AFQLIR 40 mg/ml INJECTABLE SOLUTION IN VIAL

Introduction

Package Leaflet: Information for the Patient

Afqlir 40 mg/ml Solution for Injection in Vial

Aflibercept

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Afqlir and what is it used for

Afqlir is a solution that is injected into the eye to treat certain eye diseases in adult patients, known as:

• neovascular (exudative) age-related macular degeneration, commonly known as wet AMD
• vision impairment due to macular edema caused by blockage of the retinal veins (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 Afqlir, blocks the activity of a group of factors called vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF).

In patients with wet AMD and myopic CNV, when these factors are present in excess, they influence the formation of abnormal new blood vessels in the eye. These new blood vessels can cause leakage of blood components into the eye, resulting in damage to the eye tissues responsible for vision.

In patients with CRVO, there is a blockage of the main vein that carries blood from the retina. As a result, VEGF levels increase, causing fluid leakage in the retina and subsequent swelling of the macula (the part of the retina responsible for fine vision), known as macular edema. When the macula becomes filled with fluid, central vision becomes blurred.

In patients with BRVO, there is a blockage of one or more branches of the main blood vessel that carries blood from the retina. As a result, VEGF levels increase, causing fluid leakage in the retina and subsequent swelling of the macula.

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

Afqlir has been shown to stop the growth of abnormal new blood vessels in the eye that often bleed or leak fluid. Afqlir may help stabilize and, in many cases, improve vision loss caused by wet AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you need to know before you are given Afqlir

You should not be given Afqlir

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

Warnings and precautions

Consult your doctor before you are given Afqlir:

• If you have glaucoma.
• If you have a history of flashes of light or floaters or if you suddenly experience an increase in the size and number of floaters.
• If you have had or are scheduled to have eye surgery in the previous or next four weeks.
• If you have a severe form of CRVO or BRVO (ischemic CRVO or BRVO), treatment with Afqlir is not recommended.

Additionally, it is important that you know that:

• The safety and efficacy of aflibercept when administered in both eyes at the same time have not been studied, and if used in this way, may result in a higher risk of adverse effects.
• Afqlir 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 notice pain or increased discomfort in the eye, worsening of redness, blurred or decreased vision, and increased sensitivity to light. It is essential that any symptoms that appear are diagnosed and treated as soon as possible.
• Your doctor will check if you have other risk factors that may increase the likelihood of a tear or detachment of the posterior layers of the eye (retinal tear or detachment, or retinal pigment epithelial tear or detachment), in which case Afqlir will be administered with caution.
• Afqlir should not be used during pregnancy, unless the potential benefit outweighs the potential risk to the fetus.
• Women of childbearing age must use effective contraceptive methods during treatment and for at least three months after the last injection of Afqlir.

The 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) that can lead to a heart attack or stroke. After injection of Afqlir into the eye, there is a theoretical risk that these events may occur. Data on the safety of treatment in patients with CRVO, BRVO, DME, and myopic CNV who have had a stroke, transient ischemic attack, or myocardial infarction in the last six months are limited. If any of these conditions apply to you, Afqlir will be administered with caution.

Experience is limited in the treatment of:

• Patient with DME due to type 1 diabetes.
• Diabetic patients with very high average blood sugar levels (HbA1c above 12%).
• Diabetic patients with a diabetic eye disease known as proliferative diabetic retinopathy.

There is no experience in the treatment of:

• Patient with acute infections.
• Patient with other eye diseases such as retinal detachment or macular hole.
• Diabetic patients with uncontrolled hypertension.
• Non-Asian patients with myopic CNV.
• Patient who have been previously treated for myopic CNV.
• Patient 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 into account this lack of information when treating you with Afqlir.

Children and adolescents

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

Using Afqlir with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

Pregnancy and breastfeeding

• Women of childbearing age must use effective contraceptive methods 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, consult your doctor before treatment with Afqlir.
• Small amounts of Afqlir may pass into breast milk. The effects on newborns/infants are unknown. Afqlir is contraindicated during breastfeeding. If you are breastfeeding, consult your doctor before treatment with Afqlir.

Driving and using machines

After injection of Afqlir, you may experience temporary visual disturbances. Do not drive or use machines while these disturbances last.

Important information about some of the ingredients of Afqlir

This medicine contains less than 23 mg of sodium (1 mmol) per dose unit; this is essentially "sodium-free".

This medicine contains 0.02 mg of polysorbate 20 in each 0.05 ml (50 microliters) dose of solution. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Afqlir will be given to you

Afqlir will be given to you by a doctor with experience in giving eye injections, under aseptic conditions (clean and sterile).

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

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

Before the injection, your doctor will use an antiseptic eye wash to carefully clean your eye to prevent infection. Your doctor will also give you a local anesthetic to reduce or prevent any pain you may feel with the injection.

Wet AMD

Patient with wet AMD will be treated with one injection per month for the first three doses, followed by another injection after two months.

