Eylea

aflibercept · Injection, Solution · Intravitreal

Prescription (Rx) Vascular Endothelial Growth Factor Inhibitor 2 recalls

Uses

1 INDICATIONS AND USAGE EYLEA is indicated for the treatment of: EYLEA is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.2 ) Diabetic Macular Edema (DME) ( 1.3 ) Diabetic Retinopathy (DR) ( 1.4 ) Retinopathy of Prematurity (ROP) ( 1.5 ) 1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 1.2 Macular Edema Following Retinal Vein Occlusion (RVO) 1.3 Diabetic Macular Edema (DME) 1.4 Diabetic Retinopathy (DR) 1.5 Retinopathy of Prematurity (ROP)

Dosage and administration

Neovascular (Wet) Age-Related Macular Degeneration (AMD) The recommended dose for EYLEA is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). ( 2.5 ) Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months). ( 2.5 ) Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly. ( 2.5 ) Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for EYLEA is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly). ( 2.6 ) Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR) The recommended dose for EYLEA is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). ( 2.7 , 2.8 ) Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months). (2.7 , 2.8 ) Retinopathy of Prematurity (ROP) The recommended dose for EYLEA is 0.4 mg (0.01 mL or 10 microliters of 40 mg/mL solution) administered by intravitreal injection. Treatment may be given bilaterally on the same day. Injections may be repeated in each eye. The treatment interval between doses injected into the same eye should be at least 10 days. ( 2.9 ) 2.1 Important Injection Instructions For ophthalmic intravitreal injection. EYLEA must only be administered by a qualified physician. Pre-filled Syringe: A 30-gauge × ½-inch sterile injection needle is needed but not provided. Vial: A 5-micron sterile filter needle (18-gauge × 1½-inch), a 1-mL Luer lock syringe and a 30-gauge × ½-inch sterile injection needle are needed. EYLEA is available packaged as follows: Pre-filled Syringe Vial Kit with Injection Components (filter needle, syringe, injection needle) [see How Supplied/Storage and Handling (16) ]. 2.2 Preparation for Administration – Pre-filled Syringe The EYLEA pre-filled glass syringe is sterile and for one-time use in one eye only. Do not use the EYLEA pre-filled syringe for the treatment of ROP. The pre-filled syringe should be inspected visually prior to administration. Do not use if particulates, cloudiness, or discoloration are visible, or if the package is open or damaged. The appearance of the syringe cap on the pre-filled syringe may vary (for example, color and design). Do not use if any part of the pre-filled syringe is damaged or if the syringe cap is detached from the Luer lock. The intravitreal injection should be performed with a 30-gauge × ½-inch injection needle (not provided). The pre-filled syringe contains more than the recommended dose of 2 mg aflibercept (equivalent to 50 microliters). The excess volume must be discarded prior to the administration. PRE-FILLED SYRINGE DESCRIPTION – Figure 1: Use aseptic technique to carry out the following steps: 1. PREPARE When ready to administer EYLEA, open the carton and remove sterilized blister pack. Carefully peel open the sterilized blister pack ensuring the sterility of its contents. Keep the syringe in the sterile tray until you are ready for assembly. 2. REMOVE SYRINGE Using aseptic technique, remove the syringe from the sterilized blister pack. 3. TWIST OFF SYRINGE CAP Twist off (do not snap off) the syringe cap by holding the syringe in one hand and the syringe cap with the thumb and forefinger of the other hand (see Figure 2 ). Note: To avoid compromising the sterility of the product, do not pull back on the plunger. Figure 2: 4. ATTACH NEEDLE Using aseptic technique, firmly twist a 30-gauge × ½-inch injection needle onto the Luer lock syringe tip (see Figure 3 ). Figure 3: Note: When ready to administer EYLEA, remove the plastic needle shield from the needle. 5. DISLODGE AIR BUBBLES Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure 4 ). Figure 4: 6. EXPEL AIR AND SET THE DOSE To eliminate all bubbles and to expel excess drug, slowly depress the plunger rod to align the plunger dome edge (see Figure 5a ) with the black dosing line on the syringe (equivalent to 50 microliters) (see Figure 5b ). Figure 5a: Figure 5b: 7. The pre-filled syringe is for one-time use in one eye only. After injection any unused product must be discarded. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5a Figure 5b 2.3 Preparation for Administration - Vial EYLEA should be inspected visually prior to administration. If particulates, cloudiness, or discoloration are visible, the vial must not be used. The glass vial is for one-time use in one eye only. Use aseptic technique to carry out the following preparation steps: Prepare for intravitreal injection with the following medical devices for single use: a 5-micron sterile filter needle (18-gauge × 1½-inch) a 1-mL sterile Luer lock syringe with marking to measure 0.05 mL for adults or 0.01 mL for pre-term infants with ROP a sterile injection needle (30-gauge × ½-inch) Remove the protective plastic cap from the vial (see Figure 6 ).

