XIMLUCI 10 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Ximluci 10 mg/ml Solution for Injection

ranibizumab

ADULTS

This medicinal product is subject to additional monitoring, which will allow quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

Read all of 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 further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Ximluci and what is it used for
2. What you need to know before you are given Ximluci
3. How Ximluci is given
4. Possible side effects
5. Storage of Ximluci

Contents of the pack and further information

1. What is Ximluci and what is it used for

What is Ximluci

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

What Ximluci is used for

Ximluci is used in adults to treat several eye diseases that cause vision impairment.

These diseases are the result of damage to the retina (the light-sensitive layer at the back of the eye) caused by:

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

How Ximluci works

Ximluci recognizes and binds specifically to a protein called vascular endothelial growth factor A (VEGF-A) present in the eyes. In excess, VEGF-A causes the growth of abnormal blood vessels and swelling in the eye that can cause vision impairment in diseases such as AMD, DME, PDR, RVO, PM, and CNV. By binding to VEGF-A, Ximluci can prevent it from working and prevent such abnormal growth and swelling.

In these diseases, Ximluci can help stabilize and, in many cases, improve your vision.

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

Ximluci must not be given to you

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

Warnings and precautions

Talk to your doctor before you are given Ximluci

• Ximluci is given by injection into the eye. Occasionally, after treatment with Ximluci, an infection in the inner eye, pain, or redness (inflammation), detachment, or tear of a layer in the back of the eye (retinal detachment and retinal pigment epithelial tear), or clouding of the lens (cataract) may occur. It is important to identify and treat such an infection or retinal detachment as soon as possible. Tell your doctor immediately if you notice signs such as eye pain or increased discomfort in the eye, if the redness in the eye gets worse, blurred vision, or decreased vision, an increase in the number of small spots in your vision, or increased sensitivity to light.
• In some patients, after the injection, the pressure in the eye may increase for a short period. You may not be aware of this, so your doctor may monitor your eye pressure after each injection.
• Tell your doctor if you have had eye diseases or have received any treatment in the eyes before, or if you have had a stroke or have had transient stroke-like symptoms (weakness or paralysis of a limb or face, difficulty speaking or understanding). This information will be taken into account to assess whether Ximluci is the right treatment for you.

For more detailed information on the side effects that may occur during treatment with Ximluci, see section 4 ("Possible side effects").

Children and adolescents (under 18 years)

Ximluci is not recommended for use in children and adolescents, as it has not been established in these age groups.

Other medicines and Ximluci

Tell your doctor if you are using, have recently used, or might use any other medicines.

Pregnancy and breastfeeding

• Women who may become pregnant should 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 should not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant, think you may be pregnant, or plan to become pregnant, talk to your doctor before treatment with Ximluci.
• Ximluci should not be used during breastfeeding, as it is unknown whether Ximluci passes into breast milk. Talk to your doctor or pharmacist before treatment with Ximluci.

Driving and using machines

After treatment with Ximluci, you may experience temporary blurred vision. If this happens, do not drive or use machines until this symptom disappears.

3. How Ximluci is given

Ximluci is given by an ophthalmologist as a single injection into the eye under local anesthesia. The usual dose of an injection is 0.05 ml (which contains 0.5 mg of active substance). The interval between two doses given in the same eye should be at least four weeks. All injections will be given by an ophthalmologist.

To prevent infection, before the injection, your doctor will carefully clean your eye. Your doctor will also give you a local anesthetic to reduce or prevent any pain you may feel with the injection.

Treatment is started with an injection of Ximluci every month. Your doctor will monitor the disease in your eye and, depending on how you respond to treatment, will decide whether you need further treatment and when you need to be treated.

At the end of the leaflet, in the section "How to prepare and administer Lucentis in adults", detailed instructions for use are given.

Elderly patients (65 years and older)

Ximluci can be used in people 65 years of age or older, and no dose adjustment is necessary.

