地塞米松玻璃体内植入物（Dexycu，Ozurdex）

品牌名称：Dexycu，Ozurdex

通用名称：地塞米松玻璃体内植入物

什么是地塞米松眼内（Dexycu，Ozurdex）？

地塞米松是一种用于治疗炎症的类固醇。 眼内地塞米松由医疗保健专业人员注射到眼睛中。

Dexycu是一种注入眼内的液体，用于治疗或预防白内障手术后的眼部炎症。

Ozurdex是一种溶解性植入物，注射到眼睛中以治疗眼睛中某些血管堵塞时可能发生的肿胀。 Ozurdex还用于治疗后葡萄膜炎（影响眼睛后部的炎症）。

地塞米松眼内注射也可用于本药物指南中未列出的用途。

地塞米松眼内（Dexycu，Ozurdex）有哪些可能的副作用？

如果您有过敏反应的迹象，请获得紧急医疗帮助：荨麻疹; 呼吸困难; 脸部，嘴唇，舌头或喉咙肿胀。

如果您有以下情况，请立即致电您的医生

§ 视力问题，眼睛疼痛或在灯光周围看到光晕;

§ 眼睛发红，增加眼睛对光线的敏感度; 要么

§ 愿景变化。

使用Ozurdex重复治疗可能会导致您患上白内障，这可能会影响您的视力并可能需要手术治疗。 您的医生将确定用该药治疗您的频率。

常见的副作用可能包括：

§ 在你的视野中看到“漂浮物”;

§ 模糊的视野;

§ 眼痛;

§ 感觉像是在你眼中的东西;

§ 眼睑肿胀;

§ 眼睛干涩 要么

§ 你的眼睛可能对光更敏感。

这不是副作用的完整列表，可能会出现其他副作用。 打电话给您的医生，征求有关副作用的医疗建议。 您可以在1-800-FDA-1088向FDA报告副作用。

关于地塞米松眼内（Dexycu，Ozurdex），我应该了解哪些最重要的信息？

如果您有眼部感染，晚期青光眼或眼部溃疡，手术或创伤导致眼睛晶状体受伤或破裂，您不应该接受Ozurdex治疗。

在接受地塞米松眼内（Dexycu，Ozurdex）之前，我应该与我的医务人员讨论什么？

如果您对地塞米松过敏，则不应该接受地塞米松治疗。

如果您有以下情况，您也不应该接受Ozurdex玻璃体内植入物 ：

§ 眼睛感染;

§ 晚期青光眼; 要么

§ 眼睛溃疡，手术或创伤导致眼睛晶状体受伤或破裂的病史。

如果您有过以下情况，请告诉您的医生：

§ 青光眼;

§ 一个独立的视网膜; 要么

§ 眼睛的细菌，病毒或真菌感染。

该药可能会恶化或重新激活您已经或已经患过的眼部感染（包括眼睛的疱疹感染）。

如果您怀孕或哺乳，请告诉您的医生。

如何给予地塞米松眼内（Dexycu，Ozurdex）？

地塞米松眼内注射将由医疗专业人员在诊所环境中注入您的眼睛。

注射该药后，您将密切注意眼睛的任何肿胀，炎症或压力增加。

地塞米松眼内注射会增加眼内压力。 您可能需要药物治疗或其他治疗来防止这种压力过高。 按照医生的指示。

如果我错过一剂（Dexycu，Ozurdex）会怎么样？

地塞米松眼内没有每日给药方案。

如果我服用过量会发生什么（Dexycu，Ozurdex）？

由于地塞米松眼内植入物含有特定量的药物，因此您不太可能接受过量服用。

接受地塞米松眼内（Dexycu，Ozurdex）后应该避免什么？

该药可能导致视力模糊，并可能损害您的反应。 在您能够清楚地看到之前，避免驾驶或危险活动。

还有哪些药物会影响地塞米松的眼内（Dexycu，Ozurdex）？

眼睛使用的药物不太可能受到您使用的其他药物的影响。 但是许多药物可以相互作用。 告诉您的每个医疗服务提供者您使用的所有药物，包括处方药和非处方药，维生素和草药产品。

您的医生或药剂师可以提供有关地塞米松眼内的更多信息。

Dexycu (dexamethasone) Intraocular Suspension

Date of Approval: February 9, 2018
Company: EyePoint Pharmaceuticals, Inc.
Treatment for: Postoperative Ocular Inflammation

Dexycu (dexamethasone) is a long-acting, injectable corticosteroid formulation administered intraocularly into the posterior chamber of the eye for the treatment of postoperative inflammation associated with cataract surgery.

