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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

aflibercept

This medicine is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet includes information on how to report adverse reactions.

Read all of this leaflet carefully before this medicine is administered to you, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are not listed in this leaflet. See section 4.

Contents of this leaflet

1. What MYNZEPLI is and what it is used for
2. What you need to know before being given MYNZEPLI
3. How MYNZEPLI will be administered to you
4. Possible adverse reactions
5. How to store MYNZEPLI
6. Contents of the pack and other information

1. What MYNZEPLI is and what it is used for

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

• 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 MYNZEPLI, blocks the activity of a group of factors called vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF).

In patients with exudative AMD and mCNV, excessive levels of these factors contribute to the abnormal formation of new blood vessels in the eye. These new blood vessels may leak components of the blood into the eye, resulting in damage to the ocular tissues responsible for vision.

In patients with CRVO, a blockage occurs in the main vein that carries blood away from the retina. As a result, VEGF levels increase, causing fluid leakage into the retina and thus swelling of the macula (the part of the retina responsible for sharp vision), known as macular edema. When the macula accumulates fluid, central vision becomes blurred.

In patients with BRVO, a blockage occurs in one or more branches of the main blood vessel that carries blood away from the retina. This leads to increased VEGF levels, causing fluid leakage into the retina and, consequently, macular swelling.

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

MYNZEPLI has been shown to halt the growth of abnormal new blood vessels in the eye, which often bleed or leak fluid. MYNZEPLI 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 MYNZEPLI is administered to you

Do not administer MYNZEPLI

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

Warnings and precautions

Talk to your doctor before receiving MYNZEPLI:

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

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

• The safety and efficacy of MYNZEPLI when administered in both eyes simultaneously has not been studied, and using it in this way may increase the risk of adverse effects.
• MYNZEPLI injections may cause an increase in intraocular pressure (intraocular pressure) in some patients within 60 minutes after 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 of eye redness, blurred or decreased vision, and increased sensitivity to light. It is important that any symptoms are diagnosed and treated as soon as possible.
• Your doctor will check whether you have other risk factors that may 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 MYNZEPLI will be administered with caution.
• MYNZEPLI 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 MYNZEPLI.

Systemic use of VEGF inhibitors, substances similar to those contained in MYNZEPLI, 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 MYNZEPLI into the eye, there is a theoretical risk that such events may occur. Safety data in patients with CRVO, BRVO, DME, and mCNV who have experienced a stroke, transient ischemic attack (TIA), or myocardial infarction within the past 6 months are limited. If any of these apply to you, MYNZEPLI will be administered with caution.

Experience is only limited in the treatment of:

• Patients with DME due to type 1 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 ocular 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 treating you with MYNZEPLI.

Children and adolescents

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

Other medicines and MYNZEPLI

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 MYNZEPLI.
• There is no experience with the use of MYNZEPLI in pregnant women. MYNZEPLI 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 MYNZEPLI.
• Small amounts of MYNZEPLI may pass into breast milk. The effects on newborns/infants are unknown. MYNZEPLI is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before treatment with MYNZEPLI.

Driving and use of machines

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

MYNZEPLI contains sodium

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

3. How MYNZEPLI will be administered to you

MYNZEPLI will be administered by a physician experienced in the administration of intraocular injections, under aseptic (clean and sterile) conditions.

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

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

Before the injection, your doctor will use a disinfectant eye wash to carefully clean your eye to prevent infection. Your doctor will also administer a local anesthetic to reduce or prevent any pain you might feel during the injection.

Exudative AMD

Patients with exudative AMD will receive a monthly injection for the first three doses, followed by another injection after an additional two months.

Your doctor will then decide whether the treatment interval between injections can remain every two months or be gradually extended in increments of 2 or 4 weeks if your disease has stabilized.

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

Routine visits to your doctor between injections are not required unless your doctor advises otherwise or you experience any problems.

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

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

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

Your doctor may decide to discontinue treatment with MYNZEPLI if you are not benefiting from continued therapy.

Treatment will continue with monthly injections until your disease stabilizes. You may require three or more monthly injections.

Your doctor will monitor your response to treatment and may continue 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 determined by your doctor’s examination. Your doctor will decide the follow-up visit schedule.

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

Myopic choroidal neovascularization (mCNV)

Patients with mCNV will be treated with a single injection. Additional injections will only be given if your doctor’s examinations 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 in How to prepare and administer MYNZEPLI to adults.

If you miss a dose of MYNZEPLI

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

Discontinuation of treatment with MYNZEPLI

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 experiences them.

Allergic reactions (hypersensitivity) may potentially occur. These can be serious and may require that you contact your doctor immediately.

Some adverse effects affecting the eyes may occur with the administration of MYNZEPLI, which are related to the injection procedure. Some of these may be serious, including blindness, a severe infection or inflammation inside the eye (endophthalmitis), detachment, tear or bleeding of the light-sensitive layer at the back of the eye (retinal detachment or tear), clouding of the lens (cataract), bleeding in the eye (vitreous haemorrhage), detachment of the gel-like substance inside the eye in contact with the retina (vitreous detachment), and increased pressure inside the eye (see section 2). These serious eye-related adverse effects occurred in fewer than 1 in 1900 injections during clinical trials.

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

List of reported adverse effects

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

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

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

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

• detachment or tear of one of the layers at the back of the eye causing flashes of light with floating spots, which sometimes progresses 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 reactions (anaphylactic/anaphylactoid).
• severe inflammation or infection inside the eye (endophthalmitis)
• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, cells floating 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 1000 people):

• blindness
• clouding of the lens due to injury (traumatic cataract)
• inflammation of the gel-like substance inside the eye
• pus in the eye

Frequency not known (cannot be estimated from available data):

• inflammation of the white part of the eye associated with redness and pain (scleritis)

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

Systemic use of VEGF inhibitors—substances similar to those contained in MYNZEPLI—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 after injection of MYNZEPLI into the eye.

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V.* By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of MYNZEPLI

• 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". 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 can be stored outside the refrigerator at below 25 °C for up to 24 hours.
• 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 MYNZEPLI

• The active substance is aflibercept. One pre-filled syringe contains a minimum extractable volume of 0.09 ml, equivalent to at least 3.6 mg of aflibercept. One pre-filled syringe delivers a dose of 2 mg of aflibercept in 0.05 ml.
• The other components are: L-histidine, L-histidine monohydrochloride monohydrate, trehalose dihydrate, poloxamer 188, water for injections.

Appearance of the product and contents of the pack

MYNZEPLI is an injectable solution (injectable) in a pre-filled syringe. The solution is colourless to pale yellow.

Pack containing 1 pre-filled syringe.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Advanz Pharma Limited

Unit 17 Northwood House

Northwood Crescent

Dublin 9

D09 V504

Ireland

Manufacturer

Alvotech Hf

Sæmundargata 15-19

Reykjavik, 102

Iceland

Date of the most recent review of this leaflet:

Other sources of information

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

This information is intended for healthcare professionals only:

How to prepare and administer MYNZEPLI

The pre-filled syringe must be used for the treatment of one eye only. Withdrawing multiple doses from a single pre-filled syringe may increase the risk of contamination and subsequent infection.

Do not open the sterile pre-filled syringe blister outside a clean room. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

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.

Before administration, the solution should be inspected visually for the presence of particles, discoloration, or any change in physical appearance. If any of these are observed, do not use the medicine.

For intravitreal injection, a 30 G × ½ inch (1.27 cm) injection needle should be used.

Instructions for use of the pre-filled syringe: