Abstract
The United States Food and Drug Administration (FDA) proposed removing oral phenylephrine (PE) from over-the-counter single-agent and combination products because it is ineffective at FDA-approved doses to treat sinonasal congestion. Health care providers make thousands of recommendations per month for phenylephrine-containing over-the-counter products to treat adults and children with signs and symptoms of the common cold, specifically nasal congestion. Health care providers may feel compelled by parents to recommend over-the-counter medications to treat the common cold in children, despite resources suggesting those products may be mildly effective, ineffective, or possibly unsafe. The objective of this Pharmacotherapy Update is to suggest alternative treatments to PE in children with the common cold and nasal congestion.
Introduction
Health care providers make between 2 and 3 million recommendations per month for over-the-counter (OTC) products to treat the common cold. 1 Consumers collectively spend $11 billion annually on OTC cough and cold remedies. Thus, the common cold is among the top 5 most common conditions prompting primary care and community pharmacy visits. 2 Dozens of OTC products are sold and marketed to treat the common cold, yet evidence noted these remedies may be mildly effective or ineffective to treat common cold symptoms, and possibly unsafe in children.2–4 Nonetheless, health care providers, including physicians and pharmacists, have reported recommending these products for children to reassure worried parents or due to feeling pressured by parents to recommend something for their unwell child. 5
Phenylephrine (PE) is a selective α1-receptor agonist and is used therapeutically for its vasoconstrictive properties.6,7 PE does not require a prescription and is available OTC; it has been approved by the United States Food and Drug Administration (US FDA) since 1976 for nasal congestion and sinonasal pressure associated with the common cold, hay fever [allergic rhinitis (AR)], or other upper respiratory allergies.8,9 Similar OTC sympathomimetic drugs include pseudoephedrine (PSE), ephedrine, and oxymetazoline. Unlike PE, PSE requires purchasers to provide identification and sign a logbook due to its potential use in illegal methamphetamine production. 10 Despite these restrictions, PSE products account for over 70% of pharmacist-recommended OTC oral decongestants, rather than PE products.
Although a Cochrane systematic review and meta-analysis determined PSE was mildly effective for nasal congestion, the authors of this Cochrane review noted that evidence describing PE was unavailable for analysis, and they acknowledged peer-reviewed literature evaluating oral PE was largely unpublished and often proprietary to manufacturers. 11 The effectiveness of PE to treat congestion was questioned as early as 1959 and for over 30 years, researchers, clinicians, and patients have petitioned the US FDA and advocated for the removal of PE from the market, given that it may not meaningfully improve disease- and patient-oriented outcomes attributable to the common cold.9,11 PE’s lack of efficacy has been ascribed to poor oral bioavailability, which may be as low as 1%. 12 Another systematic review and meta-analysis determined that oral PE at the FDA-approved dose, 10 mg, was ineffective for nasal congestion. 13 Though initial studies suggested that 25 mg doses of oral PE were effective to treat nasal congestion (assessed via nasal airway resistance), 13 recent data have determined that neither the 10 mg nor 25 mg oral PE doses are effective for nasal congestion [assessed via nasal congestion (symptom) score] and that congestion scores are recommended instead of nasal airway resistance to accurately measure congestion relief.14,15
In September 2023, the US FDA convened an Advisory Committee to review the evidence and controversies surrounding oral PE. The Committee unanimously agreed that oral PE was ineffective as a decongestant at FDA-approved doses. Subsequently, the US FDA proposed removing oral PE from OTC products marketed to treat nasal congestion and solicited feedback from patients, providers, and policymakers until May 7, 2025. The US FDA plans to consider all clinical evidence and public feedback before making a final determination on the availability of oral PE. 16 Notably, products containing intranasal, ophthalmic, and intravenous PE are unaffected and are generally recognized as safe.
Given the high prevalence of common colds, especially among children, and the longstanding availability of oral PE, patients and providers alike may seek alternatives if/when oral PE becomes unavailable. The objective of this Pharmacotherapy Update was to suggest alternative treatments to oral PE in children with the common cold and nasal congestion.
Consumer-use patterns of decongestants
When considering alternatives to oral PE in children, it is important to understand its current role in the OTC market. Following a 2007 FDA advisory on the use of common cold products in children and a subsequent label change by manufacturers, PE products have remained available only for children 4 years of age and older. 2
Although not specific to children’s products, a 2024 cross-sectional study of US sales identified 732 PE products, with only 21 as stand-alone PE. The remaining 711 were combination products (primarily with antihistamines or antitussives), and 86% contained 3 or more ingredients, strongly suggesting PE is predominantly being used for cough and cold relief rather than allergic conditions such as AR. 17 This consumer-use pattern aligns with the widespread burden of the common cold, a self-limiting viral infection of the upper respiratory tract. On average, adults experience 2–3 colds annually, versus children who develop between 6 and 8 episodes per year. 18 Common symptoms include sore throat, nasal congestion, rhinorrhea, sneezing, and cough, typically lasting about 1 week. 19
The 2024 consumer-use pattern also aligns with recommendations for AR, which do not recommend PE.3,4 Intranasal corticosteroids and intranasal azelastine (available OTC) are standards of care for AR, providing broader and longer-lasting symptom relief by targeting the underlying inflammatory response and/or via mast cell inhibition. While antihistamines may theoretically relieve congestion through drying effects, a 2015 systematic review found that sedating antihistamines were associated with relief of rhinorrhea and sneezing in adults but not congestion. Further, they showed no evidence of effectiveness in children. 20
Pharmacologic alternatives to oral PE for congestion in the common cold
Other available oral decongestants include PSE and ephedrine; however, oral ephedrine is only marketed for intermittent asthma in adults and adolescents 12 years of age and older, and ephedrine should not be recommended to treat nasal congestion. 2 Mechanistically and unlike PE, PSE has mixed direct and indirect sympathomimetic activity, displacing norepinephrine from presynaptic neurons and potentially leading to tachyphylaxis.6,7 Available intranasal decongestants include short-acting agents (PE and propylhexedrine) and long-acting agents (oxymetazoline). These act locally to produce rapid vasoconstriction with fewer systemic effects. 2 Intranasal PE displayed greater decongestant activity versus oral PE (plus dextromethorphan with and without acetaminophen) over 2 hours. 21 Though PE is available as a nasal spray, it is less commonly recommended and purchased compared with oxymetazoline, likely because intranasal PE is short-acting and may require 4–6 administrations per day for congestion relief. Recommending dosing regimens and clinical pearls are listed in Table 1.2,22,23
CNS, central nervous system; CV, cardiovascular; ER, extended release; IR, immediate release; kg, kilograms; mg, milligrams; PRN, as needed; yrs, years.