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS EYLEA is a clear, colorless to pale yellow solution available as: Injection: 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose pre-filled glass syringe Injection: 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose glass vial Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose pre-filled syringe ( 3 ) Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose vial ( 3 )

Contraindications

Ocular or periocular infection ( 4.1 ) Active intraocular inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections EYLEA is contraindicated in patients with ocular or periocular infections. 4.2 Active Intraocular Inflammation EYLEA is contraindicated in patients with active intraocular inflammation. 4.3 Hypersensitivity EYLEA is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation.

Warnings and precautions

Endophthalmitis, retinal detachments, and retinal vasculitis with or without occlusion may occur following intravitreal injections. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately. ( 5.1 ) Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. ( 5.2 ) In infants with ROP, treatment with EYLEA will necessitate extended periods of ROP monitoring ( 5.3 ) There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. ( 5.4 ) 5.1 Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] and, more rarely, retinal vasculitis with or without occlusion [see Adverse Reactions (6.2) ]. Proper aseptic injection technique must always be used when administering EYLEA. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately [see Dosage and Administration (2.4) and Patient Counseling Information (17) ]. 5.2 Increase in Intraocular Pressure Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA [see Adverse Reactions (6.1) ]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.4) ]. 5.3 Extended Monitoring and Additional Treatment in ROP Reactivation of abnormal angiogenesis and tortuosity may occur following treatment with EYLEA. Infants should be monitored closely after injection with EYLEA until retinal vascularization has completed or until the examiner is assured that reactivation of ROP will not occur. In infants with ROP, treatment with EYLEA will necessitate extended periods of ROP monitoring and additional EYLEA injections and/or laser treatments may be necessary. 5.4 Thromboembolic Events There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies.

