No Rebound Congestion with Short-Term Use of Oxymetazoline Hydrochloride Nasal Spray Decongestant
Abstract
Background: The duration of use of oxymetazoline hydrochloride nasal spray is limited due to the risk of rhinitis medicamentosa or rebound congestion. In the United States, there is a 3-day limit on duration of use mandated by the FDA OTC Drug Monograph, whereas in some countries in Europe, the limit is 7 days.
Design: Single center, double-blind, randomized, placebo-controlled, parallel group study in otherwise healthy adults, experiencing nasal congestion.
Objectives: The primary objective of this study was to determine whether rebound congestion occurs after 7 days of treatment with twice daily dosing using 1 of 4 doses of oxymetazoline Hydrochloride nasal spray or saline control. The secondary objective was to determine and compare the nasal decongestant dose response of the 4 dosages of oxymetazoline hydrochloride nasal spray.
Population: One hundred forty-three (143) subjects enrolled in the study, 139 completed the study and 138 included in the efficacy analysis.
Methods: Subjects were randomized to one of five groups:
- 0.025% Oxymetazoline Hydrochloride, one 50 µL spray per nostril.
- 0.025% Oxymetazoline Hydrochloride, one 100 µL spray per nostril.
- 0.05% Oxymetazoline Hydrochloride HCl, two 50 µL sprays per nostril.
- 0.05% Oxymetazoline Hydrochloride HCl, two 100 µL sprays per nostril.
- Saline control, two 100 µL sprays per nostril.
All subjects administered the assigned spray twice daily, for seven days. Efficacy evaluations were performed on Days 1, 4, 7, and 8 (12-24 hours post-treatment discontinuation). The degree of nasal congestion (primary efficacy variable) was rated on a 100 mm visual analog scale (VAS100mm).
Results: Comparison of congestion scores (VAS100mm) at baseline with scores at Day 1, 4 and 7 of continuous treatment and at Day 8 (12-16 hours post treatment discontinuation) showed lack of subjective rebound congestion at each timepoint. The mean AUCs (difference in baseline congestion score) for the two highest doses of oxymetazoline hydrochloride (0.05%, 50 µL and 100 µL) were significantly greater than that of saline, whereas the mean AUCs for the two lowest doses (0.025% 50 µL and 100 µL) were not, indicating a dose response effect.
Conclusion: Patients did not experience rebound congestion after using oxymetazoline hydrochloride at any of the evaluated doses, with twice daily application, for seven consecutive days and 12-24 hours following treatment discontinuation. There was a trend towards a dose response effect for oxymetazoline hydrochloride nasal spray.
Full text article
References
[2]Covington, T.R. et al. Decongestants. In: The American Pharmaceutical Association’s Handbook of Nonprescription Drugs. 1996;eighth Edition. p. 142.
[3] McEvoy, G.K. et al. Oxymetazoline Hydrochloride. In American Society of Health-System Pharmacists, Drug Information.2008; p. 2917-2919.
[4]Upper Respiratory Infection (URI) in Adults and Adolescents. In DynaMed [database online]. EBSCO Information Services. https://www.dynamed.com/topics/dmp~AN~T114537. Updated November 20, 2018. Accessed August 20, 2020.
[5] Pawankar et al. World Allergy Organization (WAO) White Book on Allergy: Update 2013. ISBN-13: 978-0-615-92916-3. Website: www.worldallergy.org.
[6]Graf P. Long term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyper reactivity. Rhinology 1996, 34:9—13.
[7] Vaidyanathan S, Williamson P, Clearie K, et al. Fluticasone reverses Oxymetazoline Hydrochloride-induced tachyphylaxis of response and rebound congestion. Am J Respir. Crit. Care Med 2010; 182:19—24. Ramey JT, Bailen E and Lockey RF. Rhinitis Medicamentosa. J Invesitg Allergol Clin Immunol 2006; Vol 16(3): 148-155].
[8] Toohill R, Lehman R, Grossman T et al. Rhinitis medicamentosa. Laryngoscope. 1981; 91:1614–1621.
[9] Fleece L, Mizes J, Jolly P et al. Rhinitis medicamentosa: conceptualisation, incidence and treatment. Ala J Med Sci.1984; 21:205–208.
[10] Mortuarie et al. Rebound congestion and rhinitis medicamentosa: Nasal decongestants in clinical practice. Critical review of the literature by a medical panel. European Annals of Otorhinolaryngology, Head and Neck diseases (2013) 130, 137—144.
[11] Graf P, Enerdal J, Hallén H. Ten days' use of Oxymetazoline Hydrochloride nasal spray with or without benzalkonium chloride in patients with vasomotor rhinitis. Arch Otolaryngol Head Neck Surg. 1999 Oct; 125 (10):1128-32.
[12] Baroody FM, Brown D, Gavanescu L, DeTineo M, Naclerio RM. Oxymetazoline Hydrochloride adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. J Allergy Clin. Immunol. 2011 Apr; 127(4):927-34.
[13] Yoo JK, Seikaly H, Calhoun KH. Extended use of topical nasal decongestants. Laryngoscope. 1997 Jan; 107(1):40-3.
[14] Watanabe H, Foo TH, Djazaeri B, Duncombe P, Mackay IS, Durham SR. Oxymetazoline Hydrochloride nasal spray three times daily for four weeks in normal subjects is not associated with rebound congestion or tachyphylaxis. Rhinology. 2003 Sep; 41(3):167-74
[15] CFR 21 PART 341: COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
[16] Morris S, Eccles R, Martez SJ, Riker DK, Witek TJ. An evaluation of nasal response following different treatment regimes of Oxymetazoline Hydrochloride with reference to rebound congestion. Am J Rhinol. 1997 Mar-Apr; 11(2):109-15.
[17] Graf P. Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyperreactivity. Rhinology. 1996;34(1):9-13.
[18] Graf P, Juto JE. Decongestion effect and rebound swelling of the nasal mucosa during 4-week use of oxymetazoline.ORL J Otorhinolaryngol Relat Spec. 1994 May-Jun; 56(3):157-60].
[19] Graf P, Hallén H, Juto JE. Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers. Clin Exp Allergy. 1995 May; 25(5):395-400.
[20] Graf P(1), Hallén H, Juto JE. Four-week use of oxymetazoline nasal spray (Nezeril) once daily at night induces rebound swelling and nasal hyperreactivity. Acta Otolaryngol. 1995 Jan;115(1):71-5.
[21] Hirschberg A, Rezek O. Correlation between objective and subjective assessments of nasal patency. ORL J Otorhinolaryngol Relat Spec. 1998;60(4):206-211.