Afqlir

Patient Information Leaflet

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

aflibercept
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine as 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, consult your doctor. See section 4.

Contents of this leaflet

1. What Afqlir is and what it is used for
2. What you need to know before using Afqlir
3. How to use Afqlir
4. Possible side effects
5. How to store Afqlir
6. Package contents and other information

1. What Afqlir is and what it is used for

Afqlir 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 (Diabetic Macular Oedema - DME),
• vision impairment due to myopic choroidal neovascularisation (myopic CNV).

Aflibercept, the active substance in Afqlir, 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 drains blood away from the retina. VEGF levels increase in response to this event, causing fluid leakage into the retina and thus leading to 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 blood vessel draining blood from the retina are blocked. As a result, VEGF levels are elevated, causing fluid leakage into the retina and leading to 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.
Afqlir has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Afqlir may help stabilize, and in many cases improve, vision loss associated with wet AMD, CRVO, BRVO, DME and myopic CNV.

2. What you need to know before taking Afqlir

Do not take Afqlir

• 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 Afqlir

• if you have glaucoma.
• if you have ever experienced flashes of light or floaters, or if the number and size of floaters have 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 Afqlir is not recommended.

It is also important for you to know that

• the safety and efficacy of aflibercept when administered in both eyes simultaneously have not been studied, and administering it in this way may increase the risk of experiencing adverse effects.
• Afqlir injections may cause an 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 discomfort, worsening 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 rupture of one of the layers at the back of the eye (retinal detachment or tear, or detachment or tear of the retinal pigment epithelium); in such cases, Afqlir will be administered with caution.
• Afqlir must not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child.
• women of childbearing potential must use effective contraception during treatment and for at least three additional months after the last Afqlir injection.

Systemic use of VEGF inhibitors—substances similar to those contained in Afqlir—is potentially associated with the 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 Afqlir into the eye. Limited data are available 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 previous 6 months. If any of these situations apply to you, Afqlir will be administered with caution.

Experience is limited in treating

• 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 treating

• 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) for 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 Afqlir.

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

Other medicines and Afqlir
Tell your doctor if you are taking, have recently taken, or might 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 Afqlir injection.
• There is no experience with the use of aflibercept in pregnant women. Afqlir must not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child. If you are pregnant or planning a pregnancy, discuss this with your doctor before treatment with Afqlir.
• Small amounts of Afqlir may pass into breast milk. The effects on breastfed infants are unknown. Afqlir is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with Afqlir.

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

Afqlir contains
This medicine contains less than 1 mmol (23 mg) of sodium per single dose, i.e., essentially 'sodium-free'.
This medicine contains 0.02 mg of polysorbate 20 in each administered dose of 0.05 mL (50 microliters) of solution. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to take Afqlir

A doctor experienced in eye injections will inject Afqlir into your eye under aseptic (clean and sterile) conditions.
The recommended dose is 2 mg of aflibercept (0.05 mL).
Afqlir is administered as an injection into the eye (intravitreal injection).
Before the injection, the doctor will use a disinfectant 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 2 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 have problems or are otherwise advised by your doctor, 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 injections of Afqlir.
The interval between two injections must not be less than one month.
If you have not benefited after continuous treatments, your doctor may decide to discontinue treatment with Afqlir.
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 a gradual increase in the intervals between injections to maintain a stable condition. If, when extending the duration of the interval between treatments, your condition begins to worsen, your doctor will shorten the intervals between treatments accordingly.
Based on your individual response to treatment, your doctor will decide when to schedule follow-up examinations and treatments.

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 2 months.
The interval between treatments may be maintained every 2 months or adjusted according to your condition, based on examinations performed by the doctor. Your doctor will decide the frequency of follow-up examinations.
Your doctor may decide to discontinue treatment with Afqlir if it is determined that you are not benefiting from continuing treatment.

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

Detailed instructions for use are included at the end of the package leaflet in the section “Instructions for use of the pre-filled syringe:”.

If you forget to take Afqlir
Make a new appointment for examinations and injection.

If you stop treatment with Afqlir
Consult your doctor before stopping treatment.
If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions (hypersensitivity) may potentially occur, which can be severe and may require immediate medical attention.

When aflibercept 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 out of 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 that have been 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 of 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, retinal detachment/tear)
• Degeneration of the retina causing disturbed vision
• Bleeding inside the eye (vitreous haemorrhage)
• Certain forms of lens clouding (cataract)
• Damage to the outermost layer of the eyeball (cornea)
• Increased eye 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)**
  ** Allergic reactions reported include skin rashes, itching, hives, and some cases of severe allergic reaction (anaphylactic/anaphylactoid).
• 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

Not known (frequency 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 (wet) macular degeneration (AMD) who were treated with blood-thinning medications. This increased incidence was comparable between patients treated with ranibizumab and those treated with aflibercept.

Systemic use of vascular endothelial growth factor (VEGF) inhibitors—substances similar to those contained in Afqlir—has been 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 could occur following injection of Afqlir into the eye.

As with all therapeutic proteins, use of Afqlir 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 through 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 Afqlir

• 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 “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 below 30 °C for a maximum of 7 days.
• Keep in the original packaging to protect from light.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Afqlir contains

• 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 administration of a single dose of 0.05 mL containing 2 mg of aflibercept.
• The other components are: polysorbate 20 (E432), histidine, L-histidine monohydrochloride monohydrate, trehalose dihydrate, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections. For further information, see 'Afqlir contains' in section 2.

Description of the appearance of Afqlir and contents of the pack
Afqlir is an injectable solution (preparation for injection) in a pre-filled syringe (type I glass)
marked with a dosage line, with a plunger stopper (elastomeric rubber) and a Luer lock
adapter with tip cap (elastomeric rubber). The solution is clear, colourless to slightly brownish-yellow.
Pack size: 1 pre-filled syringe.
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria
Manufacturer
Novartis Manufacturing
Rijksweg 14
Puurs-Sint-Amands, 2870
Belgium
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Latvija
Sandoz nv/sa Sandoz d.d. Latvia filiāle
Tél/Tel: +32 2 722 97 97 Tel: +371 67 892 006
България Lietuva
Сандоз България КЧТ Sandoz Pharmaceuticals d.d filialas
Тел.: +359 2 970 47 47 Tel: +370 5 2636 037
Česká republika Luxembourg/Luxemburg
Sandoz s.r.o. Sandoz nv/sa (Belgique/Belgien)
Tel: +420 234 142 222 Tél/Tel.: +32 2 722 97 97
Danmark/Norge/Ísland/Sverige Magyarország
Sandoz A/S Sandoz Hungária Kft.
Tlf./Tlf/Sími/Tel: +45 63 95 10 00 Tel.: +36 1 430 2890
Deutschland Malta
Hexal AG Sandoz Pharmaceuticals d.d.
Tel: +49 8024 908 0 Tel: +35699644126
Eesti Nederland
Sandoz d.d. Eesti filiaal Sandoz B.V.
Tel: +372 665 2400 Tel: +31 36 52 41 600
Ελλάδα Österreich
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
Τηλ: +30 216 600 5000 Tel: +43 5338 2000
España Polska
Sandoz Farmacéutica, S.A. Sandoz Polska Sp. z o.o.
Tel: +34 900 456 856 Tel.: +48 22 209 70 00
France Portugal
Sandoz SAS Sandoz Farmacêutica Lda.
Tél: +33 1 49 64 48 00 Tel: +351 21 000 86 00
Hrvatska România
Sandoz d.o.o. Sandoz Pharmaceuticals SRL
Tel: +385 1 23 53 111 Tel: +40 21 407 51 60
Ireland Slovenija
Rowex Ltd. Sandoz farmacevtska družba d.d.
Tel: +353 27 50077 Tel: +386 1 580 21 11
Italia Slovenská republika
Sandoz S.p.A. Sandoz d.d. - organizačná zložka
Tel: +39 02 81280696 Tel: +421 2 48 200 600
Κύπρος Suomi/Finland
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz A/S
(Greece) Puh/Tel: +358 10 6133 400
Τηλ: +30 216 600 5000
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

The following information is intended for healthcare professionals only:

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

Instructions for use of the pre-filled syringe:

Storage and inspection

Preparation and administration
Each pre-filled syringe must be used exclusively for the treatment of a single eye.
Do not open the sterile syringe blister outside the clean administration room.
For intravitreal injection, use a 30 G x ½ inch injection needle.
Use an aseptic technique to perform the following steps.
Description of the pre-filled syringe
Finger grip

Syringe cap
0.05 mL dose mark
Rubber stopper
Luer lock adapter Plunger rod

3 To remove the syringe cap, hold the syringe in one hand and grasp the cap with the thumb and index finger of the other hand. Pull the cap straight off (do not twist or turn).
Note: To avoid compromising the sterility of the product, do not pull back the plunger.

4 Using an aseptic technique, firmly attach the 30 G x ½ inch injection needle by rotating it onto the tip of the syringe with a Luer-lock adapter.

5 Holding the syringe with the needle pointing upward, check for the presence of air bubbles inside the syringe.
If air bubbles are present, gently tap the syringe with your finger to allow them to rise to the surface.
Carefully remove the needle cap by pulling it straight off.

