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  • CLASSES

    Prostaglandins, Ophthalmic

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    VYZULTA

    HOW SUPPLIED

    VYZULTA Ophthalmic Sol: 0.024%

    DOSAGE & INDICATIONS

    For the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
    Ophthalmic dosage
    Adults and Adolescents 17 years and older

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

    MAXIMUM DOSAGE

    Adults

    1 drop/day per affected eye.

    Geriatric

    1 drop/day per affected eye.

    Adolescents

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

    Children

    Use not recommended.

    Infants

    Use not recommended.

    Neonates

    Use not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Ophthalmic Administration

    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.

    STORAGE

    VYZULTA:
    - Protect from freezing
    - Protect from light
    - See package insert for detailed storage information
    - Store unopened containers in refrigerator (36 to 46 degrees F)
    - Use within 8 weeks of first opening

    CONTRAINDICATIONS / PRECAUTIONS

    Aphakia

    Latanoprostene bunod should be used with caution in patients with aphakia, pseudophakic patients with a torn posterior lens capsule, and patients with known risk factors for macular edema. Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs.

    Iritis, ocular inflammation, uveitis

    Avoid use of latanoprostene bunod in patients with active ocular inflammation, as the drug may exacerbate this condition. In addition, caution is advised when considering use in patients with a history of iritis or uveitis.

    Contact lenses

    Latanoprostene bunod ophthalmic solution is formulated with the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Remove contact lenses before instilling the ophthalmic drops; contact lenses may be reinserted 15 minutes after drug administration.

    Children, infants, neonates

    Latanoprostene bunod is not recommended for use in pediatric patients (i.e., neonates, infants, children, adolescents) ages 16 years or younger because of safety concerns related to increased pigmentation following long-term use. Prostaglandin analogs, like latanoprostene bunod, have been associated with increased pigmentation of the iris and periorbital tissue. These changes in pigmentation are a result of increased melanin content in the melanocytes, and are expected to increase as long as the drug is administered; however, iris color change may not be noticeable for several months to years. Typically the brown pigmentation around the pupil spreads towards the periphery of the iris and the iris becomes brownish. While treatment can be continued in patients who develop noticeable increases in iris pigmentation, these patients should undergo ophthalmic examination regularly. In addition, drug recipients may experience a gradual increase in the length, thickness, and number of eyelashes. After treatment discontinuation, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes are likely reversible. Inform patients of the possibility for increased pigmentation and changes in eyelashes prior to use of the drug.

    Keratitis

    The use of multiple dose containers of ophthalmic products has been associated with bacterial keratitis. Inadvertent contamination of the latanoprostene bunod containers may increase the risk of infection in patients with corneal disease or a disruption in ocular epithelial surface. If there is any damage to the ocular epithelial surface, the drug should be used with caution.

    Pregnancy

    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.

    Breast-feeding

    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.

    ADVERSE REACTIONS

    Severe

    keratitis / Delayed / Incidence not known

    Moderate

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

    Mild

    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

    DRUG INTERACTIONS

    There are no drug interactions associated with Latanoprostene bunod products.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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

    Other Route(s)

    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.