Eylea^® (Solution) Instructions for Use

ATC Code

S01LA05 (Aflibercept)

Active Substance

Aflibercept (Rec.INN registered by WHO)

Clinical-Pharmacological Group

A drug used for age-related macular degeneration. Monoclonal antibodies to vascular endothelial growth factor A (VEGF-A)

Pharmacotherapeutic Group

Drugs used in ophthalmology; drugs used for diseases of the uvea; agents preventing neovascularization

Pharmacological Action

Aflibercept is a recombinant hybrid protein consisting of VEGF-binding (vascular endothelial growth factor) parts of the extracellular domains of VEGF receptor 1 and VEGF receptor 2, fused to the Fc (crystallizable fragment) domain of immunoglobulin G1 (IgG1). Aflibercept is produced using recombinant DNA technology with an expression system of Chinese hamster ovary (CHO) K-1 cells.

Aflibercept acts as a soluble receptor trap that binds VEGF-A (vascular endothelial growth factor A) and P1GF (placental growth factor) with higher affinity than their natural receptors, and thus can inhibit the binding and activation of these related VEGF receptors.

Vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B), and placental growth factor (PlGF) belong to the VEGF family of angiogenic factors, which can act as potent mitogenic, chemotactic, and vascular permeability factors for endothelial cells. The action of VEGF is mediated through two receptor tyrosine kinases – VEGFR-1 and VEGFR-2, located on the surface of endothelial cells. P1GF binds only to VEGFR-1, which are also present on the surface of leukocytes. Excessive activation of these receptors by VEGF-A can lead to pathological neovascularization and excessive vascular permeability. In these processes, P1GF can exhibit synergism with VEGF-A and also stimulates leukocyte infiltration and vascular inflammation.

Pharmacokinetics

It is administered directly into the vitreous body to exert a local effect. After intravitreal administration, Aflibercept is slowly absorbed into the systemic circulation, where it is detected mainly as an inactive stable complex with VEGF; only free Aflibercept can bind endogenous VEGF. Aflibercept does not accumulate in plasma when administered intravitreally every 4 weeks. The development of systemic pharmacodynamic effects, such as changes in blood pressure, is unlikely. The mean C_max of free aflibercept in plasma, according to the results of additional pharmacokinetic studies, ranged from 0.03 to 0.05 µg/ml, with individual values not exceeding 0.14 µg/ml. Subsequently, plasma concentrations of free aflibercept decreased to values below or close to the lower limit of quantification, usually within one week. Like other large proteins, both free and bound Aflibercept are expected to be eliminated from the body by proteolytic catabolism.

Indications

For the treatment of neovascular age-related macular degeneration (“wet” form of AMD); reduction of visual acuity caused by macular edema secondary to retinal vein occlusion (central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO)); reduction of visual acuity caused by diabetic macular edema (DME); reduction of visual acuity caused by myopic choroidal neovascularization (myopic CNV).

ICD codes

Dosage Regimen

Administer Eylea^® (aflibercept) as a 2 mg dose via intravitreal injection.

For neovascular age-related macular degeneration, initiate with one injection monthly for the first 3 months. Thereafter, administer one injection every 2 months.

For diabetic macular edema and macular edema following retinal vein occlusion, initiate with one injection monthly. Continue with one injection monthly until visual and anatomical outcomes are stable. The interval may then be extended to every 2 months based on disease activity assessment.

For myopic choroidal neovascularization, initiate with one injection monthly for up to 3 months. If needed, administer additional injections monthly.

Maintain a minimum interval of one month between doses for all indications.

After the first 12 months of treatment, the dosing interval for all indications may be extended based on disease activity as assessed by visual acuity and/or anatomical parameters. Do not exceed a 4-month interval.

Monitor patients regularly and adjust the treatment schedule accordingly. The number of injections and intervals are determined by the treating physician based on individual patient response.

Adverse Reactions

Immune system disorders uncommon – hypersensitivity reactions.

Eye disorders very common – decreased visual acuity, subconjunctival hemorrhage, eye pain; common – retinal pigment epithelial tear, retinal pigment epithelial detachment, retinal degeneration, vitreous hemorrhage, cataract, cortical cataract, nuclear cataract, subcapsular cataract, corneal erosion, corneal microerosions, increased intraocular pressure, blurred vision, vitreous floaters, vitreous detachment, injection site pain, foreign body sensation in eyes, lacrimation, eyelid edema, injection site hemorrhage, punctate keratitis, palpebral conjunctival injection, bulbar conjunctival injection; uncommon – endophthalmitis, retinal detachment, retinal tear, iritis, uveitis, iridocyclitis, lens opacity, corneal epithelial defect, injection site irritation, abnormal eye tissue sensation, eyelid irritation, inflammatory reaction in the aqueous humor of the anterior chamber, corneal edema; rare – blindness, iatrogenic traumatic cataract, inflammatory reaction of the vitreous body (vitritis), hypopyon.

Contraindications

Hypersensitivity to aflibercept; active or suspected intra- or periocular infection; active severe intraocular inflammation; pregnancy and breastfeeding period, except in cases where the potential benefit to the mother outweighs the potential risk to the fetus; age under 18 years.

With caution in the treatment of patients with poorly controlled glaucoma (Aflibercept should not be administered at intraocular pressure >30 mmHg); in patients who have had a stroke, transient ischemic attack, or myocardial infarction within the last 6 months; in patients with risk factors for retinal pigment epithelium integrity impairment.

Use in Pregnancy and Lactation

Aflibercept should not be used during pregnancy, except in cases where the potential benefit to the mother outweighs the potential risk to the fetus.

Aflibercept is not recommended during breastfeeding. A decision should be made to discontinue breastfeeding or to abstain from aflibercept therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last intravitreal injection of aflibercept.

Use in Hepatic Impairment

Dosage adjustment in patients with hepatic impairment is not required.

Use in Renal Impairment

Dosage adjustment in patients with renal impairment is not required.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

No special conditions are required for elderly patients.

Special Precautions

Intravitreal injections, including aflibercept injections, have been associated with the development of endophthalmitis, inflammatory reaction of the vitreous body, rhegmatogenous retinal detachment, retinal tear, and iatrogenic traumatic cataract. When administering aflibercept, the appropriate aseptic injection technique should always be strictly followed. Patients should be monitored for 1 week after the injection to detect the first signs of inflammation and to prescribe necessary therapy in a timely manner. Patients should be informed of the need to immediately report to the doctor any symptoms indicating the development of endophthalmitis or any other reaction mentioned above.

Cases of increased intraocular pressure within the first 60 minutes after intravitreal injections, including aflibercept injections, have been observed. Special precautions are necessary when treating patients with poorly controlled glaucoma (Aflibercept should not be administered at intraocular pressure >30 mmHg). In all cases, monitoring of intraocular pressure and optic disc perfusion is necessary with the appointment of appropriate therapy for the condition.

Since Aflibercept is a protein with therapeutic properties, there is a possibility of immunogenicity. Patients should be informed of the need to report to the doctor any signs or symptoms of intraocular inflammation, such as pain, photophobia, or conjunctival or pericorneal injection, which may be clinical manifestations of hypersensitivity.

Systemic adverse events, including hemorrhages outside the visual organ and arterial thromboembolism, have been observed after intravitreal injections of VEGF inhibitors. There is a theoretical risk of association of these events with VEGF inhibition. There is limited safety data on the use of aflibercept in patients with CRVO, BRVO, DME, or myopic CNV who have a history of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to initiation of therapy. Caution should be exercised when treating such patients.

When administering aflibercept simultaneously in both eyes, an increase in its systemic exposure is possible, which, in turn, increases the risk of systemic adverse events.

Risk factors associated with impairment of the pigment cell layer integrity after anti-VEGF therapy for “wet” AMD include extensive and/or pronounced retinal pigment epithelial detachment. Caution should be exercised when initiating aflibercept therapy in patients with risk factors for the development of retinal pigment epithelial tears.

Therapy with aflibercept is not recommended for patients with rhegmatogenous retinal detachment or with macular holes of stage 3 or 4.

In case of a retinal tear, the aflibercept injection should be canceled, and treatment should not be resumed until adequate repair of the tear.

The injection should be withheld until the next scheduled injection in case of a decrease in BCVA >30 letters compared to the last visual acuity assessment; subretinal hemorrhages involving the central fovea, or if the size of the hemorrhage is >50% of the total lesion area.

The injection should be withheld for a period of 28 days before planned and 28 days after performed intraocular surgery.

In patients with clinical signs of irreversible visual function changes due to ischemic CRVO and BRVO, therapy with aflibercept is not recommended.

Effect on ability to drive and use machines

The use of aflibercept has a minimal effect on the ability to drive vehicles and use mechanisms due to possible temporary visual disturbances associated both with the injection and with the examination procedure. If temporary visual disturbances occur after the injection, it is not recommended to drive a car or operate machinery until the clarity of visual perception is restored.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.