title: Preservative use in topical glaucoma medications.
abstract: Benzalkonium chloride (BAK) is the principal preservative employed in topical ocular hypotensive medications, although alternative compounds recently have begun to be employed or examined. Individual clinical trials have shown that exposure to BAK concentrations contained in ophthalmic solutions does not produce adverse sequelae in the majority of glaucoma patients, but concerns continue with regard to its long-term use. These concerns have resulted from an extensive research effort, including preclinical studies with in vitro and in vivo models, as well as recent clinical investigations dedicated specifically to this issue. The aim of this systematic literature review of both preclinical and clinical data was to determine the relevance of these findings to clinical practice. Most preclinical studies reported negative effects of BAK exposure, but with few exceptions, BAK concentrations and exposure times greatly exceeded those likely to be experienced by patients, given the normal physiological dilution by the tear film. In addition, consistent evidence of BAK-related toxicity did not emerge from our review of dedicated clinical investigations. Thus, taken together, current evidence supports the safety of BAK for most glaucoma patients, although subpopulations with abnormal tearing may benefit from alternative preservative compounds or preservative-free formulations. Further studies to identify these populations are needed.
authors.affiliation: Pfizer Inc, New York, New York 10017, USA. Charles.S.Tressler@pfizer.com
authors.forename: Charles S
authors.initials: CS
authors.lastname: Tressler
authors.forename: Richard
authors.initials: R
authors.lastname: Beatty
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lemp
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D009883:Ophthalmic Solutions / Q000592:standards*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*
chemical_list: D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical