Kontiniya^® (Solution) Instructions for Use

Marketing Authorization Holder

Generium, JSC (Russia)

ATC Code

S01LA05 (Aflibercept)

Active Substance

Aflibercept (Rec.INN registered by WHO)

Dosage Form

Kontiniya®

Solution for intraocular administration 40 mg/1 ml: vial 0.278 ml

Dosage Form, Packaging, and Composition

Solution for intraocular administration

0.278 ml – vials – In-Bulk
0.278 ml – vials – cardboard packs – Prescription only
0.278 ml – vials – cardboard packs /in a kit with a filter needle for withdrawing the drug from the vial, an injection needle, a syringe/ – Prescription only
0.278 ml – vials – cardboard packs /in a kit with a filter needle for withdrawing the drug from the vial/ – Prescription only

Clinical-Pharmacological Group

Drug used for vascular eye diseases. Anti-neovascularization drug

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 vascular endothelial growth factor (VEGF)-binding portions of the extracellular domains of VEGF receptor 1 and VEGF receptor 2, fused to the Fc (fragment crystallizable) domain of human immunoglobulin G1 (IgG1). Aflibercept is produced using recombinant DNA technology in a Chinese hamster ovary (CHO) K-1 cell expression system.

Aflibercept acts as a soluble receptor decoy that binds VEGF-A (vascular endothelial growth factor A) and PlGF (placental growth factor) with higher affinity than their native receptors, and thus can inhibit the binding and activation of these VEGF-related 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. PlGF 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, PlGF 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 blood 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 (wet) age-related macular degeneration (AMD); reduction of visual acuity caused by macular edema following 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 2 mg as an intravitreal injection.

For neovascular (wet) age-related macular degeneration (AMD), initiate with one injection monthly for the first three months. Thereafter, administer one injection every two months.

For macular edema following retinal vein occlusion (RVO) and diabetic macular edema (DME), initiate with one injection monthly. Continue with one injection monthly until visual and anatomical stability is achieved.

For myopic choroidal neovascularization (myopic CNV), initiate with one injection monthly for up to three months. If needed, administer additional injections based on disease activity.

After the initial loading phase for all indications, the treatment interval may be extended or the injection frequency reduced based on monthly assessment of visual acuity and/or anatomical parameters.

Maintain a minimum interval of one month between doses.

Withhold injection for a decrease in best-corrected visual acuity (BCVA) of more than 30 letters compared to the last assessment.

Withhold injection for significant subretinal hemorrhage involving the central fovea or covering more than 50% of the lesion area.

Do not administer for 28 days before and after planned intraocular surgery.

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 micro-erosion, 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 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, 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 when intraocular pressure >30 mm Hg); 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 tear.

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

Dose adjustment in patients with hepatic impairment is not required.

Use in Renal Impairment

Dose 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 endophthalmitis, inflammatory reaction of the vitreous body, rhegmatogenous retinal detachment, retinal tear, and iatrogenic traumatic cataract. When administering aflibercept, the appropriate aseptic injection technique must always be strictly followed. Patients should be monitored for 1 week after the injection to detect the first signs of inflammation and to initiate necessary therapy in a timely manner. Patients should be informed of the need to immediately report to their doctor any symptoms indicative 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 when intraocular pressure >30 mm Hg). In all cases, monitoring of intraocular pressure and optic disc perfusion with appropriate therapy as indicated by the condition is necessary.

Since Aflibercept is a protein with therapeutic properties, there is a possibility of immunogenicity. Patients should be informed to report to their 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 non-ocular hemorrhages and arterial thromboembolism, have been observed following 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 the 6 months prior to initiation of therapy. Caution should be exercised when treating such patients.

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

Risk factors associated with retinal pigment epithelium tear following anti-VEGF therapy for wet AMD include large and/or significant retinal pigment epithelial detachment. At the start of aflibercept therapy, caution should be exercised when prescribing it to patients with risk factors for developing retinal pigment epithelium tears.

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

In case of a retinal tear, the aflibercept injection should be canceled; 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 (Best Corrected Visual Acuity) of >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 machines due to possible temporary visual disturbances associated with both the injection and the examination procedure. If temporary visual disturbances occur after the injection, the patient is advised not to drive a car or operate machinery until visual clarity 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.