Latanoprostene Bunod (Monograph)

Brand name: Vyzulta
Drug class: Prostaglandin Analogs
Chemical name: 4-(Nitrooxy) butyl (5Z)-7-{(1R,2R,3R,5S)-3,5- dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl] cyclopentyl}hept-5-enoate
Molecular formula: C₂₇H₄₁NO₈
CAS number: 860005-21-6

Medically reviewed by Drugs.com on Oct 23, 2023. Written by ASHP.

Introduction

Ocular hypotensive agent; synthetic analog of prostaglandin F_2α (PGF_2α).^{1 2 3 4 5 6 7 8 11}

Uses for Latanoprostene Bunod

Ocular Hypertension and Glaucoma

Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.^{1 3}

Once-daily latanoprostene bunod 0.024% ophthalmic solution appears to be more effective than or at least as effective as twice-daily timolol 0.5% ophthalmic solution in reducing IOP in adults with open-angle glaucoma or ocular hypertension.^{4 5 8 9 10}

When selecting an initial ocular hypotensive agent, consider extent of the required IOP reduction, coexisting medical conditions, and drug characteristics (e.g., dosing frequency, adverse effects, cost).^{130 132} With single-agent regimens, the reduction in IOP is approximately 25–33% with topical prostaglandin analogs; 20–25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20–30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15–20% with topical carbonic anhydrase inhibitors.^{130 131}

A prostaglandin analog frequently is considered for initial therapy in the absence of other considerations (e.g., contraindications, cost considerations, intolerance, adverse effects, patient refusal) because of relatively greater activity, once-daily administration, and low frequency of systemic adverse effects; however, ocular adverse effects can occur.^{130 131 132 134}

Goal is to maintain an IOP at which visual field loss is unlikely to substantially reduce quality of life during the patient's lifetime.^{130 132}

Reduction of pretreatment IOP by ≥25% shown to slow progression of primary open-angle glaucoma.^{130 131} Set an initial target IOP (based on extent of optic nerve damage and/or visual field loss, baseline IOP at which damage occurred, rate of progression, life expectancy, and other considerations) and reduce IOP toward this goal.^{130 131 132} Adjust target IOP up or down as needed over course of disease.^{130 131 132}

Combination therapy with drugs from different therapeutic classes often required to control IOP.^{131 133}

Related/similar drugs

epinephrine ophthalmic, latanoprost ophthalmic, timolol ophthalmic, pilocarpine ophthalmic, brimonidine ophthalmic, Lumigan, Combigan

Latanoprostene Bunod Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the affected eye(s).^{1 3}

Avoid contaminating solution container.¹ (See Bacterial Keratitis under Cautions.)

Remove contact lenses prior to administration of each dose;¹ may reinsert contact lenses 15 minutes after the dose.¹ (See Use with Contact Lenses under Cautions.)

If more than one topical ophthalmic drug used, administer the drugs at least 5 minutes apart.¹

Dosage

Adults

Ocular Hypertension and Glaucoma

Ophthalmic

Latanoprostene bunod 0.024% ophthalmic solution: One drop into conjunctival sac of affected eye(s) once daily in the evening.¹

More frequent dosing may diminish the IOP-lowering effect of the drug.¹

If target IOP not achieved, may initiate additional or alternative ocular hypotensive agents.^{130 131 133} (See Ocular Hypertension and Glaucoma under Uses.)

Special Populations

No special population dosage recommendations.¹

Cautions for Latanoprostene Bunod

Contraindications

• Manufacturer states none known.¹

Warnings/Precautions

Pigmentation

Increased pigmentation of the iris and periorbital tissue (eyelid) reported with prostaglandin analogs, including latanoprostene bunod.¹ Pigmentation expected to increase as long as latanoprostene bunod is administered.¹ Following discontinuance of the drug, pigmentation of the iris is likely to be permanent, while pigmentation of periorbital tissue likely to be reversible in most patients.¹ Long-term effects of increased pigmentation unknown.¹

Increased pigmentation of the iris may not be evident until after several months to years of therapy.¹

May continue latanoprostene bunod in patients who develop noticeably increased iris pigmentation; however, examine such patients regularly.¹

Eyelash Changes

Possible gradual change in eyelashes and vellus hair in the treated eye, including increased length, thickness, pigmentation, and number of eyelashes and/or misdirected growth of eyelashes.^{1 3} Usually reversible upon discontinuance of the drug.¹

Intraocular Inflammation

Use with caution in patients with a history of intraocular inflammation (e.g., iritis/uveitis); generally do not use in patients with active intraocular inflammation since therapy may exacerbate the condition.¹

Macular Edema

Macular edema, including cystoid macular edema, reported with prostaglandin analogs.¹

Use with caution in aphakic patients, in pseudophakic patients with torn posterior lens capsule, and in those with known risk factors for macular edema.¹

Bacterial Keratitis

Bacterial keratitis reported with use of multiple-dose containers of topical ophthalmic preparations.¹ These containers were inadvertently contaminated by patients who, in most cases, had concurrent corneal disease or disruption of the ocular epithelial surface.¹

Improper handling of ophthalmic solutions can result in contamination of the solution by common bacteria known to cause ocular infections.¹ Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions.¹ (See Advice to Patients.)

