Eylea

Italy

Brand name Eylea

Form solution for injection

Active substance / Dosage

AFLIBERCEPT

Prescription type Restricted prescription – hospital or equivalent facility use only

ATC code

S01LA05

Registration number 042510

Manufacturer BAYER AG

Table of Contents

Package leaflet: Information for the adult patient
Eylea 40 mg/mL solution for injection in pre-filled syringe
1. What Eylea is and what it is used for
2. What you should know before using Eylea
3. How to use Eylea
4. Possible side effects
5. How to store Eylea
6. Package contents and other information
The following information is intended exclusively for healthcare professionals:
Patient Information Leaflet: Information for Carers of Premature Babies
Eylea 40 mg/mL solution for injection in pre-filled syringe
1. What Eylea is and what it is used for
2. What you should know before Eylea is administered to the child
3. How to give Eylea to the child
4. Possible side effects
5. How to store Eylea
6. Package contents and other information
The following information is intended exclusively for healthcare professionals:
Patient Information Leaflet
Eylea 40 mg/mL solution for injection in vial
1. What Eylea is and what it is used for
2. What you should know before using Eylea
3. How to use Eylea
4. Possible side effects
5. How to store Eylea
6. Package contents and other information
The following information is intended exclusively for healthcare professionals:
Patient Information Leaflet
Eylea 114.3 mg/mL solution for injection
1. What Eylea is and what it is used for
2. What you need to know before receiving Eylea
3. How Eylea will be administered
4. Possible side effects
5. How to store Eylea
6. Package contents and other information
The following information is intended for healthcare professionals only:
Package leaflet: information for the patient
Eylea 114.3 mg/mL solution for injection in pre-filled syringe
1. What Eylea is and what it is used for
2. What you need to know before receiving Eylea
3. How Eylea will be administered
4. Possible side effects
5. How to store Eylea
6. Package contents and other information
The following information is intended exclusively for healthcare professionals:

Package leaflet: Information for the adult patient

Eylea 40 mg/mL solution for injection in pre-filled syringe

aflibercept
ADULTS
For information for caregivers of premature infants, please see the back of this package leaflet.
[applicable for 1 language]
For information for caregivers of premature infants, please see below on this page.
[applicable for 2 or more languages]
Read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor.
If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

What Eylea is and what it is used for
What you need to know before using Eylea
How to use Eylea
Possible side effects
How to store Eylea
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 eye diseases in adults called

neovascular age-related macular degeneration (wet AMD),
vision impairment due to macular oedema secondary to retinal vein occlusion (branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)),
vision impairment due to diabetic macular oedema (DME),
vision impairment due to myopic choroidal neovascularisation (myopic CNV).

Aflibercept, the active substance in Eylea, blocks the activity of a group of factors known as VEGF-A (vascular endothelial growth factor A) and PlGF (placental growth factor).
In patients with wet AMD and myopic CNV, these factors, when present in excess, are involved in the abnormal formation of new blood vessels in the eye. The new blood vessels may leak blood components into the eye and potentially damage ocular tissues responsible for vision.
In patients with CRVO, a blockage forms in the main blood vessel that carries blood away from the retina. VEGF levels increase in response to this event, causing fluid leakage into the retina and resulting in swelling of the macula (the part of the retina responsible for sharp vision), known as macular oedema. When the macula swells with fluid, central vision becomes blurred.
In patients with BRVO, one or more branches of the main vessel draining blood from the retina are blocked. VEGF levels consequently rise, leading to fluid leakage into the retina and causing macular oedema.
Diabetic macular oedema is a swelling of the retina that occurs in diabetic patients due to leakage of fluid from blood vessels in the macula. The macula is the part of the retina responsible for clear vision. When the macula fills with fluid, central vision becomes blurred.
Eylea has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Eylea can help stabilize, and in many cases improve, vision loss associated with wet AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you should know before using Eylea

Do not take Eylea

if you are allergic to aflibercept or to any of the other ingredients of this medicine (listed in section 6).
if you currently have or suspect an infection inside or around the 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 taking Eylea

if you have glaucoma.
if you have ever experienced flashes of light or floaters, or if the number and size of floaters has suddenly increased.
if you have had or are scheduled to have eye surgery within the past or next four weeks.
if you have a severe form of CRVO or BRVO (ischemic CRVO or BRVO), treatment with Eylea is not recommended.

It is also important for you to know that

the safety and efficacy of Eylea when administered in both eyes simultaneously have not been studied, and administering it this way may increase the risk of experiencing adverse effects.
Eylea injections may cause a temporary increase in intraocular pressure (eye pressure) within 60 minutes after injection in some patients. Your doctor will monitor for this effect after each injection.
if you develop an infection or inflammation inside the eye (endophthalmitis) or other complications, you may experience eye pain or worsening discomfort, increased eye redness, blurred or reduced 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 may increase the likelihood of detachment or tear in the back of the eye (retinal detachment or tear, or retinal pigment epithelial detachment or tear); in such cases, Eylea will be administered with caution.
Eylea should not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child.
women of childbearing age 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—may be associated with a risk of blood clots blocking blood vessels (arterial thromboembolic events), leading to heart attack or stroke. There is a theoretical risk that such events may occur following injection of Eylea into the eye. Data on the safety of treating patients with CRVO, BRVO, DME, and myopic CNV who have had a stroke or mini-stroke (transient ischemic attack) or heart attack within the past 6 months are limited. If any of these conditions 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 high average blood glucose levels (HbA1c greater than 12%).
diabetic patients with a diabetes-related eye disease called proliferative diabetic retinopathy.

There is no experience with the treatment of

patients with acute infections.
patients with other eye diseases such as retinal detachment or macular hole.
diabetic patients with uncontrolled high blood pressure.
non-Asian patients with myopic CNV.
patients previously treated for myopic CNV.
patients with lesions located outside the central part of the macula (extrafoveal lesions) in myopic CNV.

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

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

Other medicines and Eylea
Tell your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding

Women of childbearing age 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 unborn child. If you are pregnant or planning to become pregnant, discuss this with your doctor before starting treatment with Eylea.
Small amounts of Eylea may pass into breast milk. The effects on breastfed infants are unknown. Eylea is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before starting treatment with Eylea.

Driving and using machines
After receiving an Eylea injection, you may experience temporary visual disturbances. Do not drive or operate machinery until these symptoms have resolved.

Eylea contains

less than 1 mmol (23 mg) of sodium per single dose, i.e., it is essentially ‘sodium-free’.
in each 0.05 mL dose, 0.015 mg of polysorbate 20, equivalent to 0.3 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Eylea

A doctor experienced in eye injections will inject Eylea into your eye under aseptic (clean and sterile) conditions.
The recommended dose is 2 mg of aflibercept (0.05 mL).
Eylea is administered as an injection into the eye (intravitreal injection).
Before the injection, the doctor will use a disinfecting eye wash to thoroughly clean the eye and prevent infections. The doctor will also give you a local anesthetic to reduce or block pain caused by the injection.

Wet AMD
Patients with wet AMD will be treated with one injection per month for three consecutive doses, followed by another injection after a further two months.
Your doctor will then decide whether the treatment interval between injections can be maintained every two months or whether it should be gradually extended by intervals of 2 or 4 weeks if your condition is stable.
If your condition worsens, the interval between injections may be shortened.
Unless you experience problems or your doctor advises otherwise, there is no need to see your doctor between injections.

Macular edema secondary to RVO (branch RVO and central RVO)
Your doctor will determine the most appropriate treatment frequency for you. Treatment will begin with a series of monthly Eylea injections.
The interval between two injections must not be less than one month.
If you have not benefited after continuous treatment, your doctor may decide to discontinue treatment with Eylea.
Treatment will continue with monthly injections until your condition stabilizes.
Three or more monthly injections may be necessary.
Your doctor will monitor your response to treatment and may continue treatment with gradually increasing intervals between injections to maintain a stable condition. If your condition begins to worsen when the treatment interval is extended, your doctor will shorten the intervals accordingly.
Based on your individual response to treatment, your doctor will decide when follow-up examinations and treatments should be scheduled.

Diabetic macular edema (DME)
Patients with DME will be treated with one injection per month 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 according to your condition, based on examinations performed by your doctor. Your doctor will decide the frequency of follow-up examinations.
Your doctor may decide to discontinue treatment with Eylea if it is determined that you are not benefiting from continuing the treatment.

Myopic CNV
Patients with myopic CNV will be treated with a single injection. You will receive further injections only if examinations performed by your doctor indicate that the disease has not improved.
The interval between two injections must not be less than one month.
If the disease resolves and then recurs, your doctor may restart treatment.
Your doctor will determine the schedule for follow-up examinations.

Detailed instructions for use are included at the end of the package leaflet in the section “How to prepare and administer Eylea to adults”.

If you forget to use Eylea
Make a new appointment for examinations and injection.

If you stop using Eylea
Consult your doctor before stopping treatment.
If you have any doubts about how to use this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Allergic reactions (hypersensitivity) may potentially occur, which can be severe and may require immediate medical attention.
When Eylea is administered, certain side effects affecting the eyes may occur, which are related to the injection procedure. Some of these may be serious and include 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 inside the eye (vitreous haemorrhage), separation of the gel-like substance inside the eye from the retina (vitreous detachment), and increased pressure inside the eye, see section 2.
These serious eye-related side effects occurred in fewer than 1 in 1,900 injections in clinical studies.
If you experience a sudden decrease in vision, or increased eye pain and redness after the injection, contact your doctor immediately.

