Eydenzelt: Uses, Side Effects and Dosage

What EYDENZELT is used for:

EYDENZELT (“I-den-zelt”) is a solution which is injected into the eye (intravitreal injection) by your healthcare professional with local anesthesia (freezing).

In adults, EYDENZELT is used to treat the eye conditions:

• Neovascular (wet) age-related macular degeneration – (wet) AMD,
• Macular edema secondary to central retinal vein occlusion (CRVO),
• Macular edema secondary to branch retinal vein occlusion (BRVO),
• Diabetic macular edema (DME),
• Myopic choroidal neovascularization (mCNV). There is no clinical trial experience with aflibercept in the treatment of non-Asian patients with myopic CNV.

How EYDENZELT works:

Growth factors (known as VEGF-A and PIGF) can cause extra blood vessels to grow and leak in the back of the eye, which can cause loss of vision.

Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF) are proteins that play an important role in making the abnormal blood vessels that contribute to the progression of wet AMD and the macular edema (swelling) that is seen with diabetic macular edema (DME). These blood vessels are fragile and can leak fluid and blood into the macula, leading to vision loss. DME is a swelling of the retina occurring in patients with diabetes due to leaking of fluid from blood vessels within the macula. The macula is the portion of retina responsible for fine vision. When the macula swells with fluid, central vision becomes blurry.

In Central Retinal Vein Occlusion (CRVO), a blockage occurs in the main blood vessel that transports blood away from the retina (the light sensitive back part of the eye), where fluid accumulates in the back of the eye, causing swelling (called macular edema).

In patients with BRVO, one or more branches of the main blood vessel that transports blood away from the retina is blocked, which cause the fluid accumulation in the back of the eye (swelling, called macular edema).

Myopic choroidal neovascularization (mCNV) is a severe form of myopia (near sightedness) which leads to elongated eyes with additional defects such as thinning, cracks and ruptures in some of the layers in the back of the eye. This triggers the abnormal formation of new blood vessels which can cause bleeding into the eye and eventually may lead to loss of vision.

Aflibercept, the active substance in EYDENZELT, blocks these growth factors, and has been shown to help improve vision or slow vision loss from wet AMD, CRVO, BRVO, DME, and myopic CNV.

These diseases may cause decreased vision.

The ingredients in EYDENZELT are:

Medicinal ingredients: aflibercept

Non-medicinal ingredients: L-histidine; L-histidine monohydrochloride monohydrate; sodium chloride; trehalose; polysorbate 20 and water for injection.

EYDENZELT comes in the following dosage forms:

EYDENZELT is a sterile, clear to slightly opalescent, colourless to very pale brownish-yellow, solution for injection which is iso-osmotic (similar properties to the inside of your eye).

Solution for intravitreal injection 2 mg / 0.05 mL in vial or pre-filled syringe.

Vials:

Each carton includes a single-dose glass vial containing a fill volume of 283 microliters solution for injection with a rubber stopper, and an 18 gauge filter needle.

Pre-filled Syringes:

Each carton includes a single-dose pre-filled syringe containing a fill volume of 182 microliters solution for injection.

Do not use EYDENZELT if:

• you are allergic (hypersensitive) to aflibercept or any of the other ingredients of EYDENZELT listed below or component of the container
• you have inflammation of the eye (symptoms include eye pain, redness and trouble seeing)
• you have an infection in or around the eye (ocular or periocular infection)

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take EYDENZELT. Talk about any health conditions or problems you may have, including if you:

Take special care with EYDENZELT:

• Injection with EYDENZELT may trigger an increase in eye pressure (intraocular pressure) in some patients within 60 minutes of the injection. Your healthcare professional may monitor this after each injection. If you have glaucoma (increased eye pressure), please tell your healthcare professional.

• Although uncommon, all intravitreal injections, including those with EYDENZELT, carry a risk of serious infection or inflammation inside the eye (endophthalmitis), inflammation of the vessels of the retina (retinal vasculitis with or without occlusion), detachment or tear of the retina at the back of the eye (symptoms include eye pain, worsening eye redness, blurred or decreased vision, sensitivity to light, sudden loss of vision, flashing lights and black spots), and cataracts (clouding of the lens in the front of the eye). Please contact your healthcare professional immediately if you develop any

  of these symptoms.

• Inform your healthcare professional if you have already had a stroke or experienced transient signs of stroke (weakness or paralysis of limbs or face, difficulty speaking or understanding). This information will be taken into account to evaluate if EYDENZELT is the appropriate treatment for you.
• Tell your healthcare professional immediately if you develop signs of a possible allergic reaction (for example, fast pulse, low blood pressure, sweating, allergic skin reactions such as rash, itching or stinging).

