Ahzantive

Package leaflet: Information for the patient

Ahzantive 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 using 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 experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What Ahzantive is and what it is used for

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

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

Aflibercept, the active substance in Ahzantive, 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 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. As a result, VEGF levels rise and cause fluid leakage into the retina, leading to 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 can help stabilise, and in many cases improve, vision loss associated with wet AMD, CRVO, BRVO, DME, and myopic CNV.

2. What you should know before using Ahzantive

Do not take Ahzantive

• 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 Ahzantive:

• if you have glaucoma,
• if you have ever experienced flashes of light or floaters and 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 Ahzantive 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 administering it in this way may increase the risk of experiencing adverse effects.
• injections of Ahzantive may cause an increase in intraocular pressure (IOP) 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 or worsening discomfort, increased eye redness, blurred or reduced vision, and increased sensitivity to light. It is important that any symptoms are diagnosed and treated as soon as possible.
• your doctor will check whether you have other risk factors that may increase the likelihood of detachment or tear in the back of the eye (retinal detachment or tear, or retinal pigment epithelial detachment or tear); in such cases, aflibercept will be administered with caution.
• aflibercept 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 Ahzantive.

Systemic use of VEGF inhibitors—substances similar to those contained in Ahzantive—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 Ahzantive into the eye. Limited data are available on the safety of treating patients with CRVO, BRVO, DME, or myopic CNV who have had a stroke or mini-stroke (transient ischemic attack) or heart attack within the past 6 months. If any of these situations apply to you, Ahzantive 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) 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 Ahzantive.

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

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

Ahzantive contains polysorbate and sodium
Ahzantive contains polysorbate 20 (E432) and sodium chloride.
This medicine contains 0.015 mg of polysorbate 20 per 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 Ahzantive

A doctor experienced in eye injections will inject Ahzantive into your eye under aseptic conditions
(clean and sterile conditions).
The recommended dose is 2 mg of aflibercept (0.05 mL).
Ahzantive 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 the 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 an additional 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 for medical
examinations between injections.

Macular edema secondary to RVO (branch RVO and central RVO)
Your doctor will determine the most appropriate treatment frequency for you. Treatment will begin with
a series of monthly injections of Ahzantive.
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 Ahzantive.
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
increasing intervals between injections to maintain a stable condition. If your condition begins to worsen
as the treatment interval is extended, your doctor will shorten the intervals between treatments
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 Ahzantive 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 your doctor indicate that the disease has not improved.
The interval between two injections must not be less than one month.
If the disease disappears and then recurs, your doctor may resume treatment.
Your doctor will establish the schedule for follow-up examinations.

If you forget to use Ahzantive
Make a new appointment to have the examinations and injection performed.

If you stop treatment with Ahzantive
Consult your doctor before stopping treatment.
If you have any doubts about how to use this medicine, contact 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 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 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 affect up to 1 in 10 people):

• detachment or tear of one of the layers at the back of the eye, causing flashes of light with floaters and sometimes leading to vision loss (retinal pigment epithelial tear / detachment, retinal detachment/tear)
• degeneration of the retina (causing disturbed vision)
• bleeding in the eye (vitreous haemorrhage)
• certain forms of clouding of the lens (cataract)
• damage to the outermost layer of the eyeball (cornea)
• increased eye pressure
• seeing moving spots (floaters)
• separation of the gel-like substance inside the eye from the retina (vitreous detachment, causing flashes of light with floaters)
• sensation of having something in the eye
• increased tear production
• eyelid swelling
• bleeding at the injection site
• eye redness

Conditions known to be associated with neovascular age-related macular degeneration (nAMD), observed only in patients with nAMD.
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 such as skin rashes, itching, urticaria have been reported, as well as some cases of severe allergic (anaphylactic/anaphylactoid) reactions.
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 age-related neovascular macular degeneration (nAMD) 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 Ahzantive, 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 Ahzantive may lead to 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 Ahzantive

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and label after “Scad.” / “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C - 8 °C). Do not freeze.
• The closed vial may be stored outside the refrigerator at a temperature below 25 °C for up to 24 hours.
• Keep the medicine in its original packaging to protect it from light.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ahzantive contains

• The active substance is aflibercept. One vial contains a volume of at least 0.1 mL for extraction, 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), monohydrate histidine hydrochloride (for pH adjustment), histidine (for pH adjustment), sodium chloride, sucrose, water for injections. See section 2 “Ahzantive contains polysorbate and sodium”.

Description of the appearance of Ahzantive and contents of the pack
Ahzantive is an injectable solution (injection preparation) 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 medicine 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 for the treatment of one single 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 prior to administration.
Prior to administration, visually inspect the injectable solution for the presence of foreign particles and/or discoloration or any change in appearance. If such changes are observed, the medicinal product must be discarded.
The unopened vial may be stored outside the refrigerator at a temperature not exceeding 25 °C for up to 24 hours. Once the vial has been opened, handle 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 5-micron filter to a sterile 1 mL Luer-lock syringe:

3. Insert the filtered needle into the center of the vial stopper until the needle is fully inserted into the vial and the tip touches the bottom or the bottom corner of the vial.
4. Using aseptic technique, draw the entire contents of the Ahzantive vial into the syringe while keeping the vial in an upright position, slightly tilted to facilitate complete

aspiration. To avoid introducing air, ensure that the entire beveled tip of the needle is completely submerged in the liquid. Keep the vial tilted during aspiration, with the needle tip fully immersed in the liquid:

5. Ensure that the plunger rod is pulled sufficiently backward when emptying the vial to completely empty the filtered needle.
6. Remove the filtered needle and dispose of it appropriately. Note: The filtered needle must not be used for intravitreal injection.
7. Using aseptic technique, attach a 30 G × 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 presence of air bubbles. If any are 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.