openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
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 ). 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 BYOOVIZ. In addition, patients should be monitored following the injection to permit early treatment should an infection occur [ see Dosage and Administration (2.5 , 2.6) 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 BYOOVIZ and manage appropriately [ see Dosage and Administration (2.6) ]. 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 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 (PDT)], 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 two 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) [ see Clinical Studies (14.2) ]. 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. 5.4 Retinal Vasculitis with or without Occlusion Retinal vasculitis with or without occlusion, typically in the presence of preexisting intraocular inflammation or post-treatment with other intravitreal agents, have been reported with the use of ranibizumab products. Discontinue treatment with BYOOVIZ in patients who develop these events. Patients should be instructed to report any change in vision without delay [ see Patient Counseling Information (17) ].
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) ] 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 Harrow Eye, LLC™ at 1-833-442-7769 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 the same or 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. 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 AMD, and RVO Studies Adverse Reaction AMD 2-year AMD 1-year RVO 6-month Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control n=379 n=379 n=440 n=441 n=259 n=260 Conjunctival hemorrhage 74% 60% 64% 50% 48% 37% Eye pain 35% 30% 26% 20% 17% 12% Vitreous floaters 27% 8% 19% 5% 7% 2% Intraocular pressure increased 24% 7% 17% 5% 7% 2% Vitreous detachment 21% 19% 15% 15% 4% 2% Intraocular inflammation 18% 8% 13% 7% 1% 3% Cataract 17% 14% 11% 9% 2% 2% Foreign body sensation in eyes 16% 14% 13% 10% 7% 5% Eye irritation 15% 15% 13% 12% 7% 6% Lacrimation increased 14% 12% 8% 8% 2% 3% Blepharitis 12% 8% 8% 5% 0% 1% Dry eye 12% 7% 7% 7% 3% 3% Visual disturbance or vision blurred 18% 15% 13% 10% 5% 3% Eye pruritis 12% 11% 9% 7% 1% 2% Ocular hyperemia 11% 8% 7% 4% 5% 3% Retinal disorder 10% 7% 8% 4% 2% 1% Maculopathy 9% 9% 6% 6% 11% 7% Retinal degeneration 8% 6% 5% 3% 1% 0% Ocular discomfort 7% 4% 5% 2% 2% 2% Conjunctival hyperemia 7% 6% 5% 4% 0% 0% Posterior capsule opacification 7% 4% 2% 2% 0% 1% Injection site hemorrhage 5% 2% 3% 1% 0% 0% Non-Ocular Reactions Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving ranibizumab for AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with ranibizumab compared to control are shown in Table 2. Though less common, wound healing complications were also observed in some studies. Table 2 Non-Ocular Reactions in the AMD, and RVO Studies Adverse Reaction AMD 2-year AMD 1-year RVO 6-month Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control n=379 n=379 n=440 n=441 n=259 n=260 Nasopharyngitis 16% 13% 8% 9% 5% 4% Anemia 8% 7% 4% 3% 1% 1% Nausea 9% 6% 5% 5% 1% 2% Cough 9% 8% 5% 4% 1% 2% Constipation 5% 7% 3% 4% 0% 1% Seasonal allergy 4% 4% 2% 2% 0% 2% Hypercholesterolemia 5% 5% 3% 2% 1% 1% Influenza 7% 5% 3% 2% 3% 2% Renal failure 1% 1% 0% 0% 0% 0% Upper respiratory tract infection 9% 8% 5% 5% 2% 2% Gastroesophageal reflux disease 4% 6% 3% 4% 1% 0% Headache 12% 9% 6% 5% 3% 3% Edema peripheral 3% 5% 2% 3% 0% 1% Renal failure chronic 0% 1% 0% 0% 0% 0% Neuropathy peripheral 1% 1% 1% 0% 0% 0% Sinusitis 8% 7% 5% 5% 3% 2% Bronchitis 11% 9% 6% 5% 0% 2% Atrial fibrillation 5% 4% 2% 2% 1% 0% Arthralgia 11% 9% 5% 5% 2% 1% Chronic obstructive pulmonary disease 6% 3% 3% 1% 0% 0% Wound healing complications 1% 1% 1% 0% 0% 0% 6.3 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ranibizumab or of other ranibizumab products. The pre-treatment incidence of immunoreactivity to ranibizumab was 0%-5% across treatment groups. After monthly dosing with ranibizumab for 6 to 24 months, antibodies to ranibizumab were detected in approximately 1%-9% of patients. The clinical significance of immunoreactivity to ranibizumab products are unclear at this time. Among neovascular AMD patients with the highest levels of immunoreactivity, some were noted to have iritis or vitritis. Intraocular inflammation was not observed in patients with RVO patients with the highest levels of immunoreactivity. 6.4 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ranibizumab products. 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. Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD