About the Authors
Nicholas Kolano is a 2025 PharmD candidate at Duquesne University in Pittsburgh, Pennsylvania.
Tiffany Hatcher, PharmD, is an assistant professor in the School of Pharmacy at Duquesne University.
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FDA Is Evaluating the Prospect of Removing Phenylephrine From OTC Shelves
Oral phenylephrine is a common ingredient in OTC products, but its clinical efficacy is questionable. The FDA is considering removing it from the market.
Over the counter medications are abundant. These products enable patients to purchase what they need without a prescription. With cough and cold season approaching, these product aisles will be filled with patients eager to achieve symptom relief.
Nasal decongestants are popular options for managing cold symptoms, and most show benefit in improving congestion. There are numerous products that contain these types of medications, and patients frequently choose the most accessible option that will also save money. Pseudoephedrine products are kept behind the counter and require the patient to present identification for purchase because pseudoephedrine is the main ingredient used in the manufacture of methamphetamine. Due to the difficulty in obtaining pseudoephedrine products for some patients, purchasing other nasal decongestant products is more appealing, but at what cost?
Phenylephrine is a nasal decongestant that is a component in many OTC products. Image Credit: © yorgunadam - stock.adobe.com
Phenylephrine is a nasal decongestant that is a component in many OTC products. It works as an α1-adrenergic agonist, resulting in norepinephrine release, leading to systemic vasoconstriction.1 The vasoconstrictive effects in the nasal region contribute to the symptomatic relief of congestion. For the past few years, the FDA has been considering removing phenylephrine from the market due to lack of evidence supporting efficacy as a nasal decongestant when administered orally.2 In a study examining the effect of oral phenylephrine on nasal congestion symptoms compared with pseudoephedrine and placebo, phenylephrine did not provide a significant improvement in nasal symptoms.3 For this reason, the FDA is examining the generally recognized as safe and effective (GRASE) designation for oral phenylephrine.
Phenylephrine was approved by the FDA in 1976 for OTC use. At the time, the criteria the administration used to evaluate clinical efficacy of decongestants were nasal airflow and pressure.4 Now, efficacy is based on clinical symptom scores, and, using these criteria, oral phenylephrine does not provide clinical efficacy.4
Should the process lead to the removal of products containing oral phenylephrine from the market, the impact would be felt during cough and cold season especially. Furthermore, the public perception of the FDA and the trust placed in it will likely drop, as people will wonder why they have been able to purchase ineffective medications.
Products
The removal of phenylephrine would only affect products containing oral phenylephrine, not those administered intranasally. This would impact single-medication phenylephrine products and combination products containing the drug. Many products contain phenylephrine in addition to other medications, such as analgesics, cough suppressants, expectorants, and antihistamines. Notable products that would be removed from shelves and require reformulation would include:
- Phenylephrine (Sudafed PE; Kenvue Inc)
- Acetaminophen, dextromethorphan, phenylephrine (Dayquil; Procter & Gamble and Kaz Incorporated)
- Acetaminophen, dextromethorphan, guaifenesin, phenylephrine (Mucinex Sinus Max; Reckitt)
- Acetaminophen, dextromethorphan, phenylephrine (Theraflu Severe Cold Relief; Haleon)
- Diphenhydramine, phenylephrine (Benadryl Allergy Plus Congestion; Kenvue Inc)
Accessibility
If phenylephrine is removed, the number of nasal decongestant products to choose from likely will decrease, leaving patients with only pseudoephedrine if they desire an oral nasal decongestant product. Phenylephrine, unlike pseudoephedrine products, is available without needing to provide identification at purchase. Since phenylephrine is not regulated as strictly as pseudoephedrine, it is a readily accessible option for patients.
Despite the proven efficacy of pseudoephedrine as a nasal decongestant, phenylephrine products were purchased by retail stores at a greater rate from 2012 to 2021, with 19.8 billion units of phenylephrine products purchased, compared with 13.2 billion units of pseudoephedrine products purchased.5 While there were more phenylephrine products than pseudoephedrine products purchased by pharmacies, the acquisition costs of the products were $3.4 billion and $3.8 billion, respectively.5 Even though more phenylephrine was purchased by retailers, it was cheaper than obtaining pseudoephedrine products for resale. Consumers/patients could be greatly impacted to a reduced of supply of nasal decongestant products and a spike in demand during the cough and cold season. Not only could patients be limited to which products they can buy and the amount of those products they can legally obtain, but the prices on those products could also increase to counteract the acquisition costs for the retailers.
Role of the Pharmacist
It is foreseeable that pharmacists will be asked numerous questions regarding oral phenylephrine’s potential removal from the market. Pharmacists are some of the most readily accessible health care professionals in general, and may be a mere few feet from the products in question. To be prepared for these questions, reading about the studies conducted to determine the effectiveness of phenylephrine can provide a good foundation. In the article titled “A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber,” Horak et al highlight the issues with oral phenylephrine for this indication.3 If a patient approaches the counter with a product containing phenylephrine, a pharmacist can guide the patient to purchase a product that will improve their symptoms by recommending other products with different decongestants.
In addition, being prepared to discuss the use of nasal sprays that contain phenylephrine and other nasal decongestants will be relevant. Patients may not be aware that the investigation into the effectiveness of phenylephrine as a nasal decongestant only pertains to the oral formulations. There will be no impact on the availability of phenylephrine nasal spray formulations.2 Other nasal decongestants contained in nasal sprays, such as oxymetazoline, will still be available.
Patients may also be concerned about the removal of phenylephrine from the market from a safety perspective. It is important to note that the prospect of the phenylephrine removal is due to efficacy concerns, and in the FDA’s clarification memo, the GRASE designation is being investigated not for safety, but solely for efficacy.2
REFERENCES
Dean JS II, Reddivari AKR. Alpha-1 receptor agonists. StatPearls. Updated on June 5, 2023. Accessed November 20, 2024. https://www.ncbi.nlm.nih.gov/books/NBK551698/
FDA. FDA clarifies results of recent advisory committee meeting on oral phenylephrine. September 14, 2023.Accessed November 20, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine
Horak F, Zieglmayer P, Zieglmayer R, et al. A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol. 2009;102(2):116-120. doi:10.1016/S1081-1206(10)60240-2
Backman I. Phenylephrine, a common decongestant, is ineffective, say FDA advisors. It’s not alone. Yale School of Medicine. October 5, 2023.Accessed November 20, 2024.https://medicine.yale.edu/news-article/phenylephrine-a-common-decongestant-is-ineffective-say-fda-advisors-its-not-alone/
Anderson TS, Suda KJ, Gellad WF, Tadrous M. Trends in phenylephrine and pseudoephedrine sales in the US. JAMA. 2024;331(9):796-798. doi:10.1001/jama.2023.27932
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