Eylea

Eylea injection is used to treat neovascular (wet) age-related macular degeneration (nAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), and retinopathy of prematurity (ROP), all of which are vision-threatening retinal conditions. It is administered into the eye (intravitreal injection) by an eye specialist every 1 to 2 months.

Eylea HD is a longer-acting, higher-dose form of Eylea that is administered every 1 to 4 months. This guide covers Eylea injection only.

Eylea (aflibercept) gained FDA approval on November 18, 2011. Six biosimilars are available (these are like a generic version).

• Two of these, Opuviz and Yesafili, are designated as interchangeable biosimilars.
• Four others - Ahzantive, Enzeevu, Pavblu, and Eydenzelt are approved as non-interchangeable biosimilars.
• Unlike Eylea, these biosimilars are not approved for ROP.

Eylea is given as an injection into your eye. This is called an intravitreal injection.

• Your doctor will use a medicine to numb your eye before giving you the injection.
• You will receive this injection in your doctor's office or clinic.

For a short time after your injection, your eyes will be checked regularly to make sure the injection has not caused any side effects.

Do not receive Eylea if:

• You are allergic to aflibercept, Eylea, Eylea HD, or an Eylea biosimilar, or any of the inactive ingredients in the eye injection
• You have active inflammation inside your eye
• You have an infection in or around your eyes.

Before Eylea is administered, tell your healthcare provider about all your medical conditions, including if you have:

• Allergies to aflibercept or any Eylea products (Eylea, Eylea HD, Opuviz, Yesafili, Ahzantive, Enzeevu, Eydenzelt, or Pavblu)
• A history of blood clots or stroke
• Glaucoma or other conditions that increase eye pressure
• Swelling in your eyes
• Any infection in or around your eyes (bacterial, fungal, or viral)
• Redness inside your eyes
• Pregnancy plans or are pregnant
• Breastfeeding plans or are breastfeeding.

It is unknown if this medication affects male or female fertility.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant while using Eylea. You may need to take a pregnancy test before receiving this injection if you are a female who can get pregnant.

You should use effective birth control to prevent pregnancy before your first dose of this medicine, during treatment, and for at least 3 months after your last Eylea injection.

Breastfeeding

Do not breastfeed while you are using Eylea.

Common side effects

The most common side effects of Eylea injection, reported in 5% or more of people in clinical trials, are listed below. Rates come from the wet AMD trials over the first year of treatment.

Side effects reported in 1% to 4% of people include eye redness, a surface scratch on the cornea, detachment of the retinal pigment epithelium, injection site pain, a feeling of something in the eye, watery eyes, blurred vision, inflammation inside the eye, a tear in the retinal pigment epithelium, injection site bleeding, eyelid swelling, and corneal swelling.

Rates in the RVO, DME, and diabetic retinopathy trials were broadly similar, with conjunctival hemorrhage reported in 28% of people with DME at 1 year and 12% to 20% of people with RVO at 6 months.

Temporary visual disturbances may occur following an intravitreal Eylea injection. Do not drive or operate machinery until your vision recovers.

Serious side effects and warnings

Eylea may cause the following serious side effects:

• Serious Eye Complications. After receiving an Eylea injection into the eye, there is a risk you may develop: Endophthalmitis (a serious eye infection) Retinal detachment Retinal vasculitis (inflammation of blood vessels in the retina), with or without blockage.

