Aflibercept

FDA Drug Information • Also known as: Eydenzelt Boav, Eylea, Eylea Hd

Brand Names: Eydenzelt Boav, Eylea, Eylea Hd
Dosage Form: INJECTION, SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 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.

What Is Aflibercept 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 (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

2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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%...

Contraindications

4 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.

Pregnancy and Breastfeeding

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...

Overdosage

10 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.