Baiama

Package leaflet: Information for the patient

Baiama 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 Baiama is and what it is used for
2. What you need to know before using Baiama
3. How to use Baiama
4. Possible side effects
5. How to store Baiama
6. Contents of the pack and other information

1. What Baiama is and what it is used for

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

• neovascular age-related macular degeneration (exudative 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 (DME),
• vision impairment due to myopic choroidal neovascularisation (myopic CNV).

Aflibercept, the active substance in Baiama, 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 exudative 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 carrying blood away 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 leakage of fluid 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.
Aflibercept has been shown to block the growth of abnormal new blood vessels in the eye, which often leak fluid or blood. Aflibercept may help to stabilise, and in many cases improve, vision loss associated with exudative AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you need to know before using Baiama

Do not take Baiama

• 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 Baiama:

• 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 Baiama is not recommended.

It is also important for you to know that:

• the safety and efficacy of aflibercept when administered in both eyes simultaneously have not been studied, and doing so may increase the risk of experiencing adverse effects.
• Baiama injections may cause a temporary increase in intraocular pressure (eye pressure) within 60 minutes after injection in some patients. 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, 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 detachment or rupture of layers in the back of the eye (retinal detachment or tear, and detachment or rupture of the retinal pigment epithelium); in such cases, aflibercept will be administered with caution.
• aflibercept should not be used during pregnancy unless the potential benefit justifies 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 Baiama.

Systemic use of VEGF inhibitors—substances similar to those contained in Baiama—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 Baiama into the eye. 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, Baiama 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) for 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 Baiama.

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

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

Baiama contains polysorbate and sodium
Baiama contains polysorbate 20 (E432) and sodium chloride.
This medicine contains 0.015 mg of polysorbate 20 in each administered dose of 0.05 mg, equivalent to 0.3 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.
This medicine contains less than 1 mmol (23 mg) of sodium per single dose, i.e., essentially 'sodium-free'.

3. How to use Baiama

A doctor experienced in eye injections will inject Baiama into your eye under aseptic (clean and sterile) conditions.
The recommended dose is 2 mg of aflibercept (0.05 mL).
Baiama 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.

Exudative AMD
Patients with exudative 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 your doctor advises otherwise, there is no need for you to see the 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 injections of Baiama.
The interval between two injections must not be less than one month.
If you do not experience benefit after continuous treatment, your doctor may decide to discontinue treatment with Baiama.
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 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 decide the frequency of follow-up examinations.
Your doctor may decide to discontinue treatment with Baiama 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.

If you forget to use Baiama
Make a new appointment to have the examination and injection performed.

If you stop using Baiama
Consult your doctor before stopping treatment.
If you have any doubts about using this medicine, ask 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 may require
immediate medical attention.
When aflibercept 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 paragraph 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 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 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)
• 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 (AMD), observed only in patients with neovascular 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 the 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, hives, 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

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 neovascular age-related macular degeneration (AMD) who were treated with blood-thinning medicines. This increased incidence was similar 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 Baiama, 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 aflibercept into the eye.
As with all therapeutic proteins, use of Baiama may lead to an immune response (formation of antibodies).
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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Baiama

• 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 closed vial may 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 medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

What Baiama contains

• The active substance is aflibercept. One vial contains a reconstitutable 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: polysorbate 20 (E432), histidine hydrochloride monohydrate (for pH regulation), histidine (for pH regulation), sodium chloride, sucrose, water for injections. See section 2 “Baiama contains polysorbate and sodium”.

Description of the appearance of Baiama and pack contents
Baiama is an injectable solution (preparation for injection) in a vial. The solution is colourless to pale yellow.
Pack size: 1 vial.
Marketing Authorisation Holder
Formycon AG
82152 Martinsried/Planegg
Germany
Manufacturer
Midas Pharma GmbH
Rheinstrasse 49
55218 Ingelheim am Rhein
Germany
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 only 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.
Before administration, visually inspect the injectable solution for the presence of foreign particles and/or
change in colour or any other variation in appearance. If this occurs, the medicinal product must be discarded.
The closed vial may be stored outside the refrigerator at a temperature below 25 °C for up to 24 hours.
Once the vial is opened, proceed under aseptic conditions.
The following single-use medical devices are required for preparation and intravitreal injection:
a sterile 5-micron filter needle (18 gauge × ½ inch)
a sterile 1 mL syringe with Luer-lock
a sterile 30 G × ½ inch injection needle, required for intravitreal injection
These medical devices are not included in the package.
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 needle with a 5-micron filter to a sterile 1 mL syringe with Luer-lock:

3. Insert the filter needle vertically into the center of the vial stopper until the needle is fully inserted into the vial and the tip touches the bottom or the bottom corner of the vial.
4. Using aseptic technique, aspirate the entire contents of the Baiama 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 bevel of the needle is completely submerged in the liquid. Keep the vial tilted during aspiration, with the needle tip fully immersed in the liquid:

5. Ensure that the plunger rod is fully drawn back when emptying the vial to completely evacuate 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 to the tip of the Luer-lock syringe 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 medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.