Byooviz

Patient Information Leaflet

Byooviz 10 mg/mL solution for injection

ranibizumab
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.
ADULTS
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What Byooviz is and what it is used for

What Byooviz is
Byooviz is a solution that must be injected into the eye. Byooviz belongs to a group of
medicines called anti-angiogenic agents. It contains an active substance called
ranibizumab.
What Byooviz is used for
Byooviz is used in adults to treat several eye conditions that cause vision loss.
These conditions arise from damage to the retina (the light-sensitive layer at the back
of the eye) caused by:

• Growth of abnormal blood vessels that leak fluid. This occurs in conditions such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR, a condition caused by diabetes). It may also be associated with choroidal neovascularization (CNV) due to pathological myopia (PM), angioid streaks, central serous chorioretinopathy, or inflammatory CNV.
• Macular edema (swelling in the center of the retina). This swelling may be caused by diabetes (a condition called diabetic macular edema (DME)) or by blockage of retinal veins (a condition called retinal venous occlusion (RVO)).

How Byooviz works
Byooviz specifically recognizes and binds to a protein called human vascular endothelial growth factor A (VEGF-A) present in the eye. When in excess, VEGF-A causes abnormal growth of blood vessels and swelling in the eye, which can lead to vision loss in conditions such as AMD, DME, PDR, RVO, PM, and CNV. By binding to VEGF-A, Byooviz blocks its action and prevents abnormal blood vessel growth and swelling.
In these conditions, Byooviz can help stabilize vision and, in many cases, improve it.

2. What you should know before you are given Byooviz

Do not receive Byooviz

• if you are allergic to ranibizumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have an infection in or around the eye.
• if you have pain or redness (severe intraocular inflammation) in the eye.

Warnings and precautions
Talk to your doctor before receiving Byooviz.

• Byooviz is administered by injection into the eye. Occasionally, after treatment with Byooviz, an infection inside the eye, pain or redness (inflammation), detachment or tear of one of the layers at the back of the eye (retinal detachment or tear and detachment or tear of the retinal pigment epithelium), or clouding of the lens (cataract) may occur. It is important to identify and treat an infection or retinal detachment as soon as possible. Immediately inform your doctor if you experience symptoms such as eye pain or increased discomfort, worsening redness of the eye, blurred or decreased vision, an increase in floaters, or increased sensitivity to light.
• In some patients, eye pressure may temporarily increase shortly after the injection. This is something you may not notice, so your doctor must check your eye pressure after each injection.
• Inform your doctor if you have had previous eye problems or treatments, or if you have had a stroke or signs of transient ischemic attacks (weakness or paralysis of limbs or face, difficulty speaking or understanding). This information will be considered when evaluating whether Byooviz is the appropriate treatment for you.

See section 4 (“Possible side effects”) for more detailed information on side effects that may occur during treatment with Byooviz.
Children and adolescents (under 18 years of age)
The use of Byooviz in children and adolescents has not been established and is therefore not recommended.
Other medicines and Byooviz
Inform your doctor if you are using, have recently used, or might use any other medicines.
Pregnancy and breastfeeding

• Women of childbearing potential must use an effective method of contraception during treatment and for at least three months after the last injection of Byooviz.
• There is no experience with the use of Byooviz in pregnant women. Byooviz should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, discuss this with your doctor before taking Byooviz.
• Use of Byooviz during breastfeeding is not recommended, as small amounts of ranibizumab may pass into breast milk. Consult your doctor or pharmacist before treatment with Byooviz.