Your doctor will then decide if the treatment interval between injections can be maintained every two months or gradually extended to 2 or 4 weeks if your disease has stabilized.

If your disease worsens, the interval between injections may be shortened.

You do not need to visit your doctor between injections unless your doctor considers it necessary or you experience any problems.

Macular edema secondary to retinal vein occlusion (branch or central)

Your doctor will determine the most suitable treatment schedule for you. Your treatment will start with a series of Afqlir injections given once a month.

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

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

Treatment will continue with one injection per month until your disease has stabilized. You may need 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 disease worsens with a longer treatment interval, your doctor will reduce the interval between injections.

Based on your response to treatment, your doctor will decide on the follow-up and treatment schedule.

Diabetic macular edema (DME)

Patient with DME will be treated with one injection per month for the first five consecutive doses, and then one injection every two months.

The interval between treatments may be maintained every two months or adjusted according to your disease based on the examination by your doctor. Your doctor will decide on the follow-up visit schedule.

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

Myopic choroidal neovascularization (myopic CNV)

Patient with myopic CNV will be treated with a single injection. You will only receive additional injections if your doctor's examinations reveal that your disease has not improved.

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

If your disease disappears and then recurs, your doctor may restart treatment.

Your doctor will decide on the follow-up schedule.

If you miss a dose of Afqlir

Make a new appointment to be examined and given the injection.

Stopping treatment with Afqlir

Consult your doctor before stopping treatment.

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

4. Possible side effects

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

Potentially, allergic reactions(hypersensitivity) may occur. These can be serious and require you to contact your doctor immediately.

With the administration of Afqlir, some side effects may occur that affect the eyes and are due to the injection procedure. Some may be serious, including blindness, a severe infection or inflammation inside the eye(endophthalmitis), detachment, tear, or hemorrhage of the light-sensitive layer in the back of the eye(retinal detachment, retinal tear), clouding of the lens(cataract), bleeding in the eye(vitreous hemorrhage), detachment of the gel-like substance in the eye from the retina(vitreous detachment), and increased pressure inside the eye(see section 2). These serious eye side effects occurred in less 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 the injection, contact your doctor immediately.

List of reported side effects

The following is a list of reported side effects that may be related to the injection procedure or the medicine. Do not be alarmed, as you may not experience any of them. Always consult your doctor about any suspected side effect.

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

• vision decrease
• bleeding in the back of the eye (retinal hemorrhage)
• blood in the 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 in the back of the eye that produce flashes of light with floating spots that may progress to vision loss (retinal pigment epithelial tear or detachment, retinal tear or detachment)

• retinal degeneration (causing vision disturbances)

• bleeding in the eye (vitreous hemorrhage)
• certain types of clouding of the lens (cataract)
• damage to the outer layer of the eyeball (cornea)
• increased pressure inside the eye
• spots in the vision (floaters)
• detachment of the gel-like substance in 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
• swelling of the eyelid
• bleeding at the injection site
• redness of the eye

*Side effects that are known to be associated with wet AMD; observed only in patients with wet AMD.

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

• allergic reactions (hypersensitivity)**
• inflammation or severe infection inside the eye (endophthalmitis)
• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, cells in the anterior chamber)
• abnormal sensation in the eye
• irritation of the eyelid
• swelling of the outer layer of the eyeball (cornea)

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

Rare side 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 in the eye
• pus in the eye

In clinical trials, an increased incidence of bleeding from small blood vessels in the outer layers of the eye (conjunctival hemorrhage) was observed in patients with wet AMD who received treatment with anticoagulant medications. This increased incidence was comparable in patients treated with ranibizumab and aflibercept.

The 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) that can lead to a heart attack or stroke. After injection of Afqlir into the eye, there is a theoretical risk that these events may occur.

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

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 on the label after “EXP”. The expiry date refers to the last day of the month.
• Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.
• The unopened vial can be stored outside the refrigerator below 30 °C for a maximum of 14 days.
• Keep the container in the outer carton to protect it from light.
• Medicines should not be disposed of 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 Additional Information

Afqlir Composition

• The active substance is: aflibercept. Each vial contains 9.6 mg of aflibercept in 0.240 ml of solution. This provides a usable amount to administer a single dose of 0.05 ml containing 2 mg of aflibercept.

• The other ingredients are: polysorbate 20 (E 432), histidine, L-histidine monohydrochloride monohydrate, trehalose dihydrate, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injection.

Afqlir Appearance and Package Contents

Afqlir is an injectable solution (injectable) in a vial (Type I glass) with a stopper (elastomeric rubber) and a filter needle with an 18 G caliber. The solution is clear, colorless to slightly yellowish-brown. Package contains 1 vial + 1 filter needle.

Marketing Authorization 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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

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

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This information is intended only for healthcare professionals:

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

Instructions for use of the vial:

Storage and Inspection

Preparation and Administration

Each vial is for single use only.

The following single-use medical devices are required for preparation and intravitreal injection:

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

Use an aseptic technique to perform the following preparation steps.

Injection Procedure