2.1 Recommended Dosage

The recommended dosage is one drop in the affected eye(s) once daily in the evening.

2.2 Administration Instructions

Gently shake the bottle prior to administration. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of Omlonti, and may be reinserted 15 minutes after administration [see Patient Counseling Information (17)].

5.1 Pigmentation

Omlonti (omidenepag isopropyl ophthalmic solution) 0.002%, is a prodrug of omidenepag, a relatively selective EP2 receptor agonist. Pigmentation is expected to increase as long as omidenepag isopropyl 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 Omlonti, 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 Omlonti, should be informed of the possibility of increased pigmentation, including permanent changes. The long-term effects of increased pigmentation are not known.

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 Omlonti (omidenepag isopropyl ophthalmic solution), 0.002% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17)] .

5.2 Eyelash Changes

Omlonti 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.

5.3 Ocular Inflammation

Ocular inflammation has been reported in patients taking Omlonti. Omlonti should be used with caution in patients with active ocular inflammation, including iritis/uveitis.

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during clinical trials in patients with pseudophakia receiving Omlonti. Omlonti should be used with caution in aphakic patients, in pseudophakic patients, or in patients with known risk factors for macular edema.

5.5 Risk of Contamination and Potential Injury to the Eye

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 to the eye.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to Omlonti in 600 patients for up to 3 months . The most common adverse reactions with incidence ≥ 1% are conjunctival hyperemia (9%), photophobia (5%), vision blurred (4%), dry eye (3%), instillation site pain (3%), eye pain (2%), ocular hyperemia (2%), punctate keratitis (2%), headache (2%), eye irritation (1%), and visual impairment (1%).

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

The safety and effectiveness of Omlonti have not been established in pediatric patients.

8.5 Geriatric Use

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

12.1 Mechanism of Action

Omidenepag is a relatively selective EP2 receptor agonist which decreases intraocular pressure (IOP). The exact mechanism of action is unknown at this time. Elevated IOP represents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

Nasal cavity respiratory epithelium metaplasia was observed in cynomolgus monkeys receiving unilateral topical ocular instillations of omidenepag isopropyl at 0.003% (0.9 mcg/eye) [1.07 fold the MRHOD, based on ocular dose comparison]. In a 13-week monkey study, the 0.9 mcg/eye dose was associated with nasal cavity respiratory epithelial metaplasia, and increased nasal cavity goblet cell respiratory epithelium mucosa. In a 39-week monkey study, the 0.9 mcg/eye dose was associated with increased incidence and severity of nasal cavity respiratory epithelium metaplasia. These findings were present in both the treated side and untreated contralateral side, and they were also observed in the vehicle group [see Adverse Reactions (6)] .

Storage: Store unopened bottle (s) in the refrigerator at 2°C to 8°C (36°F to 46°F). Once a bottle is opened for use, it can be stored for up to 31 days at up to 30°C (86°F).

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 Omlonti.

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 Omlonti. 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.

Handling the Container

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 to the eye. The product should be refrigerated before opening, and once it is opened, it can be stored at room temperature for up to 31 days . [see How Supplied/Storage and Handling (16)] .

When to Seek Physician Advice

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 Omlonti.

Use with Contact Lenses

Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes after administration.

Use with Other Ophthalmic Drugs

Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart [see Dosage and Administration (2)] .