6 Eliminate all air bubbles and expel any excess medication by slowly depressing the plunger until the base of the rounded plunger tip aligns with the dosage marking line on the syringe (equivalent to 50 microliters).
Note: inject immediately after preparing the syringe.

7 Inject slowly until the rubber stopper reaches the end of the syringe to deliver the 0.05 mL volume. Confirm administration of the entire dose by verifying that the rubber stopper has reached the end of the syringe barrel.

8 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 medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

Patient information leaflet

Afqlir 40 mg/mL solution for injection in vial

aflibercept
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine as 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 effect, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

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

1. What Afqlir is and what it is used for

Afqlir is a solution that is injected into the eye to treat eye diseases in adults called

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

Aflibercept, the active substance in Afqlir, 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 thus 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 blood vessel draining blood from the retina are blocked. As a consequence, VEGF levels 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.
Afqlir has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Afqlir may 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 taking Afqlir

Do not take Afqlir

• 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 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 taking Afqlir:

• 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 Afqlir is not recommended.

It is also important for you to know that:

• the safety and efficacy of aflibercept when administered to both eyes simultaneously have not been studied, and doing so may increase the risk of experiencing adverse effects.
• Afqlir injections may cause an increase in intraocular pressure within 60 minutes after injection in some patients. Your doctor will monitor 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 retinal tear or detachment, or tear or detachment of the retinal pigment epithelium (retinal tear or detachment, or retinal pigment epithelium tear or detachment); in such cases, Afqlir will be administered with caution.
• Afqlir should not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child.
• women of childbearing potential must use effective contraception during treatment and for at least three months after the last injection of Afqlir.

Systemic use of VEGF inhibitors—substances similar to those contained in Afqlir—is potentially associated with the 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 intravitreal injection of Afqlir. Limited data are available on the safety of treating patients with CRVO, BRVO, DME, or myopic CNV who have experienced a stroke or mini-stroke (transient ischemic attack) or heart attack within the previous 6 months. If any of these conditions apply to you, Afqlir will be administered with caution.

Experience is limited in treating:

• 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 treating:

• 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 Afqlir.

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

Other medicines and Afqlir
Tell your doctor if you are taking, have recently taken, or might 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 Afqlir.
• There is no experience with the use of aflibercept in pregnant women. Afqlir 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 starting treatment with Afqlir.
• Small amounts of Afqlir may pass into breast milk. The effects on breastfed infants are unknown. Afqlir is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before starting treatment with Afqlir.

Driving and using machines
After receiving an injection of Afqlir, you may experience temporary visual disturbances. Do not drive or operate machinery until these disturbances resolve.

Afqlir contains
This medicine contains less than 1 mmol (23 mg) of sodium per single dose, i.e., essentially ‘sodium-free’.
This medicine contains 0.02 mg of polysorbate 20 in each administered dose of 0.05 mL (50 microliters) of solution. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to take Afqlir

A doctor experienced in eye injections will inject Afqlir into your eye under aseptic (clean and sterile) conditions.
The recommended dose is 2 mg of aflibercept (0.05 mL).
Afqlir 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.

Exudative AMD
Patients with exudative AMD will be treated with one injection per month for three consecutive doses, followed by another injection after a further 2 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 are otherwise advised by your doctor, there is no need for medical visits 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 Afqlir 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 Afqlir.
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 a gradual increase in the intervals between injections to maintain a stable condition. If your condition begins to worsen when the interval between treatments is extended, your doctor will shorten the treatment 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 2 months.
The interval between treatments can be maintained every 2 months or adjusted according to your condition, based on examinations performed by the doctor. Your doctor will decide the frequency of follow-up examinations.
Your doctor may decide to discontinue treatment with Afqlir if it is determined that you are not benefiting from continuing treatment.

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

If you forget to take Afqlir
Make a new appointment to undergo examinations and receive the injection.

If you stop treatment with Afqlir
Consult your doctor before stopping treatment.
If you have any doubts about using this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions (hypersensitivity) may potentially occur, which can be serious and may require
immediate medical attention.
When Afqlir is administered, certain eye-related side effects 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 paragraph 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 rupture of 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)
• degeneration of the retina (causing disturbed vision)
• bleeding in the eye (vitreous haemorrhage)
• certain forms of clouding of the lens (cataract)
• damage to the outermost layer of the eyeball (cornea)
• increased eye 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
  Conditions known to be associated with neovascular age-related macular degeneration (AMD), observed only in patients with neovascular AMD.

Uncommon side 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, flare in anterior chamber)
• unusual sensation in the eye
• eyelid irritation
  swelling of the outermost layer of the eyeball (cornea) ** Allergic reactions such as skin rashes, itching, urticaria, and some cases of severe allergic reaction (anaphylactic/anaphylactoid) have been reported.