Indications and Usage for Dexycu

Dexycu (dexamethasone intraocular suspension) 9% is indicated for the treatment of postoperative inflammation.

Dexycu Dosage and Administration

Dosing Information

Dexycu should be administered as a single dose, intraocularly in the posterior chamber at the end of surgery. The dose is 0.005 mL of dexamethasone 9% (equivalent to 517 micrograms).

Preparation and Administration

Each kit of Dexycu is for a single administration. After preparation, 0.005 mL will be administered.

The Dexycu administration kit contains the following items:

1. One glass vial: 0.5 mL of Dexycu

2. One sterile 1-mL syringe

3. One sterile syringe guide

4. One sterile syringe ring

5. One sterile 18-gauge needle (1½ inches long), plastic cap attached

6. One sterile 25-gauge bent cannula (8 mm long), plastic cap attached

Dosage Forms and Strengths

Dexycu contains dexamethasone 9% w/w (103.4 mg/mL) as a sterile suspension for intraocular ophthalmic administration. Dexycu is provided as a kit for administration of a single dose of 0.005 mL of 9% dexamethasone (equivalent to 517 micrograms of dexamethasone).

Contraindications

None.

Warnings and Precautions

Increase in Intraocular Pressure

Prolonged use of corticosteroids including Dexycu may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma.

Delayed Healing

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of corticosteroids.

Exacerbation of Infection

The use of Dexycu, as with other ophthalmic corticosteroids, is not recommended in the presence of most active viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal disease of ocular structures.

Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate.

Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection.

Cataract Progression

The use of corticosteroids in phakic individuals may promote the development of posterior subcapsular cataracts.

Adverse Reactions

The following adverse reactions are described elsewhere in the labeling:

· Increase in Intraocular Pressure [see Warning and Precautions (5.1)]

· Delayed Healing [see Warnings and Precautions (5.2)]

· Infection Exacerbation [see Warnings and Precautions (5.3)]

· Cataract Progression [see Warnings and Precautions (5.4)]

Clinical Trials Experience

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

The following adverse events rates are derived from three clinical trials in which 339 patients received the 517 microgram dose of Dexycu. The most commonly reported adverse reactions occurred in 5-15% of subjects and included increases in intraocular pressure, corneal edema and iritis. Other ocular adverse reactions occurring in 1-5% of subjects included, corneal endothelial cell loss, blepharitis, eye pain, cystoid macular edema, dry eye, ocular inflammation, posterior capsule opacification, blurred vision, reduced visual acuity, vitreous floaters, foreign body sensation, photophobia, and vitreous detachment.

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

There are no adequate and well-controlled studies of Dexycu (dexamethasone intraocular suspension) 9% in pregnant women. Topical ocular administration of dexamethasone in mice and rabbits during the period of organogenesis produced cleft palate and embryofetal death in mice and malformations of abdominal wall/intestines and kidneys in rabbits at doses 7 and 5 times higher than the injected recommended human ophthalmic dose (RHOD) of Dexycu (517 micrograms dexamethasone), respectively [see Data].

In the US general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Topical ocular administration of 0.15% dexamethasone (0.75 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.75 mg/kg/day in the mouse is approximately 7-times the injected RHOD of Dexycu, on a mg/m2 basis. In rabbits, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.20 mg/kg/day on gestational day 6, followed by 0.13 mg/kg/day on gestational days 7 – 18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A dose of 0.13 mg/kg/day in the rabbit is approximately 5-times the injected RHOD of Dexycu, on a mg/m2 basis. A no-observed-adverse-effect-level (NOAEL) was not identified in the mouse or rabbit studies.

Lactation

Risk Summary

Systemically administered corticosteroids are present in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects. There is no information regarding the presence of injected Dexycu in human milk, the effects on breastfed infants, or the effects on milk production to inform risk of Dexycu to an infant during lactation. The developmental and health benefits of breastfeeding should be considered, along with the mother's clinical need for Dexycu and any potential adverse effects on the breastfed child from Dexycu.

Pediatric Use

Safety and effectiveness of Dexycu in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between older and younger patients.

Dexycu Description

Dexycu (dexamethasone intraocular suspension) 9% is a corticosteroid, sterile, white to off-white opaque suspension for intraocular administration. Each vial of Dexycu contains 0.5 mL of 9% w/w dexamethasone suspension equivalent to 51.7 mg of dexamethasone. The inactive ingredient is acetyl triethyl citrate. Dexycu does not contain an antimicrobial preservative.

The chemical name of dexamethasone is pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. It has a molecular formula of C22H29FO5 and a molecular weight of 392.46 grams per mole. Its structural formula is:

Dexycu - Clinical Pharmacology

Mechanism of Action

Dexamethasone is a corticosteroid. Corticosteroids have been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage and migration of inflammatory cells.

Pharmacokinetics

Systemic exposure to dexamethasone was evaluated in a subgroup of patients enrolled in two studies (n=25 for the first study and n=13 for the second study). The patients received a single intraocular injection of Dexycu containing 342 mcg or 517 mcg of dexamethasone at the end of cataract surgery and blood samples were collected prior to surgery and at several time points post-surgery between Day 1 and up to Day 30. In the first study, the dexamethasone plasma concentrations on post-surgery Day 1 ranged from 0.09 to 0.86 ng/mL and from 0.07 to 1.16 ng/mL following administration of Dexycu 342 mcg and 517 mcg, respectively. In the second study, dexamethasone plasma concentrations on post-surgery Day 1 ranged from 0.349 to 2.79 ng/mL following administration of Dexycu 517 mcg. In both the studies, dexamethasone plasma concentrations declined over time and very few patients had quantifiable dexamethasone plasma concentrations at the final time point of sampling (Day 15 or Day 30).

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been conducted to determine whether Dexycu has the potential for carcinogenesis or mutagenesis. Fertility studies have not been conducted in animals

Clinical Studies

Clinical efficacy was evaluated in a randomized, double-masked, placebo-controlled trial (NCT02006888) in which subjects received either Dexycu or placebo (vehicle). A dose of 5 microliters of Dexycu (equivalent to 517 micrograms of dexamethasone), a dose equivalent to 342 micrograms of dexamethasone or vehicle was administered by the physician at the end of the surgical procedure. The primary efficacy endpoint for the study was the proportion of patients with anterior chamber cell clearing (i.e., cell score=0) on postoperative day (POD) 8. The presence of anterior cells was assessed using a slit lamp binocular microscope up to 30 days post treatment. The percentage of patients with anterior chamber clearing at Day 8 was 20% in the placebo group, and 57%, and 60% in the 342 and 517 microgram treatment groups, respectively (Table 1). The percentage of subjects receiving rescue medication of ocular steroid or NSAID was significantly lower at Day 3, 8, 15 and 30 in the 342 and 517 microgram treatment groups compared to placebo (Table 2).

How Supplied/Storage and Handling

Each kit of Dexycu contains a single dose for a single patient. The 2-mL glass vial is filled with 0.5 mL of 9% dexamethasone intraocular suspension and has a blue cap (NDC # 71879-001-01).

Each kit also contains one sterile 18-gauge, 1.5-inch needle with a plastic cap attached, one sterile plastic 1-mL syringe for withdrawal of the vial contents, one sterile 25-gauge 8-mm cannula with a plastic cap attached for the intraocular administration, and one syringe assembly pouch containing a sterile ring and a sterile syringe guide used for measuring and injection of the 0.005 mL dose.

Store at 20°C to 25°C (68°F to 77°F).

Manufactured for: EyePoint Pharmaceuticals US, Inc. Watertown, MA 02472

PRINCIPAL DISPLAY PANEL - 0.005 mL Vial Carton

Dexycu™
(dexamethasone intraocular suspension) 9%
0.005 mL dose in single dose vial
for intraocular administration

Please see enclosed full Prescribing Information for Instructions

Rx Only
NDC 71879-001-01

EYEPOINT™
PHARMACEUTICALS

For Intraocular Injection
Store at 20°C to 25°C (68°F to 77°F)

EyePoint Pharmaceuticals US, Inc