Bradley Marple1, Peter Roland, Michael Benninger. 1. Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, 75390, USA. bradley.marple@utsouthwestern.edu
Abstract
BACKGROUND: For most multiuse aqueous nasal, ophthalmic, and otic products, benzalkonium chloride (BKC) is the preservative of choice. The American College of Toxicology has concluded that BKC can be safely used as an antimicrobial agent at concentrations up to 0.1%. BKC has been in clinical use since 1935 and is contained in a wide variety of prescription and over-the-counter products. However, over the past several years there have been conflicting reports of damage to human nasal epithelia and/or exacerbation of rhinitis medicamentosa associated with intranasal products containing BKC. OBJECTIVE: We sought to review the published literature and determine whether there is sufficient, clinically significant data that would confirm that intranasal products containing BKC are likely to damage human nasal epithelia or exacerbate rhinitis medicamentosa. METHODS: A literature search was conducted for in vivo and in vitro studies that evaluated the effects of BKC on human nasal epithelia. RESULTS: A total of 18 studies (14 in vivo, 4 in vitro) were identified that evaluated short- and long-term exposure of concentrations of BKC in concentrations ranging from 0.00045% to 0.1%. Eight studies, including a 6-month and 1-year long-term treatment study, demonstrated no toxic effects associated with BKC, indicating that BKC was neither harmful to nasal tissue nor prone to exacerbate rhinitis medicamentosa. Furthermore, of the 10 studies that concluded that BKC resulted in degenerative changes in human nasal epithelia (eg, ciliary beat frequency, ciliary morphology, mucociliary clearance, epithelial thinning and/or destruction) or that BKC exacerbates rhinitis medicamentosa, only 2 (it was 2 according to the Results section) of these studies were supported by statistically significant differences between BKC and placebo or active control groups were compared. It is important to note that in both of these studies, the protocol incorporated the use or oxymetazoline in some or all of the subjects. Oxymetazoline is associated with rhinitis medicamentosa. CONCLUSION: Intranasal products containing the preservative BKC appear to be safe and well tolerated for both long- and short-term clinical use.
BACKGROUND: For most multiuse aqueous nasal, ophthalmic, and otic products, benzalkonium chloride (BKC) is the preservative of choice. The American College of Toxicology has concluded that BKC can be safely used as an antimicrobial agent at concentrations up to 0.1%. BKC has been in clinical use since 1935 and is contained in a wide variety of prescription and over-the-counter products. However, over the past several years there have been conflicting reports of damage to humannasal epithelia and/or exacerbation of rhinitis medicamentosa associated with intranasal products containing BKC. OBJECTIVE: We sought to review the published literature and determine whether there is sufficient, clinically significant data that would confirm that intranasal products containing BKC are likely to damage human nasal epithelia or exacerbate rhinitis medicamentosa. METHODS: A literature search was conducted for in vivo and in vitro studies that evaluated the effects of BKC on humannasal epithelia. RESULTS: A total of 18 studies (14 in vivo, 4 in vitro) were identified that evaluated short- and long-term exposure of concentrations of BKC in concentrations ranging from 0.00045% to 0.1%. Eight studies, including a 6-month and 1-year long-term treatment study, demonstrated no toxic effects associated with BKC, indicating that BKC was neither harmful to nasal tissue nor prone to exacerbate rhinitis medicamentosa. Furthermore, of the 10 studies that concluded that BKC resulted in degenerative changes in humannasal epithelia (eg, ciliary beat frequency, ciliary morphology, mucociliary clearance, epithelial thinning and/or destruction) or that BKC exacerbates rhinitis medicamentosa, only 2 (it was 2 according to the Results section) of these studies were supported by statistically significant differences between BKC and placebo or active control groups were compared. It is important to note that in both of these studies, the protocol incorporated the use or oxymetazoline in some or all of the subjects. Oxymetazoline is associated with rhinitis medicamentosa. CONCLUSION: Intranasal products containing the preservative BKC appear to be safe and well tolerated for both long- and short-term clinical use.
Authors: Minjae Kim; Michael R Weigand; Seungdae Oh; Janet K Hatt; Raj Krishnan; Ulas Tezel; Spyros G Pavlostathis; Konstantinos T Konstantinidis Journal: Appl Environ Microbiol Date: 2018-08-17 Impact factor: 4.792
Authors: Minjae Kim; Janet K Hatt; Michael R Weigand; Raj Krishnan; Spyros G Pavlostathis; Konstantinos T Konstantinidis Journal: Appl Environ Microbiol Date: 2018-05-31 Impact factor: 4.792
Authors: Sarah K Wise; Sandra Y Lin; Elina Toskala; Richard R Orlandi; Cezmi A Akdis; Jeremiah A Alt; Antoine Azar; Fuad M Baroody; Claus Bachert; G Walter Canonica; Thomas Chacko; Cemal Cingi; Giorgio Ciprandi; Jacquelynne Corey; Linda S Cox; Peter Socrates Creticos; Adnan Custovic; Cecelia Damask; Adam DeConde; John M DelGaudio; Charles S Ebert; Jean Anderson Eloy; Carrie E Flanagan; Wytske J Fokkens; Christine Franzese; Jan Gosepath; Ashleigh Halderman; Robert G Hamilton; Hans Jürgen Hoffman; Jens M Hohlfeld; Steven M Houser; Peter H Hwang; Cristoforo Incorvaia; Deborah Jarvis; Ayesha N Khalid; Maritta Kilpeläinen; Todd T Kingdom; Helene Krouse; Desiree Larenas-Linnemann; Adrienne M Laury; Stella E Lee; Joshua M Levy; Amber U Luong; Bradley F Marple; Edward D McCoul; K Christopher McMains; Erik Melén; James W Mims; Gianna Moscato; Joaquim Mullol; Harold S Nelson; Monica Patadia; Ruby Pawankar; Oliver Pfaar; Michael P Platt; William Reisacher; Carmen Rondón; Luke Rudmik; Matthew Ryan; Joaquin Sastre; Rodney J Schlosser; Russell A Settipane; Hemant P Sharma; Aziz Sheikh; Timothy L Smith; Pongsakorn Tantilipikorn; Jody R Tversky; Maria C Veling; De Yun Wang; Marit Westman; Magnus Wickman; Mark Zacharek Journal: Int Forum Allergy Rhinol Date: 2018-02 Impact factor: 3.858