A 2016 Cochrane systematic review, excluding PE, identified 14 trials conducted in adults supporting a small benefit of decongestants 11 ; however, only 1 trial conducted in children under 12 was identified and eligible for inclusion in this systematic review. 24 That trial, since published, determined PSE significantly reduced nasal congestion severity during the first 8 hours in over 500 children aged 6–11 years. No significant difference was found beyond 8 hours. Over 7 days, somnolence was the only adverse effect significantly increased; stomach upset, insomnia, headache, and nervousness were similar to placebo. 24 The Cochrane systematic review could not determine the relative effectiveness of oral versus intranasal decongestants, and no trials were found for intranasal decongestants in children. 11
In addition to limited evidence in children, several barriers exist with these agents. PSE must be purchased as a behind-the-pharmacy-counter product and is subject to access restrictions (ie, 3.6 grams/day, 9 grams/month). For intranasal decongestants, proper administration is essential for efficacy, which may be difficult for younger children. Dosing guidance is available for children as young as 2 years, though it uses more dilute concentrations that, while previously manufactured, are not currently commercially available and require extemporaneous compounding. Additionally, intranasal decongestants should be used for no more than 3 days—stricter duration of use than other cold products (ie, 7 days oral; 10 days ophthalmic)—due to the risk of rebound congestion. Although the exact cause is unknown, contributing factors may include short-acting agents, preservatives, and prolonged use. 2 Inhibition of ciliary beat has also been observed in vitro after exposure to various concentrations of topical PE. 25
Non-pharmacologic products for congestion
Nasal saline irrigation
Nasal saline irrigation may help remove mucus, pathogens, and allergens, supporting mucociliary clearance and reducing inflammation. Products range from nasal drops and sprays for infants (used with bulb syringes or snotsucker devices for clearance) to nasal squeeze bottles and irrigations, all of which should be used with sterile or home-sterilized water. 2 A 2024 systematic review evaluating nasal irrigation for upper respiratory tract infections, including children, found significant reductions in nasal congestion and no major adverse effects. 26
Humidifiers, vaporizers, and nasal strips
Increasing humidity through humidifiers and vaporizers is a common supportive measure for congestion. These devices may loosen mucus and promote sinus drainage. Humidifiers produce a cool mist but cannot accommodate additives, while vaporizers create steam and can deliver medications. Recognize that for those with allergen-induced congestion, humidity may encourage mold and mites, potentially exacerbating symptoms. 2 Additionally, medical devices such as nasal strips mechanically lift the nares to enlarge the nasal passages, which may offer temporary relief from congestion associated with colds and allergies.2,27
Topical creams, ointments, and oils
Topical vapor rubs (VR) contain aromatic oils (eg, camphor, eucalyptus, and menthol). When applied to the chest or throat, these ingredients may ease cold symptoms through sensory effects, including improved nasal airflow perception. These products have low systemic absorption, and formulations for the common cold are supplied at lower concentrations to minimize serious risks. 2 Toxicity of aromatic compounds (ie, camphor and menthol) has been observed in children 3 weeks to 10 years old who ingest topically-applied products in amounts as small as 1 teaspoonful. 28 Therefore, care must be taken to avoid application practices that may risk oral ingestion while also avoiding practices that increase systemic absorption: wearing tight clothing, socks, or wraps, and concomitant use/administration of heat.
A single trial surveyed parents of 138 children, aged 2–11 years, and found significant overnight improvement with VR, petrolatum, and no treatment. 29 When assessing between groups, VR was significantly better than no treatment but was not statistically superior to petrolatum. Adverse effects were significantly higher with VR but were mild irritant reactions that did not impact sleep outcomes. 29
Conclusion
Oral PE may be withdrawn from the market given that the US FDA determined that oral PE may be ineffective to treat congestion associated with the common cold at FDA-approved doses. At present, oral PSE is the only decongestant proven to be mildly effective at relieving nasal congestion though care should be taken to recommend age-appropriate doses for the shortest duration possible to minimize adverse drug events and rebound congestion. There are limited data describing the effectiveness of systemic decongestants in children 6 years and older and a lack of data supporting systemic decongestant use in children less than 6 years old. Non-pharmacologic remedies include nasal saline irrigation, humidifiers and vaporizers, nasal strips, and topical emollients; these interventions may relieve congestion symptoms by modifying sensation and perception rather than the underlying causes of congestion itself.
Footnotes
Authors’ Contributions
J.Y.: Resources; writing—original draft; writing—review and editing. K.N.: Resources; writing—original draft; writing—review and editing. P.B.: Conceptualization; resources; writing—original draft; writing—review and editing; supervision.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This Pharmacotherapy Update was unsupported by funding.