Ranivisio 10 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the adult patient

Ranivisio 10 mg/ml solution for injection

ranibizumab

This medicinal product is subject to additional monitoring, which will allow quicker detection of new safety information. You can help by reporting any side effects you may experience. See the end of section 4 for information on how to report side effects.

ADULTS

Read this entire leaflet carefully before you are administered this medicine, because 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.

Contents of this leaflet

1. What Ranivisio is and what it is used for
2. What you need to know before you are administered Ranivisio
3. How Ranivisio is administered
4. Possible side effects
5. How to store Ranivisio
6. Contents of the pack and other information

1. What Ranivisio is and what it is used for

What Ranivisio is

Ranivisio is a solution that is injected into the eye. Ranivisio belongs to a group of medicines called antineovascularization agents. It contains the active substance known as ranibizumab.

What Ranivisio is used for

Ranivisio 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 of 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 Ranivisio works

Ranivisio specifically recognizes and 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, which can lead to vision impairment in diseases such as AMD, DME, PDR, RVO, PM, and CNV.

By binding to VEGF-A, Ranivisio can block its activity and prevent this abnormal growth and swelling.

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

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

Do not administer Ranivisio if:

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

Warnings and precautions

Talk to your doctor before receiving Ranivisio.

• Ranivisio is administered by injection into the eye. Occasionally, after treatment with Ranivisio, 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 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 decreased 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 intraocular 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 (weakness or paralysis of a limb or face, difficulty speaking or understanding). This information will be considered when evaluating whether Ranivisio is the appropriate treatment for you.

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

Children and adolescents (under 18 years of age)

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

Other medicines and Ranivisio

Inform 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 Ranivisio.
• There is no experience with the use of Ranivisio in pregnant women. Ranivisio should not be used during pregnancy unless the potential benefit justifies 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 Ranivisio.
• Small amounts of Ranivisio may pass into breast milk; therefore, use of Ranivisio during breastfeeding is not recommended. Consult your doctor or pharmacist before treatment with Ranivisio.

Driving and using machines

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

3. How Ranivisio is administered

Ranivisio is administered by an ophthalmologist as a single injection into the eye under local anaesthesia. 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 given by an ophthalmologist.

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

Treatment starts with a monthly Ranivisio injection. Your doctor will monitor the eye condition and, depending on how it responds 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 Ranivisio”.

Elderly patients (aged 65 years and older)

Ranivisio can be used in patients aged 65 years and older, and dose adjustment is not required.

Before stopping treatment with Ranivisio

If you are considering stopping treatment with Ranivisio, attend your next appointment and discuss this with your doctor beforehand. Your doctor will advise you and decide for how long you should continue treatment with Ranivisio.

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 will experience them.

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

Below are the most serious adverse effects:

Frequent serious adverse effects (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 serious adverse effects (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 your vision, or increased sensitivity to light. Inform your doctor immediately if you experience any of these adverse effects.

Below are the most commonly reported adverse effects:

Very common adverse effects (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, eyelid margin inflammation or infection, dry eye, eye redness or itching, and increased eye pressure.

Non-ocular adverse effects include: Sore throat, nasal congestion, runny nose, headache, and joint pain.

Below are other adverse effects that may occur after treatment with Ranivisio:

Common adverse effects

Ocular adverse effects include: Decreased visual sharpness, swelling of a section 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, hives, itching, and skin redness.

Uncommon adverse effects

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 may 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 Ranivisio

• 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 after EXP 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 24 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 Ranivisio

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

Appearance of the product and contents of the pack

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

One type of pack is available:

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

Marketing Authorization Holder and Manufacturer

Midas Pharma GmbH
Rheinstraße 49
D-55218 Ingelheim
Germany

For further information about this medicinal product, please contact 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 Ranivisio is administered”.

How to prepare and administer Ranivisio in adults

Single-use vial. For intravitreal use only.

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

In neovascular (wet) age-related macular degeneration (AMD), in myopic choroidal neovascularisation (mCNV), in diabetic macular oedema (DME) and in visual impairment due to macular oedema secondary to retinal vein occlusion (RVO), the recommended dose of Ranivisio 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 into 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, diabetic retinopathy (DR) and RVO, initially three or more consecutive monthly injections may be required.

Thereafter, monitoring and treatment intervals should be determined according to medical judgment and based on disease activity, assessed by visual acuity and/or anatomical parameters.

Treatment with Ranivisio should be discontinued if, according to 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 deterioration reappear. In the case of neovascular AMD, treatment intervals should not be extended by more than two weeks at a time; in the case of DME, intervals may be extended by up to one month at a time. For DR and RVO, treatment intervals may also be gradually extended; however, available data are insufficient to determine the optimal duration of these intervals. If disease activity reappears, the treatment interval should be shortened accordingly.

Treatment for visual impairment due to mCNV 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 mCNV secondary to pathological myopia (PM), many patients may require only one or two injections during the first year.

Ranivisio and laser photocoagulation in DME and macular oedema secondary to branch retinal vein occlusion (BRVO)

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

Ranivisio and photodynamic therapy with verteporfin in mCNV secondary to PM

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

Before administration, Ranivisio should be visually inspected for particulate matter and discoloration.

The injection procedure must 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 a sterile paracentesis blade (if needed). Prior to the intravitreal injection procedure, the patient’s medical history should be carefully evaluated for hypersensitivity reactions. Prior to injection, appropriate anaesthesia and a broad-spectrum topical microbicide should be administered to disinfect the skin of the periocular area, eyelids, and ocular surface, in accordance with local practice.

The vial is for single use only. After injection, any unused portion of the product 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 single-use medical devices are required for preparation and intravitreal injection:

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

These medical devices are not included in the Ranivisio packaging. They may be obtained separately or as part of independent intravitreal injection kits (e.g., the Vortex Surgical I2 injection kit).

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 into the vitreous cavity, avoiding the horizontal meridian and directed toward the center of the globe. The injection volume of 0.05 ml should then be administered; subsequent injections should each be administered at a different scleral site.

After injection, do not cap 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.