Ranibizumab Midas

Package leaflet: Information for the adult patient

Ranibizumab Midas 10 mg/ml solution for injection

ranibizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
ADULTS
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What Ranibizumab Midas is and what it is used for
2. What you must know before you are given Ranibizumab Midas
3. How Ranibizumab Midas will be administered to you
4. Possible side effects
5. How to store Ranibizumab Midas
6. Contents of the pack and other information

1. What Ranibizumab Midas is and what it is used for

What Ranibizumab Midas is
Ranibizumab Midas is a solution to be injected into the eye. Ranibizumab Midas belongs to a group of medicines known as anti-angiogenic agents. It contains an active substance called ranibizumab.
What Ranibizumab Midas is used for
Ranibizumab Midas is used in adults to treat several eye conditions that cause vision loss.
These conditions arise from damage to the retina (the light-sensitive layer at the back of the eye) caused by:

• Abnormal blood vessel growth that leaks fluid. This occurs in conditions such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR, a condition caused by diabetes). It may also be associated with choroidal neovascularisation (CNV) due to pathological myopia (PM), angioid streaks, central serous chorioretinopathy, or inflammatory CNV.
• Macular oedema (swelling in the centre of the retina). This swelling may be caused by diabetes (a condition called diabetic macular oedema (DME)) or by blockage of the retinal veins (a condition called retinal venous occlusion (RVO)).

How Ranibizumab Midas works
Ranibizumab Midas specifically recognises and binds to a protein called human vascular endothelial growth factor A (VEGF-A) present in the eye. When present in excess, VEGF-A causes abnormal blood vessel growth and swelling in the eye, which can lead to vision loss in conditions such as AMD, DME, PDR, RVO, PM and CNV. By binding to VEGF-A, Ranibizumab Midas blocks its action and prevents abnormal blood vessel growth and swelling.
In these conditions, Ranibizumab Midas can help stabilise vision and, in many cases, improve it.

2. What you need to know before you are given Ranibizumab Midas

Do not receive Ranibizumab Midas

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

Warnings and precautions
Talk to your doctor before receiving Ranibizumab Midas.

• Ranibizumab Midas is administered by injection into the eye. Occasionally, after treatment with Ranibizumab Midas, 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 an infection or retinal detachment as soon as possible. Immediately inform your doctor if you experience symptoms such as eye pain or increased discomfort, worsening eye redness, blurred or decreased vision, an increase in floaters, or increased sensitivity to light.
• In some patients, eye pressure may temporarily increase shortly after the injection. This event may go unnoticed, therefore your doctor must perform a check-up after each injection.
• Inform your doctor if you have had previous eye problems or treatments, or if you have had a stroke or signs of transient ischaemic attacks (weakness or paralysis of limbs or face, difficulty speaking or understanding). This information will be considered when assessing whether Ranibizumab Midas is the appropriate treatment for you.

See section 4 ("Possible side effects") for more detailed information on side effects that may occur during treatment with Ranibizumab Midas.
Children and adolescents (under 18 years of age)
The use of Ranibizumab Midas in children and adolescents has not been established and is therefore not recommended.
Other medicines and Ranibizumab Midas
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding

• Women of childbearing age must use an effective method of contraception during treatment and for at least three months after the last injection of Ranibizumab Midas.
• There is no experience with the use of Ranibizumab Midas in pregnant women. Ranibizumab Midas must not be used during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, discuss this with your doctor before taking Ranibizumab Midas.
• Use of Ranibizumab Midas during breastfeeding is not recommended, as small amounts of Ranibizumab Midas may pass into breast milk. Consult your doctor or pharmacist before treatment with Ranibizumab Midas.

Driving and using machines
After treatment with Ranibizumab Midas, you may experience temporary blurred vision. If this occurs, do not drive and do not operate machinery until this condition has resolved.