Side effects

The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-855-395-3248 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 observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. A total of 2980 adult patients treated with EYLEA constituted the safety population in eight phase 3 studies. Among those, 2379 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. Neovascular (Wet) Age-Related Macular Degeneration (AMD) The data described below reflect exposure to EYLEA in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) for 24 months (with active control in year 1) [see Clinical Studies (14.1) ]. Safety data observed in the EYLEA group in a 52-week, double-masked, Phase 2 study were consistent with these results. Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD Studies Adverse Reactions Baseline to Week 52 Baseline to Week 96 EYLEA (N=1824) Active Control (ranibizumab) (N=595) EYLEA (N=1824) Control (ranibizumab) (N=595) Conjunctival hemorrhage 25% 28% 27% 30% Eye pain 9% 9% 10% 10% Cataract 7% 7% 13% 10% Vitreous detachment 6% 6% 8% 8% Vitreous floaters 6% 7% 8% 10% Intraocular pressure increased 5% 7% 7% 11% Ocular hyperemia 4% 8% 5% 10% Corneal epithelium defect 4% 5% 5% 6% Detachment of the retinal pigment epithelium 3% 3% 5% 5% Injection site pain 3% 3% 3% 4% Foreign body sensation in eyes 3% 4% 4% 4% Lacrimation increased 3% 1% 4% 2% Vision blurred 2% 2% 4% 3% Intraocular inflammation 2% 3% 3% 4% Retinal pigment epithelium tear 2% 1% 2% 2% Injection site hemorrhage 1% 2% 2% 2% Eyelid edema 1% 2% 2% 3% Corneal edema 1% 1% 1% 1% Retinal detachment <1% <1% 1% 1% Less common serious adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal tear, and endophthalmitis. Macular Edema Following Retinal Vein Occlusion (RVO) The data described below reflect 6 months exposure to EYLEA with a monthly 2 mg dose in 218 patients following central retinal vein occlusion (CRVO) in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT) [see Clinical Studies (14.2) , (14.3) ]. Table 2: Most Common Adverse Reactions (≥1%) in RVO Studies Adverse Reactions CRVO BRVO EYLEA (N=218) Control (N=142) EYLEA (N=91) Control (N=92) Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% Corneal epithelium defect 5% 4% 2% 0% Vitreous floaters 5% 1% 1% 0% Ocular hyperemia 5% 3% 2% 2% Foreign body sensation in eyes 3% 5% 3% 0% Vitreous detachment 3% 4% 2% 0% Lacrimation increased 3% 4% 3% 0% Injection site pain 3% 1% 1% 0% Vision blurred 1% <1% 1% 1% Intraocular inflammation 1% 1% 0% 0% Cataract <1% 1% 5% 0% Eyelid edema <1% 1% 1% 0% Less common adverse reactions reported in <1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal tear, hypersensitivity, and endophthalmitis. Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR) The data described below reflect exposure to EYLEA in 578 patients with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100 [see Clinical Studies (14.4) ]. Table 3: Most Common Adverse Reactions (≥1%) in DME Studies Adverse Reactions Baseline to Week 52 Baseline to Week 100 EYLEA (N=578) Control (N=287) EYLEA (N=578) Control (N=287) Conjunctival hemorrhage 28% 17% 31% 21% Eye pain 9% 6% 11% 9% Cataract 8% 9% 19% 17% Vitreous floaters 6% 3% 8% 6% Corneal epithelium defect 5% 3% 7% 5% Intraocular pressure increased 5% 3% 9% 5% Ocular hyperemia 5% 6% 5% 6% Vitreous detachment 3% 3% 8% 6% Foreign body sensation in eyes 3% 3% 3% 3% Lacrimation increased 3% 2% 4% 2% Vision blurred 2% 2% 3% 4% Intraocular inflammation 2% <1% 3% 1% Injection site pain 2% <1% 2% <1% Eyelid edema <1% 1% 2% 1% Less common adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, corneal edema, and injection site hemorrhage. Safety data observed in 269 patients with nonproliferative diabetic retinopathy (NPDR) through week 52 in the PANORAMA trial were consistent with those seen in the phase 3 VIVID and VISTA trials (see Table 3 above). Retinopathy of Prematurity (ROP) The data described below reflect exposure to EYLEA in 168 pre-term infants with ROP randomized to EYLEA and treated with the 0.4 mg dose in 2 clinical studies (BUTTERFLEYE and FIREFLEYE/FIREFLEYE NEXT) from time of first administration up to 52 weeks of chronological age [see Clinical Studies (14.6) ] .

Use in specific populations

8.1 Pregnancy Risk Summary Adequate and well-controlled studies with EYLEA have not been conducted in pregnant women. Aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level (NOAEL) was not identified. At the lowest dose shown to produce adverse embryofetal effects, systemic exposures (based on AUC for free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the recommended clinical dose [see Animal Data ]. Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept [see Clinical Pharmacology (12.1) ], treatment with EYLEA may pose a risk to human embryofetal development. EYLEA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous doses ≥0.1 mg per kg. Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification). The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was approximately 6 times higher than systemic exposure (AUC) observed in adult patients after a single intravitreal dose of 2 mg. 8.2 Lactation Risk Summary There is no information regarding the presence of aflibercept in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. Because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, EYLEA is not recommended during breastfeeding. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EYLEA and any potential adverse effects on the breastfed child from EYLEA. 8.3 Females and Males of Reproductive Potential Contraception Females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last intravitreal injection of EYLEA. Infertility There are no data regarding the effects of EYLEA on human fertility. Aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose approximately 1500 times higher than the systemic level observed in adult patients with an intravitreal dose of 2 mg. A No Observed Adverse Effect Level (NOAEL) was not identified. These findings were reversible within 20 weeks after cessation of treatment [see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use The safety and effectiveness of EYLEA have been demonstrated in two clinical studies of pre-term infants with ROP. These two studies randomized pre-term infants between initial treatment with EYLEA or laser. Efficacy of each treatment is supported by the demonstration of a clinical course which was better than would have been expected without treatment [see Dosage and Administration (2.9) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14.6) ] . 8.5 Geriatric Use In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with EYLEA were ≥65 years of age and approximately 46% (1250/2701) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies.

