地塞米松植入剂

窗体顶端

窗体底端

药品名称:

通用名称：地塞米松植入剂
英文名称：Dexamethasone Implants
商品名称：地塞米松植入剂

成分:

地塞米松

适应症:

适用于由于白内障摘除并植入人工晶体后引起的术后眼内炎症。

用法用量:

在眼科手术结束并取出粘弹物质后，用精密无齿镊从包装中取出本品一粒放入眼前房或后房。如果放在前房，应将药料放在12点虹膜基底位置；如果放在后房，应放在虹膜和人工晶体前表面之间的6点位置，然后以常规方式闭合切口。
本品在使用前和使用时必须处于无菌状态，除非立即使用本品，其他任何时候不应该打开锡箔包装。

禁忌:

1. 有单纯疱疹性角膜炎、水痘和其它角膜和结膜的病毒性疾患者；
2. 分枝杆菌感染患者；
3. 眼组织真菌疾病患者；
4. 青光眼患者或有青光眼家庭史的患者；
5. 对肾上腺皮质激素类药有过敏史者。

注意事项:

1. 本品只能由有资格的眼科手术医生使用。
2. 本品的内外包装只允许在临用前而且是在无菌手术室内方可拆开。
3. 在临床研究中没有发现在植入本品时应特别的注意事项。

不良反应:

在临床试验中没有发现与植入本品直接有关的系统性的不良反应和局部刺激作用。本品一般不会引起眼压升高，因个体差异，偶可出现眼压升高，但均为可逆性，用药后即可恢复正常..

Ozurdex

Generic Name: dexamethasone
Dosage Form: intravitreal implant

Ozurdex® (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

Ozurdex® is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.

Ozurdex® is indicated for the treatment of diabetic macular edema.

For ophthalmic intravitreal injection.

The intravitreal injection procedure should be carried out under controlled aseptic conditions which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide applied to the periocular skin, eyelid and ocular surface are recommended to be given prior to the injection.

Remove the foil pouch from the carton and examine for damage. Then, open the foil pouch over a sterile field and gently drop the applicator on a sterile tray. Carefully remove the cap from the applicator. Hold the applicator in one hand and pull the safety tab straight off the applicator. Do not twist or flex the tab. The long axis of the applicator should be held parallel to the limbus, and the sclera should be engaged at an oblique angle with the bevel of the needle up (away from the sclera) to create a shelved scleral path. The tip of the needle is advanced within the sclera for about 1 mm (parallel to the limbus), then re-directed toward the center of the eye and advanced until penetration of the sclera is completed and the vitreous cavity is entered. The needle should not be advanced past the point where the sleeve touches the conjunctiva.

Slowly depress the actuator button until an audible click is noted. Before withdrawing the applicator from the eye, make sure that the actuator button is fully depressed and has locked flush with the applicator surface. Remove the needle in the same direction as used to enter the vitreous.

Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.

Each applicator can only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new applicator must be used, and the sterile field, syringe, gloves, drapes, and eyelid speculum should be changed before Ozurdex® is administered to the other eye.

Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR® solid polymer drug delivery system.

Ozurdex® (dexamethasone intravitreal implant) is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

Ozurdex® is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8.

Ozurdex® is contraindicated in patients whose posterior lens capsule is torn or ruptured because of the risk of migration into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for Ozurdex® use.

Ozurdex® is contraindicated in patients with known hypersensitivity to any components of this product [see Adverse Reactions (6)].

Intravitreal injections, including those with Ozurdex®, have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored regularly following the injection [see Patient Counseling Information (17)].

Use of corticosteroids including Ozurdex® may produce posterior subcapsular cataracts, increased intraocular pressure, and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses [see Adverse Reactions (6.1)].

Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection.

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.

Adverse reactions associated with ophthalmic steroids including Ozurdex® include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

Retinal Vein Occlusion and Posterior Segment Uveitis

The following information is based on the combined clinical trial results from 3 initial, randomized, 6-month, sham-controlled studies (2 for retinal vein occlusion and 1 for posterior segment uveitis):

Increased IOP with Ozurdex® peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received Ozurdex® required surgical procedures for management of elevated IOP.

Following a second injection of Ozurdex® in cases where a second injection was indicated, the overall incidence of cataracts was higher after 1 year.