Before you use EYDENZELT, talk to your healthcare professional if:

• You are taking other medicines: Please tell your healthcare professional if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

• You are or plan to become pregnant: There is no experience of using aflibercept in pregnant women. In animals, high doses have been shown to have toxic effects on the fetus. Therefore, EYDENZELT is not recommended during pregnancy unless the potential benefit outweighs the potential risk to the fetus. If you are pregnant or planning to become pregnant, discuss this with your healthcare professional before treatment with EYDENZELT. Women of childbearing potential have to use effective contraception during treatment and for at least 3 months after the last intravitreal injection of EYDENZELT.

• You are breast-feeding: EYDENZELT is not recommended during breast-feeding as it is not known whether aflibercept passes into human milk. A risk to the breast-fed child cannot be excluded. Ask your healthcare professional for advice before starting EYDENZELT treatment. A decision must be made whether to discontinue breast-feeding or to abstain from EYDENZELT therapy.
• You have a history of seeing flashes of light or floaters, or if you have a sudden increase in the size or number of floaters.

The use of EYDENZELT in children and adolescents has not been studied and is therefore not recommended.

Driving and Using Machines

After your EYDENZELT injection, you may experience some temporary visual disturbances. Do not drive or use machinery as long as these last.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

How to take EYDENZELT:

Usual dose:

EYDENZELT is intended for injection into the eye. It must only be administered by a healthcare professional experienced in giving eye injections.

EYDENZELT will be injected under aseptic (clean and sterile) conditions. Before the injection, your healthcare professional will use a disinfectant eyewash to clean your eye carefully to prevent infection. Your healthcare professional will also give you a local anesthetic to reduce or prevent any pain you might have with the injection.

Treatment of AMD

The recommended dose of EYDENZELT is 2 mg (0.05 mL or 50 microliters). It will be administered once a month (every 4 weeks) for the first 3 months (12 weeks) then you may receive an injection every 2 months (8 weeks) thereafter. Your healthcare professional will decide whether the treatment interval between injections may be maintained at every 2 months (8 weeks) or it may be extended by 2 weeks. The maximum of interval between two doses is 16 weeks.

Based on examination by your healthcare professional, you may be prescribed an EYDENZELT injection every month (4 weeks) after the first 3 months. The interval between two doses should not be shorter than one month. Your healthcare professional will monitor your vision regularly.

Treatment of CRVO and BRVO

The recommended dose of EYDENZELT is 2 mg (0.05 mL or 50 microliters). EYDENZELT will be administered once every month (4 weeks) and may be extended to up to every 3 months (12 weeks) based on examination by your healthcare professional. The interval between two doses should not be shorter than one month. Your vision will be monitored by your healthcare professional every 1 to 2 months to determine the need for continued treatment.

Treatment of DME

If you are a patient with diabetic macular edema, the recommended dose of EYDENZELT is 2 mg (0.05 mL or 50 microliters). You will be treated with EYDENZELT once a month (every 4 weeks) for the first 5 consecutive months, then you may receive one injection every 2 months (8 weeks) thereafter. The treatment interval may be kept at every two months (8 weeks) or extended, by up to 2 weeks at a time, based on your healthcare professional’s examination. Your healthcare professional will decide on the schedule for follow up examinations.

Based on examination by your healthcare professional, you may be prescribed an EYDENZELT injection every month (4 weeks) after the first 5 months.

Treatment of myopic CNV

If you are a patient with myopic choroidal neovascularization you will be treated with one single injection of EYDENZELT 2 mg (0.05 mL or 50 microliters) at the beginning of your therapy. You will receive additional injections only if during examination your healthcare professional finds that your disease persists. If your disease resolves, your treatment will stop. In case your disease recurs it will be treated like a new disease.

The interval between two doses should not be shorter than one month.

Use in children: The safety and efficacy of EYDENZELT have not been studied in patients who are younger than 18 years of age. Health Canada has not authorized EYDENZELT for pediatric use.

Before stopping EYDENZELT treatment:

Consult your healthcare professional before stopping the treatment. If you have any further questions about the use of this product, ask your healthcare professional.

Overdose:

Missed dose:

If a dose of EYDENZELT is missed, make a new appointment for an examination and injection as soon as possible.

Possible side effects from using EYDENZELT:

These are not all the possible side effects you may have when taking EYDENZELT. If you experience any side effects not listed here, tell your healthcare professional.

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

With administration of EYDENZELT, there may be some side effects due to the injection procedure. Some of these may be serious and include infection or inflammation inside the eye (endophthalmitis), sudden loss or change of sharpness of vision (detachment or tear of retina), increase of pressure inside the eye (intraocular pressure), clouding of the lens due to injury (cataract traumatic), and detachment of the gel-like substance inside the eye from the retina (vitreous detachment), in AMD clinical studies; endophthalmitis, cataract and vitreous detachment in CRVO clinical studies; cataract in BRVO clinical studies; retinal detachment in DME clinical studies; and macular hole in the myopic CNV clinical study.

These serious side effects occurred in less than 1 in 1000 (16 of 26,780 injections in AMD studies; 3 out of 2,728 intravitreal injections in CRVO clinical studies; 1 out of 1,115 intravitreal injections in BRVO clinical studies; 1 out of 5940 intravitreal injections in DME clinical studies; and 1 out of 474 injections in the myopic CNV study.

The following is a list of the side effects reported to be possibly related to the injection procedure or to the medicine. Please do not get alarmed, you might not experience any of these. Always discuss any suspected side effects with your healthcare professional.

Very common side effects (more than 1 in 10 patients may be affected):

• bloodshot eye caused by bleeding from small blood vessels in the outer layers of the eye (conjunctival hemorrhage)
• eye pain

Common side effects (between 1 and 10 in every 100 patients may be affected):

• decreased sharpness of vision (retinal pigment epithelium tear*, detachment of the retinal pigment epithelium)
• certain forms of clouding of the lens (cataract, cataract cortical, cataract nuclear, cataract subcapsular)
• damage to the front layer of the eyeball (corneal erosion, corneal abrasion, punctate keratitis)
• increase in eye pressure (intraocular pressure increased)
• blurred vision
• moving spots in vision (vitreous floaters)
• detachment of the vitreous (gel-like substance inside the eye) from the retina (vitreous detachment)

If you think you, or a person you are caring for, have taken too much EYDENZELT, contact a healthcare professional, hospital emergency department, regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669) immediately, even if there are no signs or symptoms.

• a feeling of having something in the eye (foreign body sensation in eyes)
• increased tear production (lacrimation increased)
• swelling of the eyelid (eyelid edema)
• pain or bleeding at the injection site (injection site pain or hemorrhage)
• redness of the eye (conjunctival hyperemia, ocular hyperemia)

* Conditions known to be associated with wet AMD; observed in wet AMD patients only.

Uncommon side effects (between 1 and 10 in every 1,000 patients may be affected):

• abnormal sensation in the eye
• infection or inflammation inside the eye (endophthalmitis)
• irritation at the injection site
• irritation of the eyelid
• decreased sharpness of vision (retinal detachment, retinal tear)
• generalized allergic reactions (hypersensitivity)**
• inflammation of certain parts of the eye (iridocyclitis, anterior chamber flare, uveitis)
• certain forms of clouding of the lens (lenticular opacities)
• damage of the front layer of the eyeball (corneal epithelium defect)
• swelling of the front layer of the eyeball (corneal edema)
• inflammation in the iris of the eye (iritis)

** Allergic reactions like rash, itching (pruritus), hives (urticaria), and a few cases of severe allergy (anaphylactic/anaphylactoid) reactions were reported

Rare side effects (between 1 and 10 in every 10,000 patients may be affected):

• inflammation of certain parts of the eye (vitritis)
• pus in front of the iris (coloured part of the eye) (hypopyon)
• clouding of the lens due to injury (cataract traumatic)

Frequency not Known (frequency cannot be estimated from the available data):

• inflammation of the white part of the eye associated with redness and pain (scleritis)

The use of VEGF inhibitors similar to those contained in EYDENZELT, but which have an effect throughout the body (systemic effect) is potentially related to risk of arterial thromboembolic events (of blood clots blocking blood vessels) which may lead to heart attack or stroke. There is a theoretical risk of such events following injection of EYDENZELT into the eye.

As with all therapeutic proteins, EYDENZELT may cause an immune reaction (formation of antibodies).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your healthcare professional.

Serious side effects and what to do about them

Serious side effects and what to do about them

* There is a theoretical risk of Arterial Thromboembolic Events (ATEs), including stroke, following injection of EYDENZELT into the eye.

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Storage:

• Keep out of reach and sight of children.
• Store in a refrigerator (2°C to 8°C). Do not freeze.

Pre-filled Syringe:

• Prior to usage, the unopened blister pack may be stored at room temperature (up to 30°C) for up to 7 days. If necessary, the product may be returned to the refrigerator once within 7 days and provided this does not exceed the original expiry date. It must be used after subsequent removal from refrigeration. Discard EYDENZELT pre-filled syringe blister pack if not used by the original expiry date or after storage at room temperature (up to 30°C) for more than 7 days.
• Keep the pre-filled syringe in its blister pack and in the outer carton in order to protect from light.

Vial:

• Prior to usage, the unopened vial may be stored at room temperature (25°C) for up to 31 days. Discard EYDENZELT vial if not used by the original expiry date or after storage at room temperature (25°C) for more than 31 days.
• Keep the vial in its outer carton in order to protect from light.

If you want more information about EYDENZELT:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes the Patient Medication Information by visiting the Health Canada Drug Product Database website: (Drug Product Database: Access the database); or the manufacturer’s website (www.celltrionhealthcare.ca/).

*All trademark rights used under license.

All other trademarks are the property of their respective owner(s).

Reporting side effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

Visiting the Web page on Adverse Reaction Reporting (canada.ca/drug-device-reporting) for information on how to report online, by mail or by fax; or Calling toll-free at 1-866-234-2345.

NOTE: Contact your healthcare professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice.