Aflibercept

Aflibercept is an injectable eye preparation that is given by a healthcare provider every one to five months depending on the preparation, to treat the following retinal eye conditions (varies depending on the biosimilar):

• Neovascular (Wet) age-related macular degeneration (AMD) – a condition where new blood vessels grow under the retina, where they leak blood and fluid
• Macular edema following retinal vein occlusion (RVO) – a swelling in the retina caused by a blockage in the blood vessels
• Diabetic macular edema (DME) – a build-up of fluid in the retina that is caused by leaking blood vessels
• Diabetic retinopathy (DR) – an eye disorder in diabetics that can lead to a buildup of fluid in the retina and cause blindness.

One preparation of aflibercept (Eylea) is also approved to treat retinopathy of prematurity (ROP) – an eye condition in premature babies that affects the retina.

Eylea HD is a higher-dose, longer-acting injectable form of aflibercept that only needs to be given once every 2 to 5 months after an initial dosing period. This allows patients to receive less frequent injections for similar visual gains and anatomic improvements without an increased risk of side effects. Eylea HD is approved to treat:

• Neovascular (Wet) age-related macular degeneration
• Diabetic macular edema
• Diabetic retinopathy
• Macular edema following retinal vein occlusion (RVO).

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor that is made from a human antibody fragment. It works by keeping new blood vessels from forming under the retina (a sensory membrane that lines the inside of the eye).

Aflibercept was first approved on November 18, 2011, under the brand name Eylea, and Eylea HD was approved on August 18, 2023. There are six biosimilars to Eylea.

• Two biosimilars are designated interchangeable: Opuviz (May 20, 2024) and Yesafili (May 20, 2024)
• Four biosimilars are not interchangeable: Ahzantive (June 28, 2024), Enzeevu (August 9, 2024), Pavblu (August 23, 2024), and Eydenzelt (October 2, 2025).

You should not use aflibercept if you are allergic to aflibercept, Eylea, Eylea HD, Yesafili, Opuviz, or any of the inactive ingredients in these preparations. Get emergency medical help if you have any signs of an allergic reaction, such as hives, difficulty breathing, or swelling of your eyes, face, lips, tongue, or throat.

Do not receive an aflibercept injection if you have swelling or redness inside your eyes, or any type of infection (bacterial, fungal, viral) in or around your eyes.

Call your doctor at once if you have a serious side effect such as:

• eye pain or redness, swelling around your eyes;
• sudden vision problems;
• seeing flashes of light or "floaters" in your vision, seeing halos around lights;
• your eyes may be more sensitive to light;
• chest pain;
• sudden numbness or weakness, especially on one side of the body; or
• sudden severe headache, confusion, problems with speech or balance.

There is a possibility that endophthalmitis (a serious inflammation of the intraocular fluids, usually due to infection) and retinal detachments may occur following intravitreal injections. Call your doctor at once if you have eye pain or redness, swelling or puffiness around your eyes, sensitivity to light, or sudden vision problems at any time during treatment. Arterial thromboembolic events are also possible following intravitreal VEGF inhibitor injections.

Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection.

Infants with ROP may need extended periods of monitoring after injections with aflibercept.

Temporary visual disturbances may occur following an intravitreal injection with aflibercept or the associated eye examinations. Do not drive or operate machinery until your vision recovers.

You should not receive aflibercept if you are allergic to aflibercept, Eylea, Eylea HD, Yesafili, Opuviz, Eydenzelt, or any of the inactive ingredients in these preparations, or if you have:

• swelling inside your eyes
• any type of bacterial, fungal, or viral infection in or around your eyes.

To make sure this medicine is safe for you, tell your doctor if you:

• have had a blood clot or stroke
• have glaucoma or other conditions that increase pressure inside your eyes
• are pregnant or planning to become pregnant
• are breastfeeding.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant while using aflibercept. You may need to undertake a pregnancy test if you are a female with childbearing potential. Use effective birth control to prevent pregnancy before your first dose of this medicine. Keep using birth control during treatment and for at least 3 months after your last aflibercept injection.

Breastfeeding

Do not breastfeed while you are using aflibercept.

An aflibercept injection can cause serious side effects such as allergic reactions, a serious inflammation of the eye, retinal detachments, eye infections, and an increase in eye pressure. See warnings below.

Less serious aflibercept side effects may include:

• red or watery eyes;
• blurred vision;
• swelling of the eyelids; or
• mild eye pain or discomfort after the injection.

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.

Aflibercept is given as an injection into your eye. 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 other clinic setting.

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

Dosing Information

The usual recommended dose in adults is 2mg (0.05mL) (one injection) into each affected eye.

• An aflibercept injection is usually administered every 4 weeks (approximately every 28 days, monthly) initially, which may be extended to once every 8 weeks (2 months), depending on the condition.
• In some patients, treatment may be extended to one dose every 12 weeks, although this is not as effective as the recommended every 8-week dosing.
• Follow your doctor's dosing instructions very carefully.

The dosage for ROP is 0.4 mg (0.01 mL or 10 microliters) administered by intravitreal injection.

• Treatment may be given to both eyes on the same day and repeated if needed.
• The treatment interval between doses injected into the same eye should be at least 10 days.

Dosage for Eylea HD

The usual recommended adult dose of Eylea HD is 8mg (0.07mL) (one injection) into each affected eye.

All conditions start with: 8 mg every 4 weeks for the first 3 doses (RVO: 3-5 doses)

Maintenance varies by condition:

• nAMD & DME: Every 8-16 weeks. Extended dosing intervals (8 mg once every 20 weeks +/- 1 week) may be considered after 1 year of successful response based on visual and anatomic outcomes.
• DR: Every 8-12 weeks
• RVO: Every 8 weeks.

