Trends in Phenylephrine and Pseudoephedrine Sales in the US

Abstract

This study examines purchasing patterns regarding oral decongestants, concerns about their efficacy, and the need for timelier postmarket evaluation.

Phenylephrine and pseudoephedrine are the only oral formulations of nasal decongestants currently available in the US and are primarily sold over the counter (OTC). Concerns about ineffectiveness of oral phenylephrine have been raised since the 1990s.¹ In 2023, a Food and Drug Administration (FDA) advisory committee unanimously concluded existing data do not indicate oral phenylephrine is an effective nasal decongestant.² The FDA is requesting public comments as it determines whether to remove phenylephrine from the market. We describe patterns of purchasing of oral decongestants as a drug class, including phenylephrine and pseudoephedrine products.

Methods

In this serial cross-sectional study, we used IQVIA’s Multinational Integrated Data Analysis quarterly pharmaceutical sales volume (units) data licensed from IQVIA for the US for 2012 to 2021.³ This database includes sales of pharmaceutical products purchased by retail outlets (chain and independent pharmacies, mass merchandisers, food stores with pharmacies, and mail service pharmacies) and nonretail outlets. Purchased units are considered the smallest unit of consumption (eg, 1 tablet or 5 mL). To focus on consumer products, we examined all oral products containing phenylephrine or pseudoephedrine purchased by retail pharmacies and outlets, including OTC and prescription formulations.

We determined sales of oral decongestants by calculating annual number of purchased units of phenylephrine- and pseudoephedrine-containing products. We then calculated annual inflation-adjusted prerebate pharmacy expenditures on each product with the Consumer Price Index for All Urban Consumers. Mann-Kendall tests were used to assess trends in sales. Analyses were performed with Stata version 17.0, using 2-sided statistical testing with P < .05 considered significant. This study was determined not to be human subjects research by the University of Pittsburgh institutional review board.

Results

During the study period, there were 732 unique phenylephrine products (21 stand-alone, 711 combination products) and 495 pseudoephedrine products (54 stand-alone, 441 combination products). Between 2012 and 2021, there were 19.8 billion units of phenylephrine products purchased, amounting to $3.4 billion in pharmacy expenditures, and 13.2 billion units of pseudoephedrine products purchased, amounting to $3.8 billion in pharmacy expenditures (Figure 1). Units of phenylephrine purchased outpaced pseudoephedrine in all years. There was no significant monotonic trend (P = .11) in phenylephrine sales; pseudoephedrine sales declined significantly from 1.68 billion units in 2012 to 0.98 billion units in 2021 (P < .001).

Figure 1. Annual Trends in Phenylephrine and Pseudoephedrine Sales^a.

Units refer to smallest standard unit of consumption (1 tablet or 5 mL of liquid). There was a significant test of trend result for negative trend across years for total (P < .001), stand-alone (P < .001), and combination (P < .001) pseudoephedrine use, as well as a positive trend across years for phenylephrine stand-alone product sales (P = .01). There was no significant trend for total phenylephrine sales (P = .11) or combination sales (P = .11).

^aSource: author analysis based on IQVIA Multinational Integrated Data Analysis quarterly volume sales data for 2021. Source data are owned by IQVIA.

By 2021, there were 47 unique phenylephrine-containing formulations and 32 pseudoephedrine-containing formulations. For sales of phenylephrine-containing formulations, 85.5% contained 3 or more active ingredients, most commonly analgesics and antitussives, compared with 15.8% of pseudoephedrine-containing formulations (Figure 2).

Figure 2. Components of Phenylephrine- and Pseudoephedrine-Containing Drugs in 2021^a.

Units refer to smallest standard unit of consumption (1 tablet or 5 mL of liquid). Number of active ingredients includes the decongestant product; thus, bars labeled 1 active ingredient include only phenylephrine or pseudoephedrine. Total product purchases by active ingredient classes include all products that have that ingredient; products with multiple ingredients are counted in all categories that apply.

^aSource: author analysis based on IQVIA Multinational Integrated Data Analysis quarterly volume sales data for 2012-2021. Source data are owned by IQVIA.

Discussion

Despite a lack of clinical efficacy evidence, phenylephrine was the most common oral decongestant in the US from 2012-2021, with hundreds of millions of units purchased by retail pharmacies annually, and sales remained stable during this time. In contrast to pseudoephedrine, which is often formulated as a stand-alone product, most phenylephrine products were coformulated with antihistamines or antitussives, which are likely to provide some symptom relief for cough and cold symptoms.

Study limitations include that for the retail market, sales of products through outlets with no pharmacy (eg, gas stations) would not be covered. This study was not able to estimate consumer spending.

The 2020 Coronavirus Aid, Relief, and Economic Security Act revised the regulatory process for nonprescription drugs, providing a mechanism to administratively remove drugs no longer deemed effective.⁴ If the FDA follows its advisory board recommendation and issues a proposed order to remove oral phenylephrine from its “OTC monograph,” reformulation of all phenylephrine-containing products would be required, which could have ramifications for supply chains.⁵ During the time required for reformulation and introduction of new products, clinicians and consumers could consider oral pseudoephedrine or intranasal decongestants, including phenylephrine or oxymetazoline, as alternatives.

The delays between concerns about efficacy of oral phenylephrine being raised and FDA action highlight the need for continued reform of the nonprescription drug review process, such as expanding the capacity of the FDA Office of Nonprescription Drugs and investing in data infrastructure to allow timelier postmarket evaluations.

Section Editors: Kristin Walter, MD, and Jody W. Zylke, MD, Deputy Editors; Karen Lasser, MD, Senior Editor.

Supplement.

Data Sharing Statement