Mynzepli

Package leaflet: Information for the patient

MYNZEPLI 40 mg/mL injection solution in pre-filled syringe

aflibercept
This medicinal product is subject to additional monitoring. This will allow 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, consult your doctor.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet

1. What MYNZEPLI is and what it is used for
2. What you need to know before using MYNZEPLI
3. How to use MYNZEPLI
4. Possible side effects
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 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 (DMO),
• vision impairment due to myopic choroidal neovascularisation (myopic CNV).

Aflibercept, the active substance in MYNZEPLI, 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. In response to this event, VEGF levels increase, causing fluid leakage into the retina and resulting in swelling of the macula (the part of the retina responsible for sharp vision), known as macular oedema. When the macula swells with fluid, central vision becomes blurred.
In patients with BRVO, one or more branches of the main vessel draining blood from the retina are blocked. VEGF levels consequently rise and cause fluid leakage into the retina, leading to macular oedema.
Diabetic macular oedema is retinal swelling that occurs in diabetic patients due to fluid leakage from blood vessels in the macula. The macula is the part of the retina responsible for sharp vision. When the macula fills with fluid, central vision becomes blurred.
It has been shown that MYNZEPLI blocks the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. MYNZEPLI can help stabilise and, in many cases, improve vision loss associated with wet AMD, CRVO, BRVO, DMO, and myopic CNV.

2. What you should know before using MYNZEPLI

Do not take MYNZEPLI

• 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 eye inflammation (indicated by pain or redness).

Warnings and precautions
Talk to your doctor before taking MYNZEPLI

• 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 MYNZEPLI is not recommended.

It is also important for you to know that

• the safety and efficacy of MYNZEPLI when administered in both eyes simultaneously have not been studied, and administering it in this way may increase the risk of adverse effects.
• in some patients, MYNZEPLI injections may cause a temporary increase in intraocular pressure within 60 minutes after injection. 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 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 for other risk factors that may increase the likelihood of detachment or tear in one of the layers at the back of the eye (retinal detachment or tear, and retinal pigment epithelial detachment or rupture); in such cases, MYNZEPLI will be administered with caution.
• MYNZEPLI 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 MYNZEPLI.

Systemic use of VEGF inhibitors—substances similar to those contained in MYNZEPLI—has been potentially associated with blood clots blocking blood vessels (arterial thromboembolic events), leading to heart attack or stroke. Following intravitreal injection of MYNZEPLI, there is a theoretical risk that such events may occur. Data on the safety of treating patients with CRVO, BRVO, DME, and myopic CNV who have experienced a stroke or mini-stroke (transient ischemic attack) or heart attack within the previous 6 months are limited. If any of these conditions apply to you, MYNZEPLI 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 you fall into any of the above categories, your doctor will take into account the lack of data 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. Since exudative AMD, CRVO, BRVO, DME, and myopic CNV occur primarily in adults, use in this age group is not considered relevant.

Other medicines and MYNZEPLI
Inform 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 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 a pregnancy, discuss this with your doctor before starting treatment with MYNZEPLI.
• Small amounts of MYNZEPLI may pass into breast milk. The effects on breastfed infants are unknown. MYNZEPLI is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before starting treatment with MYNZEPLI.

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

MYNZEPLI contains
This medicine contains less than 1 mmol (23 mg) of sodium per unit dose, i.e., it is essentially 'sodium-free'.

3. How to use MYNZEPLI

A doctor experienced in eye injections will administer MYNZEPLI into your eye 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, 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 the pain caused by the injection.

Exudative AMD
Patients with exudative AMD will receive one injection per month for three consecutive doses, followed by another injection after an additional 2 months.
Your doctor will then decide whether the treatment interval between injections can be maintained every two months or, if your condition remains stable, gradually extended to intervals of 2 or 4 weeks.
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 MYNZEPLI injections.
The interval between two injections must not be less than one month.
If you do not benefit after continued treatment, your doctor may decide to discontinue treatment with MYNZEPLI.
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 extending the interval between treatments, your doctor will shorten the intervals 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 receive one injection per month for the first five consecutive doses, followed by an injection every 2 months.
Based on examinations performed by the doctor, the interval between treatments may be maintained every 2 months or adjusted according to your condition. The doctor will decide the frequency of follow-up examinations.
The doctor may decide to discontinue treatment with MYNZEPLI if it becomes evident that you are not benefiting from continuing the treatment.