Report any of the following signs or symptoms to a healthcare provider immediately or go to the emergency room:

• Sudden decrease or loss of vision Blurred, cloudy, or hazy vision Eye pain, aching, or increased discomfort Increased eye redness or swelling New floaters (spots or threads in your vision) Flashes of light A shadow, curtain, or veil blocking part of your vision Sensitivity to light Discharge from the eye Headache with eye symptoms Nausea or vomiting Seeing halos around lights.
• Increased Eye Pressure. Eylea may increase the pressure of fluids inside the eye (intraocular pressure), usually within 60 minutes of an intravitreal injection. Your healthcare provider should monitor you for this. Many people with elevated eye pressure have no symptoms.
• Blood Clot Risk. Eylea may increase the risk of blood clots and thromboembolic events, which may cause a life-threatening stroke or heart attack. In the wet AMD trials, these events were reported in 1.8% of people on Eylea in the first year and 3.3% through 96 weeks, compared with 1.5% and 3.2% of people on ranibizumab. In the diabetic macular edema trials, the rates were 3.3% at 52 weeks and 6.4% at 100 weeks with Eylea, compared with 2.8% and 4.2% in the control groups. No thromboembolic events were reported in the first six months of the retinal vein occlusion trials.

Call your doctor at once if you get any of the following symptoms following an Eylea injection:

• chest pain sudden numbness or weakness, especially on one side of the body sudden severe headache, confusion, problems with speech or balance.
• Allergic Reactions. Eylea may cause an allergic reaction. Get emergency medical help if you have any signs of an allergic reaction, such as: Hives Difficulty breathing Swelling of your eyes, face, lips, tongue, or throat.

Monitoring for Infants with ROP

Infants treated for retinopathy of prematurity (ROP) will need extended monitoring throughout their treatment, as abnormal blood vessel growth may recur. Additional injections or laser treatments may be needed until retinal development completes.

Temporary Blood Pressure Increase

Clinical trials have also reported a temporary increase in blood pressure following eye injections (see Does Eylea and Eylea HD raise blood pressure?).

Notes

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How common are serious side effects?

Serious side effects related to the injection procedure itself, including endophthalmitis and retinal detachment, occurred in fewer than 0.1% of Eylea injections in clinical trials. Hypersensitivity, retinal tear, and endophthalmitis were each reported in fewer than 1% of people in the wet AMD trials.

Retinal vasculitis has been reported since Eylea was approved, at a rate of about 0.6 cases per 1 million injections, and occlusive retinal vasculitis at about 0.2 cases per 1 million injections, based on reports between November 2011 and November 2023. Scleritis, which is inflammation of the white of the eye, has also been reported.

Eylea works as a decoy receptor. It binds to two proteins in the eye, vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF), which normally drive the growth of new, leaky blood vessels. By mopping these proteins up, Eylea stops them from reaching the body's own VEGF receptors, which reduces abnormal blood vessel growth and leakage in the retina.

Eylea belongs to the drug class called Vascular Endothelial Growth Factor (VEGF) inhibitors. It may also be called an anti-VEGF or an anti-angiogenic ophthalmic agent.

Eylea has been studied in more than 2,900 adults across eight Phase 3 trials, plus 168 pre-term infants with retinopathy of prematurity. Results differ by condition. Vision is measured in ETDRS letters on an eye chart, where 15 letters is about three lines of vision.

Wet age-related macular degeneration (AMD)

In two trials (VIEW1 and VIEW2) involving 2,412 people, 94% to 95% of people treated with Eylea 2 mg every 8 weeks kept their vision at 1 year, meaning they lost fewer than 15 letters. Around 31% gained at least 15 letters. Average vision improved by 7.9 letters in VIEW1 and 8.9 letters in VIEW2.

Both trials compared Eylea against ranibizumab (Lucentis) given monthly. Eylea given every 8 weeks after three starting doses was shown to be clinically equivalent to monthly ranibizumab in the first year.

Macular edema after retinal vein occlusion (RVO)

Average vision gain at 24 weeks was 17.3 letters in COPERNICUS and 18.0 letters in GALILEO, compared with a loss of 4.0 letters and a gain of 3.3 letters in the control groups. In VIBRANT, average gain was 17.0 letters with Eylea versus 6.9 letters with laser treatment.

Diabetic macular edema (DME)

In the VIVID and VISTA trials, people treated with Eylea 2 mg every 8 weeks gained an average of 10.7 letters at 1 year, compared with 1.2 letters and 0.2 letters in the control groups. About 31% to 33% gained at least 15 letters, compared with 8% to 9% of controls. These improvements were maintained at 2 years.