Use with Contact Lenses

Remove contact lenses prior to administration of each dose since the preparation contains benzalkonium chloride preservative;¹ may reinsert contact lenses 15 minutes after the dose.¹

Specific Populations

Pregnancy

No data available regarding use in pregnant women.¹

Has caused miscarriages, abortions, and fetal harm in rabbits.¹ No treatment-related teratogenic effects observed in rats.¹

Lactation

Not known if distributed into milk following topical application to the eye.¹ Data not available on effects of the drug on the breast-fed child or on milk production.¹

Consider benefits of breast-feeding along with importance of the drug to the woman and any potential adverse effects on the breast-fed child from the drug.¹

Pediatric Use

Use in pediatric patients <16 years of age not recommended because of potential safety concerns related to increased pigmentation following long-term use.¹ (See Pigmentation under Cautions.)

Geriatric Use

No overall differences in safety and efficacy relative to younger adults.¹

Common Adverse Effects

Conjunctival hyperemia,^{1 3 4 5} eye irritation,¹ eye pain,¹ instillation site pain.¹

Drug Interactions

No formal drug interaction studies to date.^{1 2} Interactions not expected because of limited systemic exposure following topical application to the eye.²

Latanoprostene Bunod Pharmacokinetics

Absorption

Bioavailability

Prodrug; absorbed through the cornea following ocular instillation and hydrolyzed to active metabolites, latanoprost acid (prostaglandin agonist) and butanediol mononitrate (nitric oxide donor).^{1 4 5 7 8 9 10 11}

Following once-daily topical application of latanoprostene bunod 0.024% to the eyes for 28 days, no quantifiable plasma concentrations of latanoprostene bunod or butanediol mononitrate observed;¹ low plasma concentrations of latanoprost acid detected.^{1 2 10}

Mean time to peak plasma concentrations of latanoprost acid occur approximately 5 minutes following administration of the prodrug.^{1 2 10} Mean maximal plasma concentrations of latanoprost acid observed above the lower limit of quantitation (30 pg/mL) were 59.1 and 51.1 pg/mL on days 1 and 28, respectively.¹

Onset

Reduction in IOP generally occurs within 1–3 hours after ocular instillation and peaks within 11–13 hours.¹

Distribution

Extent

Not known whether the drug or its metabolites distribute into milk in humans following topical ocular administration.¹

Elimination

Metabolism

Prodrug; metabolized in the eye by cellular esterases to latanoprost acid and butanediol mononitrate.^{1 2 3 5 7}

Elimination of latanoprost acid from human plasma is rapid; plasma concentrations dropped below the lower limit of quantitation (30 pg/mL) in most individuals by 15 minutes following administration of the prodrug.^{1 2}

Systemically, latanoprost acid is further metabolized in the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation.^{1 2} Butanediol mononitrate is metabolized to 1,4-butanediol and nitric oxide; the 1,4-butanediol metabolite is further oxidized to succinic acid and enters the tricarboxylic acid cycle.^{1 3}

Stability

Storage

Ophthalmic

Solution

Unopened bottles: 2–8°C; protect from light and freezing.¹ During shipment, may be maintained at up to 40°C for ≤14 days.¹

Opened bottles: 2–25°C for 8 weeks.¹

Actions

• Synthetic analog of prostaglandin F_2α (PGF_2α).^{1 3 4 5 11}

• Lowers IOP via dual mechanism of action from effects of 2 active moieties (i.e., latanoprost acid [prostaglandin agonist] and butanediol mononitrate [nitric oxide donor]).^{1 4 5 7 8 9 10 11}

• Increases aqueous humor outflow within both the trabecular meshwork and uveoscleral pathway.^{1 2 4 5 7}

• Latanoprost acid increases aqueous humor outflow via the uveoscleral pathway; butanediol mononitrate releases nitric oxide inducing relaxation of the trabecular meshwork and Schlemm’s canal, resulting in further increases in aqueous humor outflow.^{1 2 4 5 7 8 11}

Advice to Patients

• Importance of not exceeding once-daily dosing; more frequent administration may paradoxically decrease IOP-lowering effect of latanoprostene bunod.¹

• Importance of learning and adhering to proper administration techniques to avoid contaminating the ophthalmic solution with common bacteria that can cause ocular infections; instruct patients to avoid contact of tip of the container with the eyes or surrounding structures, fingers, or any other surface.¹ Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions.¹

• Importance of patients immediately informing a clinician before continuing therapy if they develop a new ocular condition (e.g., trauma, infection) or ocular reaction (particularly conjunctivitis, eyelid reactions), experience a sudden decrease in visual acuity, or have ocular surgery.¹

• Importance of removing contact lenses prior to administration of each dose since the ophthalmic solution contains benzalkonium chloride preservative; may reinsert contact lenses 15 minutes after the dose.¹

• If using more than one ophthalmic preparation, importance of administering the preparations at least 5 minutes apart.¹

• Risk of permanent increase in brown pigmentation of the iris; risk of darkening of the skin around the eyes (eyelid), which usually is reversible after discontinuance of latanoprostene bunod.¹

• Risk of changes in eyelashes and vellus hair in the treated eye.¹ Potential for disparity between eyes in length, thickness, pigmentation, or number of eyelashes or vellus hairs and/or direction of eyelash growth.¹ Eyelash changes usually reversible after discontinuance of therapy.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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