Important Safety Information
- CIMERLI™ is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI™. Hypersensitivity reactions may manifest as severe intraocular inflammation
WARNINGS & PRECAUTIONS
- 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 utilized when administering CIMERLI™. Patients should be monitored following the injection to permit early treatment, should an infection occur
- Increases in Intraocular Pressure: Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with CIMERLI™ and manage appropriately
- 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. ATEs 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 3 controlled neovascular AMD studies 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. 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 similar to rates observed in Studies AMD-1, AMD-2, and AMD-3
- In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of ranibizumab used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg ranibizumab compared to 1.1% (5 of 435) in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)])
Macular edema following retinal vein occlusion
- The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the ranibizumab and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab and 2 of 260 in the control arms). The stroke rate was 0.2% (1 of 525) in the combined group of ranibizumab-treated patients compared to 0.4% (1 of 260) in the control arms
Diabetic macular edema and Diabetic Retinopathy
- In a pooled analysis of Studies D-1 and D-2, the ATE rate at 2 years was 7.2% (18 of 250) with 0.5 mg ranibizumab, 5.6% (14 of 250) with 0.3 mg ranibizumab, and 5.2% (13 of 250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg ranibizumab, 1.2% (3 of 250) with 0.3 mg ranibizumab, and 1.6% (4 of 250) with control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg ranibizumab and 10.8% (27 of 250) with 0.3 mg ranibizumab; the stroke rate was 4.8% (12 of 249) with 0.5 mg ranibizumab and 2.0% (5 of 250) with 0.3 mg ranibizumab
- Fatal events in patients with diabetic macular edema and diabetic retinopathy at baseline: A pooled analysis of Studies D-1 and D-2 showed that fatalities in the first 2 years occurred in 4.4% (11 of 250) of patients treated with 0.5 mg ranibizumab, in 2.8% (7 of 250) of patients treated with 0.3 mg ranibizumab, and in 1.2% (3 of 250) of control patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated with 0.5 mg ranibizumab and in 4.4% (11 of 250) of patients treated with 0.3 mg ranibizumab. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded
- Serious adverse events related to the injection procedure have occurred in <0.1% of intravitreal injections, including endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
- In ranibizumab-treated patients compared with the control group, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, and intraocular pressure. The most common non-ocular side effects included nasopharyngitis, anemia, nausea, and cough.
- As with all therapeutic proteins, there is the potential for an immune response in patients treated with ranibizumab products. The clinical significance of immunoreactivity to ranibizumab products is unclear at this time
The following adverse reaction has been identified during post-approval use of ranibizumab products:
- Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD
To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences at 1-800-483-3692 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch (opens in a new tab).