Clinical Studies 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.
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):
Table 1: Adverse Reactions Reported by Greater than 2% of Patients
|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.
Diabetic Macular Edema
The following information is based on the combined clinical trial results from 2 randomized, 3year, 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:
Table 2: Ocular Adverse Reactions Reported by ≥ 1% of Patients and Non-ocular Adverse Reactions Reported by ≥ 5% of Patients
|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%)|
|Hypertension||41 (13%)||21 (6%)|
|Bronchitis||15 (5%)||8 (2%)|
|1Includes 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.
2243 of the 324 OZURDEX® subjects were phakic at baseline; 230 of 328 sham-controlled subjects were phakic at baseline.
Increased Intraocular Pressure
Table 3: Summary of Elevated Intraocular Pressure (IOP) Related Adverse Reactions
|IOP||Treatment: N (%)|
|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 iridectomy
Sham: 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.
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.