Opuviz

Patient Information Leaflet: Information for Adult Patients

Opuviz 40 mg/mL solution for injection in vial

aflibercept
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving 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 Opuviz is and what it is used for
2. What you need to know before receiving Opuviz
3. How Opuviz will be administered
4. Possible side effects
5. How to store Opuviz
6. Contents of the pack and other information

1. What Opuviz is and what it is used for

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

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

Aflibercept, the active substance in Opuviz, 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 can leak blood components into the eye and potentially damage ocular tissues responsible for vision.
In patients with CRVO, a blockage forms in the main blood vessel that carries blood away from the retina. VEGF levels increase in response to this event, causing fluid leakage into the retina and thus resulting in swelling of the macula (the part of the retina responsible for sharp vision), known as macular oedema. When the macula swells with fluid, central vision becomes blurred.
In patients with BRVO, one or more branches of the main blood vessel draining blood from the retina are blocked. VEGF levels consequently rise, causing fluid leakage into the retina and leading to macular oedema.
Diabetic macular oedema is a swelling of the retina that occurs in diabetic patients due to fluid leakage from blood vessels in the macula. The macula is the part of the retina responsible for clear vision. When the macula fills with fluid, central vision becomes blurred.
Opuviz has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Opuviz can help stabilize, and in many cases improve, vision loss associated with wet AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you should know before using Opuviz

Do not take Opuviz

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

Warnings and precautions
Talk to your doctor before using Opuviz:

• if you have glaucoma,
• if you have ever experienced flashes of light or floaters, especially if the number or 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 Opuviz is not recommended.

You should also be aware that:

• the safety and efficacy of Opuviz when administered to both eyes simultaneously have not been studied, and doing so may increase the risk of experiencing adverse effects.
• injections of Opuviz may cause a temporary increase in intraocular pressure in some patients 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 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 assess whether you have other risk factors that may increase the likelihood of retinal tear or detachment, or detachment or rupture of the retinal pigment epithelium in the back of the eye. In such cases, Opuviz will be administered with caution.
• Opuviz must not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child.
• women of childbearing potential must use effective contraception during treatment and for at least three additional months after the last injection of Opuviz.

Systemic use of VEGF inhibitors—substances similar to those contained in Opuviz—is potentially associated with the risk of blood clots blocking blood vessels (arterial thromboembolic events), leading to heart attack or stroke. There is a theoretical risk that such events may occur following injection of Opuviz into the eye. Safety data are limited in patients with CRVO, BRVO, DME, or myopic CNV who have experienced a stroke, transient ischemic attack (TIA), or heart attack within the previous 6 months. If any of these conditions apply to you, Opuviz will be administered with caution.

Experience with treatment is limited in:

• 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 treatment in:

• patients with acute infections.
• patients with other eye diseases such as retinal detachment or macular hole.
• diabetic patients with uncontrolled high blood pressure.
• non-Asian patients with myopic CNV.
• patients previously treated for myopic CNV.
• patients with lesions located outside the central part of the macula (extrafoveal lesions) in myopic CNV.

If any of the above conditions apply to you, your doctor will take into account this lack of information when treating you with Opuviz.

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

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

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

Opuviz contains

• less than 1 mmol (23 mg) of sodium per single dose, i.e., essentially 'sodium-free'.
• in each 0.05 mL dose, 0.015 mg of polysorbate 20, equivalent to 0.3 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to take Opuviz

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

Wet AMD
Patients with wet AMD will be treated with one injection per month for three consecutive doses, followed by another injection after a further 2 months.
Your doctor will then decide whether the treatment interval between injections can be maintained every two months or whether it should be gradually extended by intervals of 2 or 4 weeks if your condition is stable.
If your condition worsens, the interval between injections may be shortened.
Unless you experience problems or are otherwise advised by your doctor, there is no need to see your doctor between injections.

Macular oedema secondary to RVO (branch RVO and central RVO)
Your doctor will determine the most appropriate treatment frequency for you. Treatment will start with a series of monthly Opuviz injections.
The interval between two injections must not be less than one month.
If you have not benefited after continuous treatment, your doctor may decide to discontinue treatment with Opuviz.
Treatment will continue with monthly injections until your condition stabilizes.
Three or more monthly injections may be necessary.
Your doctor will monitor your response to treatment and may continue treatment with a gradual increase in the intervals between injections to maintain a stable condition. If your condition begins to worsen when the treatment interval is extended, your doctor will shorten the intervals accordingly.
Based on your individual response to treatment, your doctor will decide when follow-up examinations and treatments should be scheduled.

Diabetic macular oedema (DME)
Patients with DME will be treated with one injection per month for the first five consecutive doses, followed by an injection every 2 months.
The interval between treatments may be maintained every 2 months or adjusted according to your condition, based on examinations performed by the doctor. Your doctor will decide the frequency of follow-up examinations.
Your doctor may decide to discontinue treatment with Opuviz if it is determined 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 further 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.
Your doctor will establish the schedule for follow-up examinations.

Detailed instructions for use are provided at the end of this leaflet in section “How to prepare and administer Opuviz in adults”.

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

If you stop treatment with Opuviz
Consult your doctor before stopping treatment.
If you have any doubts about using this medicine, speak to 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 may require
immediate medical attention.
When Opuviz is administered, certain side effects affecting the eyes may occur, which are related to the
injection procedure. Some of these may be serious and include blindness, a severe infection or
inflammation inside the eye (endophthalmitis), detachment, tear or bleeding of the light-sensitive
layer at the back of the eye (retinal detachment or tear), clouding of the lens (cataract), bleeding
inside the eye (vitreous haemorrhage), separation of the gel-like substance inside the eye from the
retina (vitreous detachment), and increased pressure inside the eye, see section 2. These serious
eye-related side effects occurred in fewer than 1 out of 1,900 injections in clinical studies.
If you experience a sudden decrease in vision, or increased eye pain and redness after the injection,
contact your doctor immediately.
List of reported side effects
Below is a list of side effects reported as potentially related to the injection procedure or the medicine.
Do not be alarmed – you may not experience any of these. Always speak to your doctor about any
suspected side effects.
Very common side effects (may affect more than 1 in 10 people):

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

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

• detachment or rupture of one of the layers at the back of the eye, causing flashes of light with floaters and sometimes leading to vision loss (retinal pigment epithelial tear*/detachment, retinal detachment/tear) Conditions known to be associated with wet AMD; observed only in patients with wet AMD
• 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

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

• allergic reactions (hypersensitivity)** ** Allergic reactions such as skin rash, itching, urticaria have been reported, as well as some cases of serious allergic reaction (anaphylactic/anaphylactoid)
• severe inflammation or infection inside the eye (endophthalmitis)
• inflammation of the iris or other parts of the eye (iritis, uveitis, iridocyclitis, flare in the anterior chamber)
• unusual sensation in the eye
• eyelid irritation
• swelling of the outermost layer of the eyeball (cornea)

Rare side effects (may affect up to 1 in 1,000 people):

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

Not known (frequency cannot be estimated from the available data):
inflammation of the white part of the eye associated with redness and pain (scleritis)
In clinical studies, an increased incidence of bleeding from small blood vessels in the outer layer of the
eye (conjunctival haemorrhage) was observed in patients with age-related wet macular degeneration
(AMD) who were treated with blood-thinning medicines. This increased incidence was comparable
between patients treated with ranibizumab and those treated with aflibercept.
Systemic use of vascular endothelial growth factor (VEGF) inhibitors, which are substances similar to
those contained in Opuviz, is potentially associated with the risk of blood clots blocking blood vessels
(arterial thromboembolic events), which may lead to heart attack or stroke. There is a potential risk that
such events may occur following injection of Opuviz into the eye.
As with all therapeutic proteins, use of Opuviz may trigger an immune response (antibody formation).
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You can
also report side effects directly via the national reporting system listed in Annex V. By reporting side
effects, you can help provide more information on the safety of this medicine.