Note: Patients not responding to extended intervals may need to resume every 4-week dosing.

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

An overdose is unlikely because aflibercept is administered by healthcare professionals. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Aflibercept 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 inject will affect aflibercept 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.

Store aflibercept in the refrigerator at 2°C to 8°C (36°F to 46°F).

Do not freeze. Do not use it beyond the date stamped on the carton and container label.

Store in the original carton until time of use to protect from light.

Eylea ingredients

Active: aflibercept 40 mg/mL.

Inactive: 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose with a pH of 6.2.

The single-dose glass vial is designed to deliver 0.05 mL (50 microliters) of the solution containing 2 mg of aflibercept.

Eylea does not contain an antimicrobial preservative.

Eylea HD ingredients

Active: aflibercept 114.3 mg/mL solution

Inactive: a buffer containing arginine hydrochloride (0.737 mg), histidine (0.04 mg), L-histidine hydrochloride monohydrate (0.093 mg), polysorbate 20 (0.021 mg), sucrose (3.5 mg), and water for injection with a pH of 5.8.

Eylea HD does not contain an antimicrobial preservative.

The single-dose glass vial is designed to deliver 0.07 mL (70 microliters) of the solution containing 8 mg of aflibercept.

Opuviz ingredients

Active: aflibercept-yszy 40 mg/mL

Inactive: dibasic sodium phosphate (0.008 mg), monobasic sodium phosphate (0.040 mg), polysorbate 20 (0.015 mg), sucrose (4 mg), and water for injection, with a pH of 6.2.

Delivers a dose of 2mg (0.05mL) in a single-dose vial.

One vial contains more extractable volume than is needed, but only 0.05 mL should be administered into the eye, and the rest should be discarded; otherwise, an overdose may occur. One vial should be used for one eye.

Supplied as a vial only and a vial kit with injection components (filter needle, syringe, injection needle).

Yesafili ingredients

Active: aflibercept-jbvf 40 mg/mL

Inactive: histidine (0.047 mg), histidine hydrochloride monohydrate (0.042 mg), polysorbate 20 (0.015 mg), and trehalose (4.5 mg), in water for injection with a pH of 6.2.

Delivers a dose of 2mg (0.05mL) in a single-dose vial.

One vial contains more extractable volume than is needed, but only 0.05 mL should be administered into the eye, and the rest should be discarded; otherwise, an overdose may occur. One vial should be used for one eye.

Eydenzelt ingredients

Active: aflibercept-boav 40 mg/mL

Inactive: histidine (0.038 mg), L-histidine monohydrochloride monohydrate (0.033 mg), polysorbate 20 (0.015 mg), sodium chloride (0.038 mg), trehalose (5 mg), and water for injection with a pH of 6.2.

Delivers a dose of 2mg (0.05mL) in a single-dose pre-filled syringe or single-dose vial.

Pavblu ingredients

Active: aflibercept-ayyh 40 mg/mL.

Inactive polysorbate 80 (0.005 mg), sucrose (2.5 mg), trehalose (1.58 mg), and water for injection with a pH of 6.2.

The single-dose glass vial or prefilled syringe is designed to deliver 0.05 mL (50 microliters) of the solution containing 2 mg of aflibercept-ayyh

Pavblu does not contain an antimicrobial preservative.

Ahzantive ingredients

Active: aflibercept-mrbb 40 mg/mL.

Inactive: histidine (0.046 mg), L-histidine hydrochloride monohydrate (0.043 mg), polysorbate 20 (0.015 mg), sodium chloride (0.117 mg), sucrose (2.5 mg), and water for injection with a pH of 6.2.

The single-dose glass vial is designed to deliver 0.05 mL (50 microliters) of the solution containing 2 mg of aflibercept-mrbb

Ahzantive does not contain an antimicrobial preservative.

Enzeevu ingredients

Active: aflibercept-mrbb 40 mg/mL.

Inactive: histidine (0.023 mg), L-histidine hydrochloride monohydrate (0.073 mg), polysorbate 20 (0.02 mg), trehalose (3.6 mg) with a pH of 5.7. Hydrochloric acid and sodium hydroxide may be added to adjust the pH.

The single-dose glass vial is designed to deliver 0.05 mL (50 microliters) of the solution containing 2 mg of aflibercept-mrbb

Enzeevu does not contain an antimicrobial preservative.

Eylea, Eylea HD: Regeneron Pharmaceuticals, Inc.

Opuviz: Samsung Bioepis Co., Ltd. for Biogen MA Inc.

Yesafili: Biocon Biologics Inc.

Eydenzelt: Celltrion, Inc.

Pavblu: Amgen, Inc.

Ahzantive: Formycon AG

Enzeevu: Sandoz Inc.

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There are 2 for aflibercept ophthalmic.

Eylea (aflibercept) - Regeneron Pharmaceuticals, Inc.

View Eylea information in detail.

Eylea HD (aflibercept) - Regeneron Pharmaceuticals, Inc.

View Eylea HD information in detail.

Eylea interchangeable products

Interchangeable biosimilar products can be dispensed by a pharmacist without the intervention of the prescriber of the reference product.

Pharmacy laws for biosimilar prescribing may vary by state.

Yesafili (aflibercept-jbvf) - Biocon Biologics Inc.

View Yesafili information in detail.

Eylea biosimilar products

Biosimilar products can only be dispensed in place of the reference product if the healthcare provider specifically prescribes the biosimilar product by name.

Pharmacy laws for biosimilar prescribing may vary by state

Ahzantive (aflibercept-mrbb) - Formycon AG

View Ahzantive information in detail.

Pavblu (aflibercept-ayyh) - Amgen Inc.

View Pavblu information in detail.

Yesafili (aflibercept-jbvf) - Biocon Biologics Inc.

View Yesafili information in detail.