Driving and using machines
After treatment with Byooviz, temporary blurred vision may occur. If this happens, do not drive or operate machinery until this condition has resolved.
Byooviz contains polysorbate 20 (E 432)
This medicine contains 0.023 mg of polysorbate 20 (E 432) per vial (0.23 mL), equivalent to 0.005 mg/0.05 mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Byooviz will be administered to you

Byooviz is administered by your ophthalmologist as a single injection into the eye under local anaesthesia. The usual dose of one injection is 0.05 mL (containing 0.5 mg of active substance). The interval between two injections given into the same eye must be at least four weeks. All injections will be administered by your ophthalmologist.
Before the injection, your doctor will carefully clean your eye to prevent infection. Your doctor will also give you a local anaesthetic to reduce or prevent any pain that may occur during the injection.
Treatment is started with one monthly injection of Byooviz. Your doctor will monitor the condition of your eye and, based on your response to treatment, will decide whether and when further treatment is needed.
Detailed instructions for the user can be found at the end of this leaflet under the heading “How to prepare and administer Byooviz”.
Elderly (aged 65 years and over)
Byooviz can be used in patients aged 65 years and over without dose adjustments.
Before stopping treatment with Byooviz
If you are considering stopping treatment with Byooviz, please attend your next scheduled appointment and discuss this with your doctor. Your doctor will advise you and decide for how long you should continue treatment with Byooviz.
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 everyone gets them.
The side effects associated with Byooviz administration are due to both the medicine itself and the injection procedure, and most of them affect the eye.
The most serious side effects are described below:
Serious common side effects (may affect up to 1 in 10 patients): detachment or tear in the back of the eye (retinal detachment or tear), which manifests as flashes of light with moving spots, leading to temporary vision loss or clouding of the lens (cataract).
Serious uncommon side effects (may affect up to 1 in 100 patients): blindness, infection of the eyeball (endophthalmitis) with inflammation inside the eye.
The symptoms you may experience are eye pain or increased eye discomfort, worsening of eye redness, blurred vision or loss of vision, increased number of floaters, or increased sensitivity to light. Contact your doctor immediately if any of these side effects occur.
The most frequently reported side effects are described below:
Very common side effects (may affect more than 1 in 10 patients)
Visual side effects include: eye inflammation, bleeding at the back of the eye (retinal haemorrhage), visual disturbances, eye pain, floaters or spots in vision (floaters), localized eye redness, eye irritation, sensation of a foreign body in the eye, increased tear production, inflammation or infection of the eyelid margin, dry eye, eye redness or itching, and increased pressure inside the eye.
Non-visual side effects include: sore throat, nasal congestion, runny nose, headache, and joint pain.
Other side effects that may occur following treatment with Byooviz are described below:
Common side effects
Visual side effects include: decreased visual acuity, swelling of part of the eye (uvea, cornea), corneal inflammation (front part of the eye), small spots on the eye surface, blurred vision, bleeding at the injection site, bleeding in the eye, eye discharge with itching, redness and swelling (conjunctivitis), light sensitivity, eye discomfort, eyelid swelling, eyelid pain.
Non-visual side effects include: urinary tract infection, reduced red blood cells (with symptoms such as fatigue, shortness of breath, dizziness, pallor), anxiety, cough, nausea, allergic reactions such as rash, urticaria, itching, and skin redness.
Uncommon side effects
Visual side effects include: inflammation and haemorrhage in the front part of the eye, collection of pus in the eye, changes in the central part of the eye surface, pain or irritation at the injection site, abnormal sensation in the eye, eyelid irritation.
If you experience any side effect, including those not listed in this leaflet, contact your doctor.
Reporting of side effects
If you get 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 Byooviz

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after "scad." and "EXP.". The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C). Do not freeze.
• Before use, the unopened vial may be stored at temperatures not exceeding 30°C for up to 2 months.
• Keep the vial in the outer packaging to protect the medicine from light.
• Do not use a package if it is damaged.

6. Package contents and other information

What Byooviz contains

• The active substance is ranibizumab. Each mL contains 10 mg of ranibizumab. Each vial contains 2.3 mg of ranibizumab in 0.23 mL of solution. This provides a sufficient amount for administration of a single dose of 0.05 mL containing 0.5 mg of ranibizumab.
• The other components are α,α-trehalose dihydrate; histidine hydrochloride monohydrate; histidine; polysorbate 20 (E 432); water for injections.

Description of the appearance of Byooviz and contents of the pack
Byooviz is an injectable solution in a vial (0.23 mL). The solution is aqueous, clear, from colourless to pale yellow.
Two different pack sizes are available:
Single vial
Pack containing one glass vial of ranibizumab with a chlorobutyl rubber stopper. The vial is for single use only.
Vial + filter needle + injection needle
Pack containing one glass vial of ranibizumab with a chlorobutyl rubber stopper, one blunt filter needle (18G x 1½″, 1.2 mm x 40 mm, 5 micrometres) for withdrawal of the vial contents, and one injection needle (30G x 1½″, 0.3 mm x 13 mm). All components are for single use only.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
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, http://www.ema.europa.eu

THE FOLLOWING INFORMATION IS INTENDED EXCLUSIVELY FOR HEALTHCARE PROFESSIONALS:
Please also refer to section 3 “How Byooviz will be given to you”.

How to prepare and administer Byooviz in adults
Single-use vials, for intravitreal use only.
Byooviz must be administered by a qualified ophthalmologist experienced in intravitreal injections.

In neovascular (wet) age-related macular degeneration (AMD), choroidal neovascularisation (CNV), proliferative diabetic retinopathy (PDR), vision loss due to diabetic macular oedema (DME), or macular oedema secondary to retinal vein occlusion (RVO), the recommended dose of Byooviz is 0.5 mg as a single intravitreal injection. This corresponds to an injected volume of 0.05 mL. The interval between two injections in the same eye should be at least four weeks.

Treatment is initiated with monthly injections until maximum visual acuity is achieved and/or there are no signs of disease activity, such as changes in visual acuity or alterations in other signs and symptoms of the disease during continuous treatment. In patients with neovascular AMD, DME, PDR, and RVO, it may be necessary to initiate therapy with three or more consecutive monthly injections.

Therefore, monitoring and treatment intervals should be determined by the physician and should be based on disease activity, as assessed by evaluation of visual acuity and/or anatomical parameters.

If, in the physician’s opinion, visual acuity and anatomical parameters indicate that the patient is not benefiting from continued treatment, Byooviz should be discontinued.

Monitoring of disease activity may include clinical examination, functional assessments, or imaging techniques (e.g., optical coherence tomography or fluorescein angiography).

If patients are treated according to a “treat-and-extend” regimen, upon achieving maximum visual acuity and/or absence of signs of disease activity, treatment intervals may be gradually extended until signs of disease recurrence or worsening of visual function occur. The treatment interval should be gradually extended by up to two weeks in patients with neovascular AMD, and may be extended up to one month in patients with DME. Treatment intervals may also be gradually extended in the treatment of RVO and PDR; however, there are insufficient data to establish the duration of these intervals. Upon recurrence of disease activity, the treatment interval should be reduced accordingly.

The treatment of vision loss caused by CNV should be individually determined for each patient based on disease activity. Some patients may require only one injection during the first 12 months; others may require more frequent treatment, up to monthly injections. For CNV secondary to pathological myopia (PM), many patients may require only one or two injections during the first year.

Ranibizumab and laser photocoagulation in DME and macular oedema secondary to BRVO
There is some experience with ranibizumab administered concomitantly with laser photocoagulation. When used on the same day, ranibizumab should be administered at least 30 minutes after laser photocoagulation. Ranibizumab may be administered to patients who have previously received laser photocoagulation.

Ranibizumab and photodynamic therapy with verteporfin in CNV secondary to PM
There is no experience with the administration of ranibizumab in combination with verteporfin.

Prior to administration, Byooviz should be visually inspected for the presence of particles and discolouration.

The injection procedure must be performed under aseptic conditions, including surgical hand disinfection, sterile gloves, a sterile drape, a sterile eyelid speculum (or equivalent), and the possibility of performing a sterile paracentesis (if necessary). Prior to performing the intravitreal procedure, the patient’s history should be carefully evaluated for hypersensitivity reactions. Prior to injection, adequate anaesthesia and a broad-spectrum topical antimicrobial agent should be administered to disinfect the periocular, ocular, and eyelid surfaces, as per clinical practice.

