VYZULTA

Ophthalmic Prostaglandins including Analogs and Receptor Agonists

Instruct patient on proper instillation of the eye solution.
Wash hands before and after use.
Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze 1 drop into the pouch and gently close eyes for 1 to 2 minutes. Do not blink.
Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surface.
The solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

keratitis / Delayed / Incidence not known

conjunctival hyperemia / Early / 6.0-6.0
blurred vision / Early / Incidence not known

ocular irritation / Rapid / 4.0-4.0
ocular pain / Early / 3.0-3.0
hypertrichosis / Delayed / 0-1.0
skin hyperpigmentation / Delayed / Incidence not known
foreign body sensation / Rapid / Incidence not known
iridal discoloration / Delayed / Incidence not known

VYZULTA

Rx

Prostaglandin analog ophthalmic solution
Used to reduce intraocular pressure in open angle glaucoma or ocular hypertension
Potential for permanent pigmentation of iris

1 drop applied to each affected eye once daily in the evening. More frequent administration may decrease the intraocular pressure-lowering effect.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Latanoprostene bunod products.

VYZULTA Ophthalmic Sol: 0.024%

1 drop/day per affected eye.

1 drop/day per affected eye.

17 years: 1 drop/day per affected eye.
16 years and younger: Use not recommended.

Use not recommended.

Use not recommended.

Use not recommended.

Latanoprostene bunod is a prostaglandin analog that lowers intraocular pressure by increasing the outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Reductions in intraocular pressure reduces risk of glaucomatous visual field loss.

Latanoprostene bunod is administered topically to the eye. Following topical ocular administration, the drug is rapidly metabolized in the eye to latanoprost acid (active moiety), an F2 alpha prostaglandin analog, and butanediol mononitrate. Latanoprost acid distributes into systemic circulation, where it is further metabolized in the liver to 1,2-dinor and 1,2,3,4-tetranor metabolites by fatty acid beta-oxidation. 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 (TCA) cycle. Elimination of latanoprost acid from human plasma is rapid with concentrations dropping below the lower limits of quantification (LLOQ, 30 pg/mL) by 15 minutes post-dose.
 
Affected cytochrome P450 isoenzymes and drug transporters: None

Ophthalmic Route
The pharmacokinetics of latanoprostene bunod were evaluated in a study involving 22 healthy subjects. Each subject was administered 1 drop bilaterally each morning for 28 days. A measure of post-dose systemic exposures on treatment days 1 and 28 found no quantifiable plasma concentrations for latanoprostene bunod (LLOQ of 10 pg/mL) or butanediol mononitrate (LLOQ of 200 pg/mL). For latanoprost acid, the mean maximal plasma concentrations (Cmax) were 59.1 pg/mL and 51.1 pg/mL on day 1 and day 28, respectively. The mean time of maximal plasma concentration (Tmax) for latanoprost acid was approximately 5 minutes post-dose on both treatment day.

Human data are limited regarding use of latanoprostene bunod during pregnancy, and it is unknown if the drug produces an adverse effect on human reproduction or the fetus. In animal studies, the drug was shown to be abortifacient and teratogenic when administered intravenously to pregnant rabbits at exposures greater than or equal to 0.28-times the clinical dose. Structural abnormalities observed in rabbit fetuses included anomalies of the great vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, limb hyperextension and malrotation, abdominal distension, and edema. Higher doses (i.e., 23-times the clinical dose) produced 100% embryofetal lethality.

According to the manufacturer, it is not known whether latanoprostene bunod is excreted in breast milk. In addition, it is unknown if the drug produces an adverse effect on milk product or the breast-fed infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.