5. How to store Opuviz

• 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 unopened vial may be stored outside the refrigerator at room temperature not exceeding 30°C for a maximum period of 3 days.
• Keep in the original packaging to protect from light.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Opuviz contains

• The active substance is aflibercept. One vial contains a minimum extractable volume of 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: disodium phosphate dihydrate, monosodium phosphate dihydrate, sucrose, polysorbate 20 (E 432), water for injections.

See 'Opuviz contains' in section 2 for further information.
Description of the appearance of Opuviz and contents of the pack
Opuviz is an injectable solution (preparation for injection) in a vial. The solution is clear, colourless to pale yellow.
Pack of 1 vial + 1 filter needle.
Pack of 1 vial.
Marketing Authorisation Holder and Manufacturer
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

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The following information is intended exclusively for healthcare professionals:

How to prepare and administer Opuviz in adults
The vial is single-use and intended for one eye only.
The vial contains more than the recommended dose of 2 mg aflibercept (equivalent to 0.05 mL).
The excess volume must be discarded before administration.
Before administration, visually inspect the injectable solution for the presence of foreign particles and/or discoloration or any change in appearance. If any of these are observed, the product must be discarded.

Pack containing vial only
For preparation and intravitreal injection, the following single-use medical devices are required:

• a 5-micron filter needle (18 G × 1 ½ inch)
• an injection needle (30 G × ½ inch)
• a sterile 1 mL syringe (with 0.05 mL graduation mark)
  These medical devices are not included in the pack.

Pack containing vial + filter needle
For preparation and intravitreal injection, the following single-use medical devices are required:

• a 5-micron filter needle (18 G × 1 ½ inch, 1.2 mm × 40 mm, provided)
• an injection needle (30 G × ½ inch, not included in the pack)
• a sterile 1 mL syringe (with 0.05 mL graduation mark, not included in the pack)

Filter needle:
Filter needle, not for subcutaneous injection. Do not autoclave the filter needle.
Do not use if the individual packaging is damaged. Dispose of the used filter needle in approved sharps containers.
Warning: reusing the filter needle may lead to infection or other illness/injury. For intravitreal injection, a 30 G × ½ inch injection needle must be used.

Instructions for use of the vial:

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

2. Attach the 18 G × 1 ½ inch 5-micron filter needle to a sterile 1 mL syringe.

3. Insert the filter needle into the center of the vial’s stopper until the needle is fully inserted into the vial and the tip touches the bottom or corner of the vial’s base.

4. Using aseptic technique, draw the entire contents of the Opuviz vial into the syringe while keeping the vial in an upright position, slightly tilted to facilitate complete aspiration. To avoid introducing air, ensure the tip of the filter needle remains fully immersed in the liquid. Keep the vial tilted during aspiration, ensuring

the tip of the filter needle remains fully immersed in the liquid.

5. Ensure the plunger rod is pulled back sufficiently when emptying the vial to completely empty the filter needle.

6. Remove the filter needle and dispose of it appropriately. Note: the filter needle must not be used for intravitreal injection.

7. Using aseptic technique, attach a 30 G × ½ inch injection needle by firmly rotating it onto the tip of the syringe.

8. Holding the syringe with the needle pointing upward, check for 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.

0.05 mL

10. The vial is for single use only. Withdrawing multiple doses from a single vial may increase the risk of contamination and subsequent infection. Unused medication and waste material from this medication must be disposed of in accordance with local regulations.

