OZURDEX: Package Insert and Label Information
OZURDEX- dexamethasone implant
Allergan, Inc.
1 INDICATIONS AND USAGE
1.1 Retinal Vein Occlusion
OZURDEX ® (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
1.2 Posterior Segment Uveitis
OZURDEX ® is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.
1.3 Diabetic Macular Edema
OZURDEX ® is indicated for the treatment of diabetic macular edema.
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
For ophthalmic intravitreal injection.
2.2 Administration
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.
3 DOSAGE FORMS AND STRENGTHS
Intravitreal implant containing dexamethasone 0.7 mg in the N OVADUR ® solid polymer drug delivery system.
4 CONTRAINDICATIONS
4.1 Ocular or Periocular Infections
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.
4.2 Glaucoma
OZURDEX ® is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8.
4.3 Torn or Ruptured Posterior Lens Capsule
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.
4. 4 Hypersensitivity
OZURDEX ® is contraindicated in patients with known hypersensitivity to any components of this product [see Adverse Reactions ( 6)].
5 WARNINGS AND PRECAUTIONS
5.1 Intravitreal Injection-related Effects
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)].
5.2 Steroid-related Effects
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.
6 ADVERSE REACTIONS
Figure 1: Mean IOP during the study6.1 Clinical Trials Experience
Because clinical trials 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):
| MedDRA Term | OZURDEX ® N=497 (%) | Sham N=498 (%) |
| Intraocular pressure increased | 125 (25%) | 10 (2%) |
| Conjunctival hemorrhage | 108 (22%) | 79 (16%) |
| Eye pain | 40 (8%) | 26 (5%) |
| Conjunctival hyperemia | 33 (7%) | 27 (5%) |
| Ocular hypertension | 23 (5%) | 3 (1%) |
| Cataract | 24 (5%) | 10 (2%) |
| Vitreous detachment | 12 (2%) | 8 (2%) |
| Headache | 19 (4%) | 12 (2%) |
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.
In a 2 year observational study, among patients who received >2 injections, the most frequent adverse reaction was cataract 54% (n= 96 out of 178 phakic eyes at baseline). Other frequent adverse reactions from the 283 treated eyes, regardless of lens status at baseline, were increased IOP 24% (n = 68) and vitreous hemorrhage 6.0% (n = 17).
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:
| MedDRA Term | OZURDEX ® N=324 (%) | Sham N=328 (%) |
| Ocular | ||
| Cataract1 | 166/2432 (68%) | 49/230 (21%) |
| Conjunctival hemorrhage | 73 (23%) | 44 (13%) |
| Visual acuity reduced | 28 (9%) | 13 (4%) |
| Conjunctivitis | 19 (6%) | 8 (2%) |
| Vitreous floaters | 16 (5%) | 6 (2%) |
| Conjunctival edema | 15 (5%) | 4 (1%) |
| Dry eye | 15 (5%) | 7 (2%) |
| Vitreous detachment | 14 (4%) | 8 (2%) |
| Vitreous opacities | 11 (3%) | 3 (1%) |
| Retinal aneurysm | 10 (3%) | 5 (2%) |
| Foreign body sensation | 7 (2%) | 4 (1%) |
| Corneal erosion | 7 (2%) | 3 (1%) |
| Keratitis | 6 (2%) | 3 (1%) |
| Anterior Chamber Inflammation | 6 (2%) | 0 (0%) |
| Retinal tear | 5 (2%) | 2 (1%) |
| Eyelid ptosis | 5 (2%) | 2 (1%) |
| Non-ocular | ||
| Hypertension | 41 (13%) | 21 (6%) |
| Bronchitis | 15 (5%) | 8 (2%) |
1 Includes cataract, cataract nuclear, cataract subcapsular, lenticular opacities in patients who were phakic at baseline. Among these patients, 61% of OZURDEX ® subjects vs. 8% of sham-controlled subjects underwent cataract surgery.
2 243 of the 324 OZURDEX ® subjects were phakic at baseline; 230 of 328 sham-controlled subjects were phakic at baseline.
Increased Intraocular Pressure
| IOP | Treatment: N (%) | |
| OZURDEX ® N=324 | Sham N=328 | |
| IOP elevation ≥10 mm Hg from Baseline at any visit | 91 (28%) | 13 (4%) |
| ≥30 mm Hg IOP at any visit | 50 (15%) | 5 (2%) |
| Any IOP lowering medication | 136 (42%) | 32 (10%) |
| Any surgical intervention for elevated IOP * | 4 (1.2%) | 1 (0.3%) |
* OZURDEX ®: 1 surgical trabeculectomy for steroid-induced IOP increase, 1 surgical trabeculectomy for iris neovascularization,
1 laser iridotomy, 1 surgical iridectomySham: 1 laser iridotomy
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.
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