Libby Wirth, PharmD, Cash Wise/CentraCare
Background: The Food and Drug Administration (FDA) recently determined oral phenylephrine to be ineffective for nasal decongestion. The Kefauver-Harris amendment to the Federal Food Drug and Cosmetic Act maintains that prescription and non-prescription medications must be safe and effective for their intended use. Oral phenylephrine has not yet been removed from shelves due to a lack of safety concerns.
Oral phenylephrine is not the only over-the-counter (OTC) cough and cold product with poor evidence for efficacy. Evidence for guaifenesin and dextromethorphan for cough due to acute illness is also lacking.
Evidence: A 2007 meta-analysis from Hatton et al. compiled studies measuring nasal airway resistance in oral phenylephrine vs placebo and found no significant difference for the 10 mg dose and a reduction in resistance of 27.6% for the 25 mg dose (95% CI, 17.5% to 37.7%). However, subjective patient reports of congestion were not different for either dose compared to placebo. OTC approved dosing is 10 mg every four hours.
A 2014 randomized controlled trial (RCT) from Hoffer-Schaefer et al. measured guaifenesin’s mucolytic and expectorant effects and found no significant difference in six measures of sputum. The OTC approved dose of 1200 mg extended-release guaifenesin twice daily was used for one week and it was determined to be not effective in breaking up or thinning mucus in cough due to acute infection.
A 2014 review from Smith et al. summarized the results of 29 RCTs comparing oral OTC cough products to placebo in acute cough. Evidence for antitussives and expectorants alone were conflicting. Evidence for antihistamines alone in cough proved ineffective. There were multiple low-quality studies measuring various combination products also with conflicting evidence.
A 2015 meta-analysis from De Sutter et al. found antihistamines were only significantly effective in reducing overall cold symptom severity within the first two days of treatment. Patients taking an antihistamine in this timeframe had a positive response 45% of the time compared to 38% with placebo (odds ratio, 0.74; 95% CI, 0.60 to 0.92). Individual symptoms including rhinorrhea and sneezing showed a statistically significant decrease with first-generation antihistamines, although clinically insignificant (less than 1-point change on a 4- or 5-point severity scale).
Discussion/Clinical Impact: OTC medications that have evidence to provide symptomatic relief from cold symptoms including nasal congestion are listed in the following table. Redirect patients away from medications with poor efficacy and towards those with clinical benefit. In contrast to oral phenylephrine, intranasal decongestants, including nasal phenylephrine, are effective and have minimal systemic action. Consultation on the proper use of nasal sprays may improve patient willingness to use this treatment option.
Evidence for OTC cough medications is poor, not supporting the use of guaifenesin or dextromethorphan. Guaifenesin is considered safe, but dextromethorphan should be used with caution in patients on monoamine oxidase inhibitors (MAOIs) or other serotonergic medications. Dextromethorphan also has misuse potential. Neither antihistamines nor medicated lozenges have shown benefit in cough, but non-medicated lozenges may provide temporary sore throat relief.
At any time during treatment, with or without medication, non-pharmacologic interventions can be recommended. These include drinking fluids, saline nasal spray, saline nasal irrigation, nasal suctioning, salt water gargle, and in children >12 months of age, honey for sore throats.
Cold Symptoms (nasal congestion, rhinorrhea, sneezing, sore throat, aches, fever) | ||
Drug | Symptom | Notes |
Intranasal decongestants (oxymetazoline, phenylephrine) | Nasal congestion | 1. Preferable for patients with uncontrolled HTN or BPH 2. Use oxymetazoline for no more than 3 days at a time 3. Phenylephrine has a shorter duration of action than oxymetazoline |
Oral pseudoephedrine | Nasal congestion | 1. Use if intranasal agents aren’t enough 2. Avoid in uncontrolled HTN and BPH 3. An oral decongestant and antihistamine combo may reduce post-nasal drip |
Pain/fever relievers (e.g. acetaminophen, ibuprofen) | Pain, fever | |
Oral antihistamines (e.g. diphenhydramine, loratadine) | Overall symptom severity | 1. Most benefit within first two days of treatment |
Lozenges | Sore throat | 1. For temporary relief |
Hypertension, HTN; benign prostatic hyperplasia, BPH
References:
- FDA clarifies results of recent advisory committee meeting on oral phenylephrine. FDA. Published September 14, 2023. Accessed December 28, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine
- Hatton RC, Winterstein AG, McKelvery RP, Shuster J, Hendeles L. Ambulatory care: Efficacy and safety of oral phenylephrine: Systematic review and meta-analysis. Ann Pharmacother. 2007;41(3):381-390. DOI 10.1345/aph.1H679
- Hoffer-Schaefer A, Rozycki HJ, Yopp MA, Rubin BK. Guaifenesin has no effect on sputum volume or sputum properties in adolescents and adults with acute respiratory tract infections. Respir Care. 2014;59(5):631-636. DOI 10.4187/respcare.02640
- Smith SM, Schroeder K, Fahey T. Over‐the‐counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev. 2014;(11). DOI 10.1002/14651858.CD001831.pub5
- De Sutter AIM, Saraswat A, van Driel ML. Antihistamines for the common cold. Cochrane Database Syst. Rev. 2015;(11). DOI 10.1002/14651858.CD009345.pub2
- Weinberger M, Hendeles L. Nonprescription medications for respiratory symptoms: Facts and marketing fictions. Allergy Asthma Proc. 2018;39(3):169-176. DOI 10.2500/aap.2018.39.4117
- Clinical resource, managing cough and cold symptoms. Pharmacist’s Letter/Prescriber’s Letter. Published December 2022. Accessed December 28, 2023. https://pharmacist.therapeuticresearch.com/Home/PL