Patient information leaflet: information for the adult patient

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

aflibercept
This medicinal product is subject to additional monitoring. This will allow for the 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.
ADULTS
Please read this leaflet carefully before receiving 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 Opuviz is and what it is used for
2. What you need to know before receiving Opuviz
3. How Opuviz will be administered
4. Possible side effects
5. How to store Opuviz
6. Contents of the pack and other information

1. What Opuviz is and what it is used for

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

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

Aflibercept, the active substance in Opuviz, 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 can leak blood components into the eye and potentially damage ocular tissues responsible for vision.
In patients with CRVO, a blockage forms in the main blood vessel that carries blood away from the retina. VEGF levels increase in response to this event, causing fluid leakage into the retina and thus resulting in swelling of the macula (the part of the retina responsible for sharp vision), known as macular oedema. When the macula swells with fluid, central vision becomes blurred.
In patients with BRVO, one or more branches of the main blood vessel draining blood from the retina are blocked. 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 clear vision. When the macula fills with fluid, central vision becomes blurred.
Opuviz has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Opuviz can help stabilize and, in many cases, improve vision loss associated with wet AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you should know before taking Opuviz

Do not take Opuviz

• 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 Opuviz:

• 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 recently undergone or are scheduled to undergo 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 Opuviz is not recommended.

It is also important for you to know that:

• the safety and efficacy of Opuviz when administered in both eyes simultaneously have not been studied, and administering it in this way may increase the risk of experiencing adverse effects.
• Opuviz injections may cause a temporary increase in intraocular pressure in some patients within 60 minutes after injection. Your doctor will monitor this effect after each injection.
• if you develop an infection or inflammation inside the eye (endophthalmitis) or other complications, you may experience eye pain, worsening discomfort, increased eye redness, blurred or reduced vision, and increased sensitivity to light. It is important that any symptoms are diagnosed and treated as soon as possible.
• your doctor will check whether you have other risk factors that may increase the likelihood of retinal tear or detachment, or retinal pigment epithelial tear or detachment at the back of the eye. In such cases, Opuviz will be administered with caution.
• Opuviz must not be used during pregnancy unless the potential benefit outweighs the potential risk to the unborn child.
• women of childbearing potential must use effective contraception during treatment and for at least three months after the last injection of Opuviz.

Systemic use of VEGF inhibitors—substances similar to those contained in Opuviz—has been potentially associated with the risk of blood clots blocking blood vessels (arterial thromboembolic events), leading to heart attack or stroke. There is a theoretical risk that such events may occur following intravitreal injection of Opuviz. Data on the safety of treating patients with CRVO, BRVO, DME, or myopic CNV who have experienced a stroke or transient ischemic attack (TIA), or heart attack within the previous 6 months are limited. If any of these conditions apply to you, Opuviz will be administered with caution.

Experience is limited in treating:

• patients with DME due to type I diabetes.
• diabetic patients with high average blood glucose levels (HbA1c greater than 12%).
• diabetic patients with a diabetes-related eye disease called proliferative diabetic retinopathy.

There is no experience with treating:

• patients with acute infections.
• patients with other eye diseases such as retinal detachment or macular hole.
• diabetic patients with uncontrolled high blood pressure.
• non-Asian patients with myopic CNV.
• patients previously treated for myopic CNV.
• patients with lesions located outside the central part of the macula (extrafoveal lesions) in myopic CNV.

If any of the above conditions apply to you, your doctor will take into account this lack of information when treating you with Opuviz.

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

Other medicines and Opuviz
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 Opuviz.
• There is no experience with the use of Opuviz in pregnant women. Opuviz must 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 starting treatment with Opuviz.
• Small amounts of Opuviz may pass into breast milk. The effects on breastfed infants are unknown. Opuviz is not recommended during breastfeeding. If you are breastfeeding, discuss this with your doctor before starting treatment with Opuviz.

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

Opuviz contains

• less than 1 mmol (23 mg) of sodium per single dose, i.e., essentially ‘sodium-free’.
• in each 0.05 mL dose, 0.015 mg of polysorbate 20, equivalent to 0.3 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to take Opuviz

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

Wet AMD
Patients with wet AMD will be treated with one injection per month for three consecutive doses, followed
by another injection after a further 2 months.
Your doctor will then decide whether the treatment interval between injections can be maintained every
two months or should be gradually extended by intervals of 2 or 4 weeks if your condition is stable.
If your condition worsens, the interval between injections may be shortened.
Unless you experience problems or your doctor advises otherwise, there is no need to see your doctor
between injections.