Myopic CNV
Patients with myopic CNV will receive 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 resolves and then recurs, the doctor may restart treatment. The doctor will establish the follow-up examination schedule.

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

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

If you stop treatment with MYNZEPLI
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 everyone will experience them.
Allergic reactions (hypersensitivity) may potentially occur, which can be serious and require immediate medical attention.
When MYNZEPLI 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 section 2. In clinical studies, these serious eye-related side effects occurred in fewer than 1 in 1,900 injections.
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 them. 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 of small blood vessels in the outer layers of the eye
• eye pain

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

• detachment or tear in one of the layers at the back of the eye, causing flashes of light with floaters and sometimes leading to vision loss (retinal pigment epithelial tear*, detachment, retinal detachment/tear) or *Conditions known to be associated with neovascular age-related macular degeneration (wet AMD), observed only in patients with wet AMD.
• degeneration of the retina causing disturbed vision
• bleeding inside the eye (vitreous haemorrhage)
• certain forms of clouding of the lens (cataract)
• damage to the outermost layer of the eyeball (cornea)
• increased 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)** or **Allergic reactions such as skin rash, itching, urticaria, and some cases of severe allergic (anaphylactic/anaphylactoid) reactions have been reported.
• severe inflammation or infection inside the eye (endophthalmitis)
• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, flare in 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 the available data):

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

In clinical studies of patients with age-related wet macular degeneration (AMD) who were treated with blood-thinning medicines, an increased incidence of bleeding from small blood vessels in the outer layer of the eye (conjunctival haemorrhage) was observed. This increased incidence was comparable between patients treated with ranibizumab and those treated with MYNZEPLI.
Systemic use of vascular endothelial growth factor (VEGF) inhibitors, which are substances similar to those contained in MYNZEPLI, is potentially associated with a 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 MYNZEPLI into the eye.
As with all therapeutic proteins, use of MYNZEPLI may trigger an immune response (antibody formation).

Reporting of side effects
If you experience any side effect, 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 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 “Scad.” / “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C). Do not freeze.
• The closed blister can be stored outside the refrigerator at a temperature below 25 °C for up to 24 hours.
• Keep in the original packaging to protect the medicine from light.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MYNZEPLI contains

• 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.

Description of the appearance of MYNZEPLI and package contents
MYNZEPLI is an injectable solution (preparation for injection) in a pre-filled syringe. The solution is colourless to pale yellow.
Pack size: 1 pre-filled syringe.
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
Other sources of information
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 exclusively for healthcare professionals:

How to prepare and administer MYNZEPLI
The pre-filled syringe must be used solely for the treatment of one eye only. Withdrawing multiple doses from the pre-filled syringe may increase the risk of contamination and subsequent infection.
Do not open the sterile syringe blister pack outside the clean administration area. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local applicable regulations.
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.
Prior to administration, the injectable solution should be inspected visually for the presence of extraneous particles and/or discoloration or any change in physical appearance. If any of these occur, the product must be discarded.
For intravitreal injection, a 30 G x ½ inch injection needle should be used.

Instructions for using the pre-filled syringe:

1. When ready to administer MYNZEPLI, open the package and remove the sterilized blister pack. Carefully open the blister, ensuring sterility of the contents. Keep the syringe on the sterile tray until ready for assembly.
2. Using aseptic technique, remove the syringe from the sterilized blister pack.
3. To remove the syringe cap, hold the

syringe with one hand and grasp the cap with the
thumb and index finger of the other hand. Caution:
the cap must be twisted (not pulled) off the syringe.

4. To avoid compromising the sterility of the product, do not pull back the plunger.
5. Using aseptic technique, firmly attach the injection

needle by twisting it onto the tip of the syringe with
a Luer-lock adapter.

6. Hold the syringe with the needle pointing upward and check for air bubbles inside. If air bubbles are present, gently tap the syringe with the finger to allow them to rise to the surface.
7. The excess volume must be discarded before administration. Remove all air bubbles and expel the excess medication by slowly depressing the plunger until the base of the rounded tip of the plunger (not the tip's apex) aligns with the dosage marking line on the syringe (corresponding to 0.05 mL, i.e., 2 mg of aflibercept). Note: Accurate positioning of the plunger is very important, as incorrect positioning may result in administration of a dose higher or lower than the recommended amount.

