ypically, 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.

ials 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%).

mum recommended human ocular dose [mrhod], based on estimated plasma c max ). additional fetal skeletal anomalies were observed at 0.08 mg/kg (absent thoracic arch, fused rib) and 0.8 mg/kg (misaligned and misshapen cervical vertebrae), corresponding to 256 times and 3,696 times the mrhod based on estimated plasma c max , respectively. increases in preimplantation loss and post-implantation loss were observed at 0.8 mg/kg/day. the rabbit maternal, no observed adverse effect level [noael] was 0.8 mg/kg/day. an embryofetal development study was conducted in pregnant rats administered omidenepag isopropyl once daily by subcutaneous injection at 0.01, 0.1, or 1 mg/kg/day from gestation day 6 to 17, to target the period of organogenesis. omidenepag isopropyl was not found to have any effect on embryo-fetal development in rats at up to 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ). the rat maternal noael was 1 mg/kg/day. in a pre/postnatal development study, treatment of pregnant rats with omidenepag isopropyl subcutaneously from gestation day 6 to lactation day 20 at 0.01, 0.1, or 1 mg/kg/day resulted in no adverse effects. the noael for pre- and postnatal development was 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ). 8.2 lactation risk summary there are no data on the presence of omlonti in human milk, the effects on the breastfed infant, or the effects on milk production. however, systemic exposure to omidenepag following topical ocular administration is low [see clinical pharmacology (12.3) ], and it is not known whether measurable levels of omidenepag would be present in maternal milk following topical ocular administration. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omlonti and any unknown potential adverse effects on the breast-fed child from omlonti. 8.3 females and males of reproductive potential infertility there are no data on the effects of omlonti on human fertility. no impairment of fertility has been reported in animals receiving omidenepag isopropyl subcutaneously at doses up to 2,452 times the clinical dose based on estimated plasma c max [see nonclinical toxicology (13.1) ] . 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.

ose [mrhod], based on estimated plasma c max ). additional fetal skeletal anomalies were observed at 0.08 mg/kg (absent thoracic arch, fused rib) and 0.8 mg/kg (misaligned and misshapen cervical vertebrae), corresponding to 256 times and 3,696 times the mrhod based on estimated plasma c max , respectively. increases in preimplantation loss and post-implantation loss were observed at 0.8 mg/kg/day. the rabbit maternal, no observed adverse effect level [noael] was 0.8 mg/kg/day. an embryofetal development study was conducted in pregnant rats administered omidenepag isopropyl once daily by subcutaneous injection at 0.01, 0.1, or 1 mg/kg/day from gestation day 6 to 17, to target the period of organogenesis. omidenepag isopropyl was not found to have any effect on embryo-fetal development in rats at up to 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ). the rat maternal noael was 1 mg/kg/day. in a pre/postnatal development study, treatment of pregnant rats with omidenepag isopropyl subcutaneously from gestation day 6 to lactation day 20 at 0.01, 0.1, or 1 mg/kg/day resulted in no adverse effects. the noael for pre- and postnatal development was 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ).

erase-1. the pharmacologically active form, omidenepag is further metabolized by liver through oxidation, n -dealkylation, glucuronidation, sulfate conjugation or taurine conjugation. excretion in rats, 0.03% 14 c-omlonti was instilled in both eyes as a single dose (5 mcl/eye, 3 mcg/animal). by 168 hours after ocular instillation, 89% of the administered radioactive dose had been excreted. specifically, 83% and 4% of the administered radioactive dose were excreted in the feces and urine, respectively, and radioactivity in expired air was below the lower limit of quantitation.

n excreted. specifically, 83% and 4% of the administered radioactive dose were excreted in the feces and urine, respectively, and radioactivity in expired air was below the lower limit of quantitation.

isopropyl did not affect male or female fertility at doses up to 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ). the rabbit embryofetal development study administered omidenepag isopropyl to pregnant rabbits beginning on gestation day 6, covering the period of implantation [see use in specific populations (8.1) ] . preimplantation losses were observed at 0.8 mg/kg/day (3,696 times the mrhod based on estimated plasma c max ). the noael for rabbit preimplantation loss was 0.08 mg/kg/day (256 times the mrhod based on estimated plasma c max ) [see use in specific populations (8.1) ] . 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) ] .

male or female fertility at doses up to 1 mg/kg/day (2,452 times the mrhod based on estimated plasma c max ). the rabbit embryofetal development study administered omidenepag isopropyl to pregnant rabbits beginning on gestation day 6, covering the period of implantation [see use in specific populations (8.1) ] . preimplantation losses were observed at 0.8 mg/kg/day (3,696 times the mrhod based on estimated plasma c max ). the noael for rabbit preimplantation loss was 0.08 mg/kg/day (256 times the mrhod based on estimated plasma c max ) [see use in specific populations (8.1) ] .

ye 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) ] .