Diabetic retinopathy (DR)

Diabetic retinopathy severity is graded on the ETDRS Diabetic Retinopathy Severity Scale (DRSS). A 2-step improvement is considered meaningful.

In VIVID and VISTA, 32% to 38% of people on Eylea every 8 weeks improved by at least 2 steps at 2 years, compared with 7% to 16% of controls.

In the PANORAMA trial, which enrolled people with moderately severe to severe nonproliferative diabetic retinopathy without central-involved DME, 80% of people receiving Eylea every 8 weeks and 65% of those receiving it every 16 weeks improved by at least 2 steps at 1 year, compared with 15% on sham treatment. Progression to proliferative diabetic retinopathy or anterior segment neovascularization occurred in 2.4% and 4.0% of Eylea-treated people, compared with 20.1% of controls.

Retinopathy of prematurity (ROP)

Two studies (BUTTERFLEYE and FIREFLEYE/FIREFLEYE NEXT) compared a single 0.4 mg Eylea injection against laser photocoagulation in pre-term infants. At 52 weeks of chronological age, 79.6% of Eylea-treated infants in BUTTERFLEYE and 78.7% in FIREFLEYE had no active ROP and no unfavorable structural outcomes, compared with 77.8% and 81.6% of laser-treated infants. Neither trial showed one treatment to be better or worse than the other. Five-year follow-up studies are ongoing.

Dose of Eylea for Neovascular (Wet) Age-Related Macular Degeneration (AMD)

• Initial: 2 mg via intravitreal injection once every 4 weeks for the first 3 months.
• Month 4: 2 mg via intravitreal injection every 8 weeks (2 months).

Some patients may need every 4 week (monthly) injections after the first 12 weeks (3 months).

After 1 year of effective treatment, some patients may be treated with 1 dose every 12 weeks, although this is not as effective as the recommended 8-week dosing interval.

Dose of Eylea for Macular Edema Following Retinal Vein Occlusion (RVO)

• Initial and maintenance: 2 mg via intravitreal injection once every 4 weeks (approximately every 25 days, monthly).

Dose of Eylea for Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR)

• Initial: 2 mg via intravitreal injection every 4 weeks for the first 5 injections.
• 6th Injection and Thereafter: 2 mg via intravitreal injection every 8 weeks (2 months).

Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months)

Dose of Eylea for Retinopathy of Prematurity (ROP)

• Initial: 0.4 mg via intravitreal injection.
• Treatment may be given bilaterally on the same day.
• Injections may be repeated if necessary. The treatment interval between doses injected into the same eye should be at least 10 days.

Call your doctor to reschedule if you miss an appointment for your Eylea injection.

Eylea may cause blurred vision and may impair your reactions. Avoid driving or hazardous activities until you know how this medicine will affect you.

It is not likely that other drugs you take orally or by injection will have an effect on Eylea used in the eyes.

However, many drugs can interact with each other. Tell your doctor about all the medicines you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Eylea is stored and handled by your eye clinic, not at home. It is refrigerated at 2°C to 8°C (36°F to 46°F) and must not be frozen. It is kept in the original carton until use to protect it from light, and the sealed blister tray is not opened until the injection is about to be given. It is not used beyond the date stamped on the carton and container label.

Each pre-filled syringe or vial is for single use in one eye only. Any unused portion is discarded. The pre-filled syringe is not used to treat retinopathy of prematurity.

Active: aflibercept 40 mg/mL.

Inactive: polysorbate 20, sodium chloride, sodium phosphate monobasic monohydrate, sodium phosphate dibasic heptahydrate, sucrose, and water for injection with a pH of 6.2.

Eylea injection is available as:

• 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose pre-filled syringe
• 2 mg (0.05 mL of a 40 mg/mL solution) in a single-dose glass vial.

Eylea does not contain an antimicrobial preservative.