Long-term safety evaluation of latanoprost 0.005% without benzalkonium chloride in patients with open-angle glaucoma and ocular hypertension

Abstract

Purpose : Latanoprost, a prostanoid-selective FP receptor agonist, is indicated to reduce intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Benzalkonium chloride (BAK), a preservative in currently marketed latanoprost 0.005% ophthalmic solutions (reference), can cause cellular toxicity and inflammation following chronic use. This phase 3 study assessed the long-term safety of BAK-free latanoprost 0.005%, recently approved to treat OAG or OHT.

Methods : In this nonrandomized, single-group, open-label safety extension study, patients who completed a prior phase 3 noninferiority study were eligible. Patients self-administered 1 drop of BAK-free latanoprost nightly for 36 weeks in the affected eye(s). Intraocular pressure (triplicate values), visual acuity (VA), and slit lamp biomicroscopy were assessed predose at baseline and on days 28, 56, 84, 112, 140, and 168 (end of evaluations); dilated ophthalmoscopy and visual field (VF) at baseline and day 168; ocular and systemic adverse events (AE) were recorded throughout the study.

Results : A total of 161 patients (n = 80, prior BAK-free latanoprost; n = 81, prior reference) were enrolled and analyzed. BAK-free latanoprost maintained lowered IOP for both the study and nonstudy eye in all patients relative to baseline throughout the study. No important changes were noted in VA, slit lamp biomicroscopy, or VF measurements. There were 5 patients with clinically significant retinal or optic nerve changes (1 mild-to-moderate change, prior BAK-free latanoprost; 4 mild changes, prior reference). Ocular AEs occurred in 66 (82.5%) vs 74 (91.4%) patients on prior BAK-free latanoprost and reference, respectively; the most frequent being eye pain (50.0% vs 64.2%) and ocular hyperemia (47.5% vs 54.3%). Most reported AEs were mild. There were 5 serious systemic AEs in 5 patients (n = 3, prior BAK-free latanoprost; n = 2, prior reference); 3 were considered unrelated and 2 not likely related to treatment. One patient discontinued due to follicular conjunctivitis (prior reference); no patient discontinued due to systemic AEs. There were no deaths or serious ocular AEs.

Conclusions : BAK-free latanoprost appears to be safe and well tolerated. These findings support the chronic use of BAK-free latanoprost as a treatment for primary OAG or OHT.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.