List of reported side effects
Below is a list of side effects reported as potentially related to the injection procedure or the medicine. Do not be alarmed—you may not experience any of these. Always speak to your doctor about any suspected side effects.

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

worsening of vision
bleeding at the back of the eye (retinal haemorrhage)
bloodshot eye due to bleeding from small blood vessels in the outer layers of the eye
eye pain

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

detachment or tear in one of the layers at the back of the eye, causing flashes of light with floaters and sometimes leading to vision loss (retinal pigment epithelial tear*, detachment, retinal detachment/tear)
or *Conditions known to be associated with neovascular age-related macular degeneration (AMD), observed only in patients with neovascular AMD.
retinal degeneration causing disturbed vision
bleeding inside the eye (vitreous haemorrhage)
certain forms of clouding of the lens (cataract)
damage to the outermost layer of the eyeball (cornea)
increased intraocular pressure
seeing moving spots (floaters)
separation of the gel-like substance inside the eye from the retina (vitreous detachment, causing flashes of light with floaters)
sensation of having something in the eye
increased tear production
eyelid swelling
bleeding at the injection site
eye redness

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

allergic reactions (hypersensitivity)**
or **Allergic reactions such as skin rash, itching, urticaria, and some cases of severe allergic reaction (anaphylactic/anaphylactoid) have been reported.
severe inflammation or infection inside the eye (endophthalmitis)
inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, flare in the anterior chamber)
unusual sensation in the eye
eyelid irritation
swelling of the outermost layer of the eyeball (cornea)

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

blindness
clouding of the lens following 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 studies, an increased incidence of bleeding from small blood vessels in the outer layer of the eye (conjunctival haemorrhage) was observed in patients with age-related neovascular macular degeneration (AMD) who were treated with blood-thinning medications. This increased incidence was comparable between patients treated with ranibizumab and those treated with Eylea.

Systemic use of vascular endothelial growth factor (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 potential risk that such events may occur following intravitreal injection of Eylea.

As with all therapeutic proteins, use of Eylea may trigger an immune response (antibody formation).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor. You may also report side effects directly via the National Reporting System listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Eylea

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 “Exp.” / “EXP”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
The unopened blister can be stored outside the refrigerator at a temperature not exceeding 25 °C for up to 24 hours.
Keep in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Eylea contains

The active substance is aflibercept. One pre-filled syringe contains a deliverable volume of at least 0.09 mL, equivalent to at least 3.6 mg of aflibercept. One pre-filled syringe provides a dose of 2 mg of aflibercept in 0.05 mL.
The other components are: polysorbate 20 (E432), monobasic sodium phosphate monohydrate (for pH adjustment), dibasic sodium phosphate heptahydrate (for pH adjustment), sodium chloride, sucrose, water for injections.

See 'Eylea contains' in section 2 for further information.
Description of the appearance of Eylea and the contents of the pack
Eylea is an injectable solution (injectable preparation) in a pre-filled syringe. The solution appears colourless to pale yellow.
Pack containing 1 pre-filled syringe.
Marketing Authorisation Holder
Bayer AG
51368 Leverkusen
Germany
Manufacturer
Bayer AG
Müllerstraße 178
13353 Berlin
Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België / Belgique / Belgien Lietuva
Bayer SA-NV UAB Bayer
Tél/Tel: +32-(0)2-535 63 11 Tel: +370-5-233 68 68
България Luxembourg / Luxemburg
Байер България ЕООД Bayer SA-NV
Тел: +359-(0)2-424 72 80 Tél/Tel: +32-(0)2-535 63 11
Česká republika Magyarország
Bayer s.r.o. Bayer Hungária KFT
Tel: +420-266 101 111 Tel: +36-1-487 4100
Danmark Malta
Bayer A/S Alfred Gera and Sons Ltd.
Tlf: +45-45 235 000 Tel: +356-21 44 62 05
Deutschland Nederland
Bayer Vital GmbH Bayer B.V.
Tel: +49-(0)214-30 513 48 Tel: +31-23-799 1000
Eesti Norge
Bayer OÜ Bayer AS
Tel: +372-655 85 65 Tlf: +47-23 13 05 00
Ελλάδα Österreich
Bayer Ελλάς ΑΒΕΕ Bayer Austria Ges. m. b. H.
Τηλ: +30-210-618 75 00 Tel: +43-(0)1-711 460
España Polska
Bayer Hispania S.L. Bayer Sp. z. o. o.
Tel: +34-93-495 65 00 Tel: +48-22-572 35 00
France Portugal
Bayer HealthCare Bayer Portugal, Lda
Tél (N° vert): +33-(0)800 87 54 54 Tel: +351-21-416 42 00
Hrvatska România
Bayer d.o.o. SC Bayer SRL
Tel: + 385-(0)1-6599 900 Tel: +40-(0)21-529 59 00
Ireland Slovenija
Bayer Limited Bayer d. o .o.
Tel: +353-(0)1-216 3300 Tel: +386-(0)1-58 14 400
Ísland Slovenská republika
Icepharma hf. Bayer, spol. s. r. o.
Sími: +354-540 80 00 Tel: +421-(0)2-59 21 31 11
Italia Suomi/Finland
Bayer S.p.A. Bayer Oy
Tel: +39-02-3978 1 Puh/Tel: +358-(0)20-78521
Κύπρος Sverige
NOVAGEM Limited Bayer AB
Τηλ: +357-22-48 38 58 Tel: +46-(0)8-580 223 00
Latvija
SIA Bayer
Tel: +371-67 84 55 63
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .
For local information, scan here to access the website https://www.pi.bayer.com/eylea1 .
The QR code linking to the package leaflet is included.

