omidenepag isopropyl ophthalmic (Rx)

1-10%

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%)

Visual impairment (1%)

Contraindications

None

Cautions

May gradually change eyelashes and vellus hair in treated eye; changes include increased length, thickness, and number of lashes or hairs; eyelash changes are usually reversible upon discontinuing treatment

Ocular inflammation reported; use with caution in patients with active ocular inflammation, including iritis/uveitis

Macular edema, including cystoid macular edema, reported; caution in aphakic patients, in pseudophakic patients, or in patients with known risk factors for macular edema

Advise patients to avoid touching bottle tip to eye or any surface, as this may contaminate solution

Advise patients not to touch tip to their eye to avoid the potential for injury to eye

Pigmentation changes

• Pigmentation changes are expected to occur and increase if omidenepag isopropyl ophthalmic solution is administered
• Pigmentation change is due to increased melanin content in melanocytes rather than increased number of melanocytes
• Iris color change may not be noticeable for several months to years
• Long term effects of pigmentation are not known
• The brown pigmentation around the pupil may spread concentrically towards the periphery ofthe 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 can be continued in patients who develop noticeably increased iris pigmentation, examine regularly
• After discontinuing, iris pigmentation is likely to be permanent, while pigmentation of periorbital tissue and eyelash changes are reversible in most patients
• Inform patient receiving prostaglandin analogs of possible increased pigmentation, including permanent changes

Pregnancy

Data are unavailable on use in pregnant females

Animal data

• SC administration of omidenepag isopropyl to pregnant rabbits throughout organogenesis produced fetal skeletal anomalies at a dose of 24x the clinical dose, based on estimated peak plasma concentration
• Omidenepag isopropyl was not teratogenic in rats when administered SC at 1 mg/kg/day, 2,452x the clinical dose

Lactation

There are no data on drug presence in human milk, effects on breastfed infants, or effects on milk production

Systemic exposure to omidenepag following topical ocular administration is low, and it is unknown whether measurable levels of omidenepag would be present in maternal milk following topical ocular administration

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Prodrug of omidenepag

Relatively selective prostaglandin E2 (EP2) receptor agonist that decreases intraocular pressure (IOP)

Currently, exact mechanism of action is unknown

Elevated IOP represents a major risk factor for glaucomatous field loss

Higher IOP is likely to damage optic nerve and cause visual field loss

Absorption

Absorbed through cornea where prodrug omidenepag isopropyl is hydrolyzed to become biologically active metabolite, omidenepag

Peak plasma time: 10-15 min

Metabolism

Rapidly metabolized in the eye to omidenepag (active moiety) by carboxylesterase-1

Omidenepag is further metabolized by liver through oxidation, N-dealkylation, glucuronidation, sulfate conjugation, or taurine conjugation

Elimination

By 168 hr after ocular instillation, 89% of administered radioactive dose was excreted

Excretion: 83% (feces); 4% (urine)

Ophthalmic Administration

Remove contact lenses before administering solution; lenses may be reinserted 15 minutes after administration

Advise patients to avoid touching tip of bottle to eye or any surface, as this may contaminate solution

Advise patients not to touch tip to their eye to avoid potential eye injury

Gently shake bottle before administering

Storage

Unopened bottle

• Refrigerate at 2-8ºC (36-46ºF)

Opened bottle

• Store for up to 31 days at up to 30ºC (86ºF)