Ximluci 10 mg/ml solution for injection

Package Leaflet: Information for the User

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 rapid identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read this entire leaflet carefully before you are administered this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

Pack contents and other information

1. What Ximluci is and what it is used for

What Ximluci is

Ximluci is a solution that is injected into the eye. Ximluci belongs to a group of medicines known as 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 result from 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 occurs in conditions 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 pathological myopia (PM), angioid streaks, central serous chorioretinopathy, or inflammatory CNV.
• Macular edema (swelling in the center of the retina). The cause of this swelling may be diabetes (a condition known as diabetic macular edema (DME)) or blockage of the retinal veins (a disease known as retinal vein occlusion (RVO)).

How Ximluci works

Ximluci specifically recognizes and binds to a protein called human vascular endothelial growth factor A (VEGF-A) present in the eyes. Excess VEGF-A causes the growth of abnormal blood vessels and swelling in the eye, which can lead to vision impairment in diseases such as AMD, DME, PDR, RVO, PM, and CNV. By binding to VEGF-A, Ximluci prevents it from acting and thereby inhibits abnormal vessel growth and swelling.

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

2. What you need to know before Ximluci is administered to you

Do not administer Ximluci

• If you are allergic to ranibizumab or to any of the other components 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 Ximluci is administered to you

• Ximluci is administered by injection into the eye. Occasionally, after treatment with Ximluci, an infection inside the eye may occur, along with 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). It is important to identify and treat such infection or retinal detachment as early as possible. Immediately inform your doctor if you notice symptoms such as eye pain or increased discomfort in the eye, worsening redness of the eye, blurred vision or loss of vision, an increase in the number of small floating spots in your vision, or increased sensitivity to light.
• In some patients, eye pressure may increase for a short period of time after the injection. You may not notice this, so your doctor may monitor your eye pressure after each injection.
• Inform your doctor if you have had eye diseases or previous eye treatments, or if you have had a stroke or transient signs of stroke (such as weakness or paralysis of a limb or face, difficulty speaking or understanding speech). This information will be considered when evaluating whether Ximluci is the appropriate treatment for you.

For more detailed information on adverse reactions that could occur during treatment with Ximluci, see section 4 (“Possible side effects”).

Children and adolescents (under 18 years of age)

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

Other medicines and Ximluci

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

• Women who could become pregnant 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 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, consult your doctor before treatment with Ximluci.
• The use of Ximluci during breastfeeding is not recommended, as it is unknown whether Ximluci passes into breast milk. Consult your doctor or pharmacist before treatment with Ximluci.

Driving and use of machines

After treatment with Ximluci, you may experience temporary blurred vision. If this occurs, do not drive or operate machinery until this symptom has resolved.

3. How Ximluci is administered

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

To prevent infection, your doctor will carefully wash your eye before the injection. Your doctor will also administer a local anesthetic to reduce or prevent any pain you might feel during the injection.

Treatment starts with a monthly injection of Ximluci. Your doctor will monitor your eye disease and, depending on your response to treatment, will decide whether you need further treatment and when it should be given.

Detailed instructions for use are provided at the end of the leaflet in the section "How to prepare and administer Lucentis in adults".

Elderly patients (aged 65 years and older)

Ximluci can be used in individuals aged 65 years or older, and no dose adjustment is necessary.

Before stopping treatment with Ximluci

If you are considering stopping treatment with Ximluci, please attend your next scheduled appointment and discuss this with your doctor beforehand. Your doctor will provide advice and determine how long you should continue treatment with Ximluci.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

Serious adverse effects:

Frequent (may affect up to 1 in 10 patients)

• detachment or tear of a layer in the inner part of the eye (retinal detachment or tear), resulting 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 patients)

• blindness,
• infection of the eyeball (endophthalmitis) with inflammation of the inner part of the eye

Symptoms you may experience include:

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

Contact your doctor immediately if you experience any of these adverse effects.

Other adverse effects:

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

Ocular adverse effects include

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

Non-ocular adverse effects include

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

Frequent (may affect up to 1 in 10 patients)

Ocular adverse effects include

• decreased visual acuity
• swelling of a part of the eye (uvea, cornea)
• corneal inflammation (front part of the eye)
• small marks 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-ocular adverse effects include

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

Uncommon (may affect up to 1 in 100 patients)

Ocular adverse effects include

• inflammation and bleeding in the front part of the eye
• accumulation 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 adverse effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2°C and 8°C). Do not freeze.
• Before use, the unopened vial may be stored at room temperature (25°C) for up to 48 hours.
• Keep the vial in the outer packaging to protect it from light.
• Do not use any container that is damaged.

6. Contents of the pack and other information

Composition of Ximluci

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

Appearance of the product and contents of the pack

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

Two different types of packaging are available:

Pack with vial only

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

Pack with vial + filter needle

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

All components are for single use.

Marketing Authorization Holder and Manufacturer

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

You can request further information about this medicinal product by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

Other sources of information

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

THIS INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY:

See also section 3 “How Ximluci is administered”.

How to prepare and administer Ximluci in adults

Single-use vial. For intravitreal use only.

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

In neovascular (wet) age-related macular degeneration (AMD), choroidal neovascularisation (CNV), retinal vein occlusion (RVO), and visual impairment due to diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion, 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 injections administered 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, i.e., no change in visual acuity or other signs and symptoms of the disease under continued treatment. In patients with neovascular AMD, DME, RVO, and macular edema secondary to branch retinal vein occlusion (BRVO), initially three or more consecutive monthly injections may be required.

Thereafter, monitoring and treatment intervals should be determined at the physician’s discretion based on disease activity, 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 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 may be gradually extended until signs of disease activity or visual impairment reappear. In the case of neovascular AMD, treatment intervals should not be extended by more than two weeks at a time; in DME, intervals may be extended by up to one month at a time. For RVO and BRVO, treatment intervals may also be gradually extended; however, available data are insufficient to determine the optimal duration of these intervals. If disease activity reappears, treatment intervals should be shortened accordingly.

Treatment of visual impairment due to CNV should be individualized 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 pathological 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 concomitant administration of Ximluci and laser photocoagulation. When administered on the same day, Ximluci should be given at least 30 minutes after laser photocoagulation. Ximluci may be administered in patients who have previously received laser photocoagulation.

Ximluci and photodynamic therapy with verteporfin in CNV secondary to PM

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

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

The injection procedure should be performed under aseptic conditions, including surgical hand washing, use of sterile gloves, a sterile field, a sterile eyelid speculum (or equivalent), and availability of sterile paracentesis equipment (if needed). Prior to the intravitreal injection procedure, the patient’s medical history should be carefully evaluated for hypersensitivity reactions. Prior to injection, appropriate anesthesia and a broad-spectrum topical microbicide should be administered to disinfect the periocular skin, eyelids, and ocular surface, in accordance with local practice.

Vial-only pack

The vial is for single use only. Any unused product remaining after injection must be discarded. Do not use any vial showing signs of damage or tampering. Sterility can only be guaranteed if the container’s seal remains intact.

The following sterile medical devices (for single use) are required for preparation and intravitreal injection:

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

These medical devices are not included in the Ximluci pack.

Vial + filter needle pack

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

The following sterile medical devices (for single use) are required for preparation and intravitreal injection:

• a sterile 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, supplied)
• a sterile 1 ml syringe (with a 0.05 ml mark, 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 administration in adult patients, follow the instructions below:

The injection needle should be inserted 3.5–4.0 mm behind the limbus into the vitreous cavity, avoiding the horizontal meridian and directed toward the center of the globe. Subsequently, release the injection volume of 0.05 ml; subsequent injections should each be administered at a different scleral site.

After injection, do not cover the needle with the closure cap or detach it from the syringe. Dispose of the used syringe together with the needle in a sharps container or according to local regulations.