8. Inject by gently and steadily depressing the plunger. Do not apply additional pressure once the plunger has reached the bottom of the syringe. Do not administer the residual solution remaining in the syringe.
9. 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. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local applicable regulations.

Package leaflet: information for the patient

MYNZEPLI 40 mg/mL solution for injection in vial

aflibercept
This medicinal product is subject to additional monitoring. This will allow 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, consult 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 MYNZEPLI is and what it is used for
2. What you need to know before using MYNZEPLI
3. How to use MYNZEPLI
4. Possible side effects
5. How to store MYNZEPLI
6. Package contents and other information

1. What MYNZEPLI is and what it is used for

MYNZEPLI is a solution 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 (Diabetic Macular Oedema - DME),
• vision loss due to myopic choroidal neovascularisation (myopic CNV).

Aflibercept, the active substance of MYNZEPLI, 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. These new blood vessels may leak components of the blood 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. In response to this event, VEGF levels increase, causing fluid leakage into the retina and resulting in swelling of the macula (the part of the retina responsible for sharp vision), known as macular oedema. When the macula swells with fluid, central vision becomes blurred.
In patients with BRVO, one or more branches of the main blood vessel draining blood from the retina are blocked. VEGF levels consequently rise, leading to fluid leakage into the retina and causing macular oedema.
Diabetic macular oedema is a swelling of the retina that occurs in diabetic patients due to fluid leakage from blood vessels in the macula. The macula is the part of the retina responsible for sharp vision. When the macula accumulates fluid, central vision becomes blurred.
It has been shown that MYNZEPLI blocks the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. MYNZEPLI 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 using MYNZEPLI

Do not take MYNZEPLI

• 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 MYNZEPLI:

• 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 MYNZEPLI is not recommended.

It is also important for you to know that:

• the safety and efficacy of MYNZEPLI when administered in both eyes simultaneously have not been studied, and administering it in this way may increase the risk of adverse effects.
• in some patients, MYNZEPLI injections may cause a temporary increase in eye pressure (intraocular pressure) within 60 minutes after the injection. Your doctor will monitor for this effect after each injection.
• if you develop an infection or inflammation inside the eye (endophthalmitis) or other complications, you may experience eye pain or worsening discomfort, increased eye redness, blurred or reduced vision, and increased sensitivity to light. It is important that any symptoms are diagnosed and treated as soon as possible.
• your doctor will check for 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 retinal pigment epithelial detachment or tear); in such cases, MYNZEPLI will be administered with caution.
• MYNZEPLI 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 MYNZEPLI.

Systemic use of VEGF inhibitors—substances similar to those contained in MYNZEPLI—has been potentially associated with the risk of blood clots blocking blood vessels (arterial thromboembolic events), leading to heart attack or stroke. After injection of MYNZEPLI into the eye, there is a theoretical risk that such events may occur. Data on the safety of treating patients with CRVO, BRVO, DME, and myopic CNV who have had a stroke or mini-stroke (transient ischemic attack) or heart attack within the past 6 months are limited. If any of these situations apply to you, MYNZEPLI 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 you fall into any of the above categories, your doctor will take into account the lack of available information when treating you with MYNZEPLI.

Children and adolescents
In children or adolescents under 18 years of age, the use of MYNZEPLI 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 MYNZEPLI
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 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 unborn child. 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 breastfed 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 receiving an injection of MYNZEPLI, you may experience temporary visual disturbances. Do not drive or operate machinery until these disturbances have resolved.

MYNZEPLI contains
This medicine contains less than 1 mmol (23 mg) of sodium per unit dose, i.e., it is essentially 'sodium-free'.

3. How to use MYNZEPLI

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

Wet AMD
Patients with wet AMD will be treated with one injection per month for three consecutive doses, followed by
another injection after an additional 2 months.
Your doctor will then decide whether the treatment interval between injections can be maintained every two
months or, if your condition remains stable, gradually extended to intervals of 2 or 4 weeks.
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
examinations 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 MYNZEPLI.
The interval between two injections must not be less than one month.
If you have not benefited after continued treatment, your doctor may decide to discontinue treatment with
MYNZEPLI.
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 as 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.
Based on examinations performed by the doctor, the interval between treatments may be maintained every
2 months or adjusted according to your condition. The doctor will decide the frequency of follow-up
examinations (follow-up).
The doctor may decide to discontinue treatment with MYNZEPLI if it becomes evident that you are not benefiting
from continuing the treatment.

