Omlonti

Pigmentation (5.1) Eyelash changes (5.2) Ocular Inflammation (5.3) Macular Edema (5.4)

5.1Pigmentation 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.

The following clinically significant adverse reactions are described elsewhere in the labeling: Pigmentation [see Warnings and Precautions (5.1)] Eyelash Changes [see Warnings and Precautions (5.2)] Ocular Inflammation [see Warnings and Precautions (5.3)] Macular Edema [see Warnings and Precautions (5.4)] 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%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Ocuvex at 1-877-622-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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%).

8.1Pregnancy Risk Summary

There are no available data on the use of Omlonti in pregnant women. In animal reproduction studies, subcutaneous administration of omidenepag isopropyl to pregnant rabbits throughout the period of organogenesis produced fetal skeletal anomalies at a dose of 24 times the clinical dose, based on estimated plasma C max. Omidenepag isopropyl was not teratogenic in rats when administered subcutaneously at 1 mg/kg/day, 2,452 times the clinical dose, based on estimated plasma C max (see Data). Data Animal Data An embryofetal development study was conducted in pregnant rabbits administered omidenepag isopropyl once daily by subcutaneous injection at 0.008, 0.08, or 0.8 mg/kg/day from gestation Day 6 to 18, a period which covers implantation and the period of organogenesis in rabbits. Fetal skeletal anomalies (thoracic misaligned centrum and hemivertebra, fused sternebra, absent rib) were observed at 0.008 mg/kg/day (24 times the maximum 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.

Risk Summary There are no available data on the use of Omlonti in pregnant women. In animal reproduction studies, subcutaneous administration of omidenepag isopropyl to pregnant rabbits throughout the period of organogenesis produced fetal skeletal anomalies at a dose of 24 times the clinical dose, based on estimated plasma C max. Omidenepag isopropyl was not teratogenic in rats when administered subcutaneously at 1 mg/kg/day, 2,452 times the clinical dose, based on estimated plasma C max (see Data). Data Animal Data An embryofetal development study was conducted in pregnant rabbits administered omidenepag isopropyl once daily by subcutaneous injection at 0.008, 0.08, or 0.8 mg/kg/day from gestation Day 6 to 18, a period which covers implantation and the period of organogenesis in rabbits. Fetal skeletal anomalies (thoracic misaligned centrum and hemivertebra, fused sternebra, absent rib) were observed at 0.008 mg/kg/day (24 times the maximum 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).