Eybelis

Omidenepag isopropyl.

Each mL of aqueous ophthalmic solution contains 20 mcg of Omidenepag isopropyl.
The product has pH 5.5 - 6.1.
Excipients/Inactive Ingredients: This product contains Benzalkonium chloride (as preservative), Sodium citrate hydrate, Citric acid hydrate, Polyoxyl 35 castor oil, Disodium edetate hydrate, Concentrated glycerin, Sodium hydroxide, Dilute hydrochloric acid, Purified water.

Pharmacology: Pharmacodynamics: Mechanism of action: The mechanism of IOP-lowering effect of Omidenepag isopropyl (Eybelis) ophthalmic solution is considered to increase aqueous outflow via both trabecular and uveoscleral outflow pathways by stimulating EP2 receptor.
Omidenepag (active metabolite) selectively bound to EP2 receptor (Ki=3.6 nM), and showed potent agonistic activity to EP2 receptor (EC₅₀=8.3 nM).
Aqueous humor dynamics in monkeys with laser-induced ocular hypertension was determined by using a fluorophotometry method when 0.002% omidenepag isopropyl ophthalmic solution was instilled into the monkey eyes once daily for 7 days: No change was observed in aqueous humor production while significant increases were observed in outflow facility (assumed to be via the trabecular outflow pathway) and in uveoscleral outflow.
Clinical efficacy and safety: By using Omidenepag isopropyl (Eybelis) (once daily administration) and the comparator (0.005% latanoprost ophthalmic solution, once daily administration), Phase II/III clinical study was conducted in 189 patients with primary open angle glaucoma or ocular hypertension in Japan. Intraocular pressure (IOP) lowering effect was observed from week 1 at first scheduled visit. The results demonstrated that change in IOP levels (Mean±SD) of this product was -5.96±2.45 mmHg at Week 4, and verified that the product was non-inferior to the comparator. (See Figure and Table 1.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Pharmacokinetics: Plasma concentrations: Plasma concentrations of omidenepag (active metabolite) were determined when 0.0025% omidenepag isopropyl ophthalmic solution was instilled into both eyes of 14 healthy adult volunteers (7 Japanese and 7 Caucasian subjects) one drop a time, once daily for 7 days. The concentrations reached the peak of about 34 pg/mL at 10 minutes after the instillation (Day 1), and that of about 35 pg/mL at 15 minutes after instillation (Day 7), respectively. The half-life was about 30 minutes (Days 1 and 7). (Note: The concentration of Omidenepag isopropyl (Eybelis) is 0.002%).
Ocular tissue distribution in animals: (Monkeys): Concentrations in the ocular tissues reached the maximum between 15 minutes to 4 hours after a single ocular instillation of 0.03% ¹⁴C-omidenepag isopropyl ophthalmic solution into monkey eyes. High concentrations were observed especially in the cornea, conjunctiva and trabecular meshwork. In these tissues, the concentrations reached the peak level at 15 minutes after instillation, and ¹⁴C-omidenepag isopropyl was eliminated thereafter.

Glaucoma and ocular hypertension.

Dosage: The recommended dose is one drop in the affected eye(s) once daily. If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.
Paediatric population: The safety and efficacy of Omidenepag isopropyl (Eybelis) in children and adolescents have not yet been established. No data are available.
Method of administration: For ocular use.
Be careful not to touch the tip of the bottle to the eye directly in order to avoid the contamination of the drug. If more than one topical ophthalmic product is being used, each one should be administered at least 5 minutes apart.
Benzalkonium chloride may change the color of the contact lenses. Contact lens wearers should remove the contact lenses before using this product and wait at least 5 to 10 minutes before re-wearing them.

Overdose is unlikely to occur after ocular administration. If overdose occurs, treatment should be symptomatic.

Hypersensitivity to the active substance or to any of the excipients.
Patients with aphakic eyes or intraocular lens (IOL) inserted eyes.
Concomitant use with tafluprost.