Diabetic Macular Edema

The following information is based on the combined clinical trial results from 2 randomized, 3-year, sham-controlled studies in patients with diabetic macular edema. Discontinuation rates due to the adverse reactions listed in Table 2 were 3% in the Ozurdex® group and 1% in the Sham group. The most common ocular (study eye) and non-ocular adverse reactions are shown in Tables 2 and 3:

Increased Intraocular Pressure

The increase in mean IOP was seen with each treatment cycle, and the mean IOP generally returned to baseline between treatment cycles (at the end of the 6 month period) shown below:

Figure 1: Mean IOP during the study

Cataracts and Cataract Surgery

At baseline, 243 of the 324 Ozurdex® subjects were phakic; 230 of 328 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the Ozurdex® group (68%) compared with Sham (21%). The median time of cataract being reported as an adverse event was approximately 15 months in the Ozurdex® group and 12 months in the Sham group. Among these patients, 61% of Ozurdex® subjects vs. 8% of sham-controlled subjects underwent cataract surgery, generally between Month 18 and Month 39 (Median Month 21 for Ozurdex® group and 20 for Sham) of the studies.

The following reactions have been identified during post-marketing use of Ozurdex® in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to Ozurdex®, or a combination of these factors, include: complication of device insertion (implant misplacement), device dislocation with or without corneal edema, endophthalmitis, hypotony of the eye (associated with vitreous leakage due to injection), and retinal detachment.

Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies with Ozurdex® in pregnant women. Animal reproduction

studies using topical ocular administration of dexamethasone were conducted in mice and rabbits. Cleft palate and embryofetal death in mice and malformations of the intestines and kidneys in rabbits were observed. Ozurdex® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal Data

Topical ocular administration of 0.15% dexamethasone (0.375 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.375 mg/kg/day in the mouse is approximately 3 times an Ozurdex® injection in humans (0.7 mg dexamethasone) on a mg/m2 basis. In rabbits, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.13 mg/kg/day, on gestational day 6 followed by 0.20 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 4 times an Ozurdex® injection in humans (0.7 mg dexamethasone) on a mg/m2 basis.

Systemically administered corticosteroids are present in human milk and can suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of dexamethasone following intravitreal treatment with Ozurdex® is low [see Clinical Pharmacology (12.3)]. It is not known whether intravitreal treatment with Ozurdex® could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when Ozurdex® is administered to a nursing woman.

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

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

Ozurdex® is an intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR®solid polymer sustained-release drug delivery system. Ozurdex® is preloaded into a single-use, DDS®applicator to facilitate injection of the rod-shaped implant directly into the vitreous. The NOVADUR®system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix without a preservative. The chemical name for dexamethasone is Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. Its structural formula is:

MW 392.47; molecular formula: C22H29FO5

Dexamethasone occurs as a white to cream-colored crystalline powder having not more than a slight odor, and is practically insoluble in water and very soluble in alcohol.

The PLGA matrix slowly degrades to lactic acid and glycolic acid.

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

Plasma concentrations were obtained from 21 patients with macular edema due to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), and 21 patients with diabetic macular edema (DME) prior to dosing and at 4 to 5 additional post-dose timepoints on Days 1, 7, 21, 30, 45, 60, and 90 following the administration of the first intravitreal implant containing 0.7 mg dexamethasone. In RVO and DME patients, the majority of plasma dexamethasone concentrations were below the lower limit of quantitation (LLOQ = 50 pg/mL). Plasma dexamethasone concentrations from 12% of samples were above the LLOQ, ranging from 52 pg/mL to 102 pg/mL. Plasma dexamethasone concentration did not appear to be related to age, body weight, or sex of patients.

In an in vitro metabolism study, following the incubation of [14C]-dexamethasone with human cornea, iris-ciliary body, choroid, retina, vitreous humor, and sclera tissues for 18 hours, no metabolites were observed.

No adequate studies in animals have been conducted to determine whether Ozurdex®(dexamethasone intravitreal implant) has the potential for carcinogenesis.

Although no adequate studies have been conducted to determine the mutagenic potential of Ozurdex®, dexamethasone has been shown to have no mutagenic effects in bacterial and mammalian cells in vitro or in the in vivo mouse micronucleus test.

Adequate fertility studies have not been conducted in animals.

Retinal Vein Occlusion

The efficacy of Ozurdex® for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) was assessed in two, multicenter, double-masked, randomized, parallel studies.

