Prospect: information for the patient

Ximluci 10 mg/ml injectable solution

ranibizumab

ADULTS

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before you are administered this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are adverse effects that do not appear in this prospect. See section 4.

Contents of the package and additional information

What is Ximluci

Ximluci is a solution that is injected into the eye. Ximluci belongs to a group of medications known as anti-neovascularization agents. It contains the active ingredient called ranibizumab.

How is Ximluci used

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

These diseases are the result of a lesion in the retina (the light-sensitive layer at the back of the eye) caused by:

• The growth of abnormal blood vessels, which 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 can also be associated with coroidal neovascularization (CNV) due to pathological myopia (PM), angioid streaks, central serous chorioretinopathy or inflammatory CNV.
• Macular edema (swelling of the center of the retina). The cause of this swelling can be diabetes (a disease known as diabetic macular edema (DME)) or blockage of the retinal veins in the retina (a disease known as retinal vein occlusion (RVO)).

How Ximluci works

Ximluci recognizes and specifically binds to a protein called vascular endothelial growth factor A (VEGF-A) human 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 acting and prevent said abnormal growth and swelling.

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

Do not administer Ximluci

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

Warnings and precautions

Consult your doctor before Ximluci is administered to you.

• Ximluci is administered by an injection into the eye. Occasionally, after treatment with Ximluci, an infection in the inner part of the eye, eye pain, or redness (inflammation), retinal detachment or tear, or clouding of the lens (cataract) may appear. It is essential to identify and treat such an infection or retinal detachment as soon as possible. Inform your doctor immediately if you notice signs such as eye pain or increased eye discomfort, worsening eye redness, blurry vision or decreased vision, an increase in small spots in your vision or increased sensitivity to light.
• In some patients, the pressure in the eye may increase temporarily after the injection. It is possible that you may not be aware of this, so your doctor may monitor your eye pressure after each injection.
• Inform your doctor if you have had eye diseases or have received any eye treatment previously, or if you have had a stroke or have had transient signs of a stroke (weakness or paralysis of a limb or face, difficulty speaking or understanding). This information will be taken into consideration to evaluate if Ximluci is the appropriate treatment for you.

To consult more detailed information about the adverse effects that may occur during treatment with Ximluci, see section 4 ("Possible adverse 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 medications and Ximluci

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Pregnancy and breastfeeding

• Women who may become pregnant should use an effective contraceptive method during treatment and for at least three months after the last Ximluci injection.
• 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 intend to become pregnant, consult your doctor before treatment with Ximluci.
• Ximluci is not recommended during breastfeeding, as it is unknown if Ximluci passes into breast milk. Consult your doctor or pharmacist before treatment with Ximluci.

Driving and operating machinery

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

Ximluci is administered by an ophthalmologist in the form of 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 ingredient). The interval between two doses applied in the same eye must be at least four weeks. All injections will be administered by an ophthalmologist.

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

Treatment begins with a Ximluci injection every month. Your doctor will monitor the disease in your eye and, depending on how you respond to treatment, will decide if you need or do not need further treatment and when you need to be treated.

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

Patients aged 65 and over

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

Before interrupting treatment with Ximluci

If you are considering interrupting treatment with Ximluci, attend the next consultation and discuss it with your doctor beforehand. Your doctor will advise you and decide for how long you should be treated with Ximluci.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

Severe side 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), resulting in flashes of light with floating particles that progress to transient vision loss or to a clouding of the lens (cataract)

Infrequent(may affect up to 1 in 100 patients)

• Blindness,
• Infection of the eyeball (endophthalmitis) with inflammation of the inner part of the eye

You may experience the following symptoms:

• Pain or increase in discomfort in the eye
• Worsening of redness in the eye
• Blurred vision or decreased vision
• An increase in the number of small spots in vision
• Increased sensitivity to light

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

Other side effects:

Frequent(may affect more than 1 in 10 patients)

The eye-related side effects include

• Inflammation of the eye
• Bleeding in the back of the eye (retinal hemorrhage)
• Visual disturbances
• Pain in the eye
• Small particles or spots in vision (floaters)
• Blood in the eye
• Irritation of the eye
• Sensation of having something in the eye
• Increased tear production
• Inflammation or infection at the edge of the eyelids
• Dry eye
• Redness or itching in the eye
• Increased pressure in the eye

The non-eye-related side effects include

• Sore throat, nasal congestion, nasal discharge
• Headache
• Joint pain

Frequent(may affect up to 1 in 10 patients)

The eye-related side effects include

• Decreased visual acuity
• 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
• Discharge from the eye with itching, redness, and swelling (conjunctivitis)
• Sensitivity to light
• Discomfort in the eye
• Swelling of the eyelid
• Pain in the eyelid

The non-eye-related side 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, itching, and skin redness

Infrequent(may affect up to 1 in 100 patients)

The eye-related side 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
• Irritation of the eyelid

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and on the vial label after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C). Do not freeze.
• Before use, the unopened vial can be stored at room temperature (25°C) for a maximum of 48 hours.
• Store the vial in the outer packaging to protect it from light.
• Do not use any damaged container.

Composition of Ximluci

• The active principle 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 provide a single dose of 0.05 ml, which contains 0.5 mg of ranibizumab.
• The other components are trehalose dihydrate; hydrochloride of histidine monohydrate; histidine; polisorbate 20; water for injections.

Appearance of the product and contents of the pack

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

Two types of packaging are available:

Single vial pack

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

Vial + needle with filter pack

Pack 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 responsible manufacturer

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

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

THIS INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY:

See also section 3 “How to administer Ximluci”.

How to prepare and administer Ximluci in adults

Single-use vial. Only for intravitreal use.

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

In the exudative macular degeneration, in the neovascular glaucoma, in the retinal detachment and in the visual alteration due to EMD or secondary macular edema to OVR, the recommended dose of Ximluci is 0.5 mg administered as a single intravitreal injection. This corresponds to a volume of injection of 0.05 ml. The interval between two injections in the same eye should be at least four weeks.

Treatment should start with a monthly injection until maximum visual acuity is reached 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 macular degeneration, EMD, retinal detachment and OVR, initially three or more consecutive injections may be required, administered monthly.

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

Treatment with Ximluci should be discontinued if, under medical 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 control 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 has been reached and/or there are no signs of disease activity, treatment intervals may be gradually extended until signs of disease activity or visual alteration reappear. In the case of exudative macular degeneration, treatment intervals should not be extended by more than two weeks at a time, and in the case of EMD, treatment intervals may be extended up to one month at a time. For retinal detachment and OVR, treatment intervals may also be gradually extended, but data are insufficient to determine the duration of these intervals. If disease activity reappears, treatment intervals should be shortened accordingly.

Treatment of visual alteration due to NVC should be determined on an individual basis for each patient, based on disease activity. Some patients may only require one injection in the first 12 months; others may require more frequent treatment, including monthly injections. In the case of NVC secondary to pathological myopia (MP), many patients may only require one or two injections in the first year.

Ximluci and laser photocoagulation in EMD and secondary macular edema to retinal vein occlusion (ORVR)

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 may be administered in patients who have previously received laser photocoagulation.

Ximluci and verteporfin photodynamic therapy in NVC secondary to MP

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

Before administering Ximluci, the absence of particles and discoloration should be visually checked.

The injection procedure should be carried out under aseptic conditions, including surgical hand washing, the use of sterile gloves, a sterile field, a sterile eyelid retractor (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, an adequate anesthetic and a broad-spectrum topical antimicrobial should be administered to disinfect the periocular skin, eyelid, and ocular surface, in accordance with local practice.

Single vial pack

The vial is for single use. Any unused product remaining after injection should be discarded. Any vial showing signs of deterioration or manipulation should not be used. Sterility can only be guaranteed if the packaging seal remains intact.

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

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

These medical devices are not included in the Ximluci packaging.

Vial + needle with filter pack

All components are sterile and for single use. Any component showing signs of deterioration or manipulation should not be used. Sterility can only be guaranteed if the packaging seal remains intact. Reuse may lead to infection or other disease/lesion.

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

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

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 in the vitreous cavity, avoiding the horizontal meridian and directed towards the center of the globe. Subsequently, the 0.05 ml injection volume should be released; subsequent injections should be applied each time in a different scleral point.

After injection, do not cap the needle with the closure cap or separate it from the syringe. Remove the used syringe along with the needle in a sharp object container or according to local regulations.