Eylea 40 mg/ml solution for injection in vial

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Eylea 40 mg/ml solution for injection in vial

aflibercept

Read the entire leaflet carefully before you are administered this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Eylea is and what it is used for
2. What you need to know before Eylea is administered to you
3. How Eylea will be administered
4. Possible side effects
5. How to store Eylea
6. Contents of the pack and other information

1. What Eylea is and what it is used for

Eylea is a solution injected into the eye to treat certain eye diseases in adult patients, namely:

• neovascular (exudative) age-related macular degeneration, commonly known as exudative AMD
• vision impairment due to macular edema caused by retinal vein occlusion (central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO))
• vision impairment due to diabetic macular edema (DME)
• vision impairment due to myopic choroidal neovascularization (myopic CNV).

Aflibercept, the active substance in Eylea, blocks the activity of a group of factors called vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF).

In patients with exudative AMD and myopic CNV, excessive levels of these factors contribute to the abnormal formation of new blood vessels in the eye. These new blood vessels may leak blood components into the eye, causing damage to the ocular tissues responsible for vision.

In patients with CRVO, a blockage occurs in the main vein that carries blood away from the retina. As a result, VEGF levels rise, causing fluid leakage into the retina and consequently swelling of the macula (the part of the retina responsible for sharp vision), a condition known as macular edema.

When fluid accumulates in the macula, central vision becomes blurred.

In patients with BRVO, a blockage occurs in one or more branches of the main retinal vein. This leads to increased VEGF levels, causing fluid leakage into the retina and resulting in macular swelling.

Diabetic macular edema is retinal swelling occurring in patients with diabetes, caused by fluid leakage from blood vessels in the macula. The macula is the part of the retina responsible for sharp vision. When the macula swells due to fluid accumulation, central vision becomes blurred.

Eylea has been shown to inhibit the growth of abnormal new blood vessels in the eye, which often bleed or leak fluid. Eylea can help stabilize, and in many cases improve, vision loss caused by exudative AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you need to know before being given Eylea

Do not administer Eylea to you if:

• you are allergic to aflibercept or to any of the other components of this medicine (listed in section 6)
• you have an active infection or suspect you may have an infection in or around your eye (ocular or periocular infection)
• you have severe inflammation of the eye (indicated by pain or redness).

Warnings and precautions

Talk to your doctor before receiving Eylea:

• If you have glaucoma.
• If you have a history of seeing flashes of light or floaters, or if there is a sudden increase in the size or number of floaters.
• If you have undergone or have scheduled eye surgery within the previous four weeks or the next four weeks.
• If you have a severe form of CRVO or BRVO (ischemic CRVO or BRVO), treatment with Eylea is not recommended.

Additionally, it is important for you to know that:

• The safety and efficacy of Eylea when administered in both eyes simultaneously has not been studied, and using it in this way may increase the risk of adverse effects.
• Eylea injections may cause an increase in pressure inside the eye (intraocular pressure) in some patients within 60 minutes after the injection. Your doctor will monitor you after each injection.
• If you develop an infection or inflammation inside the eye (endophthalmitis) or other complications, you may experience eye pain or increased discomfort, worsening eye redness, blurred or decreased vision, and increased sensitivity to light. It is important that any symptoms are diagnosed and treated as soon as possible.
• Your doctor will check whether you have other risk factors that could increase the likelihood of developing a tear or detachment of the back layers of the eye (retinal tear or detachment, or tear or detachment of the retinal pigment epithelium), in which case Eylea will be administered with caution.
• Eylea should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus.
• Women of childbearing potential must use effective contraception during treatment and for at least three months after the last injection of Eylea.

Systemic use of VEGF inhibitors—substances similar to those contained in Eylea—is potentially associated with the risk of blood vessel blockage due to blood clots (arterial thromboembolic events), which may lead to myocardial infarction or stroke. After Eylea injection into the eye, there is a theoretical risk that such events could occur. Safety data on the treatment of patients with CRVO, BRVO, DME, and myopic CNV who have experienced a stroke, transient ischemic attack (TIA), or myocardial infarction within the past 6 months are limited. If any of these apply to you, Eylea will be administered with caution.

Experience is limited in the treatment of:

• Patients with DME due to type I diabetes.
• Diabetic patients with very high average blood sugar levels (glycated hemoglobin above 12%).
• Diabetic patients with an eye disease caused by diabetes, known as proliferative diabetic retinopathy.