Before stopping treatment with Ximluci

If you are considering stopping treatment with Ximluci, go to your next appointment and discuss it with your doctor beforehand. Your doctor will advise you and decide how long you should be treated with Ximluci.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects associated with the use of Ximluci are either due to the medicine itself or the injection procedure, and most affect the eye.

Serious side effects:

Common(may affect up to 1 in 10 people)

• detachment or tear of a layer in the inner eye (retinal detachment), which results in flashes of light with floating particles progressing to transient 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 of the inner eye

The symptoms you may experience are:

• eye pain or increased discomfort in the eye
• worsening of redness in the eye
• blurred vision or decreased vision
• an increase in the number of small spots in your vision
• increased sensitivity to light

Tell your doctor immediately if you experience any of these side effects.

Other side effects:

Very common(may affect more than 1 in 10 people)

Ocular side effects include

• eye inflammation
• bleeding in the back of the eye (retinal hemorrhage)
• visual disturbances
• eye pain
• small particles or spots in the vision (floaters)
• blood in the eye
• eye irritation
• feeling of having something in the eye
• increased tear production
• inflammation or infection of the eyelid margin
• dry eye
• redness or itching of the eye
• increased pressure in the eye

Non-ocular side effects include

• sore throat, nasal congestion, runny nose
• headache
• joint pain

Common(may affect up to 1 in 10 people)

Ocular side effects include

• decreased sharpness of vision
• swelling of a section of the eye (uvea, cornea)
• inflammation of the cornea (front part of the eye)
• small marks on the surface of the eye
• blurred vision
• bleeding at the injection site
• bleeding in the eye
• eye discharge with itching, redness, and swelling (conjunctivitis)
• sensitivity to light
• eye discomfort
• eyelid swelling
• eyelid pain

Non-ocular side effects include

• urinary tract infection
• low red blood cell count (with symptoms such as tiredness, difficulty breathing, dizziness, paleness)
• anxiety
• cough
• nausea, allergic reactions such as rash, hives, itching, and redness of the skin

Uncommon(may affect up to 1 in 100 people)

Ocular side effects include

• inflammation and bleeding in the front part of the eye
• pus accumulation 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

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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. The expiry date is the last day of the month stated.
• Store in a refrigerator (2°C - 8°C). Do not freeze.
• Before use, the unopened vial can be stored at room temperature (25°C) for a maximum of 48 hours.
• Keep the vial in the outer packaging to protect it from light.
• Do not use any packaging that is damaged.

6. Package Contents and Additional Information

Ximluci Composition

• The active ingredient 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 usable amount to deliver a single dose of 0.05 ml, which contains 0.5 mg of ranibizumab.
• The other components are trehalose dihydrate; histidine hydrochloride monohydrate; histidine; polysorbate 20; water for injectables.

Product Appearance and Package Contents

Ximluci is a clear to slightly opalescent, colorless to slightly brownish injectable solution contained in a vial (0.23 ml).

There are two types of packaging available:

Package with vial only

Package containing a glass vial with ranibizumab, with a bromobutyl rubber stopper. The vial is for single use.

Package with vial and needle with filter

Package containing a glass vial with ranibizumab, with a bromobutyl rubber stopper and a sterile, blunt needle with a 5 µm filter (18G x 1½″, 1.2 mm x 40 mm) for extracting the vial contents.

All components are for single use.

Marketing Authorization 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 authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

THIS INFORMATION IS INTENDED ONLY FOR HEALTHCARE PROFESSIONALS:

See also section 3 “How to administer Ximluci”.

How to Prepare and Administer Ximluci in Adults

Single-use vial. For intravitreal use only.

Ximluci should be administered by an ophthalmologist experienced in administering intravitreal injections.