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

Not known (frequency cannot be estimated from the 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 neovascular age-related macular degeneration
(AMD) who were treated with blood-thinning medications. This increased incidence was comparable between
patients treated with ranibizumab and those treated with aflibercept.
Systemic use of vascular endothelial growth factor (VEGF) inhibitors, which are substances similar to those
contained in Afqlir, 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 injection of Afqlir into the eye.
As with all therapeutic proteins, use of Afqlir may trigger an immune response (antibody formation).
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You can
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 Afqlir

• 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 “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 vial may be stored outside the refrigerator at a temperature below 30 °C for up to 7 days.
• Keep in the original packaging to protect from light.
• Do not dispose of medicines 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 Afqlir contains

• The active substance is aflibercept. One vial contains a fill volume of at least 0.1 mL, equivalent to at least 4 mg of aflibercept. This provides a sufficient amount for administration of a single dose of 0.05 mL containing 2 mg of aflibercept.
• The other components are: polysorbate 20 (E432), histidine, L-histidine monohydrochloride monohydrate, trehalose dihydrate, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections. For further information, see 'Afqlir contains' in section 2.

Description of the appearance of Afqlir and contents of the pack
Afqlir is an injectable solution (preparation for injection) in a vial (type I glass) with a
stopper (elastomeric rubber) and an 18 G filter needle. The solution appears as a clear,
colourless to slightly brownish-yellow liquid.
Pack: 1 vial + 1 filter needle.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria
Lek Pharmaceuticals d.d.
Verovškova ulica 57
1526 Ljubljana
Slovenia

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Latvija
Sandoz nv/sa Sandoz d.d. Latvia filiāle
Tél/Tel: +32 2 722 97 97 Tel: +371 67 892 006

България Lietuva
Сандоз България КЧТ Sandoz Pharmaceuticals d.d filialas
Тел.: +359 2 970 47 47 Tel: +370 5 2636 037

Česká republika Luxembourg/Luxemburg
Sandoz s.r.o. Sandoz nv/sa (Belgique/Belgien)
Tel: +420 234 142 222 Tél/Tel.: +32 2 722 97 97

Danmark/Norge/Ísland/Sverige Magyarország
Sandoz A/S Sandoz Hungária Kft.
Tlf./Tlf/Sími/Tel: +45 63 95 10 00 Tel.: +36 1 430 2890

Deutschland Malta
Hexal AG Sandoz Pharmaceuticals d.d.
Tel: +49 8024 908 0 Tel: +35699644126

Eesti Nederland
Sandoz d.d. Eesti filiaal Sandoz B.V.
Tel: +372 665 2400 Tel: +31 36 52 41 600

Ελλάδα Österreich
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
Τηλ: +30 216 600 5000 Tel: +43 5338 2000

España Polska
Sandoz Farmacéutica, S.A. Sandoz Polska Sp. z o.o.
Tel: +34 900 456 856 Tel.: +48 22 209 70 00

France Portugal
Sandoz SAS Sandoz Farmacêutica Lda.
Tél: +33 1 49 64 48 00 Tel: +351 21 000 86 00

Hrvatska România
Sandoz d.o.o. Sandoz Pharmaceuticals SRL
Tel: +385 1 23 53 111 Tel: +40 21 407 51 60

Ireland Slovenija
Rowex Ltd. Sandoz farmacevtska družba d.d.
Tel: +353 27 50077 Tel: +386 1 580 21 11

Italia Slovenská republika
Sandoz S.p.A. Sandoz d.d. - organizačná zložka
Tel: +39 02 81280696 Tel: +421 2 48 200 600

Κύπρος Suomi/Finland
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz A/S
(Greece) Puh/Tel: +358 10 6133 400
Τηλ: +30 216 600 5000

More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

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

Instructions for use of the vial:

Storage and inspection

Preparation and administration
Each vial must be used exclusively for the treatment of a single eye.
The following single-use medical devices are required for preparation and intravitreal injection:

• A sterile 5 µm filter, blunt needle (18 G x 1 inch), sterile, supplied with the vial
• A 1 mL syringe with a 0.05 mL dose marking, sterile
• A 30 G x ½ inch injection needle, sterile.

Use an aseptic technique to perform the following steps.
Injection procedure

To eliminate all air bubbles and expel excess medicine,
press the plunger slowly until the tip of the plunger aligns
with the mark indicating 0.05 mL on the syringe.
Note: inject immediately after preparation.
11 Inject slowly until the rubber stopper reaches the end of the
syringe to deliver the 0.05 mL volume. Confirm administration of the full dose
by checking that the rubber stopper has reached the end
of the syringe barrel.
12 The vial is for single use only. Withdrawing multiple doses from a single vial 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.