3. How Ranibizumab Midas will be administered to you

Ranibizumab Midas is administered by your ophthalmologist as a single injection into the eye under local anaesthesia. The usual dose is 0.05 ml (containing 0.5 mg of active substance). The interval between two injections given into the same eye must be at least four weeks. All injections will be administered by your ophthalmologist.
Before the injection, your doctor will carefully clean the eye to prevent infection. Your doctor will also give you a local anaesthetic to reduce or prevent any pain that may occur during the injection.
Treatment is initiated with one monthly injection of Ranibizumab Midas. Your doctor will monitor the condition of your eye and, based on your response to treatment, will decide whether and when further treatment is needed.
Detailed instructions for the user can be found at the end of this leaflet under the heading “How to prepare and administer Ranibizumab Midas”.
Elderly (aged 65 years and over)
Ranibizumab Midas may be used in patients aged 65 years and over without dose adjustments.
Before stopping treatment with Ranibizumab Midas
If you are considering stopping treatment with Ranibizumab Midas, attend your next scheduled appointment and discuss this with your doctor. Your doctor will advise you and decide how long you should continue treatment with Ranibizumab Midas.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects associated with Ranibizumab Midas administration are due to both the medicine itself and the injection procedure, and most of them affect the eye.

The most serious side effects are described below:

Common serious side effects (may affect up to 1 in 10 patients)
Detachment or tear in the back of the eye (retinal detachment or tear), presenting as flashes of light, floaters, temporary reduction in vision, or clouding of the lens (cataract).

Uncommon serious side effects (may affect up to 1 in 100 patients)
Blindness, infection of the eyeball (endophthalmitis) with inflammation inside the eye.
Symptoms you may experience include eye pain or increased eye discomfort, worsening eye redness, blurred or decreased vision, increased number of floaters, or increased sensitivity to light. Seek immediate medical advice if any of these side effects occur.

The most frequently reported side effects are described below:

Very common side effects (may affect more than 1 in 10 patients)
Visual side effects include: eye inflammation, bleeding in the back of the eye (retinal haemorrhage), visual disturbances, eye pain, floaters or spots in vision (floaters), localized eye redness, eye irritation, sensation of a foreign body in the eye, increased tear production, inflammation or infection of the eyelid margin, dry eye, eye redness or itching, and increased intraocular pressure.

Non-visual side effects include: sore throat, nasal congestion, runny nose, headache, and joint pain.

Other side effects that may occur following treatment with Ranibizumab Midas are described below:

Common side effects
Visual side effects include: decreased visual acuity, swelling of part of the eye (uvea, cornea), corneal inflammation (front part of the eye), small lesions 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-visual side effects include: urinary tract infection, reduction in red blood cells (with symptoms such as fatigue, shortness of breath, dizziness, pallor), anxiety, cough, nausea, allergic reactions such as rash, urticaria, itching, and skin redness.

Uncommon side effects
Visual side effects include: inflammation and bleeding in the front of the eye, accumulation of pus in the eye, changes in the central part of the eye surface, pain or irritation at the injection site, abnormal sensation in the eye, eyelid irritation.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You may also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ranibizumab Midas

• 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." and "EXP.". The expiry date refers to the last day of that month.
• Store in a refrigerator (2°C - 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 from light.
• Do not use a package if it is damaged.

6. Package contents and other information

What Ranibizumab Midas contains

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

Description of the appearance of Ranibizumab Midas and contents of the pack
Ranibizumab Midas is an injectable solution in a vial (0.23 ml). The solution is aqueous,
clear, colourless to pale yellow.
One pack size is available:
Pack containing one glass vial of ranibizumab with a chlorobutyl rubber stopper. The
vial is for single use only.
Marketing Authorisation Holder and Manufacturer
Midas Pharma GmbH
Rheinstraße 49
D-55218 Ingelheim
Germany
Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, http://www.ema.europa.eu
THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY:
Please also refer to section 3 “How Ranibizumab Midas will be administered to you”.
How to prepare and administer Ranibizumab Midas to adults
Single-use vial, for intravitreal use only.
Ranibizumab Midas must be administered by a qualified ophthalmologist experienced in intravitreal injections.
In neovascular age-related macular degeneration (AMD), choroidal neovascularisation (CNV), proliferative diabetic retinopathy (PDR), and vision loss due to diabetic macular oedema (DME), or macular oedema secondary to retinal vein occlusion (RVO), the recommended dose of Ranibizumab Midas is 0.5 mg given as a single intravitreal injection. This corresponds to an injected volume of 0.05 ml. The interval between two injections 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 such as changes in visual acuity and alterations in other disease signs and symptoms during continuous treatment. In patients with neovascular AMD, DME, PDR and RVO, it may be necessary to initiate therapy with three or more consecutive monthly injections.
Therefore, monitoring and treatment intervals should be determined by the physician and should be based on disease activity, as assessed by evaluation of visual acuity and/or anatomical parameters.
If, in the physician’s opinion, visual acuity and anatomical parameters indicate that the patient is not benefiting from continued treatment, Ranibizumab Midas should be discontinued.
Monitoring of disease activity may include clinical examination, functional assessments or imaging techniques (e.g. optical coherence tomography or fluorescein angiography).
If patients are treated according to a “treat-and-extend” regimen, upon achieving maximum visual acuity and/or absence of signs of disease activity, treatment intervals may be gradually extended until signs of disease recurrence or worsening of visual function occur. The treatment interval may be gradually extended by up to two weeks in patients with neovascular AMD and up to one month in patients with DME. Treatment intervals may also be gradually extended in the management of RVO and PDR; however, there are insufficient data to establish the duration of these intervals. Upon recurrence of disease activity, the treatment interval should be reduced accordingly.
Treatment of vision loss caused by CNV should be individually determined based on disease activity. Some patients may require only one injection during the first 12 months; others may require more frequent treatment, up to monthly injections. For CNV secondary to pathological myopia (PM), many patients may require only one or two injections during the first year.
Ranibizumab Midas and laser photocoagulation in DME and macular oedema secondary to BRVO
There is some experience with ranibizumab administered concomitantly with laser photocoagulation.
When used on the same day, Ranibizumab Midas should be administered at least
30 minutes after laser photocoagulation. Ranibizumab Midas may be administered to patients who have previously received laser photocoagulation.
Ranibizumab Midas and photodynamic therapy with verteporfin in CNV secondary to PM
There is no experience with the administration of ranibizumab in combination with verteporfin.
Prior to administration, Ranibizumab Midas should be visually inspected for particulate matter and discoloration.
The injection procedure must be performed under aseptic conditions, including surgical hand disinfection, sterile gloves, a sterile drape, a sterile eyelid speculum (or equivalent), and the possibility of performing a sterile paracentesis (if necessary). Prior to the intravitreal procedure, the patient’s history should be carefully evaluated for hypersensitivity reactions. Prior to injection, appropriate anaesthesia and a broad-spectrum topical antimicrobial agent should be administered to disinfect the periocular, ocular and eyelid surfaces, according to clinical practice.
The vial is for single use only. After injection, any unused product must be discarded. Any vial showing signs of damage or tampering must not be used. Sterility cannot be guaranteed if the package seal is not 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 Ranibizumab Midas pack. They may be obtained separately or found within third-party intravitreal injection kits (e.g. the I2 injection kit from Vortex Surgical).

To prepare Ranibizumab Midas for intravitreal injection in adult patients, please follow the
instructions below:

1. Before withdrawal, remove the closure cap of the vial and clean the vial septum (e.g. with a 70% alcohol swab).
2. Aseptically attach a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, 5 µm) to a 1 ml syringe. Insert the filter needle into the center of the stopper until it reaches the bottom of the vial.
3. Withdraw all the liquid from the vial while holding it in a vertical position, slightly tilted to facilitate complete withdrawal.

4. Ensure that the syringe plunger is pulled back sufficiently when emptying the vial to completely empty the filter needle.
5. Leave the filter needle inserted in the vial and detach the syringe from it. Discard the filter needle after withdrawing the vial contents and do not use it for intravitreal injection.

6. Aseptically and securely attach an injection needle (30G x ½″, 0.3 mm x 13 mm) to the syringe.
7. Carefully remove the cap from the injection needle without disconnecting the needle from the syringe.

Note: Hold the base of the injection needle while
removing the cap.

8. Carefully expel air and excess solution from the syringe and adjust the dose to 0.05 ml marked on the syringe. The syringe is now ready for injection.

Note: Do not clean the injection needle. Do not pull back the
plunger.
Insert the injection needle 3.5–4.0 mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and directing the needle toward the centre of the globe. Inject the volume of 0.05 ml; change the scleral site for subsequent injections.
After injection, do not recap or detach the needle from the syringe. Dispose of the used syringe with the attached needle in a dedicated sharps container or in accordance with local regulations.