Single vial
The vial is for single use only. After injection, any unused product must be discarded. Any vial showing signs of damage or tampering must not be used. Sterility cannot be guaranteed if the package seal is not intact.

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

• a 5 µm filter needle (18G)
• an injection needle (30G x ½″)
• a sterile 1 mL syringe (with a 0.05 mL mark). These devices are not included in the Byooviz pack.

Vial + filter needle + injection needle
All components are sterile and for single use only. Any component with packaging showing signs of damage or tampering must not be used. Sterility cannot be guaranteed if the component’s package seal is not intact. Reuse may cause infection or other illness/injury.

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

• a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, provided)
• an injection needle (30G x 1½″, 0.3 mm x 13 mm, provided)
• a sterile 1 mL syringe (with a 0.05 mL mark, not included in the Byooviz pack)

To prepare Byooviz for intravitreal injection in adult patients, please follow the instructions below:

1. Disinfect the outer surface of the vial’s rubber stopper

before withdrawal.

2. Aseptically attach a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, 5 µm) to a 1 mL syringe. Insert the filter needle into the centre of the stopper until it touches the bottom of the vial.
3. Withdraw all liquid from the vial while holding it in an upright, slightly tilted position to facilitate complete withdrawal.
4. Ensure the syringe plunger is pulled back

sufficiently when emptying the vial to fully empty the filter needle.

5. Leave the filter needle inserted in the vial and detach the syringe. Discard the filter needle after withdrawing the vial contents and do not use it for intravitreal injection.
6. Aseptically and securely attach an injection needle

(30G x ½″, 0.3 mm x 13 mm) to the syringe.

7. Carefully remove the cap from the injection needle without disconnecting the needle from the syringe.
   Note: Hold the base of the injection needle while removing the cap.

8. Carefully expel air and excess solution from the syringe and adjust the dose to 0.05 mL as marked on the syringe. The syringe is now ready for injection.
   Note: Do not clean the injection needle. Do not pull back the plunger.

Insert the injection needle 3.5–4.0 mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and directing the needle toward the centre of the globe. Inject the 0.05 mL dose; change the scleral injection site for subsequent injections.

After injection, do not recap or detach the needle from the syringe. Dispose of the used syringe with the attached needle in a dedicated sharps container or in accordance with local regulations.

Package leaflet: information for the patient

Byooviz 10 mg/mL solution for injection in pre-filled syringe

ranibizumab
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 this medicine is administered to you, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

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

1. What Byooviz is and what it is used for

What Byooviz is
Byooviz is a solution that must be injected into the eye. Byooviz belongs to a group of medicines called anti-angiogenic agents. It contains an active substance called ranibizumab.

What Byooviz is used for
Byooviz is used in adults to treat several eye conditions that cause vision loss.
These conditions arise from damage to the retina (the light-sensitive layer at the back of the eye) caused by:

• Growth of abnormal blood vessels that leak fluid. This occurs in conditions such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR, a condition caused by diabetes). It may also be associated with choroidal neovascularization (CNV) due to pathological myopia (PM), angioid streaks, central serous chorioretinopathy, or inflammatory CNV.
• Macular edema (swelling in the center of the retina). This swelling may be caused by diabetes (a condition called diabetic macular edema (DME)) or by blockage of retinal veins (a condition called retinal vein occlusion (RVO)).

How Byooviz works
Byooviz specifically recognizes and binds to a protein called human vascular endothelial growth factor A (VEGF-A) present in the eye. When present in excess, VEGF-A causes abnormal blood vessel growth and swelling in the eye, which can lead to vision loss in conditions such as AMD, DME, PDR, RVO, PM, and CNV. By binding to VEGF-A, Byooviz blocks its action and prevents abnormal blood vessel growth and swelling.
In these conditions, Byooviz may help stabilize vision and, in many cases, improve it.

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

Do not receive Byooviz

• if you are allergic to ranibizumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have an infection in or around the eye.
• if you have pain or redness (severe intraocular inflammation) in an eye.

Warnings and precautions
Talk to your doctor before receiving Byooviz.

