Lucentis® (Lucentis®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceRanibizumabRanibizumab
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  • Lucentis®
    solution d / eye 
    Novartis Pharma AG     Switzerland
    • Dosage form: & nbspintraocular solution
    Composition:

    1 ml of intraocular solution / vial / prefilled syringe contains:

    active substance: ranibizumab - 10 / 2.3 / 1.65 mg;

    atExcipients: a, Trigalose dihydrate 100/23 / 16.5 mg, Histidine hydrochloride monohydrate 1.662 / 0.382 / 0.274 mg, Histidine 0.321 / 0.074 / 0.053 mg, polysorbate 20 0.1 / 0.023 / 0.0165 mg, water for injection up to 1 ml (0.23) to 0.165 ml.

    Description:Transparent or slightly opalescent colorless solution
    Pharmacotherapeutic group:means of different groups for use in ophthalmology
    ATX: & nbsp

    S.01.L.A   Preparations preventing neovascularization

    S.01.L.A.04   Ranibizumab

    Pharmacodynamics:

    Ranibizumab selectively binds with isoforms of endothelial vascular growth factor, VEGF-A (VEGF110, VEGF121, VEGF165), and prevents interaction VEGF-A with its receptors on the surface of endothelial cells (VEGR1 and VEGR2), which leads to suppression of neovascularization and proliferation of blood vessels. Suppressing the growth of newly formed choroid vessels in the retina, ranibizumab stops the progression of the exudative hemorrhagic form of age-related macular degeneration (AMD) and macular edema in diabetes mellitus and occlusion (thrombosis) of retinal veins.

    With ranibizumab for 24 months in patients with AMD with minimally expressed chassis and concealed subfoveal choroidal neovascularization (CNV) at In most cases (90%), the risk of reducing visual acuity (O3) significantly decreased (loss less than 15 letters on the scale of detection OZ ETDRS or 3 lines according to the Snellen table), in a third of patients (33%) there was an improvement OZ on 15 letters and more on a scale ETDRS (p <0.01). In patients with imitation injections, the drug loss of less than 15 letters on a scale ETDRS (3 lines according to Snellen table) and improvement OZ more than 15 letters on the scale ETDRS, were noted in 53 and 4% of cases, respectively.

    In the majority of patients (90%) suffering from AMD with predominantly classical subfoveal CNV, against treatment with ranibizumab within 24 months, the incidence of marked decrease in vision (more than 3 lines) decreased, in a third of patients (41%) there was an improvement OZ (more than 3 lines). AT group of patients receiving photodynamic therapy with verteporfinom (WFDT), decreased risk of visual acuity reduction (more than on 3 lines) were observed respectively in 64% and 6% of cases. According to the quality of life questionnaire NEI-VFQ (National Eye Institute Visual Function Questionnaire) across 12 months of use ranibizumab in patients with AMD with minimal expressed classical and hidden subfoveal CNV average improvement visual acuity near and far compared to the original value was between +10.4 and + 7.0 letters, respectively (p <0.01). In the control group imitation of injection, this indicator decreased by 4.7 letters (p <0.01). When applying ranibizumab in patients with AMD with minimal expressed classical and hidden subfoveal CNV improvement in visual acuity persisted for 24 months.

    Most patients suffering from AMD with predominantly classical subfoveal CNV, against the backdrop of treatment with Lucentis for 12 months, the average change in visual acuity near and far from baseline was +9.1 and + 9.3 letters, respectively (p <001). In the control group in patients who received photodynamic therapy verteporfinom, the average change in visual acuity near and far compared to the original value was +3.7 and +1.7 letters (p <0.01). Patients who received Lucentis had an increase in vision capacity by +8.9 points, and in patients receiving simulated injections, this index improved by 1.4 points (p <0.01).

    Patients with a decrease in visual acuity (03) associated with diabetic edema of the macula the change in 03 after 12 months of therapy compared with the initial value was +6.8 letters against ranibizumab monotherapy, +6.4 letters - with combination ranibizumab with laser coagulation (LC) and 0.9 letters - only with LC (p <0 , 0001). Improvement 03 more than 15 letters on the scale ETDRS was observed in 22.6%, 22.9% and 8.2% of patients,received, only ranibizumab, the drug in combination with LC and only LC,respectively (p <0.0001). When appointing both methods of therapy for one day, ranibizumab injected at least 30 minutes after LC.

