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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

aflibercept

This medicinal product is subject to additional monitoring, which will allow for quicker detection 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 this entire leaflet carefully before you are administered this medicine, because 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.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Afqlir is and what it is used for
2. What you need to know before you are administered Afqlir
3. How Afqlir is administered
4. Possible adverse reactions
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 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 blockage of 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 (mCNV).

Aflibercept, the active substance in Afqlir, blocks the activity of a group of factors known as vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF).

In patients with exudative AMD and mCNV, 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 the ocular tissues responsible for vision.

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

Diabetic macular edema is retinal swelling in diabetic patients caused by 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 due to fluid accumulation, central vision becomes blurred.

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

2. What you need to know before being given Afqlir

Do not use Afqlir

• if you are allergic to aflibercept or to 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 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 Afqlir:

• 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 or next four weeks.
• If you have a severe form of CRVO or BRVO (ischemic CRVO or BRVO), treatment with Afqlir is not recommended.

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

• The safety and efficacy of aflibercept 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 Afqlir 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 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 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 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 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 vessel blockage due to blood clots (arterial thromboembolic events), which may lead to myocardial infarction or stroke. After injection of Afqlir into the eye, there is a theoretical risk that such events may occur. Safety data on treatment of patients with CRVO, BRVO, DME, and mCNV who have experienced stroke, transient ischemic attack (TIA), or myocardial infarction within the previous 6 months are limited. If any of these apply to you, Afqlir will be administered with caution.

Experience is limited in the treatment of:

• Patients with DME due to type I diabetes.
• Diabetic patients with very high average blood sugar levels (glycated hemoglobin above 12%).
• Diabetic patients with an eye disease caused by diabetes, known as proliferative diabetic retinopathy.

There is no experience in the treatment of:

• Patients with acute infections.
• Patients with other eye diseases such as retinal detachment or macular hole.
• Diabetic patients with uncontrolled hypertension.
• Non-Asian patients with mCNV.
• Patients previously treated for mCNV.
• Patients with damage outside the central part of the macula (extrafoveal lesions) due to mCNV.

If any of the above applies to you, your doctor will take this lack of information into account when deciding on your treatment with Afqlir.

Children and adolescents

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

Other medicines and Afqlir

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

• Women of childbearing potential must use effective contraception during treatment and for at least three months after the last injection of 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 treatment with Afqlir.
• Small amounts of Afqlir may pass into breast milk. The effects on newborns or breastfed infants are unknown. Afqlir is contraindicated during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with Afqlir.

Driving and use of machines

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

Important information about some of the ingredients of 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 administered dose of 0.05 ml (50 microliters) of solution. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergy.

3. How Afqlir will be administered to you

Afqlir will be administered by a physician experienced in performing intravitreal injections, under sterile conditions.

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

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

Prior to 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 monthly injections 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 RVO (branch or central)

Your doctor will determine the most appropriate treatment regimen for you. Your treatment will begin with a series of monthly Afqlir injections.

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

Your doctor may decide to discontinue treatment with Afqlir if you do not benefit 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 therapy, gradually increasing the interval between injections to maintain disease stability. 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 determine 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 assessed by your doctor. Your doctor will determine the follow-up visit schedule.

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

Myopic choroidal neovascularization (mCNV)

Patients with mCNV will be treated with a single injection. Additional injections will only be given if examinations by your doctor show that your condition has not improved.

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

If your condition resolves and later recurs, your doctor may restart treatment.

Your doctor will determine the follow-up examination schedule.

Detailed instructions for use are provided at the end of this leaflet under “Instructions for use of the pre-filled syringe:”.

If you miss a dose of Afqlir

Schedule a new appointment to be examined and receive the injection.

Discontinuation of Afqlir treatment

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 that you contact your doctor immediately.

Some adverse effects affecting the eyes may occur with administration of aflibercept, 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 from the retina (vitreous detachment), and increased pressure inside the eye (see section 2). These serious eye-related adverse effects occurred in fewer than 1 in 1,900 injections during clinical trials.

If you notice a sudden decrease in vision or increased pain and redness in the eye after the injection, contact your doctor immediately.

List of reported adverse effects

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

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

• vision deterioration
• 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 and floating spots, which sometimes progress to vision loss (tear/detachment of the retinal pigment epithelium, tear/detachment of the retina)

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

• retinal degeneration (causing visual disturbances)

• bleeding in the eye (vitreous haemorrhage)

• certain forms of clouding of the lens (cataract)

• damage to the surface layer of the eyeball (cornea)

• increased pressure inside the eye

• spots in vision (floaters)

• detachment of the gel-like substance inside the eye from the retina (vitreous detachment, resulting in flashes of light and floaters)

• sensation of having something in the eye

• increased tear production

• eyelid swelling

• bleeding at the injection site

• eye redness

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

• allergic reactions (hypersensitivity)**
• **Allergic reactions reported include rash, itching (pruritus), hives (urticaria), and some cases of serious allergic (anaphylactic/anaphylactoid) reactions.
• inflammation or severe 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)

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

In clinical trials, an increased incidence of bleeding from small blood vessels in the outer layers of the eye (conjunctival haemorrhage) was observed in patients with exudative AMD who were receiving anticoagulant therapy. This increased incidence was comparable in patients treated with ranibizumab and aflibercept.

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), which may lead to heart attack or stroke. There is a theoretical risk that such events could occur following injection of Afqlir into the eye.

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

Reporting of adverse effects

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

5. Afqlir Storage

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and label after “CAD/EXP”. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.
• The unopened blister pack may be stored outside the refrigerator at temperatures below 30 °C for a maximum of 7 days.
• Keep 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 medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Afqlir

• 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 to administer a single dose of 0.05 ml containing 2 mg of aflibercept.
• The other components are: polysorbate 20 (E 432), histidine, L-histidine monohydrochloride monohydrate, trehalose dihydrate, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections.

Appearance of Afqlir and contents of the pack

Afqlir is an injectable solution 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 a closure cap at the end (elastomeric rubber). The solution is clear, colourless to slightly yellowish-brown.

Pack containing 1 pre-filled syringe.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Manufacturer responsible for batch release

Novartis Manufacturing

Rijksweg 14

Puurs-Sint-Amands, 2870

Belgium

Further information on this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

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

This information is intended for healthcare professionals only:

The pre-filled syringe contains more volume 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 pre-filled syringe:

Storage and inspection

Preparation and Administration

Each pre-filled syringe must be used exclusively for the treatment of one eye only.

Do not open the blister containing the sterile pre-filled syringe outside a clean room.

A 30 G x ½ inch (1.27 cm) injection needle must be used for intravitreal injection.

Use an aseptic technique to carry out the following steps.

Description of the pre-filled syringe