Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions.

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.