In exudative age-related macular degeneration (AMD), choroidal neovascularization (CNV), retinal pigment epithelial detachment (RPED), and visual impairment due to diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion (RVO), the recommended dose of Ximluci is 0.5 mg administered as a single intravitreal injection. This corresponds to an injection volume of 0.05 ml. The interval between two doses injected into 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, i.e., no change in visual acuity or other signs and symptoms of the disease under continued treatment. In patients with exudative AMD, DME, RPED, and RVO, three or more consecutive monthly injections may initially be necessary.

From that point on, monitoring and treatment intervals should be determined based on medical judgment and the activity of the disease, assessed by visual acuity and/or anatomical parameters.

Treatment with Ximluci should be discontinued if, in the physician's judgment, visual and anatomical parameters indicate that the patient is not benefiting from continued treatment.

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

If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is achieved and/or there are no signs of disease activity, treatment intervals can be gradually extended until signs of disease activity or visual impairment recur. For exudative AMD, the treatment interval should not be extended by more than two weeks at a time, and for DME, it can be extended up to one month at a time. For RPED and RVO, treatment intervals can also be gradually extended; however, available data are insufficient to determine the duration of these intervals. If disease activity recurs, the treatment interval should be shortened accordingly.

Treatment of visual impairment due to CNV should be determined on an individual basis 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, including monthly injections. In the case of CNV secondary to pathologic myopia (PM), many patients may require only one or two injections during the first year.

Ximluci and Laser Photocoagulation in DME and Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)

There is some experience with Ximluci administered concomitantly with laser photocoagulation. When administered on the same day, Ximluci should be administered at least 30 minutes after laser photocoagulation. Ximluci can be administered in patients who have received prior laser photocoagulation.

Ximluci and Photodynamic Therapy with Verteporfin in CNV Secondary to Pathologic Myopia

There is no experience with the concomitant administration of Ximluci and verteporfin.

Before administering Ximluci, visually inspect for particulate matter and discoloration.

The injection procedure should be carried out under aseptic conditions, including surgical hand washing, use of sterile gloves, a sterile field, a sterile blepharostat (or equivalent), and the availability of a sterile paracentesis (if necessary). Before performing the intravitreal injection procedure, the patient's medical history should be thoroughly evaluated for hypersensitivity reactions. Before injection, adequate anesthesia and a broad-spectrum topical microbicide should be administered to disinfect the periocular skin, eyelid, and ocular surface, according to local practice.

Package with vial only

The vial is for single use. After injection, any unused product should be discarded. Do not use any vial that shows signs of damage or tampering. Sterility can only be guaranteed if the package seal remains intact.

For preparation and intravitreal injection, the following medical devices (for single use) are required:

• a sterile needle with a 5 µm filter (18G x 1½″, 1.2 mm x 40 mm)
• a sterile 1 ml syringe (including a 0.05 ml mark)
• a sterile injection needle (30G x ½″, 0.3 mm x 13 mm).

These medical devices are not included in the Ximluci package.

Package with vial and needle with filter

All components are sterile and for single use. Do not use any component whose package shows signs of damage or tampering. Sterility can only be guaranteed if the package seal of the components remains intact. Reuse may lead to infection or other disease/injury.

For preparation and intravitreal injection, the following medical devices (for single use) are required:

• a sterile needle with a 5 µm filter (18G x 1½″, 1.2 mm x 40 mm, supplied)
• a sterile 1 ml syringe (including a 0.05 ml mark, not included in the Ximluci package)
• a sterile injection needle (30G x ½″, 0.3 mm x 13 mm, not included in the Ximluci package)

To prepare Ximluci for intravitreal administration in adult patients, follow these instructions:

The injection needle should be inserted 3.5-4.0 mm behind the limbus into the vitreous cavity, avoiding the horizontal meridian and aiming towards the center of the globe. The injection volume of 0.05 ml should then be delivered; subsequent injections should be administered at a different scleral location each time.

After injection, do not cover the needle with the needle cap or separate it from the syringe. Dispose of the used syringe and needle in a puncture-resistant container or dispose of according to local regulations.