Mild, reversible ocular inflammation has been reported during clinical trials. Omidenepag isopropyl (Eybelis) should be used with caution in patients with active ocular inflammation, including iritis/uveitis.
Macular edema including cystoid macular edema as well as iritis may occur. Patients should be instructed to immediately consult with medical professionals if they experience abnormalities such as worsening vision.
There is no clinical experience in patients with angle-closure glaucoma. It is advisable to use with caution in patients with angle-closure glaucoma.
Effects on ability to drive and use machine: Because temporary blurred vision or photophobia may develop after instilling this product, patients should be instructed not to drive or to operate machines until the symptom disappears.

Pregnancy: There are no adequate data from the use of Omidenepag isopropyl (Eybelis) in pregnant women. A study in rabbits has shown reproductive toxicity. Therefore, Omidenepag isopropyl (Eybelis) should be used in pregnant women or women who may possibly be pregnant only if the expected therapeutic benefits are judged to outweigh the possible risks associated with the treatment.
Breast-Feeding: It is unknown whether Omidenepag isopropyl (Eybelis) or its metabolites are excreted in human milk. A study in rats has shown Omidenepag isopropyl (Eybelis) was not detected in their milk after a single subcutaneous administration. When Omidenepag isopropyl (Eybelis) is used in breast-feeding women, breast feeding should be weighed, taking into consideration benefits of the therapy and breast-feeding.
Fertility: It is unknown whether Omidenepag isopropyl (Eybelis) or its metabolites affect fertility in humans. In rats, no treatment-related changes were noted in the parameters on fertility and early embryonic development. Risk benefit should be weighed when considering to use Omidenepag isopropyl (Eybelis) while trying to conceive.

Summary of the safety profile: In clinical studies conducted in Japan, 267 patients were treated with Omidenepag isopropyl (Eybelis) for up to 52 weeks. The most frequently reported adverse reaction was ocular hyperemia including conjunctival hyperemia (22.8%). It was mild in most cases and did not lead to discontinuation of treatment.
Tabulated list of adverse reaction: The following adverse reactions have been reported with omidenepag during clinical trials in Japan: (See Table 2).

Click on icon to see table/diagram/image

Description of selected adverse reactions: Macular edema (including cystoid macular edema): There were 14 cases (5.2%) with macular edema including cystoid macular edema. Events were mild to moderate in severity and vision returned to baseline with local treatment of corticosteroids or Nonsteroidal anti-inflammatory drugs (NSAIDs) and discontinuation of Omidenepag isopropyl (Eybelis). All of the events were found in patients with IOL inserted eye and the only currently identified risk factor for developing macular edema is pseudophakia (see Contraindications).
If symptoms such as worsening vision or visual impairment are found, vision should be checked and detailed ophthalmoscopy should be performed immediately. Additional testing such as optical coherence tomography (OCT) or fluorescence fundus angiography may be considered if available. If macular edema is present, appropriate measures such as discontinuation of this product should be taken (see Precautions).
Iritis: There were 4 cases (1.5%) with iritis and 5 cases (1.9%) with anterior chamber cells. Inflammation was generally mild in severity and resolved with local treatment with corticosteroids or NSAIDs, or discontinuation of Omidenepag isopropyl (Eybelis). No significant impact to IOP or vision was reported (see Precautions).

Tafluprost: Moderate to severe photophobia and ocular inflammation such as iritis were frequently seen in a clinical trial with concomitant administration of tafluprost and Omidenepag isopropyl (Eybelis) at dose of 0.003% to 0.03%. Although concomitant use of Omidenepag isopropyl (Eybelis) with tafluprost has not been studied, concomitant use may increase the risk of ocular inflammation because tafluprost is known to be associated with ocular inflammation. Therefore, Omidenepag isopropyl (Eybelis) must not be used concomitantly with tafluprost.
Glaucoma/ocular hypertension medications (such as timolol maleate) excluding tafluprost: Frequency of ocular inflammatory adverse reactions including conjunctival hyperemia was elevated in a clinical trial with concomitant administration of Omidenepag isopropyl (Eybelis) and timolol maleate. There is no experience of concomitant use with other drugs. Therefore, concomitant use of Omidenepag isopropyl (Eybelis) with other glaucoma/ocular hypertension medications should be done with caution.

Store at 2-8°C. After opening, store below 30°C and use within one month. Protect from light.

Antiglaucoma Preparations

S01EX06 - omidenepag ; Belongs to the class of other antiglaucoma preparations.

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