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Latanoprostene Bunod

Class: Prostaglandin Analogs
Chemical Name: 4-nitrooxybutyl (Z)-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
Brands: Vyzulta

Medically reviewed on November 20, 2017

Introduction

Latanoprostene bunod is a prostaglandin analog.

Uses for Latanoprostene Bunod

Latanoprostene bunod has the following uses:

Latanoprostene bunod is a prostaglandin analog indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension.1

Latanoprostene Bunod Dosage and Administration

General

Latanoprostene bunod is available in the following dosage form(s) and strength(s):

Topical ophthalmic solution: 0.24 mg/mL latanoprostene bunod (0.024%).1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

One drop in the affected eye(s) once daily in the evening.1

Cautions for Latanoprostene Bunod

Contraindications

None.1

Warnings/Precautions

Pigmentation

Latanoprostene bunod ophthalmic solution 0.024% may cause changes to pigmented tissues. The most frequently reported changes with prostaglandin analogs have been increased pigmentation of the iris and periorbital tissue (eyelid).1

Pigmentation is expected to increase as long as latanoprostene bunod ophthalmic solution is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of latanoprostene bunod, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes are likely to be reversible in most patients. Patients who receive prostaglandin analogs, including latanoprostene bunod, should be informed of the possibility of increased pigmentation, including permanent changes. The long-term effects of increased pigmentation are not known.1

Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with latanoprostene bunod ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.1

Eyelash Changes

Latanoprostene bunod may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and the number of lashes or hairs. Eyelash changes are usually reversible upon discontinuation of treatment.1

Intraocular Inflammation

Latanoprostene bunod should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation as it may exacerbate this condition.1

Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs. Latanoprostene bunod should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.1

Bacterial Keratitis

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.1

Use with Contact Lens

Contact lenses should be removed prior to the administration of latanoprostene bunod because this product contains benzalkonium chloride. Lenses may be reinserted 15 minutes after administration.1

Specific Populations

Pregnancy

Risk Summary: There are no available human data for the use of latanoprostene bunod during pregnancy to inform any drug associated risks. 1

Latanoprostene bunod has caused miscarriages, abortion, and fetal harm in rabbits. Latanoprostene bunod was shown to be abortifacient and teratogenic when administered intravenously (IV) to pregnant rabbits at exposures ≥0.28 times the clinical dose. Doses ≥20 mcg/kg/day (23 times the clinical dose) produced 100% embryofetal lethality. 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 distention and edema. Latanoprostene bunod was not teratogenic in the rat when administered IV at 150 mcg/kg/day (87 times the clinical dose).1

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.1

Animal Data: Embryofetal studies were conducted in pregnant rabbits administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 19, to target the period of organogenesis. The doses administered ranged from 0.24 to 80 mcg/kg/day. Abortion occurred at doses ≥0.24 mcg/kg/day latanoprostene bunod (0.28 times the clinical dose, on a body surface area basis, assuming 100% absorption). Embryofetal lethality (resorption) was increased in latanoprostene bunod treatment groups, as evidenced by increases in early resorptions at doses ≥0.24 mcg/kg/day and late resorptions at doses ≥6 mcg/kg/day (approximately 7 times the clinical dose). No fetuses survived in any rabbit pregnancy at doses of 20 mcg/kg/day (23 times the clinical dose) or greater. Latanoprostene bunod produced structural abnormalities at doses ≥0.24 mcg/kg/day (0.28 times the clinical dose). Malformations included anomalies of sternum, coarctation of the aorta with pulmonary trunk dilation, retroesophageal subclavian artery with absent brachiocephalic artery, domed head, forepaw hyperextension and hindlimb malrotation, abdominal distention/edema, and missing/fused caudal vertebrae. 1

An embryofetal study was conducted in pregnant rats administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 17, to target the period of organogenesis. The doses administered ranged from 150 to 1500 mcg/kg/day. Maternal toxicity was produced at 1500 mcg/kg/day (870 times the clinical dose, on a body surface area basis, assuming 100% absorption), as evidenced by reduced maternal weight gain. Embryofetal lethality (resorption and fetal death) and structural anomalies were produced at doses ≥300 mcg/kg/day (174 times the clinical dose). Malformations included anomalies of the sternum, domed head, forepaw hyperextension and hindlimb malrotation, vertebral anomalies and delayed ossification of distal limb bones. A no observed adverse effect level (NOAEL) was established at 150 mcg/kg/day (87 times the clinical dose) in this study. 1

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. The 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.1

Pediatric Use

Use in pediatric patients aged 16 years and younger is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.1

Geriatric Use

No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.1

Common Adverse Effects

Most common ocular adverse reactions with incidence ≥2% are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%).1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism Of Action

Latanoprostene bunod is thought to lower intraocular pressure by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Intraocular pressure is a major modifiable risk factor for glaucoma progression. Reduction of intraocular pressure reduces risk of glaucomatous visual field loss.1

Advice to Patients

Potential for Pigmentation: Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which is usually reversible after discontinuation of latanoprostene bunod.1

Potential for Eyelash Changes: Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with latanoprostene bunod. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment. 1

Handling the Container: Patients should be instructed 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. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.1

When to Seek Physician Advice: Advise patients that if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of latanoprostene bunod.1

Use with Contact Lenses: Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of latanoprostene bunod.1

Use with Other Ophthalmic Drugs: If more than one topical ophthalmic drug is being used, the drugs should be administered with at least five (5) minutes between applications.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

Latanoprostene Bunod

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.24 mg/1 mL

Vyzulta

Bausch & Lomb Incorporated

AHFS Drug Information. © Copyright 2018, Selected Revisions November 20, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Bausch & Lomb Incorporated. Vyzulta (latanoprostene bunod) OPHTHALMIC prescribing information. 2017 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60ce7900-a677-4fc2-88d0-1603baa9dbd4

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