VYZULTA

Dosing Considerations  Do not administer VYZULTA™ more than once daily since it has been shown that more frequent administration of prostaglandin analogues may lessen the intraocular pressure lowering effect.  If VYZULTATM is to be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure, administer each drug product at least 5 minutes apart.

Recommended Dose and Dosage Adjustment The recommended dosage is one drop in the conjunctival sac of the affected eye(s) once daily in the evening. Health Canada has not authorized an indication for pediatric use (≤ 16 years of age).

Administration Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections.

Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Contact lenses should be removed prior to administration of VYZULTATM, because this product contains Benzalkonium Chloride. Lenses may be reinserted 15 minutes following administration PrVYZULTATM Product Monograph Page 4 of 21 of VYZULTATM.

Missed Dose If a dose is missed, treatment should continue with the next dose as normal.

Adverse Reaction Overview VYZULTA™ was evaluated in 811 patients in two Phase 3 controlled clinical trials of up to 12 months duration. The most common ocular adverse reactions observed in patients treated with latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (5%), and eye pain (4%), and instillation site pain (2%).

7% of patients discontinued therapy due to ocular adverse reactions including ocular hyperemia, conjunctival irritation, eye irritation, eye pain, conjunctival edema, conjunctivitis, vision blurred, punctate keratitis and foreign body sensation.

Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. A summary of all Treatment-Emergent Adverse Events (TEAEs) by system organ class (SOC) and preferred term (PT) for any PT that occurred in ≥ 2% of subjects in any treatment group for the Phase 3 controlled clinical trials is presented in Table 1.

The TEAEs that occurred in ≥ 2% of subjects treated with VYZULTA™ included conjunctival hyperemia, eye irritation, eye pain, and instillation site pain. 4%) subjects in the VYZULTA™ group had at least 1 ocular TEAE in the study eye leading to discontinuation.

2%) subjects. Conjunctival hyperemia, a common side effect of most prostaglandins, was evaluated in the Phase 3 clinical trials. 5% with crossover to the VYZULTA™ group across study visits and across time points assessed. Few subjects had severe conjunctival hyperemia at any study visit.

A slightly higher proportion of subjects had mild or moderate conjunctival hyperemia at study visits post baseline than at baseline for the study eye and the treated fellow eye in both treatment groups. There were a few subjects who had severe conjunctival hyperemia in either the study or the treated fellow eye.

Ophthalmologic Bacterial Keratitis There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

Eyelash Changes VYZULTA™ may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and the number of lashes or hairs. Eyelash changes are usually reversible upon discontinuation of treatment.

024%) latanoprostene bunod Benzalkonium Chloride, Citric acid, EDTA, Glycerin, Polysorbate 80, Sodium Citrate and Water. PrVYZULTATM Product Monograph Page 5 of 21 Intraocular Inflammation VYZULTA™ should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation as it may exacerbate this condition.

Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogues. These reports mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

VYZULTA™ should be used with caution in patients who do not have an intact posterior capsule or who have known risk factors for macular edema. Pigmentation VYZULTA™ may cause changes to pigmented tissues. The most frequently reported changes with prostaglandin analogues have been increased pigmentation of the iris and periorbital tissue (eyelid).

Pigmentation is expected to increase as long as VYZULTA™ is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of VYZULTA™, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes are likely to be reversible in most patients.

Latanoprostene bunod is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.