Omidenepag Isopropyl (Monograph)

Brand name: Omlonti
Drug class: Antiglaucoma Agents, Miscellaneous
Chemical name: propan-2-yl 2-[[6-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]methyl]pyridin-2-yl]amino]acetate
Molecular formula: C₂₆H₂₈N₆O₄S
CAS number: 1187451-19-9

Medically reviewed by Drugs.com on Mar 24, 2023. Written by ASHP.

Introduction

Selective prostaglandin E2 (EP2) receptor agonist; antiglaucoma agent.

Uses for Omidenepag Isopropyl

Open-Angle Glaucoma or Ocular Hypertension

Used for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Place in therapy for omidenepag isopropyl not yet established; in general, IOP-lowering therapy should be selected based on dosing, cost, and adherence in the context of the patient’s age, preferences, and degree of optic nerve damage.

Omidenepag Isopropyl Dosage and Administration

General

Patient Monitoring

Regularly examine patients who develop noticeably increased iris pigmentation.

Dispensing and Administration Precautions

Remove contact lenses prior to administration of omidenepag isopropyl, and reinsert 15 minutes after administration.

Administration

Ophthalmic Administration

Administer once daily in the evening.

If more than 1 topical ophthalmic drug is being used, administer drugs at least 5 minutes apart. Remove contact lenses prior to administration of omidenepag isopropyl, and reinsert 15 minutes after administration.

Dosage

Adults

Open-Angle Glaucoma or Ocular Hypertension

Ophthalmic

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

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Omidenepag Isopropyl

Contraindications

None.

Warnings/Precautions

Pigmentation

Iris pigmentation is expected to increase with increasing administration. After discontinuation, pigmentation of iris is likely permanent; pigmentation of periorbital tissue and eyelash changes likely reversible in most patients. Inform patients of possibility of increased pigmentation, including permanent changes. Long-term effects of increased pigmentation are not known.

Iris color change may not be noticeable for several months to years. While treatment can be continued in patients who develop noticeably increased iris pigmentation, examine these patients regularly.

Eyelash Changes

Omidenepag isopropyl may gradually change eyelashes and vellus hair in the treated eye (e.g., increased length, thickness, and number of lashes or hairs). Eyelash changes are usually reversible upon discontinuation of treatment.

Ocular Inflammation

Ocular inflammation reported. Use with caution in patients with active ocular inflammation, including iritis/uveitis.

Macular Edema

Macular edema, including cystoid macular edema, reported during clinical trials in patients with pseudophakia. Use with caution in aphakic patients, in pseudophakic patients, or in patients with known risk factors for macular edema.

Risk of Contamination and Potential Injury to the Eye

Advise patients to avoid touching tip of the bottle to eye or any surface to avoid solution contamination. Advise patients to not touch the tip to their eye to avoid the potential for injury.

Specific Populations

Pregnancy

No available data on use in pregnant patients. In animal studies, subcutaneous administration at doses higher than recommended human dose resulted in fetal skeletal anomalies in rabbits, and was not teratogenic in rats.

Lactation

No data on presence in human milk, effects on breast-fed infant, or effects on milk production. Systemic exposure following topical ocular administration is low; unknown whether measurable levels of omidenepag would be present in maternal milk following topical ocular administration. Consider developmental and health benefits of breastfeeding along with mother's clinical need for omidenepag isopropyl and any unknown potential adverse effects on breast-fed child from omidenepag isopropyl.

Females and Males of Reproductive Potential.

No data on effects on human fertility. No impairment of fertility reported in animals receiving omidenepag isopropyl subcutaneously at doses up to 2452 times the clinical dose.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety or effectiveness observed between elderly and other adult patients.

Hepatic Impairment

No specific information at this time.

Renal Impairment

No specific information at this time.

Common Adverse Effects

The most common adverse reactions with incidence ≥1% are conjunctival hyperemia, photophobia, blurred vision, dry eye, instillation site pain, eye pain, ocular hyperemia, punctate keratitis, headache, eye irritation, and visual impairment.

Drug Interactions

Rapidly metabolized in the eye to omidenepag (the active moiety) by carboxylesterase-1. Pharmacologically active form, omidenepag, further metabolized in liver through oxidation, N-dealkylation, glucuronidation, sulfate conjugation, or taurine conjugation.

No formal drug interaction studies.

Omidenepag Isopropyl Pharmacokinetics

Absorption

Bioavailability

No systemic accumulation.

Distribution

Extent

Not known whether distributed into milk.

Elimination

Metabolism

Rapidly metabolized in the eye to omidenepag (the active moiety) by carboxylesterase-1. Pharmacologically active form (omidenepag) further metabolized in liver through oxidation, N-dealkylation, glucuronidation, sulfate conjugation, or taurine conjugation.

Elimination Route

Eliminated in feces (83%) and urine (4%); 89% of administered dose excreted by 168 hours.

Half-life

Approximately 0.5 hours.

Stability

Storage

Ophthalmic

Solution

2–8°C. Once a bottle is opened for use, store up to 31 days at up to 30°C.

Actions

Selective prostaglandin E2 (EP2) receptor agonist which decreases intraocular pressure (IOP).
Binds specifically to EP2 receptor; does not bind to other prostanoid receptors.
Exact mechanism unknown; hypothesized to promote aqueous outflow by increasing trabecular outflow facility and uveoscleral outflow.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).
Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Inform patients about the possibility of eyelid skin darkening, which is usually reversible after discontinuation of omidenepag isopropyl.
Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with omidenepag isopropyl. 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.
Advise patients to avoid touching the tip of the bottle to the eye or any surface, as this may contaminate the solution. Advise patients to not touch the tip to their eye to avoid the potential for injury.
Advise patients that if they develop a new ocular condition (e.g., trauma, infection, or inflammation), 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 omidenepag isopropyl.
Inform patients that contact lenses should be removed prior to administration of the solution and may be reinserted 15 minutes after administration.
Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.
Advise patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.