Pregnancy

8.1 Pregnancy Risk Summary Adequate and well-controlled studies with EYLEA have not been conducted in pregnant women. Aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level (NOAEL) was not identified. At the lowest dose shown to produce adverse embryofetal effects, systemic exposures (based on AUC for free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the recommended clinical dose [see Animal Data ]. Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept [see Clinical Pharmacology (12.1) ], treatment with EYLEA may pose a risk to human embryofetal development. EYLEA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous doses ≥0.1 mg per kg. Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification). The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was approximately 6 times higher than systemic exposure (AUC) observed in adult patients after a single intravitreal dose of 2 mg.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of EYLEA have been demonstrated in two clinical studies of pre-term infants with ROP. These two studies randomized pre-term infants between initial treatment with EYLEA or laser. Efficacy of each treatment is supported by the demonstration of a clinical course which was better than would have been expected without treatment [see Dosage and Administration (2.9) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14.6) ] .

Geriatric use

8.5 Geriatric Use In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with EYLEA were ≥65 years of age and approximately 46% (1250/2701) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies.

Overdosage

Overdosing with increased injection volume may increase intraocular pressure. Therefore, in case of overdosage, intraocular pressure should be monitored and if deemed necessary by the treating physician, adequate treatment should be initiated.

Description

Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells. EYLEA (aflibercept) Injection is a sterile, clear, and colorless to pale yellow solution. EYLEA does not contain anti-microbial preservative and is supplied as a sterile, aqueous solution for intravitreal injection in a single-dose pre-filled glass syringe or a single-dose glass vial designed to deliver 0.05 mL (50 microliters) of solution containing 2 mg of aflibercept in polysorbate 20 (0.015 mg), sodium chloride (0.117 mg), sodium phosphate monobasic monohydrate (0.055 mg), sodium phosphate dibasic heptahydrate (0.027 mg), sucrose (2.5 mg) and water for injection with a pH of 6.2.

Mechanism of action

12.1 Mechanism of Action Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability. Aflibercept acts as a soluble decoy receptor that binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors.

How supplied

16.1 How Supplied Each pre-filled syringe or vial is a clear, colorless to pale yellow solution and is for single eye use only. EYLEA is supplied in the following presentations [see Dosage and Administration (2.1) , (2.2) , (2.3) , (2.4) and (2.9) ]. Discard unused portion. NDC NUMBER CARTON TYPE CARTON CONTENTS 61755-005-01 Pre-filled Syringe one blister pack containing one EYLEA 2 mg (0.05 mL of a 40 mg/mL solution) sterile, single-dose pre-filled glass syringe one Prescribing Information 61755-005-02 Vial Kit with Injection Components one EYLEA 2 mg (0.05 mL of a 40 mg/mL solution) single-dose glass vial one 18-gauge × 1½-inch, 5-micron, filter needle for withdrawal of the vial contents one 30-gauge × ½-inch injection needle for intravitreal injection one 1-mL syringe for administration one Prescribing Information 16.2 Storage and Handling Refrigerate EYLEA at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use beyond the date stamped on the carton and container label. Store in the original carton until time of use to protect from light. Do not open sealed blister tray until time of use.

Storage

16.2 Storage and Handling Refrigerate EYLEA at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use beyond the date stamped on the carton and container label. Store in the original carton until time of use to protect from light. Do not open sealed blister tray until time of use.

Patient information

In the days following EYLEA administration, patients are at risk of developing endophthalmitis, retinal detachment, or retinal vasculitis with or without occlusion. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients and/or caregivers to seek immediate care from an ophthalmologist [see Warnings and Precautions (5.1) ] . Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye examinations [see Adverse Reactions (6) ] . Advise patients not to drive or use machinery until visual function has recovered sufficiently. In infants with ROP, treatment with EYLEA will necessitate extended periods of ROP monitoring.

Label text from the FDA structured product label by Regeneron Pharmaceuticals, Inc. (revised Jul 7, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Eylea NDC products (1)

NDCStrength & formLabelerType
61755-005Aflibercept 40 mg/mL
Injection, Solution		Regeneron Pharmaceuticals, Inc.BLA

Eylea recalls

Frequently asked questions

What is Eylea used for?

1 INDICATIONS AND USAGE EYLEA is indicated for the treatment of: EYLEA is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.2 ) Diabetic Macular Edema (DME) ( 1.3 ) Diabetic Retinopathy (DR) ( 1.4 ) Retinopathy of Prematurity…

What are the side effects of Eylea?

The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.4) ]… See the full label for the complete list.

Who makes Eylea?

Eylea is listed by 1 labeler in the FDA NDC directory, including Regeneron Pharmaceuticals, Inc..

Has Eylea been recalled?

The FDA enforcement database lists 2 recalls for Eylea, most recently D-0531-2024 (class ii): Lack of Assurance of Sterility: Complaints of syringe breakage