• Byooviz is administered by injection into the eye. Occasionally, after treatment with Byooviz, an infection inside the eye, eye pain or redness (inflammation), detachment or tear in one of the layers at the back of the eye (retinal detachment or tear and retinal pigment epithelial detachment or tear), or clouding of the lens (cataract) may occur. It is important to identify and treat an infection or retinal detachment as soon as possible. Immediately inform your doctor if you experience symptoms such as eye pain or increased discomfort, worsening of eye redness, blurred or decreased vision, an increase in floaters, or increased sensitivity to light.
• In some patients, eye pressure may increase shortly after the injection for a short period. This event may go unnoticed, therefore your doctor must check your eye pressure after each injection.
• Inform your doctor if you have had previous eye problems or treatments, or if you have had a stroke or signs of transient ischaemic attacks (weakness or paralysis of limbs or face, difficulty speaking or understanding). This information will be considered when evaluating whether Byooviz is the appropriate treatment for you.

See section 4 (“Possible side effects”) for more detailed information on adverse reactions that may occur during treatment with Byooviz.
Children and adolescents (under 18 years of age)
The use of Byooviz in children and adolescents has not been established and is therefore not recommended.
Other medicines and Byooviz
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 an effective method of contraception during treatment and for at least three months after the last injection of Byooviz.
• There is no experience with the use of ranibizumab in pregnant women. Byooviz should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, discuss this with your doctor before taking Byooviz.
• Byooviz is not recommended during breastfeeding as small amounts of ranibizumab may pass into breast milk. Consult your doctor or pharmacist before treatment with Byooviz.

Driving and using machines
After treatment with Byooviz, temporary blurred vision may occur. If this happens, do not drive and do not operate machinery until this condition has resolved.
Byooviz contains polysorbate 20 (E 432)
This medicine contains 0.0165 mg of polysorbate 20 (E 432) per pre-filled syringe (0.165 mL), equivalent to 0.005 mg/0.05 mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Byooviz will be administered to you

Byooviz is administered by your ophthalmologist as a single injection into the eye under local anaesthesia. The usual dose of one injection is 0.05 mL (containing 0.5 mg of active substance). The pre-filled syringe contains more than the recommended dose of 0.5 mg. The extractable volume from the pre-filled syringe must not be used completely. The excess volume must be discarded before performing the injection. Injecting the entire volume of the pre-filled syringe may result in overdose.
The interval between two doses injected into the same eye must be at least four weeks. All injections will be administered by your ophthalmologist.
Before the injection, your doctor will carefully clean your eye to prevent infection. Your doctor will also give you a local anaesthetic to reduce or prevent any pain that may occur during the injection.
Treatment is initiated with one monthly injection of Byooviz. Your doctor will monitor the condition of your eye and, based on your response to treatment, will decide whether and when further treatment is needed.
Detailed instructions for the user can be found at the end of this leaflet under the section “How to prepare and administer Byooviz”.
Elderly patients (aged 65 years and over)
Byooviz can be used in patients aged 65 years and over without dose adjustments.
Before stopping treatment with Byooviz
If you are considering stopping treatment with Byooviz, attend your next scheduled appointment and discuss this with your doctor. Your doctor will advise you and decide for how long you should continue treatment with Byooviz.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The side effects associated with Byooviz administration are due to both the medicine itself and the injection procedure, and most of them affect the eye.
The most serious side effects are described below:
Common serious side effects (may affect up to 1 in 10 people): detachment or tear in the back of the eye (retinal detachment or tear), manifesting as flashes of light, floaters, temporary reduction in vision, or clouding of the lens (cataract).
Uncommon serious side effects (may affect up to 1 in 100 people): blindness, infection of the eyeball (endophthalmitis), with inflammation inside the eye.
The symptoms you may experience include eye pain or increased eye discomfort, worsening eye redness, blurred vision or loss of vision, increased number of floaters, or increased sensitivity to light. Seek immediate medical advice if any of these side effects occur.
The side effects reported most frequently are described below:
Very common side effects (may affect more than 1 in 10 people)
Visual side effects include: eye inflammation, bleeding in the back of the eye (retinal haemorrhage), visual disturbances, eye pain, floaters or spots in vision, localized eye redness, eye irritation, sensation of a foreign body in the eye, increased tear production, inflammation or infection of the eyelid margin, dry eyes, eye redness or itching, and increased intraocular pressure.
Non-visual side effects include: sore throat, nasal congestion, runny nose, headache, and joint pain.
Other side effects that may occur following treatment with Byooviz are described below:
Common side effects
Visual side effects include: decreased visual acuity, swelling of part of the eye (uvea, cornea), corneal inflammation (front part of the eye), small lesions on the eye surface, blurred vision, bleeding at the injection site, bleeding in the eye, eye discharge with itching, redness and swelling (conjunctivitis), light sensitivity, eye discomfort, eyelid swelling, eyelid pain.
Non-visual side effects include: urinary tract infection, reduced red blood cells (with symptoms such as fatigue, breathlessness, dizziness, pallor), anxiety, cough, nausea, allergic reactions such as rash, urticaria, skin itching, and skin redness.
Uncommon side effects
Visual side effects include: inflammation and haemorrhage in the front of the eye, accumulation of pus in the eye, changes in the central part of the eye surface, pain or irritation at the injection site, abnormal sensation in the eye, eyelid irritation.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor.
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 Byooviz

• 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 on the label of the pre-filled syringe after exp. and after EXP. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C). Do not freeze.
• Before use, the sealed tray may be stored at temperatures not exceeding 30°C for up to 1 week.
• Keep the pre-filled syringe in its closed tray to protect the medicine from light.
• Do not use a pack if it is damaged.

6. Contents of the pack and other information

What Byooviz contains

• The active substance is ranibizumab. Each mL contains 10 mg of ranibizumab. A pre-filled syringe contains 0.165 mL, equivalent to 1.65 mg of ranibizumab. This provides sufficient quantity for administration of a single dose of 0.05 mL containing 0.5 mg of ranibizumab.
• The other components are α,α-trehalose dihydrate; histidine hydrochloride monohydrate; histidine; polysorbate 20 (E 432); water for injections.

Description of the appearance of Byooviz and contents of the pack
Byooviz is an injectable solution in a pre-filled syringe. The pre-filled syringe contains 0.165 mL of sterile, clear, aqueous solution, from colourless to pale yellow. The pre-filled syringe contains more than the recommended dose of 0.5 mg. The extractable volume of the pre-filled syringe must not be used completely. The excess volume must be discarded before performing the injection. Injecting the entire volume of the pre-filled syringe may cause overdose.
Pack containing one pre-filled syringe in a sealed tray. The pre-filled syringe is for single use only.
Marketing Authorisation Holder and Manufacturer
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: http://www.ema.europa.eu.
THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY:
Please also refer to section 3 “How Byooviz will be administered to you”.
How to prepare and administer Byooviz
Single-use pre-filled syringe, for intravitreal use only.
Byooviz must be administered by a qualified ophthalmologist experienced in intravitreal injections.
In neovascular (wet) AMD, CNV, PDR and vision loss due to DME, or macular oedema secondary to RVO, the recommended dose of Byooviz is 0.5 mg as a single intravitreal injection. This corresponds to an injected volume of 0.05 mL. The interval between two injections administered in the same eye should be at least four weeks.
Treatment is initiated with one injection per month until maximum visual acuity is achieved and/or there are no signs of disease activity such as changes in visual acuity and alterations in other signs and symptoms of the disease during continued treatment. In patients with neovascular AMD, DME, PDR and RVO, it may be necessary to initiate therapy with three or more consecutive monthly injections.
Therefore, monitoring and treatment intervals should be determined by the physician and should be based on disease activity, as assessed by evaluation of visual acuity and/or anatomical parameters.
If, in the physician’s opinion, visual acuity and anatomical parameters indicate that the patient is not benefiting from continued treatment, Byooviz should be discontinued.
Monitoring of disease activity may include clinical examination, functional assessments, or imaging techniques (e.g., optical coherence tomography or fluorescein angiography).
If patients are treated according to a “treat-and-extend” regimen, upon achieving maximum visual acuity and/or absence of signs of disease activity, treatment intervals may be gradually extended until signs of disease recur or visual function worsens. The treatment interval should be gradually extended by up to two weeks in patients with neovascular AMD and may be extended up to one month in patients with DME. Treatment intervals may also be gradually extended in the treatment of RVO and PDR; however, there are insufficient data to establish the duration of these intervals. Upon recurrence of disease activity, the treatment interval should be reduced accordingly.