    When using ranibizumab for 12 months (if necessary in combination with LC) in patients with a decrease of 03, associated with diabetic edema of the macula, the average change of 03 compared to the original value was +10.3 letters compared to -1.4 letters when imitating the injection. Improvement 03 more than 10 and 15 letters on the scale ETDRS 60.8% and 32.4% of patients who received ranibizumab compared with 18.4% and 10.2% when imitating injections (p <0.0001). The discontinuation of the drug administration was possible with the achievement of stable visual acuity in three consecutive examinations.If necessary to resume treatment with ranibizumab, at least 2 consecutive monthly injections of the drug were carried out.

    With the use of ranibizumab, there was a pronounced persistent decrease in the thickness of the central zone of the retina, measured with an optical coherent tomography. After 12 months of ranibizumab therapy, the thickness of the retina in the central zone decreased by 194 mkm compared with 48 μm when imitating injection. Safety profile of the drug in patients with diabetic the macular edema was similar to that in the treatment of the wet form of AMD.

    Patients with a decrease in OC caused by CNV caused by pathological myopia (PM), the change in OZ after 1-3 months of therapy compared with the initial value was +10.5 letters on the background of ranibizumab therapy, depending on the achievement of the criteria for stabilizing OZ, +10.6 letters - with ranibizumab therapy depending on the activity of the disease; the change in OZ after 6 months of therapy compared with the initial value was +11.9 letters and + 11.7 letters, respectively; in 12 months - +12.8 and +12.5 letters, respectively. When assessing the dynamics of the mean changes of the OZ from the initial value within 12 months, a rapid achievement of the results was recorded,while the maximum improvement was already reached by 2 months. Improvement of OZ persisted throughout the 12-month period period.

    The proportion of patients with an increase of 03 by 10 letters or more, or reached the value of> 84 letters, was higher with ranibizumab compared with wFDT. After 3 months of therapy, an increase of 03 by 10 letters or more (or reaching 03> 84 letters) compared with baseline was observed in 61.9% of patients on the background of ranibizumab therapy, depending on the achievement of the stabilization criteria 03 and 65.5% of patients with therapy ranibizumab, depending on the activity of the disease; in 6 months - in 71.4% and 64.7% of patients, respectively; in 12 months - in 69.5% and 69.0% of patients, respectively. An increase of 03 by 10 letters or more (or reaching 03> 84 letters) in the group of PDPH after 3 months of therapy was observed only in 27.3% of patients.

    After 3 months of therapy, an increase of 03 by 15 letters or more (or reaching 03> 84 letters) compared with the initial value was observed in 38.1% of patients on the background of ranibizumab therapy, depending on the achievement of the stabilization criteria 03 and 43.1% therapy with ranibizumab, depending on the adisease activity; in 6 months - in 46.7% and 44.8% of patients, respectively; in 12 months - 53.3% and 51.7% of patients, respectively.The increase in OZ by 15 letters or more (or the achievement of OZ> 84 letters) in the group of PDPH after 3 months of therapy was observed only in 14.5% of patients.

    It should be noted that in patients who underwent condition monitoring and treatment on the basis of disease activity criteria, the number of injections during the 12-month period was, on average, one less than in patients receiving therapy, depending on the achievement of the criteria for stabilizing OZ. Immediately after the suspension of therapy, no adverse effect on OZ was found. After the resumption of therapy, recovery of the lost OZ was observed within one month.

    There was a decrease in the proportion of patients with subretinal fluid, intra-retinal edema and / or intra-retinal cysts compared with baseline, and an improvement in the overall evaluation of the questionnaire NEI-VFQ-25.

    Pharmacokinetics:

    When ranibizumab is administered to the vitreous body (once a month), the maximum concentration of ranibizumab in patients with neovascular form of AMD (FROMmax) in blood plasma was low and insufficient to inhibit biological activity VEGF-A by 50% (11-27 ng / ml according to the data of cell proliferation studies in vitro). When ranibizumab is administered to the vitreous humor in the dose range from 0.05 to 1.0 mg Cmax in the plasma was proportional to its dose. Based on the results of pharmacokinetic analysis and taking into account the removal of ranibizumab from blood plasma, the average half-life of ranibizumab (0.5 mg dose) from the vitreous humus averaged about 9 days.

    When ranibizumab is administered to the vitreous body (once a month), the concentration of ranibizumab in the blood plasma reaches its maximum value within 24 hours after the injection and is in the range of 0.79-2.90 ng / ml. The minimum concentration of ranibizumab in the blood plasma is in the range of 0.07-0.49 ng / ml. The concentration of ranibizumab in serum is approximately 90,000 times lower than that in the vitreous.

    Patients with impaired renal function

    Patients with renal dysfunction did not undergo special pharmacokinetic studies using ranibizumab. 68% (136 of 200) of patients with AMD, included in the pharmacokinetic analysis, had renal dysfunction (46.5% - mild, 20% moderate and 1.5% severe).In 48.2% (253 of 525) patients with retinal vein occlusion, there were renal dysfunction (36.4% - mild, 9.5% moderate and 2.3% severe). Against the backdrop of drug treatment in patients with impaired renal function, there was a minimal decrease in clearance of ranibizumab, which was not clinically significant.

    Patients with impaired function liver

    In patients with impaired liver function, special pharmacokinetic studies on the use of ranibizumab have not been conducted.

    Indications:

    Treatment of neovascular (wet) forms of age-related macular degeneration in adults.

    Treatment of visual acuity reduction, associated with diabetic edema of the macula as a monotherapy or in combination with laser coagulation (LC) in patients who had previously undergone LC.

    Treatment of visual acuity reduction caused by edema of the macula due to retinal vein occlusion (OVC).

    Contraindications:
    - Hypersensitivity to ranibizumab or any other component of the drug.
    - Proven or suspected eye infections or infectious processes of periocular localization.
    - Intraocular inflammation.
    - Children under 18 years of age (efficacy and safety of the drug in this category of patients has not been studied).
    - Pregnancy and lactation.
    Carefully:Patients with a known history of hypersensitivity can be given the drug only after a thorough assessment of the risk / benefit ratio.

    If you have one of the listed diseases, before using the drug, be sure to consult a doctor
    consult a doctor. Patients with a history of hypersensitivity, in the presence of risk factors for stroke, the drug should be administered only after a thorough assessment of the risk / benefit ratio. VEGF inhibitors Purpose patients with diabetic macular edema and macular edema due SMF with stroke or transient cerebral ischemia in history should be used with caution because of the risk of thromboembolic phenomena. Lucentis drug should not be administered concurrently with other drugs that affect the vascular endothelial growth factor (local or systemic application). Clinical conditions in which therapy with Lucentis should be stopped and should not be resumed:
    - reduction of visual acuity by> 30 letters in comparison with the last definition;
    - intraocular pressure> 30 mm Hg. p.
    - retinal rupture;
    - subretinal hemorrhages affecting the central fossa, or lesion area> 50%;
    - condition after intraocular surgery or planned in the next 28 days. It is necessary to comply with aseptic conditions during injections of Lucentis to prevent the development of complications such as endophthalmitis, retinal rupture, iatrogenic traumatic cataract. The drug should be administered with caution in patients at risk of developing rheumatogenic retinal detachment. In patients with rheumatogenic retinal detachment or macular rupture of stage 3.4, treatment with Lucentis should be stopped.
    Experience of ranibizumab in patients with a history of SMF and in patients with ischemic central retinal vein occlusion (CMC) or CMC branches is limited. In patients with OBC who have clinical manifestations of irreversible ischemic loss of visual function, the drug is not recommended.
    Pregnancy and lactation:
    Use during pregnancy and during breastfeeding is not recommended. Ranibizumab systemic effects after its intraocular injection is low, but taking into account the mechanism of action of the drug, ranibizumab should be considered as a potentially teratogenic and embryotoxic drug. Women of childbearing age with the use of the drug Lucentis recommended to use methods of contraception. The interval between the end of Lucentis treatment and conception should not be less than 3 months.

