Eilea
Eilea: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Eylea
ATX code: S01LA05
Active ingredient: aflibercept (Aflibercept)
Manufacturer: Regeneron Pharmaceuticals Inc (USA); Bayer Pharma AG (Germany)
Description and photo update: 2018-27-11
Prices in pharmacies: from 43,000 rubles.
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Eilea is an ophthalmic drug used to improve visual acuity.
Release form and composition
Eilea's dosage form is a solution for intraocular administration: light yellow or colorless, transparent or somewhat opalescent (in a cardboard box 1 glass bottle of type I, 0.1 ml each, complete with a filter needle and instructions for using Eilea).
Composition of 1 ml solution:
- active substance: aflibercept - 40 mg;
- auxiliary components: polysorbate 20, sodium dihydrogen phosphate monohydrate, sodium hydrogen phosphate heptahydrate, sucrose, sodium chloride, water for injection.
One vial contains 100 μl of solution (extractable volume), which corresponds to 4 mg of aflibercept.
Pharmacological properties
Aflibercept, the active substance of Eylea, is a recombinant fusion protein consisting of fragments of the extracellular domains of human VEGF receptors 1 and 2 (VEGFR-1 and -2), which are connected to the Fc fragment of human immunoglobulin G (IgG1).
The substance is produced by recombinant DNA technology by the K1 cells of the Chinese hamster ovary (CHO; CHO).
Aflibercept acts as a soluble decoy receptor that binds VEGF-A (vascular endothelial growth factor A) to PIGF (placental growth factor), which have a higher affinity than their natural receptors. This inhibits the binding and activation of these related VEGF receptors.
The mechanism of action of VEGF-A and PIGF is due to their belonging to the VEGF family of angiogenic factors that have a powerful chemotactic mitogenic effect on endothelial cells and increase vascular permeability.
VEGF acts through two types of tyrosine kinase receptors, VEGFR-1 and -2, which are present on the surface of endothelial cells. PIGF binding occurs only with VEGFR-1, also present on the surface of leukocytes. With excessive activation of these VEGF-A receptors, pathological neovascularization and excessive vascular permeability may develop. In these processes, PIGF can synergize with VEGF-A, as well as stimulate vascular inflammation and leukocyte infiltration.
Pharmacodynamics
Neovascular or wet age-related macular degeneration (AMD)
The disease is characterized by pathological neovascularization of the choroid. Leakage of fluid and blood from the pathologically neovascularized choroid can lead to thickening of the central region of the retina, as well as edema / hemorrhage into the retina and / or subretinal space and, as a result, to a decrease in visual acuity.
The safety profile of the drug was assessed in randomized, multicenter, double-blind, active-controlled studies VIEW1 and VIEW2.
In the vast majority of cases, during long-term treatment, there was a steady improvement in visual acuity and a decrease in the area of pathological neovascularization in all groups using a different dosage regimen.
Macular edema associated with central retinal vein occlusion (RCVO) or central retinal vein occlusion (RCVO)
Against the background of RCVS and RCVS, the development of retinal ischemia is observed - a signal for the release of VEGF. This, in turn, becomes the cause of the destabilization of tight junctions and the stimulation of the proliferation of endothelial cells. With increased expression of VEGF, complications such as violation of the blood-ophthalmic barrier, retinal edema (associated with increased vascular permeability), neovascularization are noted.
Eilea's efficacy and safety profile was evaluated in the COPERNICUS and GALILEO randomized, multicenter, double-blind, controlled trials. In most cases, there was an increase in MCVA (maximum corrected visual acuity) and visual acuity.
Diabetic macular edema (DME)
DME is a consequence of diabetic retinopathy. The pathology is characterized by an increase in vascular permeability and damage to retinal capillaries, which can cause loss of visual acuity.
Eilea's efficacy and safety profile was evaluated in two studies. In most cases, an increase in BCVA was observed.
Myopic choroidal neovascularization (CNV)
Myopic CNV is one of the common causes of vision loss in adult patients with pathological myopia. Pathology is characterized by the appearance of varnish cracks due to ruptures of the Bruch membrane. In pathological myopia, they are the most vision-threatening phenomenon.
Eilea's efficacy and safety profile was evaluated in untreated patients with myopic CNV. In most cases, an increase in BCVA was observed.
Pharmacokinetics
To provide a local effect, the introduction of Eilea is carried out directly into the vitreous body (intravitreal).
Aflibercept after intravitreal administration is slowly absorbed into the systemic circulation, it is found mainly in the form of an inactive stable complex with VEGF (endogenous VEGF can only bind free aflibercept).
The systemic C max (maximum plasma concentration) of free aflibercept, determined during pharmacokinetic studies in patients with wet AMD for 1-3 days after intravitreal injection of 2 mg of the substance, was low, on average, about 0.02 μg / ml (in the range 0-0.054 μg / ml), and in almost all patients, it was undetectable two weeks after injection. With intravitreal administration of Eilea, the substance does not accumulate in the blood plasma every 4 weeks.
The average C max of free aflibercept is approximately 50-500 times lower than the concentrations required to inhibit the biological activity of VEGF in the systemic circulation. It is expected that the average value of this indicator after administration of 2 mg aflibercept will be more than 100 times lower than the concentration of the substance required in healthy volunteers to bind half of the systemic VEGF (2.91 μg / ml). This means that the development of systemic pharmacodynamic effects, including changes in blood pressure, is unlikely.
According to the results of additional pharmacokinetic studies with the participation of patients with PCVO, PCVO, DMO and myopic CNV, the mean C max of free aflibercept in plasma is in the range of 0.03-0.05 μg / ml, individual variability is insignificant (no more than 0.14 μg / ml). Plasma concentrations of free matter are subsequently (usually within one week) reduced to values below or near the lower limit of assay. After 4 weeks, concentrations are undetectable.
Free aflibercept binds to VEGF to form a stable inert complex. Free / bound aflibercept is expected to be cleared from the body by proteolytic catabolism, like other large proteins.
Experience with Eilea in patients over 75 years of age with DMO is limited.
Indications for use
- wet form of AMD;
- decreased visual acuity caused by macular edema associated with CVV or CVV;
- decreased visual acuity caused by DMO;
- decreased visual acuity caused by myopic CNV.
Contraindications
Absolute:
- peri- or intraocular infection (active or suspected);
- severe active intraocular inflammation;
- age up to 18 years;
- lactation period;
- individual intolerance to the components of the drug.
Relative (Eilea is prescribed under medical supervision):
- poorly controlled glaucoma (with intraocular pressure ≥ 30 mm Hg);
- conditions after a stroke, transient ischemic attack or myocardial infarction within the last 6 months (in the treatment of CVD, CVV, DMO or myopic CNV);
- the presence of risk factors for violation of the integrity of the retinal pigment epithelium;
- pregnancy.
Eilea, instructions for use: method and dosage
Eilea should only be injected into the vitreous humor.
The contents of the vial are designed for one administration. The solution should be administered by a doctor who has experience in intravitreal injections and the appropriate qualifications.
The recommended dose is 2 mg aflibercept (50 μl of Eilea).
Wet AMD
Therapy begins with the introduction of three consecutive injections once a month, then 1 injection is performed once every two months. Control is not required between injections.
After a year of using the drug, based on the results of changes in visual acuity and anatomical parameters, the interval between injections can be increased. In the case of therapy in the "treat and increase the interval" mode, the interval between doses is gradually increased in order to maintain the achieved stable anatomical parameters and / or visual acuity, but there is not enough information to establish the length of these intervals.
If visual acuity and anatomical parameters deteriorate, the intervals between injections should be shortened. In this case, the attending physician draws up a schedule of control examinations, which can be carried out more often than injections.
Macular edema associated with HCVO or HCVO
The drug is administered monthly. The interval between two injections should not be less than one month.
In the absence of positive dynamics as a result of continuous therapy, Eilea is canceled.
The drug is used until the maximum possible visual acuity is achieved in the absence of signs of disease activity. This requires three or more consecutive monthly injections.
Treatment can be continued in the "treat and increase the interval" mode, when the interval between injections is gradually increased in order to maintain the achieved stable visual acuity and anatomical parameters, however, there is insufficient information to establish the duration of the intervals.
If visual acuity and anatomical parameters deteriorate, the intervals between injections should be reduced accordingly.
The choice of the regimen and monitoring of treatment is carried out by the attending physician, based on the patient's individual response.
Monitoring the manifestations of disease activity may include the following activities: standard ophthalmological examination, functional diagnostics, or imaging (optical coherence tomography or fluorescence angiography).
DMO
The drug is administered once a month for five months, after which the injections are carried out once every two months. Control between injections is not required.
After a year, the interval between injections can be increased based on the results of changes in visual acuity and anatomical parameters. In particular, with the regimen "treat and increase the interval", when the intervals between the doses of the drug are gradually increased in order to maintain the achieved stable visual acuity and / or anatomical parameters (there is not enough information to establish the duration of these intervals).
If the performance deteriorates, the intervals between drug administration should be reduced accordingly. In this case, the attending physician draws up a schedule of control examinations, which can be performed more often than injections. If there is no improvement, Eilea is canceled.
Myopic CNV
If, while observing the standard dosage regimen, symptoms of the disease persist, additional doses may be administered. Relapses should be treated as a new manifestation of the disease.
The schedule of follow-up examinations is determined by the doctor.
The interval between doses should be at least one month.
Method of administration
Intravitreal injections should be performed in accordance with medical standards and current guidelines by a qualified physician experienced in administering such injections.
With the introduction of Eilea, it is required to provide adequate anesthesia and aseptic conditions, including the use of local bactericidal preparations of a wide spectrum of action (in particular, application of Povidone-iodine to the skin around the eye, eyelid and eye surface is shown). Disinfection of the surgeon's hands, use of sterile wipes and gloves and a sterile eyelid dilator (or its equivalent) is recommended.
An injection needle is inserted into the vitreous cavity 3.5–4 mm posterior to the limbus, while avoiding the horizontal meridian and directing the needle to the center of the eyeball. The next injections must be given in a different area of the sclera.
After the end of the introduction of Eilea, it is required to monitor the patient's condition for an increase in intraocular pressure. Adequate monitoring activities may include ophthalmotonometry or optic nerve head perfusion testing. Where necessary, sterile paracentesis equipment should be available.
It is necessary to inform the doctor if any symptoms appear that may indicate the development of endophthalmitis, including eye pain, blurred vision, photophobia.
The vial contains a dose of aflibercept that exceeds the recommended dose of 2 mg. The volume of the bottle is not fully used. The excess volume must be removed prior to injection. With the introduction of the full volume of the vial, an overdose is possible. In order to remove air bubbles and excess volume of solution, you need to slowly press the syringe plunger, moving the cylindrical base of the piston dome to the black mark on the syringe (corresponds to 2 mg aflibercept).
All unused drug after injection must be disposed of.
Before the introduction of the solution, it is necessary to carefully inspect the bottle for a violation of the integrity of the package, significant discoloration, turbidity, the presence of visible particles. In such cases, the drug cannot be used.
The solution should be aspirated with an 18 G, 5 micron filter needle placed in a carton box. After the bottle is completely empty, the needle is removed and disposed of. Eylea is injected with a 30 G x 1 / 2- inch injection needle that is tightly attached to the syringe tip with a Luer lock adapter.
Side effects
The incidence of serious adverse reactions from the organ of vision, which were noted in the studied eye and associated with the administration procedure - less than 1 case in 1900 intravitreal injections. In this case, the development of endophthalmitis, blindness, retinal detachment, cataract, iatrogenic traumatic cataract, vitreous hemorrhage, increased intraocular pressure and vitreous detachment are possible.
The most common adverse reactions (in at least 5% of cases) include: decreased visual acuity, subconjunctival hemorrhage, floating opacities of the vitreous humor, detachment of the vitreous body, cataracts, eye pain, increased intraocular pressure.
Possible adverse reactions [> 10% - very common; (> 1% and 0.1% and 0.01% and <0.1%) - rarely; <0.01% - very rare]:
- organ of vision: very often - subconjunctival hemorrhage, pain in the eye, decreased visual acuity; often - microerosion and erosion of the cornea, detachment of the vitreous humor, cataract, retinal degeneration, rupture of the pigment epithelium of the retina (as a rule, it is observed only in the treatment of a wet form of AMD), detachment of the pigment epithelium of the retina, hemorrhage into the vitreous, increased intraocular pressure, blurred vision floating opacities of the vitreous body, pain at the injection site, feeling of a foreign body in the eye, eyelid edema, lacrimation, punctate keratitis, injection of the eyelid conjunctiva, injection of the conjunctiva of the eyeball, hemorrhages at the injection site, subcapsular, cortical and / or nuclear cataract; infrequently - irritation of the eyelid, corneal edema, suspension of blood corpuscles in the anterior chamber, irritation at the injection site, uveitis,iritis, iridocyclitis, endophthalmitis (with sowing and non-sowing cultures), retinal detachment or rupture, lens opacity, corneal epithelial defect, abnormal sensitivity of eye tissues; rarely - an inflammatory reaction from the vitreous body (vitreitis), iatrogenic traumatic cataract, blindness, hypopyon;
- immune system: infrequently - hypersensitivity (during the post-registration observation period, reports of hypersensitivity reactions included urticaria, pruritus, rash, in some cases the development of severe anaphylactic / anaphylactoid reactions was noted).
In studies of wet AMD in phase III, there was an increase in the incidence of subconjunctival hemorrhage in patients who received antithrombotic agents. The increase in the incidence of this disorder is comparable to that in patients receiving Eilea and ranibizumab.
Overdose
Main symptoms: increased intraocular pressure.
Therapy: control of intraocular pressure, if necessary, adequate measures are prescribed to correct it.
special instructions
There is a connection between the intravitreal route of administration of the drug and the development of rupture and rhegmatogenous retinal detachment, endophthalmitis, iatrogenic traumatic cataract, and an inflammatory reaction from the vitreous body. In order to minimize the development of this disorder, it is necessary to follow the appropriate aseptic injection technique. Within 7 days after the administration of the drug, the patient's condition should be monitored, which will allow timely detection of the first signs of inflammation and prescribe the necessary therapy.
There is information about an increase in intraocular pressure during the first hour after the introduction of Eilea. In this regard, when treating patients with poorly controlled glaucoma, special precautions are recommended (with intraocular pressure ≥ 30 mm Hg, the drug should not be administered). In all cases, monitoring of optic nerve head perfusion and intraocular pressure is indicated with the appointment of therapy appropriate to the condition.
Eilea is a protein with therapeutic properties, so there is a potential for immunogenicity. In cases of the appearance of any signs of intraocular inflammation, it is necessary to consult a doctor, as this may indicate clinical manifestations of hypersensitivity to the drug.
There is evidence of the development of systemic undesirable disorders, including hemorrhages outside the organ of vision and thromboembolism of the arteries. There is a theoretical possibility of the relationship between these phenomena and VEGF inhibition.
The safety profile of Eylea when administered simultaneously in both eyes has not been studied. With simultaneous bilateral administration, it is possible to increase the systemic exposure of aflibercept and, as a result, the risk of systemic adverse events.
There is no information on the combined use of Eilea and other anti-VEGF drugs (systemic or ophthalmic).
Patients with stage III or IV macular tears, or rhegmatogenous retinal detachment are advised to refrain from treatment.
In the event of a retinal rupture, the injection should be canceled; treatment cannot be resumed until the break is adequately repaired.
Cancellation of a scheduled injection until the next scheduled injection is indicated in the following cases:
- decrease in BCVA ≥ 30 letters in comparison with the last assessment of visual acuity;
- subretinal hemorrhages affecting the central fossa, or cases when the size of the hemorrhage exceeds 50% of the total area of the lesion.
It is recommended to refrain from using Eilea within 28 days before intraocular surgery, as well as during the same period after it.
The experience of using the drug against the background of ischemic RCVO and RCVO is limited. If patients have clinical signs of irreversible changes in visual functions associated with ischemia, therapy should not be carried out.
The experience of treating DME in patients with type 1 diabetes mellitus, proliferative diabetic retinopathy, as well as with a glycated hemoglobin level of more than 12% is limited.
Information on the use of Eilea is limited or absent in patients with the following diseases:
- active systemic infections;
- comorbid eye conditions, including retinal detachment or macular rupture;
- diabetes;
- uncontrolled hypertension.
In the treatment of myopic CNV, the experience of using the drug is absent in patients of the non-Asian population with extrafoveal injuries, as well as in patients who have previously received treatment for myopic CNV.
Influence on the ability to drive vehicles and complex mechanisms
Eilea has minimal impact on the ability to drive vehicles associated with the examination procedure and drug administration. If temporary visual impairment occurs after the administration of the solution, it is recommended to refrain from driving until the moment when the clarity of visual perception is restored.
Application during pregnancy and lactation
During pregnancy, the use of Eilea is possible only in cases where the expected benefit is higher than the possible harm. The safety profile has not been studied; in animal studies, the embryo- and fetotoxicity of aflibercept was established.
During lactation, the drug is contraindicated. It is not known whether Eilea passes into breast milk, so a risk to the baby cannot be ruled out.
Women of reproductive age are advised to use effective contraception during treatment and for at least 3 months after the last intravitreal administration of aflibercept.
It has been established that aflibercept can interfere with fertility in females and males. However, with intraocular administration of the substance, such effects are unlikely, due to its low systemic exposure.
Pediatric use
For patients under 18 years of age, the drug is not prescribed.
Drug interactions
There are no data on the interaction of Eilea with other drugs.
The safety profile of the combined use of Eylea and PDT (photodynamic therapy) has not been studied.
Analogs
Aylea's analogues are Ailia, Vizudin, Lucentis, Makugen.
Terms and conditions of storage
Store in a place protected from light at a temperature of 2-8 ° C. Do not freeze. Keep out of the reach of children.
An unopened bottle can be stored for 24 hours at a temperature not exceeding 25 ° C before use.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Eilea
The few reviews about Eilea are mostly positive. In most cases, patients indicate a return to visual acuity.
The cost of the drug is estimated to be high.
Price for Eilea in pharmacies
The approximate price for Eilea (1 bottle of 0.1 ml) is 46,680 rubles.
Eilea: prices in online pharmacies
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Drug name Price Pharmacy |
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Eilea 40 mg / ml solution for intraocular administration 0.1 ml 1 pc. RUB 43,000 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
