FDA label a7e43b10-ebb6-2d40-e053-2a95a90a4914

5 WARNINGS AND PRECAUTIONS Decreases in vision due to progression of the condition with traction may occur requiring surgical intervention. Patients should be monitored and instructed to report any symptoms without delay. ( 5.1 ) Intravitreal injection procedure associated effects (intraocular inflammation/infection, intraocular hemorrhage and increased intraocular pressure (IOP)) may occur following an intravitreal injection. Patients should be monitored and instructed to report any symptoms without delay. ( 5.2 ) Potential for lens subluxation. ( 5.3 ) 5.1 Decreased Vision A decrease of ≥ 3 line of best corrected visual acuity (BCVA) was experienced by 5.6% of patients treated with JETREA and 3.2% of patients treated with vehicle in the controlled trials [see Clinical Studies (14) ]. The majority of these decreases in vision were due to progression of the condition with traction and many required surgical intervention. Patients should be monitored appropriately [see Dosage And Administration (2.4) ] . 5.2 Intravitreal Injection Procedure Associated Effects Intravitreal injections are associated with intraocular inflammation / infection, intraocular hemorrhage and increased intraocular pressure (IOP). In the controlled trials, intraocular inflammation occurred in 7.1% of patients injected with JETREA vs. 3.7% of patients injected with vehicle. Most of the post-injection intraocular inflammation events were mild and transient. Intraocular hemorrhage occurred in 2.4% vs. 3.7% of patients injected with JETREA vs. vehicle, respectively. Increased intraocular pressure occurred in 4.1% vs. 5.3% of patients injected with JETREA vs. vehicle, respectively. 5.3 Potential for Lens Subluxation One case of lens subluxation was reported in a premature infant who received an intravitreal injection of 0.175 mg (1.4 times higher than the recommended dose) [see Use in Specific Populations (8.4) ]. Lens subluxation was observed in three animal species (monkey, rabbit, minipig) following a single intravitreal injection that achieved vitreous concentrations of ocriplasmin 1.4 times higher than achieved with the recommended treatment dose. Administration of a second intravitreal dose in monkeys, 28 days apart, produced lens subluxation in 100% of the treated eyes [see Nonclinical Toxicology (13.2) ]. 5.4 Retinal Breaks In the controlled trials, the incidence of retinal detachment was 0.9% in the JETREA group and 1.6% in the vehicle group, while the incidence of retinal tear (without detachment) was 1.1% in the JETREA group and 2.7% in the vehicle group. Most of these events occurred during or after vitrectomy in both groups. The incidence of retinal detachment that occurred pre-vitrectomy was 0.4% in the JETREA group and none in the vehicle group, while the incidence of retinal tear (without detachment) that occurred pre-vitrectomy was none in the JETREA group and 0.5% in the vehicle group. 5.5 Dyschromatopsia Dyschromatopsia (generally described as yellowish vision) was reported in 2% of all patients injected with JETREA. In approximately half of these dyschromatopsia cases there were also electroretinographic (ERG) changes reported (a- and b-wave amplitude decrease).

6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Decreased Vision [see Warnings and Precautions (5.1) ] Intravitreal Injection Procedure Associated Effects [see Warnings and Precautions (5.2) and Dosage And Administration (2.4) ] Potential for Lens Subluxation [see Warnings and Precautions (5.3) ] Retinal Breaks [see Warnings and Precautions (5.4) and Dosage And Administration (2.4) ] Dyschromatopsia [see Warnings and Precautions (5.5) ] The most commonly reported reactions (≥ 5%) in patients treated with JETREA were vitreous floaters, conjunctival hemorrhage, eye pain, photopsia, blurred vision, macular hole, reduced visual acuity, visual impairment, and retinal edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ThromboGenics Inc. at 1-855-253-7396 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates in one clinical trial of a drug cannot be directly compared with rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice. Approximately 800 patients have been treated with an intravitreal injection of JETREA. Of these, 465 patients received an intravitreal injection of ocriplasmin 0.125 mg (187 patients received vehicle) in the 2 vehicle-controlled studies (Study 1 and Study 2). The most common adverse reactions (incidence 5% - 20% listed in descending order of frequency) in the vehicle-controlled clinical studies were: vitreous floaters, conjunctival hemorrhage, eye pain, photopsia, blurred vision, macular hole, reduced visual acuity, visual impairment, and retinal edema. Less common adverse reactions observed in the studies at a frequency of < 5% in patients treated with JETREA included macular edema, increased intraocular pressure, anterior chamber cell, photophobia, vitreous detachment, ocular discomfort, iritis, cataract, dry eye, metamorphopsia, pupillary reflex impaired, conjunctival hyperemia, retinal degeneration, and visual symptoms perceived in the contralateral eye. Dyschromatopsia was reported in 2% of patients injected with JETREA, with the majority of cases reported from two uncontrolled clinical studies. In approximately half of these dyschromatopsia cases there were also electroretinographic (ERG) changes reported (a- and b-wave amplitude decrease). 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. Immunogenicity for this product has not been evaluated. 6.3 Postmarketing Experience Night blindness has been identified during post-approval use of JETREA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.