaminophen, dextromethorphan). OTC Monograph M012: Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use currently permits phenylephrine hydrochloride and oral phenylephrine bitartrate (an effervescent dosage) as oral nasal decongestant active ingredients in OTC drug products. The FDA’s proposed order, if finalized, will amend OTC Monograph M012 to remove these as nasal decongestant active ingredients because they are not effective.
The FDA reviewed all available data regarding oral phenylephrine’s safety and efficacy as a nasal decongestant, including historical data that supported its original approval 30 years ago. The 14 studies with clinical efficacy data that supported the FDA’s original decision used nasal airway resistance (NAR), an indirect measure of the level of congestion, as a primary clinical endpoint to assess effectiveness. NAR has not been clinically evaluated as an endpoint, and the FDA has since recommended that allergic rhinitis trials instead use patient self-rated symptom scoring to evaluate efficacy. Additionally, three more recent studies failed to demonstrate any benefit of oral phenylephrine over placebo. Thus, the FDA concluded that the drug is ineffective as a nasal decongestant within the dosage limits outlined in its OTC monograph and proposed its withdrawal as an active ingredient.
If the FDA issues a final order based on this recommendation, drug products would no longer be permitted to contain oral phenylephrine as a nasal decongestant. Manufacturers would be required to either reformulate products containing the drug or remove them from the market entirely. This change would not affect the use of phenylephrine as a nasal spray formulation. The FDA is accepting comments on this proposal until May 7, 2025.