The following information is intended exclusively for healthcare professionals:

How to prepare and administer Eylea to adults
The pre-filled syringe must be used only for the treatment of one single eye.
Do not open the sterile blister of the pre-filled syringe outside the clean administration room.
The pre-filled syringe contains more than the recommended dose of 2 mg of aflibercept (equivalent to 0.05 mL). The excess volume must be discarded before administration.
Before administration, visually inspect the injectable solution for the presence of foreign particles and/or discoloration or any change in appearance. If any of these conditions occur, the product must be discarded.
The unopened sterile blister may be stored outside the refrigerator at a temperature below 25 °C for up to 24 hours. Once the blister is opened, handle under aseptic conditions. A 30 G x ½ inch injection needle must be used for intravitreal injection.

Instructions for using the pre-filled syringe:

When ready to administer Eylea, open the carton and remove the sterilized blister. Carefully open the blister, ensuring sterility of its contents. Keep the syringe on the sterile tray until ready for assembly.
Using aseptic technique, remove the syringe from the sterilized blister.

Two hands hold a medical vial with a black curved arrow indicating the rotating motion of the cap, with the word TURN at the top

To remove the syringe cap, hold the syringe with one hand and grasp the cap with the thumb and index finger of the other hand. Caution: rotate (do not pull off) the syringe cap.
To avoid compromising the product's sterility, do not pull back the plunger.

Two hands twisting and separating a cylindrical container into two parts through a rotational movement indicated by curved arrows

Using aseptic technique, firmly attach the injection needle by twisting it onto the tip of the syringe with a Luer-lock adapter.

Two hands holding a syringe with needle and internal liquid, while one hand points to the upper part of the medical device

With the syringe held needle-up, check for the presence of air bubbles inside. If air bubbles are present, gently tap the syringe with the finger to allow them to rise to the surface.
Remove all air bubbles and expel the excess medication by slowly depressing the plunger to align the base of the rounded tip (not the tip apex) with the dosage marking line on the syringe (equivalent to 0.05 mL, i.e., 2 mg of aflibercept).

Note: Accurate positioning of the plunger is very important, as incorrect plunger positioning may result in administration of a dose higher or lower than recommended.

Diagram of a syringe with labels indicating air bubbles

Medical diagram showing the rounded tip of the plunger, the base of the tip, the dosage line, and the solution after

Inject by carefully and steadily depressing the plunger. Do not apply additional pressure once the plunger reaches the bottom of the syringe. Do not administer any residual solution remaining in the syringe.
The pre-filled syringe is for single use only. Withdrawing multiple doses from a single pre-filled syringe may increase the risk of contamination and subsequent infection.

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

Patient Information Leaflet: Information for Carers of Premature Babies

Eylea 40 mg/mL solution for injection in pre-filled syringe

aflibercept
PRETERM BORN INFANTS
For information regarding adults, please see the back of this leaflet. [applicable
for 1 language]
For information regarding adults, please see the top of the page. [applicable for 2 or more
languages]
Please read this leaflet carefully before this medicine is administered to the child
as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult the child's doctor.
If you notice any symptoms of side effects, including side effects not listed in this leaflet, consult the child's doctor. See section 4.

Contents of this leaflet

What Eylea is and what it is used for
What you need to know before Eylea is given to the child
How to give Eylea to the child
Possible side effects
How to store Eylea
Contents of the pack and other information