Macular edema secondary to RVO (branch RVO and central RVO)
Your doctor will determine the most appropriate treatment frequency for you. Treatment will begin with
a series of monthly Opuviz injections.
The interval between two injections must not be less than one month.
If you do not experience benefit after continued treatment, your doctor may decide to discontinue
treatment with Opuviz.
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 gradually
increased 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 intervals accordingly.
Based on your individual response to treatment, your doctor will decide when follow-up examinations
and treatments should be scheduled.

Diabetic macular edema (DME)
Patients with DME will be treated with one injection per month for the first five consecutive doses,
followed by an injection every 2 months.
The interval between treatments may be maintained every 2 months or adjusted according to your
condition, based on examinations performed by your doctor. Your doctor will determine the frequency
of follow-up examinations.
Your doctor may decide to discontinue treatment with Opuviz if it is determined that you are not
benefiting from continuing treatment.

Myopic CNV
Patients with myopic CNV will be treated with a single injection. You will receive additional injections
only if examinations performed by your 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, your doctor may restart treatment. Your doctor will establish the
schedule for follow-up examinations.

Detailed instructions for use are provided at the end of this leaflet in section “How to prepare and
administer Opuviz in adults”.

If you forget to take Opuviz
Make a new appointment to have the examination and injection.

If you stop treatment with Opuviz
Consult your doctor before stopping treatment.
If you have any questions about how to use this medicine, ask 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 severe and may require
immediate medical attention.
When Opuviz 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. These serious
eye-related side effects occurred in fewer than 1 in 1,900 injections in clinical studies.
If you experience a sudden decrease in vision, or increased eye pain and redness after the injection,
contact your doctor immediately.
List of reported side effects
Below is a list of side effects reported as potentially related to the injection procedure or the medicine.
Do not be alarmed—you may not experience any of these. Always speak to your doctor about any
suspected side effects.
Very common side effects (may occur in more than 1 out of 10 people):

• worsening of vision
• bleeding in 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 occur in up to 1 out of 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) Conditions known to be associated with wet AMD; observed only in patients with wet AMD
• retinal degeneration (causing disturbed vision)
• bleeding into the eye (vitreous haemorrhage)
• certain forms of lens clouding (cataract)
• damage to the outermost layer of the eyeball (cornea)
• increased intraocular 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 occur in up to 1 out of 100 people):

• allergic reactions (hypersensitivity)** ** Allergic reactions such as skin rash, itching, urticaria, and some cases of severe allergic reaction (anaphylactic/anaphylactoid) 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 occur in up to 1 out of 1,000 people):

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

Not known (frequency cannot be estimated from available data):
inflammation of the white part of the eye associated with redness and pain (scleritis)
In clinical studies, an increased incidence of bleeding from small blood vessels in the outer layer of the
eye (conjunctival haemorrhage) was observed in patients with age-related wet macular degeneration
(AMD) who were treated with blood-thinning medications. This increased incidence was comparable
between patients treated with ranibizumab and those treated with aflibercept.
Systemic use of vascular endothelial growth factor (VEGF) inhibitors, which are substances similar to
those contained in Opuviz, is potentially associated with the risk of blood clots blocking blood vessels
(arterial thromboembolic events), which may lead to heart attack or stroke. There is a potential risk that
such events may occur following injection of Opuviz into the eye.
As with all therapeutic proteins, treatment with aflibercept may trigger an immune response (antibody
formation).
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You can
also report side effects directly through the national reporting system listed in Annex V. By reporting
side effects, you can help provide more information on the safety of this medicine.

