By: Christine Mauceri, PharmD Candidate c/o 2025

On November 7^th, 2024, the Food and Drug Administration (FDA) announced its proposal to remove oral phenylephrine from over-the-counter (OTC) drug products. Phenylephrine has been widely used, both orally and intranasally, for the temporary relief of nasal decongestion due to the common cold or allergies. It is marketed alone as Sudafed PE and in combination with other ingredients as Tylenol, Mucinex, and Benadryl. While this is not a final order, companies may continue to market products taken orally that contain phenylephrine as a nasal decongestant, and pharmacies may individually choose to remove some products that contain oral phenylephrine as an active ingredient.¹ This proposal does not apply to the nasal spray form.

The FDA has a responsibility to ensure the safeness and effectiveness of the drug products on the market. This proposal is based on the recent data concerning the effectiveness of oral phenylephrine, not its safety. In September 2023, the FDA held a Non-Prescription Drug Advisory Committee (NDAC) meeting to discuss the status of oral phenylephrine as a nasal decongestant. Based on recent scientific data, the committee unanimously concluded that the recommended dose of phenylephrine is ineffective as a nasal decongestant; however, the FDA makes the final decision to act on this conclusion.²

Now that the FDA has proposed to remove oral phenylephrine, the public is able to comment on this through the Federal Register until May 7^th, 2025, upon when the FDA will review those comments before making a final decision. If the final order is to be made, then the FDA would work closely with drug manufacturers to adjust their formulations accordingly to comply with the preferred management of cold and allergy symptoms.¹

Phenylephrine was first approved by the FDA for OTC use in 1976 when it was determined to be safe and suggested to be effective for nasal decongestion. It acts as a selective alpha-1 adrenergic receptor agonist causing temporary constriction of blood vessels in the nasal passage. In 2006, its popularity as a main ingredient in many OTC products soared when an FDA law required another oral decongestant, pseudoephedrine, be moved behind pharmacy counters since it can illegally be made into methamphetamine.³ Compared to phenylephrine, pseudoephedrine is a non-selective, alpha- and beta-agonist, and is more lipophilic which allows it to easily cross into the central nervous system.³

At the time of phenylephrine’s approval, seven of fourteen studies that were evaluated showed positive efficacy. Despite the original panel ultimately noting the data as not strong evidence for efficacy, they recommended oral phenylephrine be marketed due to a lack of safety concern.⁴ However, the NDAC notes a few issues with the original studies. Most used a congestion severity scale that measured airflow and air pressure in the nasal passage.⁴ Using this scale, phenylephrine is effective as a decongestant. Presently, the FDA switched to a scale that uses clinical symptom scores based on a patient’s answers to a questionnaire to measure symptom severity, a scale on which phenylephrine is ineffective compared to placebo.⁴ Furthermore, the majority of the studies evaluated patients with the common cold, a condition that is highly variable compared to allergic rhinitis which would yield more reliable results.⁴ In addition, at a 2007 NDAC meeting, the available clinical pharmacology data was presented showing less than 1% bioavailability of oral phenylephrine, which is not adequate to provide efficacy.⁴

The FDA’s proposal to remove oral phenylephrine from OTC shelves is in line with the evolving recommendations to assess and manage the common cold and allergies. If a final order were to be made, some positive outcomes are avoiding unnecessary costs, eliminating a delay in care, and avoiding potential adverse reactions that are associated with taking combination products.⁴ This discussion raises opportunities for pharmacists to educate patients in their community on this possible change as well as alternatives to oral phenylephrine to treat their symptoms. These alternatives include oral pseudoephedrine or nasal sprays that contain phenylephrine and other decongestants, corticosteroids, or antihistamines. Overall, this is a significant, ongoing conversation on the management of the common cold and allergic rhinitis.

References:

1. ‌Key Information about Nonprescription, OTC Oral Phenylephrine. U.S. Food and Drug Administration. Published 2024. https://www.fda.gov/drugs/understanding-over-counter-medicines/key-information-about-nonprescription-over-counter-otc-oral-phenylephrine
2. FDA Proposes Ending Use of Oral Phenylephrine as OTC Monograph Nasal Decongestant Active Ingredient After Extensive Review. U.S. Food and Drug Administration. Published 2024. https://www.fda.gov/news-events/press-announcements/fda-proposes-ending-use-oral-phenylephrine-otc-monograph-nasal-decongestant-active-ingredient-after
3. Backman I. Phenylephrine, a Common Decongestant, Is Ineffective, Say FDA Advisors. It’s Not Alone. medicine.yale.edu. Published October 5, 2023. https://medicine.yale.edu/news-article/phenylephrine-a-common-decongestant-is-ineffective-say-fda-advisors-its-not-alone/
4. NDAC Briefing Document: Oral Phenylephrine in the CCABA Monograph. https://www.fda.gov/media/171915/download.