Vyzulta - Drug Monograph

Introduction

Vyzulta (latanoprostene bunod ophthalmic solution) 0.024% is a novel prostaglandin analog approved by the FDA in 2017 for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. It represents an advanced therapeutic option that combines the IOP-lowering effects of latanoprost with nitric oxide-mediated outflow enhancement.

Mechanism of Action

Vyzulta exerts its therapeutic effects through a dual mechanism of action: 1. Latanoprost acid component: Acts as a prostaglandin F2α analog that increases uveoscleral outflow by remodeling extracellular matrix 2. Butanediol mononitrate component: Metabolizes to release nitric oxide (NO), which enhances trabecular meshwork and Schlemm's canal outflow facility by relaxing vascular smooth muscle and improving aqueous humor drainage

This unique combination provides superior IOP reduction compared to traditional prostaglandin analogs through simultaneous enhancement of both major aqueous outflow pathways.

Indications

• FDA-approved: Reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension
• Off-label uses: Currently no established off-label indications

Dosage and Administration

• Standard dosage: One drop (approximately 30-40 μL) in the affected eye(s) once daily in the evening
• Administration: Instill in the conjunctival sac of affected eye(s)
• Special populations:

- Renal impairment: No dosage adjustment required - Hepatic impairment: No dosage adjustment required - Elderly: No dosage adjustment required - Pediatric: Safety and effectiveness not established

Pharmacokinetics

• Absorption: Latanoprostene bunod is rapidly hydrolyzed to latanoprost acid and butanediol mononitrate upon corneal penetration
• Distribution: Latanoprost acid is 87% protein-bound; distributes primarily to anterior segment tissues
• Metabolism: Extensive hydrolysis in cornea and aqueous humor; butanediol mononitrate metabolized to nitric oxide
• Elimination: Latanoprost acid metabolites excreted primarily in urine (88%) with half-life of 17 minutes in aqueous humor
• Systemic exposure: Minimal systemic absorption following topical administration

Contraindications

• Hypersensitivity to latanoprostene bunod or any component of the formulation
• Active ocular infections (bacterial, viral, or fungal)
• Active ocular inflammation

Warnings and Precautions

• Pigmentation changes: May gradually increase brown pigmentation of iris, which may be permanent
• Eyelash changes: May increase length, thickness, and number of lashes
• Intraocular inflammation: Use with caution in patients with history of intraocular inflammation
• Macular edema: May occur in aphakic patients, pseudophakic patients with torn posterior lens capsule, or patients with known risk factors
• Contact lens wear: Contains benzalkonium chloride; remove lenses prior to administration and wait 15 minutes before reinsertion
• Herpetic keratitis: Reactivation may occur; use with caution in patients with history of herpes simplex keratitis

Drug Interactions

• Other topical ophthalmic agents: Separate administration by at least 5 minutes to prevent wash-out effect
• Drugs affecting nitric oxide pathway: Theoretical potential for enhanced systemic effects, though unlikely due to minimal systemic absorption
• Cyclooxygenase inhibitors: NSAIDs may reduce prostaglandin analog efficacy

Adverse Effects

• Common (≥5%): Conjunctival hyperemia (up to 19%), eye irritation (6%), eye pain (5%)
• Less common (1-5%): Eyelash growth, eyelid erythema, iris pigmentation changes, vision blurred
• Serious but rare: Intraocular inflammation, cystoid macular edema, herpetic keratitis, anterior uveitis
• Systemic effects: Rare reports of headache, common cold symptoms

Monitoring Parameters

• Baseline: Complete ophthalmic examination including visual acuity, slit-lamp biomicroscopy, funduscopy, and IOP measurement
• Ongoing:

- IOP measurement every 3-6 months - Iris color and periocular pigmentation changes at each visit - Eyelash changes and eyelid skin darkening - Signs and symptoms of ocular inflammation or infection - Macular edema in at-risk patients

• Long-term: Regular assessment of visual field and optic nerve head changes

Patient Education

• Administer one drop in affected eye(s) once daily in the evening
• Wait at least 15 minutes before inserting contact lenses after administration
• Do not touch dropper tip to any surface to avoid contamination
• May cause permanent eye color change (increased brown pigmentation)
• May gradually increase eyelash length, thickness, and darkness
• Report any eye pain, conjunctival redness, or vision changes immediately
• Do not discontinue without consulting healthcare provider
• Store at 2-8°C (36-46°F); may be stored at room temperature up to 25°C (77°F) for 8 weeks after opening

References

1. Weinreb RN, Scassellati Sforzolini B, Vittitow J, et al. Latanoprostene bunod 0.024% versus timolol maleate 0.5% in subjects with open-angle glaucoma or ocular hypertension: The APOLLO study. Ophthalmology. 2016;123(5):965-973.

2. Medeiros FA, Martin KR, Peace J, et al. Comparison of latanoprostene bunod 0.024% and timolol maleate 0.5% in open-angle glaucoma or ocular hypertension: The LUNAR study. Am J Ophthalmol. 2016;168:250-259.

3. Cavet ME, Vittitow JL, Impagnatiello F, et al. Nitric oxide (NO): An emerging target for the treatment of glaucoma. Invest Ophthalmol Vis Sci. 2014;55(8):5005-5015.

4. Vyzulta [package insert]. Bridgewater, NJ: Bausch + Lomb; 2021.

5. Kaufman PL. Latanoprostene bunod: A new prostaglandin analog for the treatment of glaucoma. Expert Rev Ophthalmol. 2016;11(4):257-269.

6. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2021;105(Suppl 1):1-169.