Eiyeze 40 mg/ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Eiyzey 40 mg/ml solution for injection in a pre-filled syringe

aflibercept

This medicinal product is subject to additional monitoring, which will allow for rapid identification of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

Read the entire leaflet carefully before you are administered this medicine, as 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 not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Eiyzey is and what it is used for

Eiyzey 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 Eiyzey, 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, when these factors are present in excessive amounts, they contribute to the abnormal formation of new blood vessels in the eye. These new blood vessels may leak components of the blood 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 the macula fills with fluid, central vision becomes blurred.

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

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

Eiyzey has been shown to inhibit the growth of abnormal new blood vessels in the eye that often bleed or leak fluid. Eiyzey 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 Eiyzey is administered to you

Do not administer Eiyzey if:

• you are allergic to aflibercept or to any of the other ingredients 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 Eiyzey:

• 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 had eye surgery or have eye surgery scheduled within the previous four weeks or the next four weeks.
• If you have a severe form of CRVO or BRVO (ischemic CRVO or ischemic BRVO), treatment with Eiyzey is not recommended.

In addition, it is important for you to know that:

• The safety and efficacy of Eiyzey when administered in both eyes simultaneously has not been studied, and using it in this way may increase the risk of adverse effects.
• Eiyzey 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 of eye redness, blurred or decreased vision, and increased sensitivity to light. It is important that any new symptoms are diagnosed and treated as soon as possible.
• Your doctor will check whether you have other risk factors that may 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 Eiyzey will be administered with caution.
• Eiyzey 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 Eiyzey.

Systemic use of VEGF inhibitors—substances similar to those contained in Eiyzey—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 injection of Eiyzey into the eye, there is a theoretical risk that such events may occur. Data on the safety of treating 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, Eiyzey 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 who have previously been 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 applies to you, your doctor will take this lack of information into account when deciding whether to treat you with Eiyzey.

Children and adolescents

The use of Eiyzey has not been studied in children and adolescents under 18 years of age for indications other than retinopathy of prematurity (ROP).

Other medicines and Eiyzey

Tell 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 Eiyzey.
• There is no experience with the use of Eiyzey in pregnant women. Eiyzey 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 Eiyzey.
• Small amounts of Eiyzey may pass into breast milk. The effects on newborns/breastfed infants are unknown. Eiyzey is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with Eiyzey.

Driving and use of machines

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

Important information about some of the ingredients of Eiyzey

This medicine 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 Eiyzey will be administered to you

Eiyzey will be administered by a physician experienced in the administration of ocular injections, under sterile conditions (clean and sterile environment).

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

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

Prior to the injection, your doctor will use a disinfectant eye rinse 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 a monthly injection 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.

It is not necessary for you to visit your doctor between injections 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 Eiyzey injections.

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

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

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

Your doctor will monitor your response to treatment and may continue treatment, gradually increasing the interval between injections to stabilize your disease. 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 decide on 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 determined by your doctor’s examination. Your doctor will decide the follow-up visit schedule.

Your doctor may decide to discontinue treatment with aflibercept if it is determined that you do not benefit from continued treatment.

Myopic choroidal neovascularization (mCNV)

Patients with mCNV will be treated with a single injection. You will only receive additional injections 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 disease resolves and then recurs, your doctor may restart treatment.

Your doctor will decide on the follow-up examination schedule.

Detailed instructions for use are provided at the end of this leaflet under “How to prepare and administer Eiyzey to adults.”

If you miss a dose of Eiyzey

Schedule a new appointment for examination and administration of the injection.

Discontinuation of treatment with Eiyzey

Consult your doctor before stopping 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 may require you to contact your doctor immediately.

With administration of Eiyzey, some adverse effects affecting the eyes may occur, which are related to the injection procedure. Some of these may be serious, including blindness, a severe 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 an increase in pain and redness in the eye after injection, contact 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 impairment
• 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 with floating spots, which sometimes progresses to vision loss (tear/detachment of the retinal pigment epithelium, tear/detachment of the retina)

O *Adverse effects known to be associated with exudative AMD; observed only in patients with exudative AMD.

• Retinal degeneration (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

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

• Allergic reactions (hypersensitivity)**

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

• Severe inflammation or infection inside the eye (endophthalmitis)
• Inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, floating cells in the anterior chamber)
• Abnormal sensation in the eye
• Eyelid irritation
• Swelling of the surface layer of the eyeball (cornea)

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 medications. This increased incidence was comparable in patients treated with ranibizumab and aflibercept.

Systemic use of VEGF inhibitors—substances similar to those contained in Eiyzey—is potentially associated with the risk of blood clot formation 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 intravitreal injection of aflibercept.

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

Reporting of adverse effects

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

5. Storage of Eiyzey

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date 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°C and 8°C). Do not freeze.
• The unopened blister pack may be stored outside the refrigerator at temperatures below 25°C for a maximum of 24 hours.
• Keep in the original packaging to protect from light.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines and their packaging. This helps protect the environment.

6. Contents of the pack and other information

Composition of Eiyzey

• The active substance is: aflibercept. Each pre-filled syringe contains 6.6 mg of aflibercept in 0.165 ml of solution. This provides a usable amount for administering a single dose of 0.05 ml containing 2 mg of aflibercept.
• The other components are: sodium acetate trihydrate, acetic acid (glacial) 100%, sucrose, sodium chloride, polysorbate 20 (E 432), water for injections.

See “Eiyzey contains” in section 2 for more information.

Presentation of the product and contents of the pack

Eiyzey is an injectable solution (injectable) in a pre-filled syringe. The solution is colourless to pale yellow.

Single-dose 1 ml pre-filled syringe with Luer Long closure (PFS; fill volume: 165 microlitres of solution), made from cyclic olefin polymer (COP) resin, with a chlorobutyl rubber stopper. The syringe is closed with a chlorobutyl rubber plunger coated with cross-linked silicone.

Each carton contains one PFS with a nominal volume of 165 microlitres of solution for intravitreal injection.

Pack size: 1 pre-filled syringe.

Marketing Authorisation Holder

Zaklady Farmaceutyczne POLPHARMA S.A.

ul. Pelplinska 19, 83-200 Starogard Gdanski

Poland

Manufacturer responsible for manufacturing

KYMOS S.L.

Ronda De Can Fatjó 7b P

arc Tecnològic Del Vallès

Cerdanyola Del Vallès

Barcelona

08290

Spain

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this summary:

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

This information is intended for healthcare professionals only:

How to prepare and administer Eiyzey

The pre-filled syringe must be used for the treatment of one eye only. Do not open the blister containing the sterile pre-filled syringe outside a clean room environment.

The pre-filled syringe contains a volume greater than the recommended dose of 2 mg aflibercept (equivalent to 0.05 ml). The excess volume must be discarded prior to administration.

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

The unopened blister may be stored outside the refrigerator at temperatures below 25 °C for a maximum of 24 hours.

After opening the blister, proceed under aseptic conditions.

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

Instructions for use of the pre-filled syringe: