Ximluci

Package leaflet: Information for the patient

Ximluci 10 mg/mL solution for injection

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

1. What is Ximluci and what is it used for

What is Ximluci
Ximluci is a solution to be injected into the eye. Ximluci belongs to a group of medicines called anti-angiogenic agents. It contains an active substance called ranibizumab.
What Ximluci is used for
Ximluci is used in adults to treat several eye conditions that cause vision loss.
These conditions result 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 diabetes-related condition). 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 Ximluci works
Ximluci specifically recognizes and binds to a protein called 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, Ximluci blocks its action and prevents abnormal vessel growth and swelling.
In these conditions, Ximluci can help stabilize vision and, in many cases, improve it.

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

Do not receive Ximluci

• 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 Ximluci.

• Ximluci is administered by injection into the eye. Occasionally, after treatment with Ximluci, 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 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 increasing discomfort, worsening of eye redness, 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 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 ischemic attacks (weakness or paralysis of limbs or face, difficulty speaking or understanding). This information will be considered when determining whether Ximluci 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 Ximluci.
Children and adolescents (under 18 years of age)
The use of Ximluci in children and adolescents has not been established and is therefore not recommended.
Other medicines and Ximluci
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 Ximluci.
• There is no experience with the use of Ximluci in pregnant women. Ximluci must not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, discuss this with your doctor before taking Ximluci.
• Ximluci is not recommended during breastfeeding, as it is not known whether Ximluci is excreted in human milk. Ask your doctor or pharmacist for advice before treatment with Ximluci.

Driving and using machines
After treatment with Ximluci, you may experience temporary blurred vision. If this occurs, do not drive and do not operate machinery until this condition has resolved.

3. How Ximluci will be administered to you

Ximluci 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 starts with one monthly injection of Ximluci. 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 Ximluci to adults”.
Elderly (aged 65 years and over)
Ximluci can be used in patients aged 65 years and over without dose adjustments.
Before stopping treatment with Ximluci
If you are considering stopping treatment with Ximluci, attend your next scheduled visit and discuss this with your doctor. Your doctor will advise you and decide how long you should continue treatment with Ximluci.
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 administration of Ximluci are due to both the medicine itself and the injection procedure, and most of them affect the eye.

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

• Detachment or tear in the back of the eye (retinal detachment or tear), presenting as flashes of light with floaters, progressing to temporary vision loss, or clouding of the lens (cataract)

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

• Blindness
• Infection of the eyeball (endophthalmitis) with inflammation inside the eye

Symptoms you may experience include:

• Eye pain or increased eye discomfort
• Worsening of eye redness
• Blurred or reduced vision
• Increase in the number of floaters in vision
• Increased sensitivity to light

Seek immediate medical advice if any of these side effects occur.

Other side effects:
Very common (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 (floaters)
• Localised eye redness
• Eye irritation
• Foreign body sensation in the eye
• Increased tear production
• Inflammation or infection of the eyelid margin
• Dry eye
• Eye redness or itching
• Increased intraocular pressure

Non-visual side effects include:

• Sore throat, nasal congestion, runny nose
• Headache
• Joint pain

Common (may affect up to 1 in 10 people):
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
• Decrease in 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 (may affect up to 1 in 100 people):
Visual side effects include:

• Inflammation and haemorrhage in the front of the eye
• Collection of pus in the eye
• Changes in the central part of the ocular surface
• Pain or irritation at the injection site
• Abnormal sensation in the eye
• Eyelid irritation

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ximluci

• 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 "exp." 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 closed vial may be stored at room temperature (25°C) for up to 48 hours.
• Keep the vial in the outer packaging to protect the medicine from light.
• Do not use a pack if it is damaged.

6. Package contents and other information

What Ximluci 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 trehalose dihydrate; histidine hydrochloride monohydrate; histidine; polysorbate 20; water for injections.

Description of the appearance of Ximluci and contents of the pack
Ximluci is an injectable solution, from clear to slightly opalescent, from colourless to slightly brownish, in a vial (0.23 mL).
Two different pack sizes are available:
Vial only
Pack containing one glass vial of ranibizumab with a bromobutyl rubber stopper. The vial is for single use only.
Vial + filter needle
Pack containing one glass vial of ranibizumab with a bromobutyl rubber stopper and one sterile blunt filter needle 5 µm (18G x 1½″, 1.2 mm x 40 mm) for withdrawal of the vial contents. All components are for single use only.

Marketing Authorisation Holder and Manufacturer
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
EG (Eurogenerics) NV UAB „STADA Baltics“
Tél/Tel: + 32 4797878 Tel: + 370 52603926

България Luxembourg/Luxemburg
STADA Bulgaria EOOD EG (Eurogenerics) NV
Тел.: + 359 29624626 Tél/Tel: + 32 4797878

Česká republika Magyarország
STADA PHARMA CZ s.r.o. STADA Hungary Kft
Tel: + 420 257888111 Tel.: + 36 18009747

Danmark Malta
STADA Nordic ApS Pharma MT Ltd
Tlf: + 45 44859999 Tel: + 356 21337008

Deutschland Nederland
STADAPHARM GmbH Centrafarm B.V.
Tel: + 49 61016030 Tel: + 31 765081000

Eesti Norge
UAB „STADA Baltics“ STADA Nordic ApS
Tel: + 370 52603926 Tlf: + 45 44859999

Ελλάδα Österreich
RAFARM A.E.B.E. STADA Arzneimittel GmbH
Τηλ: +30 2106776550 Tel: + 43 136785850

España Polska
Laboratorio STADA, S.L. STADA Poland Sp. z.o.o.
Tel: + 34 934738889 Tel.: + 48 227377920

France Portugal
EG LABO - Laboratoires EuroGenerics Stada, Lda.
Tél: + 33 146948686 Tel: + 351 211209870

Hrvatska România
STADA d.o.o. STADA M&D SRL
Tel. + 385 13764111 Tel: + 40 213160640

Ireland Slovenija
Clonmel Healthcare Ltd. Stada d.o.o.
Tel: + 353 526177777 Tel: + 386 15896710

Ísland Slovenská republika
STADA Arzneimittel AG STADA PHARMA Slovakia, s.r.o.
Sími: + 49 61016030 Tel: + 421 252621933

Italia Suomi/Finland
EG SpA STADA Nordic ApS, Suomen sivuliike
Tel: + 39 028310371 Puh/Tel: + 358 207416888

Κύπρος Sverige
STADA Arzneimittel AG STADA Nordic ApS
Τηλ: +30 2106664667 Tel: + 45 44859999

Latvija United Kingdom (Northern Ireland)
UAB „STADA Baltics“ STADA Arzneimittel AG
Tel: + 370 52603926 Tel: +49 61016030

Additional 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 Ximluci will be administered to you”.

How to prepare and administer Ximluci in adults
Single-use vials, for intravitreal use only.
Ximluci 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 Ximluci 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 must 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 and alterations in other signs and symptoms of the disease during continuous treatment. In patients with wet AMD, DME, PDR and RVO, it may be necessary to initiate therapy with three or more consecutive monthly injections.
Therefore, monitoring and treatment intervals must 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, Ximluci 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 recurrence of disease signs or worsening of visual function occurs. The treatment interval may be gradually extended by up to two weeks in patients with wet AMD and up to one month in patients with DME. Treatment intervals may also be gradually extended in the management 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 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. In CNV secondary to pathological myopia (PM), many patients may require only one or two injections during the first year.

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

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

Before administration, Ximluci should be visually inspected for the presence of particles and discoloration.

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 should be administered to disinfect the periocular, ocular and eyelid surfaces, as per clinical practice.

Vial only
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.

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

• a sterile 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm)
• a sterile 1 mL syringe (with a mark at 0.05 mL)
• an injection needle (30G x ½″, 0.3 mm x 13 mm). These devices are not included in the Ximluci pack.

Vial + filter 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 seal of the component’s packaging is not intact. Reuse may cause infection or other illness/injury.

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

• a sterile 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, provided)
• a sterile 1 mL syringe (with a mark at 0.05 mL, not included in the Ximluci pack)
• an injection needle (30G x ½″, 0.3 mm x 13 mm; not included in the Ximluci pack)

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

1. Before withdrawal, remove

the vial cap and clean the vial septum (e.g., with a 70% alcohol swab).

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

of the syringe is pulled back sufficiently when emptying the vial to completely 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 wipe 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.