There is no experience in the treatment of:

• Patients with acute infections.
• Patients with other eye diseases such as retinal detachment or macular hole.
• Diabetic patients with uncontrolled hypertension.
• Non-Asian patients with myopic CNV.
• Patients previously treated for myopic CNV.
• Patients with damage outside the central part of the macula (extrafoveal lesions) due to myopic CNV.

If any of the above apply to you, your doctor will take this lack of information into account when deciding on treatment with Eylea.

Children and adolescents

The use of Eylea has not been studied in children and adolescents under 18 years of age, as exudative AMD, CRVO, BRVO, DME, and myopic CNV occur primarily in adults. Therefore, its use is not recommended in this age group.

Use of Eylea with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

• Women of childbearing potential must use effective contraception during treatment and for at least three months after the last injection of Eylea.
• There is no experience with the use of Eylea in pregnant women. Eylea should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant or planning to become pregnant, discuss this with your doctor before treatment with Eylea.
• Small amounts of Eylea may pass into breast milk. The effects on newborns or breastfed infants are unknown. Eylea is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with Eylea.

Driving and use of machines

After Eylea injection, you may experience some transient visual disturbances. Do not drive or operate machinery while these disturbances persist.

Eylea contains

• less than 1 mmol of sodium (23 mg) per dose unit; this is essentially “sodium-free”.
• 0.015 mg of polysorbate 20 in each 0.05 ml dose, equivalent to 0.3 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Eylea will be administered to you

Eylea will be administered by a physician experienced in administering intraocular injections, under sterile (clean and aseptic) conditions.

The recommended dose is 2 mg of aflibercept (0.05 ml).

Eylea is given as an injection into the eye (intravitreal injection).

Prior to the injection, your doctor will use a disinfectant eye wash to carefully clean your eye to prevent infection. Your doctor will also administer a local anesthetic to reduce or prevent any pain you might feel during the injection.

Exudative AMD

Patients with exudative AMD will receive monthly injections for the first three doses, followed by another injection after an additional two months.

Your doctor will then decide whether the treatment interval between injections can remain every two months or be gradually extended in increments of 2 or 4 weeks if your disease has stabilized. If your condition worsens, the interval between injections may be shortened.

Routine visits to your doctor between injections are not necessary unless your doctor advises otherwise or you experience any problems.

Macular edema secondary to RVO (branch or central)

Your doctor will determine the most appropriate treatment schedule for you. Your treatment will begin with a series of monthly Eylea injections.

The interval between two injections must not be less than one month.

Your doctor may decide to discontinue treatment with Eylea if you do not benefit from continued therapy.

Treatment will continue with monthly injections until your disease stabilizes. You may require three or more monthly injections.

Your doctor will monitor your response to treatment and may continue therapy, gradually increasing the interval between injections to maintain disease stability. If your condition worsens with a longer treatment interval, your doctor will shorten the interval between injections.

Depending on your response to treatment, your doctor will determine the follow-up and treatment schedule.

Diabetic macular edema (DME)

Patients with DME will receive monthly injections for the first five consecutive doses, followed by an injection every two months.

The interval between treatments may be maintained every two months or adjusted based on your disease status as assessed by your doctor. Your doctor will determine the follow-up visit schedule.

Your doctor may decide to discontinue treatment with Eylea if it is determined that you are not benefiting from continued therapy.

Myopic choroidal neovascularization (mCNV)

Patients with mCNV will be treated with a single injection. Additional injections will only be given if examinations by your doctor show that your condition has not improved.

The interval between two injections must not be less than one month.

If your condition resolves and later recurs, your doctor may restart treatment.

Your doctor will determine the follow-up examination schedule.

If you miss a dose of Eylea

Schedule a new appointment to be examined and receive the injection.

Discontinuation of Eylea treatment

Consult your doctor before discontinuing treatment.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Allergic reactions (hypersensitivity) may potentially occur. These can be serious and require that you contact your doctor immediately.

Some adverse effects affecting the eyes may occur with the administration of Eylea, which are related to the injection procedure. Some of these may be serious, including blindness, a serious infection or inflammation inside the eye (endophthalmitis), detachment, tear, or bleeding of the light-sensitive layer at the back of the eye (retinal detachment or tear), clouding of the lens (cataract), bleeding in the eye (vitreous haemorrhage), detachment of the gel-like substance inside the eye in contact with the retina (vitreous detachment), and increased pressure inside the eye (see section 2). These serious eye-related adverse effects occurred in fewer than 1 in 1,900 injections during clinical trials.

If you notice a sudden decrease in vision or increased pain and redness in the eye after the injection, consult your doctor immediately.