Following a single injection, Ozurdex® demonstrated the following clinical results for the percent of patients with ≥ 15 letters of improvement from baseline in best-corrected visual acuity (BCVA):

In each individual study and in a pooled analysis, time to achieve ≥ 15 letters (3-line) improvement in BCVA cumulative response rate curves were significantly faster with Ozurdex® compared to sham (p < 0.01), with Ozurdex® treated patients achieving a 3-line improvement in BCVA earlier than sham-treated patients.

The onset of a ≥ 15 letter (3-line) improvement in BCVA with Ozurdex® occurs within the first two months after implantation in approximately 20-30% of subjects. The duration of effect persists approximately one to three months after onset of this effect.

Posterior Segment Uveitis

The efficacy of Ozurdex® was assessed in a single, multicenter, masked, randomized study of 153 patients with non-infectious uveitis affecting the posterior segment of the eye.

After a single injection, the percent of patients reaching a vitreous haze score of 0 (where a score of 0 represents no inflammation) was statistically significantly greater for patients receiving Ozurdex®versus sham at week 8 (primary time point) (47% versus 12%). The percent of patients achieving a 3-line improvement from baseline BCVA was 43% for patients receiving Ozurdex® versus 7% for sham at week 8.

Diabetic Macular Edema

The efficacy of Ozurdex® for the treatment of diabetic macular edema was assessed in two, multicenter, masked, randomized, sham-controlled studies. Subjects were to be evaluated for retreatment eligibility every three months starting from Month 6 but could only receive successive treatments at least 6 months apart. Retreatment was based on physician's discretion after examination including Optical Coherence Tomography. Patients in the Ozurdex® arm received an average of 4 treatments during the 36 months.

The primary endpoint was the proportion of patients with 15 or more letters improvement in BCVA from baseline at Month 39 or final visit for subjects who exited the study at or prior to Month 36. The Month 39 extension was included to accommodate the evaluation of safety and efficacy outcomes for subjects who received re-treatment at Month 36. Only fourteen percent of the study patients completed the Month 39 visit (16.8% from Ozurdex® and 12.2% from Sham).

Visual acuity outcomes by lens status (Phakic or Pseudophakic) at different visits are presented in Figure 2 and Figure 3. The occurrence of cataracts impacted visual acuity during the study. The visual acuity improvement from baseline increases during a treatment cycle, peaks at approximately 3 Months posttreatment and diminishes thereafter. Patients who were pseudophakic at baseline achieved greater mean BCVA change from baseline at the final study visit.

Figure 2: Proportion of Subjects with ≥ 15 Letters Improvement from Baseline BCVA in the Study Eye

Figure 3: Mean BCVA Change from Baseline

The best corrected visual acuity outcomes for the Pseudophakic and Phakic subgroups from Studies 1 and 2 at Month 39 are presented in Table 6.

Ozurdex® (dexamethasone intravitreal implant) 0.7 mg is supplied in a foil pouch with 1 single-use plastic applicator, NDC 0023-3348-07.

Storage: Store at 15°-30°C (59°-86°F).

Steroid-related Effects

Advise patients that a cataract may occur after repeated treatment with Ozurdex®. If this occurs, advise patients that their vision will decrease, and they will need an operation to remove the cataract and restore their vision.

Advise patients that they may develop increased intraocular pressure with Ozurdex® treatment, and the increased IOP will need to be managed with eye drops, and, rarely, with surgery.

Intravitreal Injection-related Effects

Advise patients that in the days following intravitreal injection of Ozurdex®, patients are at risk for potential complications including in particular, but not limited to, the development of endophthalmitis or elevated intraocular pressure.

When to Seek Physician Advice

Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist.

Driving and Using Machines

Inform patients that they may experience temporary visual blurring after receiving an intravitreal injection. Advise patients not to drive or use machines until this has been resolved.

© 2014Allergan, Inc.
Irvine, CA 92612, U.S.A.
® marks owned by Allergan, Inc.
Patented. See: www.allergan.com/products/patent_notices
Made inIreland.

72212US18

Ozurdex ®
(dexamethasone
intravitreal implant) 0.7 mg

Contents include:
One Sterile, Single-Use Applicator

NDC 0023-3348-07 
For Intravitreal Injection Only
Rx only
ALLERGAN

Revised: 09/2014

Allergan, Inc.