latanoprostene bunod ophthalmic (Rx)

1-10%

Hyperemia (6%)

Eye irritation (4%)

Eye pain (3%)

Instillation site pain (2%)

Contraindications

None

Cautions

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

Pregnancy

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)

Lactation

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

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

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