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warnings and cautions
5 WARNINGS AND PRECAUTIONS • Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be monitored following the injection ( 5.1 ). • Increases in intraocular pressure (IOP) have been noted both pre- and post-intravitreal injection ( 5.2 ). • There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors ( 5.3 ). • Fatal events occurred more frequently in patients with DME and DR at baseline, who were treated monthly with ranibizumab compared with control ( 5.4 ). 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering CIMERLI. In addition, patients should be monitored following the injection to permit early treatment should an infection occur [see Dosage and Administration ( 2.6 , 2.7) and Patient Counseling Information ( 17 )] . 5.2 Increases in Intraocular Pressure Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with CIMERLI and manage appropriately [see Dosage and Administration ( 2.7 )] . 5.3 Thromboembolic Events Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). Neovascular (Wet) Age-Related Macular Degeneration The ATE rate in the three controlled neovascular AMD studies (AMD-1, AMD-2, AMD-3) during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab compared with 1.1% (5 of 441) in patients from the control arms [see Clinical Studies ( 14.1 )] . In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of ranibizumab-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were simil...
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adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Endophthalmitis and Retinal Detachments [see Warnings and Precautions ( 5.1 )] • Increases in Intraocular Pressure [see Warnings and Precautions ( 5.2 )] • Thromboembolic Events [see Warnings and Precautions ( 5.3 )] • Fatal Events in patients with DME and DR at baseline [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (reported more frequently in ranibizumab-treated subjects than control subjects) are conjunctival hemorrhage, eye pain, vitreous floaters, and increased IOP ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Injection Procedure Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings and Precautions ( 5.1 )] , rhegmatogenous retinal detachment, and iatrogenic traumatic cataract. 6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data below reflect exposure to 0.5 mg ranibizumab in 440 patients with neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients with macular edema following RVO. The data also reflect exposure to 0.3 mg ranibizumab in 250 patients with DME and DR at baseline [see Clinical Studies ( 14 )] . Safety data observed in 224 patients with mCNV, as well as Studies AMD-4 and D-3, were consistent with these results. On average, the rates and types of adverse reactions in patients were not significantly affected by dosing regimen. Ocular Reactions Table 1 shows frequently reported ocular adverse reactions in ranibizumab-treated patients compared with the control group. Table 1 Ocular Reactions in the DME and DR, AMD, and RVO Studies Adverse Reaction DME and DR 2-year AMD 2-year AMD 1-year RVO 6-month Ranibizumab 0.3 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 Conjunctival hemorrhage 47% 32% 74% 60% 64% 50% 48% 37% Eye pain 17% 13% 35% 30% 26% 20% 17% 12% Vitr...
adverse reactions table
Table 1 Ocular Reactions in the DME and DR, AMD, and RVO StudiesAdverse ReactionDME and DR 2-yearAMD 2-yearAMD 1-yearRVO 6-monthRanibizumab 0.3 mg ControlRanibizumab 0.5 mg ControlRanibizumab 0.5 mg ControlRanibizumab 0.5 mg Controln=250n=250n=379n=379n=440n=441n=259n=260Conjunctival hemorrhage47%32%74%60%64%50%48%37%Eye pain17%13%35%30%26%20%17%12%Vitreous floaters10%4%27%8%19%5%7%2%Intraocular pressure increased18%7%24%7%17%5%7%2%Vitreous detachment11%15%21%19%15%15%4%2%Intraocular inflammation4%3%18%8%13%7%1%3%Cataract28%32%17%14%11%9%2%2%Foreign body sensation in eyes10%5%16%14%13%10%7%5%Eye irritation8%5%15%15%13%12%7%6%Lacrimation increased5%4%14%12%8%8%2%3%Blepharitis3%2%12%8%8%5%0%1%Dry eye5%3%12%7%7%7%3%3%Visual disturbance or vision blurred8%4%18%15%13%10%5%3%Eye pruritis4%4%