Myopic CNV
Patients with myopic CNV will be treated with a single injection. You will receive 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 resolves and then recurs, the doctor may resume treatment. The doctor will establish the
schedule for follow-up examinations.

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

If you stop treatment with MYNZEPLI
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 require immediate
medical attention.
When MYNZEPLI 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. In clinical studies, these serious eye-related
side effects occurred in fewer than 1 in 1,900 injections.
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 talk 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/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 (wet AMD), observed only in patients with wet 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 have been reported, including skin rashes, itching, urticaria, and some cases of severe allergic reaction (anaphylactic/anaphylactoid).

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 of patients with age-related wet macular degeneration (AMD) who were treated with blood-
thinning medicines, an increased incidence of bleeding from small blood vessels in the outer layer of the eye
(conjunctival haemorrhage) was observed. This increased incidence was comparable between patients treated
with ranibizumab and those treated with MYNZEPLI.
Systemic use of vascular endothelial growth factor (VEGF) inhibitors, which are 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 following injection of MYNZEPLI into the eye.
As with all therapeutic proteins, use of MYNZEPLI may trigger an immune response (antibody formation).
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor. You can also
report side effects directly via the National Reporting System listed in Annex V. Reporting side effects can help
provide more information on the safety of this medicine.

5. How to store 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.” / “EXP”. The expiry date refers to the last day of that month.
• Store in the refrigerator (2 °C - 8 °C). Do not freeze.
• The unopened vial may be stored outside the refrigerator at a temperature below 25 °C for up to 24 hours.
• Keep the medicine in the original packaging to protect it 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 MYNZEPLI contains

• The active substance is aflibercept. One vial contains a volume of at least 0.1 mL, equivalent to at least 4 mg of aflibercept. One vial provides 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.

Description of the appearance of MYNZEPLI and contents of the container
MYNZEPLI is an injectable solution (preparation for injection) in a vial. The solution is colourless to pale yellow.
Pack: 1 vial + 1 filter needle.
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
Other sources of information
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 exclusively for healthcare professionals:

The vial must be used solely for the treatment of one single eye.
The vial contains more than the recommended dose of 2 mg aflibercept (equivalent to 0.05 mL). The excess volume must be discarded prior to administration.
The injectable solution should be visually inspected prior to administration to check for the presence of extraneous particulate matter and/or discoloration or any other change in appearance. If such changes are observed, the product must be discarded.
Blunt Filter Needle:
Blunt Filter Needle (Fill), not for subcutaneous injection. Do not autoclave the Blunt Filter Needle.
The blunt filter needle is non-pyrogenic. Do not use if the individual package is damaged. Dispose of the Blunt Filter Needle (Fill) in approved sharps containers.
Warning: Reuse of the filter needle may lead to infection or other illness/injury.
For intravitreal injection, a 30 G x ½ inch injection needle should be used.

Instructions for use of the vial:

1. Remove the plastic cap and disinfect the outer surface of the rubber stopper of the vial.

2. Connect the 18 G needle with 5-micron filter

supplied in the pack to a sterile 1 mL syringe with
Luer-lock adapter.

3. Insert the filtered needle into the center of the vial stopper until the needle is fully inserted into the vial and the tip touches the bottom or the corner at the bottom of the vial.
4. Using aseptic technique, draw the entire contents of the MYNZEPLI vial into the syringe, keeping the vial in an upright position, slightly tilted to facilitate complete aspiration. To avoid introducing air, ensure that the entire beveled tip of the needle is completely submerged in the liquid. Keep the vial tilted during aspiration, ensuring the needle tip remains fully immersed in the liquid.

5. When emptying the vial, ensure that the plunger rod is sufficiently pulled back to completely empty the filtered needle.
6. Remove the filtered needle and dispose of it appropriately. Note: The filtered needle must not be used for intravitreal injection.
7. Using aseptic technique, attach a 30 G x ½ inch

injection needle to the tip of the syringe
with Luer-lock adapter by firmly rotating it into place.

8. With the syringe held upright and the needle pointing upward,
   check for the absence of air bubbles. If present, gently tap the syringe with your finger to allow bubbles to rise to the surface.

9. Remove all air bubbles and expel excess medication by slowly depressing the plunger until the flat end of the plunger aligns with the 0.05 mL mark on the syringe.

10. 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 materials derived from this medicine must be disposed of in accordance with local regulations.