5. How to store Opuviz

• 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 "Exp." / "EXP". The expiry date refers to the last day of that month.
• Store in a refrigerator (2°C - 8°C). Do not freeze.
• The unopened blister can be stored outside the refrigerator at a temperature below 30°C for a maximum of 3 days.
• Keep in the original packaging to protect from light.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Opuviz contains

• The active substance is aflibercept. One pre-filled syringe contains a deliverable volume of at least 0.1 mL, equivalent to at least 4 mg of aflibercept. One pre-filled syringe provides a dose of 2 mg of aflibercept in 0.05 mL.
• The other components are: polysorbate 20 (E 432), monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, sucrose, water for injections.

See 'Opuviz contains' in section 2 for further information.
Description of the appearance of Opuviz and contents of the pack
Opuviz is an injectable solution (injection preparation) in a pre-filled syringe. The solution is clear and colourless to pale yellow.
Pack containing 1 pre-filled syringe.
Marketing Authorization Holder
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/.

The following information is intended exclusively for healthcare professionals:

How to prepare and administer Opuviz in adults
The pre-filled syringe is for single use only for one eye only.
Do not open the sterile syringe blister pack outside of a clean administration area.
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, inspect the injectable solution visually for the presence of foreign particles and/or discoloration or any change in appearance. If any of these are observed, the product must be discarded.
The sealed blister may be stored outside the refrigerator at a temperature below 30°C for up to 3 days. Once the blister is opened, proceed under aseptic conditions. A 30 G × ½ inch injection needle must be used for intravitreal injection.
Note: the dose must be set to 0.05 mL.
Instructions for using the pre-filled syringe:
Device description

Figure 1
The pre-filled syringe contains more than the recommended dose (0.05 mL); part of the volume in the syringe must be discarded before administration.
Step 1: Preparation

• Ensure the package contains a sterile pre-filled syringe in a sealed tray.
• Keep the syringe in the sterile tray until ready for use.
• Peel off the tray cover and, using aseptic technique, remove the syringe.

Step 2: Syringe inspection

• Opuviz should be colorless to pale yellow.
• Do not use the pre-filled syringe if:
• particles, cloudiness, or color changes are visible;
• the syringe is damaged;
• the syringe cap is not fully closed;
• when holding the syringe vertically at eye level, grey rubber is visible in the transparent part of the cap (see Figure 2), indicating that the syringe has been tampered with.

Figure 2
Step 3: Removal of the syringe cap

• Unscrew ( do not pull or tear off) the cap, holding the syringe in one hand and the cap between the thumb and index finger of the other hand (see Figure 3).

Figure 3
Step 4: Attaching the needle

• Firmly attach a sterile 30G × ½ inch injection needle to the syringe by securely screwing it onto the Luer lock (see Figure 4).
• Carefully remove the needle cap by pulling it straight off when ready to administer Opuviz. Note: never clean the needle.

Figure 4
Step 5: Removal of air bubbles

• Hold the syringe vertically with the needle pointing upward.
• If air bubbles are present, gently tap the syringe with your finger to allow them to rise to the surface (see Figure 5). Note: never pull back the plunger, to avoid compromising the sterility of the product.

Figure 5
Step 6: Expelling air and adjusting the drug dose

• Hold the syringe at eye level.
• Carefully look and identify the translucent dose mark.
• Gently press the plunger until the upper edge below the rounded end of the rubber stopper is aligned with the translucent 0.05 mL dose mark (see Figure 6).
• Resistance may be felt when the rubber stopper reaches the dose mark. This resistance indicates that the correct Opuviz dose volume of 0.05 mL has been reached.

Figure 6
Step 7: Injection

• The injection procedure must be performed under aseptic conditions.
• Insert the needle into the injection site.
• Inject slowly until the rubber stopper reaches the bottom of the syringe, to deliver the 0.05 mL volume.
• Change the scleral injection site for subsequent injections.

Step 8: Disposal
Note: after injection, do not recap the needle or detach it from the syringe. This may cause a needle-stick injury.

• 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.
• Dispose of unused medicine or used syringe with attached needle in accordance with local regulations or in a dedicated container.