List of reported adverse effects

Below is a list of adverse effects reported as possibly related to either the injection procedure or the medicine. Do not be alarmed, as you may not experience any of these. Always consult your doctor if you suspect any adverse effect.

Very common adverse effects (may affect more than 1 in 10 people):

• Vision deterioration
• Bleeding at the back of the eye (retinal haemorrhage)
• Blood in the eye due to bleeding from small blood vessels in the outer layers of the eye
• Eye pain

Common adverse effects (may affect up to 1 in 10 people):

• Detachment or tear of one of the layers at the back of the eye, causing flashes of light and floaters, which may sometimes progress to vision loss (tear/detachment of the retinal pigment epithelium, tear/detachment of the retina)
• Degeneration of the retina (causing visual disturbances)
• Bleeding in the eye (vitreous haemorrhage)
• Certain forms of lens clouding (cataract)
• Damage to the surface layer of the eyeball (cornea)
• Increased pressure inside the eye
• Spots in vision (floaters)
• Detachment of the gel-like substance inside the eye from the retina (vitreous detachment, resulting in flashes of light and floaters)
• Sensation of having something in the eye
• Increased tear production
• Eyelid swelling
• Bleeding at the injection site
• Eye redness
  • Adverse effects known to be associated with exudative AMD; observed only in patients with exudative AMD.

Uncommon adverse effects (may affect up to 1 in 100 people):

• Allergic reactions (hypersensitivity)**

• Inflammation or serious infection inside the eye (endophthalmitis)

• Inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, cells floating in the anterior chamber)

• Abnormal sensation in the eye

• Eyelid irritation

• Swelling of the surface layer of the eyeball (cornea)

• Allergic reactions reported included rash, itching (pruritus), hives (urticaria), and some cases of serious allergic (anaphylactic/anaphylactoid) reactions.

Rare adverse effects (may affect up to 1 in 1,000 people):

• Blindness
• Clouding of the lens due to injury (traumatic cataract)
• Inflammation of the gel-like substance inside the eye
• Pus in the eye

Frequency not known (cannot be estimated from available data):

• Inflammation of the white part of the eye associated with redness and pain (scleritis)

In clinical trials, an increased incidence of bleeding from small blood vessels in the outer layers of the eye (conjunctival haemorrhage) was observed in patients with exudative AMD who were receiving anticoagulant treatment. This increased incidence was comparable in patients treated with ranibizumab and with Eylea.

The systemic use of VEGF inhibitors—substances similar to those contained in Eylea—is potentially associated with the risk of blood clots blocking blood vessels (arterial thromboembolic events), which may lead to heart attack or stroke. There is a theoretical risk that such events could occur following Eylea injection into the eye.

As with all therapeutic proteins, there is a possibility of an immune reaction (antibody formation) with Eylea.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Eylea

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and label after “CAD/EXP”. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2 ºC and 8 ºC). Do not freeze.
• The unopened vial may be stored outside the refrigerator at temperatures below 25 ºC for up to 24 hours.
• Keep in the original packaging to protect from light.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Eylea

• The active substance is: aflibercept. One vial contains a recoverable volume of at least 0.1 ml, equivalent to at least 4 mg of aflibercept. One vial provides a dose of 2 mg of aflibercept in 0.05 ml.
• The other components are: polysorbate 20 (E 432), monosodium phosphate monohydrate (for pH adjustment), disodium hydrogen phosphate heptahydrate (for pH adjustment), sodium chloride, sucrose, water for injections.

See "Eylea contains" in section 2 for more information.

Appearance of the product and contents of the pack

Eylea is an injectable solution in a vial. The solution is colourless to pale yellow.

Pack containing 1 vial + 1 filter needle.

Marketing Authorization Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer responsible for manufacturing

Bayer AG
Müllerstraße 178
13353 Berlin
Germany

More information on this medicinal product is available by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

For local information, scan here to access the website https://www.pi.bayer.com/eylea2.

A QR code with a link to the package leaflet is included.

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This information is intended for healthcare professionals only:

The vial must be used for the treatment of one eye only.

The vial contains more than the recommended dose of 2 mg aflibercept (equivalent to 0.05 ml). The excess volume must be discarded before administration.

Before administration, the solution should be inspected visually for the presence of particles and/or discoloration or any change in physical appearance. If any of these are observed, do not use the medicine.

Unopened Eylea vials may be stored outside the refrigerator at temperatures below 25°C for up to 24 hours. After opening the vial, proceed under aseptic conditions.

For intravitreal injection, a 30 G x ½ inch (1.27 cm) injection needle should be used.

Instructions for use of the vial: