Prospect: information for the patient

Rimmyrah 10 mg/ml injectable solution

ranibizumab

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You may 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 have 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.

What is Rimmyrah

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

How is Rimmyrah used

Rimmyrah 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 may 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 Rimmyrah works

Rimmyrah 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, Rimmyrah can prevent it from acting and prevent said abnormal growth and swelling.

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

Do not administer Rimmyrah

• 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 it.
• If you have eye pain or redness (severe intraocular inflammation) in the eye.

Warnings and precautions

Consult your doctor before Rimmyrah is administered to you.

• Rimmyrah is administered by an injection into the eye. Occasionally, after treatment with Rimmyrah, 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 it, so your doctor may monitor your eye pressure after each injection.
• Inform your doctor if you have had eye diseases or received any eye treatment previously, or if you have had a stroke or 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 if Rimmyrah is the appropriate treatment for you.

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

Children and adolescents (under 18 years of age)

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

Other medications and Rimmyrah

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

Driving and operating machinery

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

Rimmyrah 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 ranibizumab). 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 Rimmyrah 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, detailed instructions for use are given.

Patients aged 65 and over

Rimmyrah can be used in people aged 65 and over, and no dose adjustment is necessary.

Before interrupting treatment with Rimmyrah

If you are considering interrupting treatment with Rimmyrah, 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 Rimmyrah.

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

The following are the most serious side effects:

Common serious side effects(may affect up to 1 in 10 people):

• 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 a cloudy cornea (cataract).

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

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

The symptoms you may experience are eye pain or increased discomfort, if the redness in the eye worsens, blurry vision or decreased vision, an increase in 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 common side effects(may affect more than 1 in 10 people)

Eye-related 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,
• 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 eye pressure.

Non-eye-related side effects include:

• Sore throat,
• Stuffy nose,
• Nasal discharge,
• Headache,
• Joint pain.

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

Common side effects(may affect up to 1 in 10 people)

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),
• Sensitivity to light,
• Eye discomfort,
• Swelling of the eyelid,
• Pain in the eyelid.

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.

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

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 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 Rimmyrah

• 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 an adequate 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 (E432), water for injectable preparations.

Aspect of the product and content of the packaging

Rimmyrah is an injectable solution contained in a vial (0.23 ml). The solution is transparent to slightly opalescent, colorless to brownish and aqueous.

Two types of packaging are available:

Package only with vial

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

Package with vial + needle with filter

Package that contains a glass vial with ranibizumab, with a chlorobutyl rubber stopper and a blunt needle with filter (18G x 1½ inches, 1.2 mm x 40 mm, 5 micrometers) to extract the contents of the vial. All components are for single use.

Marketing Authorization Holder

QILU PHARMA SPAIN S.L.

Paseo de la Castellana 40, 8th floor

28046 Madrid

Spain

Responsible for manufacturing

KYMOS, S.L.

Ronda De Can Fatjo 7 B

Parc Tecnologic Del Valles

Cerdanyola Del Valles

Barcelona

08290

Spain

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet:

Other sources of information

The detailed information on 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 Rimmyrah”.

Single-use vial. Only for intravitreal use.

Rimmyrah should be administered by an ophthalmologist with experience in administering intravitreal injections.

In exudative macular degeneration, in neovascular glaucoma, in retinal detachment and in visual alteration due to EMD or secondary macular edema to OVR, the recommended dose of Rimmyrah 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 no signs of disease activity are present, 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 necessary, administered monthly.

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

Treatment with Rimmyrah 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 no signs of disease activity are present, treatment intervals may be gradually spaced until signs of disease activity or visual alteration reappear. In the case of exudative macular degeneration, treatment intervals should not be spaced more than two weeks at a time, and in the case of EMD, treatment intervals may be spaced up to one month at a time. For retinal detachment and OVR, treatment intervals may also be gradually spaced, but data are not sufficient to determine the duration of these intervals. If disease activity reappears, treatment intervals should be consecutively shortened.

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

Ranibizumab 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, ranibizumab should be administered at least 30 minutes after laser photocoagulation. Ranibizumab may be administered in patients who have previously received laser photocoagulation.

Ranibizumab and verteporfin photodynamic therapy in neovascular glaucoma secondary to MP

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

Before administering Rimmyrah, the medication should be visually checked to ensure the absence of particles, discoloration or alteration. If particles, discoloration or alteration are observed, the vial should be discarded according to local waste disposal regulations.

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 (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, according to local practice.

Package only with vial

The vial is for single use. Any unused product remaining after injection should be discarded. No vial that shows signs of deterioration or manipulation should 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 5 µm filter needle (18G x 1½ inches, 1.2 mm x 40 mm)
• a 1 ml sterile syringe (including a 0.05 ml mark)
• a 30G x ½ inch injection needle. These medical devices are not included in the Rimmyrah package.

Package with vial + needle with filter

All components are sterile and for single use. No component whose packaging shows signs of deterioration or manipulation should 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 5 µm filter needle (18G x 1½ inches, 1.2 mm x 40 mm, supplied)
• a 1 ml sterile syringe (including a 0.05 ml mark, not included with the Rimmyrah package)
• a 30G x ½ inch injection needle (not included with the Rimmyrah package)

To prepare Rimmyrah for intravitreal administration in adult patients, follow the instructions below:

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered medication should be clearly recorded.

The injection needle should be inserted 3.5 to 4.0 mm behind the limbus in the vitreous cavity, avoiding the horizontal meridian and in the direction of the center of the globe. The volume of injection of 0.05 ml should then be released. A different location on the sclera should be used for subsequent injections.

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