Drug information of latanoprostene bunod

latanoprostene bunod

Drug group:

Latanoprostene Bunod has been used in trials studying the treatment of Glaucoma, Ocular Hypertension, Open-Angle Glaucoma, Open Angle Glaucoma, and Intraocular Pressure.

As of November 2, 2017 the FDA approved Bausch + Lomb's Vyzulta (latanoprostene bunod opthalmic solution), 0.024% for the indication of reducing intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Latanoprostene bunod is the first prostaglandin analog with one of its metabolites being nitric oxide (NO). The novelty of this agent subsequently lies in the proposed dual mechanism of action that stems from both its prostaglandin F2-alpha analog latanoprost acid metabolite and its ability to donate NO for proposed tissue/cell relaxation effects.

In comparison, both latanoprost and latanoprostene bunod contain a latanoprost acid backbone. Conversely however, latanoprostene bunod integrates an NO-donating moiety in lieu of the isopropyl ester typically found in latanoprost.

Mechanism of effect

Believed to lower intraocular pressure by increasing outflow of aqueous humor through the trabecular meshwork and uveoscleral routes

Intraocular pressure is a major risk factor for glaucoma progression; reduction of intraocular pressure reduces risk of glaucomatous visual field loss

Pharmacodynamic

Upon applying an appropriate dose of latanoprost bunod, reduction in intraocular pressure begins approximately 1 to 3 hours later with a maximum intraocular pressure reduction effect demonstrated after 11 to 13 hours

Pharmacokinetics

Absorption

Peak plasma time, post Day 1 and Day 28 administration: 5 minutes

Peak plasma concentration, latanoprost acid [LLOQ] 30 pg/mL: 59.1 pg/mL (Day 1); 51.1 pg/mL (Day 28)

Metabolism

After topical ocular administration, latanoprostene bunod is rapidly metabolized in the eye to latanoprost acid (active moiety), an F2-alpha prostaglandin analog, and butanediol mononitrate

After latanoprost acid reaches the systemic circulation, it is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid beta-oxidation Butanediol mononitrate is metabolized to 1,4-butanediol and nitric oxide

The metabolite 1,4-butanediol is further oxidized to succinic acid and enters the tricarboxylic acid (TCA) cycle

Excretion

Elimination of latanoprost acid from human plasma is rapid as latanoprost acid plasma concentration dropped below the LLOQ (30 pg/mL) in the majority of subjects by 15 min following ocular administration of latanoprostene bunod 0.024% in human

Dosage

Indicated for reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension

≤16 years: Not recommended due to potential safety concerns related to increased pigmentation following long-term chronic use

>16 years: Instill 1 drop in affected eye(s) qDay in the evening

Alerts

Increased pigmentation to tissues may occur; most frequently reported changes with prostaglandin analogs have been of the iris and periorbital tissue (eyelid) and is expected to increase for the duration of treatment; regularly examine patients who develop noticeably increased iris pigmentation

Gradual increases in length, thickness, and number of lashes have been reported

Caution with a history of intraocular inflammation (iritis/uveitis); avoid if active intraocular inflammation exists, as it may exacerbate this condition

Macular edema, including cystoid macular edema, reported; caution in patients with aphakia pseudophakia with a torn posterior lens capsule, or with known risk factors for macular edema

Bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products has been reported; containers may be inadvertently contaminated by patients who typically had a concurrent corneal disease or an ocular epithelial surface disruption

Remove contact lenses before administration because product contains benzalkonium chloride; lenses may be reinserted 15 minutes after administration

Points of recommendation

Ophthalmic Administration

For ophthalmic use only

Remove contact lenses before administering ophthalmic solution (if applicable)

If ≥1 topical ophthalmic drug is being used, wait least 5 minutes between applications

Instruct patients 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

Storage

Unopened bottle: Store in refrigerator at 2-8ºC (36-46ºF)

Opened bottles: Store at 2-25ºC (36-77ºF) for up to 8 weeks

During shipment, bottles may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 14 days

Protect from light

Do not freeze

Pregnancy level

HAVE NOT BEEN ESTABLISHED

There are no available human data for the use during pregnancy to inform any drug associated risks

Latanoprostene bunod has caused miscarriages, abortion, and fetal harm in rabbits; when administered IV to pregnant rabbits at exposures ≥0.28 times the clinical dose was shown to be abortifacient and teratogenic

Doses ≥20 mcg/kg/day (23 times the clinical dose) produced 100% embryofetal lethality; structural abnormalities (eg, anomalies of the great vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, limb hyperextension and malrotation, abdominal distension and edema) were observed in rabbit fetuses

Latanoprostene bunod was not teratogenic rats when administered IV at 150 mcg/kg/day (87 times the clinical dose)

Breast feeding warning

There are no data on the presence of latanoprostene bunod in human milk, the effects on the breastfed infant, or the effects on milk production

Developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for latanoprostene bunod, and any potential adverse effects on the breastfed infant from latanoprostene bunod

Drug forms

Vyzulta

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