Eiyezy 40 mg/ml solution for injection in vial

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Eiyzey 40 mg/ml solution for injection in vial

aflibercept

This medicine is subject to additional monitoring, which will allow for faster 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 adverse reactions 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 side effects
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, 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 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, leading to 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 blood vessel 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 from fluid accumulation, central vision becomes blurred.

Eiyzey has been shown to halt 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 be given Eiyzey

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

Warnings and precautions

Talk to your doctor before you are given 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 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 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.
• Injections of Eiyzey 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 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 contraceptive methods 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 could 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 only limited in treating:

• 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 treating:

• 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 apply to you, your doctor will take this lack of information into account when deciding 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, 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 Eiyzey with other medicines

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 contraceptive methods 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 or 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 injection of Eiyzey, you may experience some transient visual disturbances. Do not drive or operate machinery while these disturbances last.

Important information about some of the components 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 performing ocular injections, under sterile (clean and sterile) conditions.

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

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

Before 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 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 be maintained every two months or 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 required unless your doctor advises otherwise or you experience any problems.

Macular edema secondary to BRVO (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 are not benefiting 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 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. Your doctor will decide the follow-up visit schedule.

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

Myopic choroidal neovascularization (mCNV)

Patients with mCNV will be treated with a single injection. You will receive additional injections only if examinations by your doctor show that your disease 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.

If a dose of Eiyzey is not administered

Schedule a new appointment to be examined and receive 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 require you to contact your doctor immediately.

Some adverse effects affecting the eyes may occur with the administration of Eiyzey, 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 out of 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, seek immediate medical advice.

List of reported adverse effects

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

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

• visual 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 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 with floating spots)

• 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 neovascular (wet) AMD; observed only in patients with neovascular (wet) AMD.

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

• allergic reactions (hypersensitivity)**

• severe inflammation or infection inside the eye (endophthalmitis)

• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, floaters 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 severe 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 neovascular (wet) 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 aflibercept injection.

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed 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 vial may be stored outside the refrigerator at temperatures below 25°C for a maximum of 24 hours.
• Store 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 unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Eiyzey

• The active substance is: aflibercept. Each pack contains one type I glass vial with a nominal volume of 278 microliters of solution for intravitreal injection, fitted with an elastomeric rubber stopper and an aluminum seal, and one 18 G filter needle. Each vial provides a usable amount to administer a single dose of 50 microliters 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 further information.

Nature and contents of the container

Eiyzey is an injectable solution (injectable) in a vial. The solution is colorless to pale yellow.

Pack containing 1 vial + 1 filter needle.

Marketing Authorization Holder

Zaklady Farmaceutyczne POLPHARMA S.A.

ul. Pelplinska 19, 83-200 Starogard Gdanski

Poland

Manufacturer responsible

KYMOS S.L.

Ronda De Can Fatjó 7b P

arc Tecnològic Del Vallès

Cerdanyola Del Vallès

Barcelona

08290

Spain

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

Date of the most recent review of this leaflet:

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

This information is intended for healthcare professionals only:

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

The vial contains a larger volume than the recommended dose of 2 mg of 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 medicinal product.

The unopened vial of Eiyzey may be stored outside the refrigerator at temperatures below 25°C for a maximum of 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: