Patient Information Leaflet: Adult

Ranivisio 10 mg/ml Injectable Solution

ranibizumab

This medicine is subject to additional monitoring, which will speed up 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.

ADULTS

Read this leaflet carefully before you receive this medicine, as it contains important information for you.

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

1.What is Ranivisio and what is it used for

2.What you need to know before you receive Ranivisio

3.How to administer Ranivisio

4.Possible adverse effects

5.Storage of Ranivisio

6.Contents of the pack and additional information

What is Ranivisio

Ranivisio is a solution that is injected into the eye. Ranivisio belongs to a group of medications called anti-neovascular agents. It contains the active ingredient called ranibizumab.

What is Ranivisio used for

Ranivisio 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 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 can also be associated with choroidal 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 Ranivisio works

Ranivisio recognizes and specifically binds to a protein called human 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, Ranivisio can prevent it from acting and prevent said abnormal growth and swelling.

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

Do not administer Ranivisio

• 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 Ranivisio is administered.

• Ranivisio is administered by injection into the eye. Occasionally, after treatment with Ranivisio, 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 with speech or understanding). This information will be taken into consideration to evaluate whether Ranivisio is the appropriate treatment for you.

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

Children and adolescents (under 18 years)

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

Other medications and Ranivisio

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 injection of Ranivisio.
• There is no experience with the use of Ranivisio in pregnant women. Ranivisio 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 Ranivisio.
• Small amounts of Ranivisio may pass into breast milk, so Ranivisio is not recommended during breastfeeding. Consult your doctor or pharmacist before treatment with Ranivisio.

Driving and operating machinery

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

Ranivisio is administered by an ophthalmologist in the form of a single injection into the eye under local anesthesia. The usual dose of a single 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, 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 may feel with the injection.

Treatment begins with a monthly injection of Ranivisio. Your doctor will monitor the disease in your eye and, depending on how you respond to treatment, will decide whether 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 Ranivisio" detailed use instructions are given.

Patients aged 65 and over

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

Before interrupting treatment with Ranivisio

If you are considering interrupting treatment with Ranivisio, 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 Ranivisio.

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 Ranivisio are due either to the medicine itself or to the injection procedure, and most of them affect the eye.

The following are the most serious side effects:

Frequent serious side effects(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 clouding of the lens (cataract).

Rare serious side effects(may affect up to 1 in 100 patients)

Blindness, endophthalmitis (infection of the inner part of the eye) with inflammation of the inner part of the eye.

You may experience symptoms such as eye pain or increased discomfort, worsening of redness in the eye, blurry vision or decreased vision, an increase in the number of small spots in the vision or increased sensitivity to light.Inform your doctor immediately if you experience any of these side effects.

The following are the most frequently reported side effects:

Very frequent side effects(may affect more than 1 in 10 patients)

Eye-related side effects include: Inflammation of the eye, 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, 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, and increased eye pressure.

Non-eye-related side effects include: Sore throat, nasal congestion, nasal discharge, headache, and joint pain.

The following are other side effects that may occur after treatment with Ranivisio:

Frequent side effects

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, blurry vision, bleeding at the injection site, bleeding in the eye, eye discharge with itching, redness, and swelling (conjunctivitis), light sensitivity, eye discomfort, eyelid swelling, and eyelid pain.

Non-eye-related side effects include: Urinary tract infection, low red blood cell count (with symptoms such as fatigue, difficulty breathing, dizziness, pallor), anxiety, cough, nausea, allergic reactions such as rash, urticaria, itching, and skin redness.

Rare side effects

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, eyelid irritation.

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 on 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 after CAD and on the vial label after EXP. 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 24 hours.
• Store the vial in the outer packaging to protect it from light.
• Do not use any damaged container.

Composition of Ranivisio

• The active ingredient is ranibizumab. Each milliliter contains 10 mg of ranibizumab. Each vial contains 2.3 mg of ranibizumab in 0.23 ml of solution. This provides an adequate amount to provide a single dose of 0.05 ml, which contains 0.5 mg of ranibizumab.
• The other components are α,α-trehalosa dihydrate; hydrochloride of histidine monohydrate; histidine; polisorbate 20; water for injectable preparations.

Aspect of the product and content of the package

Ranivisio is an injectable solution contained in a vial (0.23 ml). The solution is transparent, colorless to pale yellow and aqueous.

There is a type of packaging available:

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

Holder of the marketing authorization and responsible for manufacturing

Midas Pharma GmbH

Rheinstraße 49

D-55218 Ingelheim

Germany

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu

---------------------------------------------------------------------------------------------------------------------------

THIS INFORMATION IS INTENDED ONLY FOR HEALTHCARE PROFESSIONALS:

See also section 3 “How to administer Ranivisio”.

How to prepare and administer Ranivisio in adults

Single-use vial. Only for intravitreal use.

Ranivisio should be administered by an ophthalmologist experienced in the administration of intravitreal injections.

In exudative macular degeneration, in NVC, in RDP and in visual alteration due to EMD or secondary macular edema to OVR, the recommended dose of Ranivisio 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 administered 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, RDP and OVR, initially three or more consecutive injections may be required, administered monthly.

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

Treatment with Ranivisio should be discontinued if, under medical judgment, the parameters of visual acuity and anatomy indicate that the patient is not benefiting from continued treatment.

Monitoring to determine the activity of the disease 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, the treatment intervals can be gradually spaced until signs of disease activity or visual alteration reappear. In the case of exudative macular degeneration, the treatment interval should not be spaced more than two weeks at a time, and in the case of EMD, it can be spaced up to one month at a time. For RDP and OVR, the treatment intervals can also be gradually spaced, but the data available are not sufficient to determine the duration of these intervals. If disease activity reappears, the treatment interval should be shortened accordingly.

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

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

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

Ranivisio and verteporfin photodynamic therapy in NVC secondary to MP

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

Before administering Ranivisio, 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 blepharostat for the eyelids (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 in terms of 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.

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

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

• a 5 µm filter needle (18G)
• a 1 ml sterile syringe (including a 0.05 ml mark)
• a 30G x ½″ injection needle.

These medical products are not included in the Ranivisio packaging. They can be obtained separately or in independent intravitreal injection kits (e.g. the I2 injection kit from Vortex Surgical).

To prepare Ranivisio 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 injection needle with the closure cap or separate it from the syringe. Remove the used syringe along with the injection needle in a sharp object container or according to local regulations.