Treatment of vision loss caused by CNV should be individually determined for each patient based on disease activity. Some patients may require only one injection during the first 12 months; others may require more frequent treatment, up to monthly injections. For CNV secondary to pathological myopia (PM), many patients may require only one or two injections during the first year.
Ranibizumab and laser photocoagulation in DME and macular oedema secondary to BRVO
There is some experience with ranibizumab administered concomitantly with laser photocoagulation. When used on the same day, ranibizumab should be administered at least 30 minutes after laser photocoagulation. Ranibizumab may be administered to patients who have previously received laser photocoagulation.
Ranibizumab and photodynamic therapy with verteporfin in CNV secondary to PM
There is no experience with administration of ranibizumab in combination with verteporfin.
Before administration, Byooviz must be visually inspected for the presence of particles and discolouration.
Prior to performing the intravitreal procedure, the patient’s history should be carefully evaluated for hypersensitivity reactions. Prior to injection, adequate anaesthesia and a broad-spectrum topical antimicrobial agent should be administered to disinfect the periocular, ocular, and eyelid surfaces, as per clinical practice.
The pre-filled syringe is sterile and for single use only. Do not use the product if the packaging is damaged or has been tampered with.
To prepare Byooviz for intravitreal injection, please follow the instructions for use. Read all instructions carefully before using the pre-filled syringe.
Opening the sealed tray and all subsequent steps must be performed under aseptic conditions, including surgical hand disinfection, use of sterile gloves, sterile drape, sterile eyelid speculum (or equivalent), and the possibility of performing a sterile paracentesis (if necessary).
For intravitreal injection, a sterile 30G × ½″ injection needle (not supplied) must be used.
Note: the sterile 30G × ½″ injection needle is not included in the pack.
Note: the dose must be set to 0.05 mL.
Device description

The pre-filled syringe contains more than the recommended dose of 0.5 mg. The excess volume must be discarded before performing the injection.
Step 1: • Ensure the pack contains a sterile pre-filled syringe in a sealed tray.
Preparation

• Keep the syringe in the sterile tray until ready for use.
• Peel off the tray cover and, using an aseptic technique, remove the syringe.
  Step 2: • Byooviz should be

Inspection colourless to pale yellow.
of the syringe • Do not use the pre-filled syringe if:

• visible particles, cloudiness, or discolouration are present;
• 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.
  Note: the plunger is
  completely or partially
  attached to the rubber stopper. Do
  not attempt to attach the plunger
  to the rubber stopper.
  Step 3: • Unscrew ( do not pull or remove)

Removal the cap, holding the syringe in one hand and the cap between the thumb and index finger of the other hand (see Figure 3).
of the syringe cap
Step 4: • Firmly attach a sterile 30G × ½″ injection needle to the syringe, screwing it tightly onto the Luer lock (see Figure 4).

• Carefully remove the needle cap by pulling it straight off when ready to administer Byooviz.

Note: never clean the needle.
Step 5: • Hold the syringe in a vertical

Removal position with the needle pointing upwards.
of air bubbles • If air bubbles are present, gently tap the syringe with your finger until they rise to the top (see Figure 5).
Note: never pull back the plunger, to avoid compromising the sterility of the product.
Step 6: • Hold the syringe at eye level.

Expulsion • Look carefully and identify the translucent dose mark.
of air and • 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).
adjustment of the drug dose

• You may **feel a