    Dosing and Administration:

    The drug Lucentis is used only in the form of injections into the vitreous. The contents of one vial of Lucentis should be used for only one intravitreal injection.

    Enter ranibizumab (in aseptic conditions) should only an ophthalmologist who has experience in performing intravitreal injections.

    Between the introduction of two doses of the drug should be observed interval of at least 1 month.

    The recommended dose of Lucentis is 0.5 mg (0.05 ml) once a month as an intravitreal injection.

    Treatment of a moist form of age-related macular degeneration in adults.

    ANDinjections of Lucentis are performed on a monthly basis and continue until the maximum stable 03, defined on three consecutive monthly visits against the background of the drug Lucentis.

    During treatment with Lucentis, a monthly monitoring of OZ is carried out. Ltreatment with Lucentis renews if the visual acuity of 1 or more lines (> 5 letters) associated with AMD defined during monitoring and continues until achieving stable visual acuity also in three consecutive monthly visits. In the treatment of visual acuity reduction, caused by DMO, injections of the drug Lutsentis are performed monthly and continue until maximum stable visual acuity, determined on three consecutive monthly visits on the background of the introduction preparation of Lucentis.

    Therapy with Lucentis can be combined with the use of LC in patients with DME (including patients with prior use of LC). In the appointment of both methods of therapy for one day, the drug Lucentis should be administered after at least 30 minutes after the LC.

    Treatment for reducing visual acuity caused by edema of the macula due to retinal vein occlusion (the central vein of the retina or its branches)

    Injections of the drug Lucentis are performed monthly and continue until a maximum of 03, determined by three consecutive monthly visits against the background of the introduction of the drug Lucentis.

    During the treatment, the drug is subject to monthly monitoring. 03.

    Treatment with Lucentis is resumed as a monthly injection in the case of a decrease in 03, associated with OVC, determined by monthly monitoring and continues until a stable 03 on three consecutive monthly visits. Therapy with Lucentis can be combined with application of LC in patients. When the appointment of both methods of therapy for one day, the drug Lucentis should be administered after at least 30 minutes after the LC. Lucentis can also be used in patients with previous use of LC.

    Treatment of visual acuity reduction caused by choroidal

    neovascularization, caused by pathological myopia.

    Treatment with Lucentis begins with a single injection. When identifying signs of disease activity, determined by periodic monitoring of the condition, which may include clinical examination, optical coherence tomography (OCT) or fluorescent angiography (FA), it is recommended to resume treatment with Lucentis.

    In most cases, one or two injections of Lucentis are needed during the first year of therapy. However, in some cases, more frequent application of the drug. In this regard, during the first two months it is recommended to monitor the condition on a monthly basis and, at least once every three months during the first year of treatment with Lucentis. In the future, the frequency of control is determined by the attending physician.

    Before the administration of Lucentis, the quality of dissolution and the color of the solution should be checked. The drug can not be used when changing the color of the solution and the appearance of insoluble visible particles.

    Injection of the drug into the vitreous humor should be performed under aseptic conditions, including the treatment of the hands of medical personnel, the use of sterile gloves, napkins, the eyelid (or its analog) and, if necessary, tools for paracentesis.

    Before the introduction of the drug, appropriate disinfection of the skin of the eyelids and the eye area, conjunctival anesthesia and antimicrobial therapy of a wide spectrum should be carried out.Antimicrobial drugs should be instilled in the conjunctival sac 3 times a day for 3 days before and after the administration of the drug.

    The Lucentis drug should be injected into the vitreous for 3.5-4 mm posterior to the limbus, avoiding the horizontal meridian and directing the needle towards the center eyeball. The volume of the injected preparation is 0.05 ml. The next injection of the drug is carried out in the other half of the sclera. Since intraocular pressure (IOP) may temporarily increase during 60 min after the injection of Lucentis, IOP should be monitored, optic nerve perfusion should be performed and, if necessary, appropriate treatment should be applied. There were also cases of a steady increase in IOP after the injection of Lucentis.

    In one session, the administration of Lucentis is carried out only in one eye.

    Patients with impaired hepatic function

    The use of the drug in patients with impaired liver function has not been studied. Given the low concentration of the drug Lucentis in blood plasma, there is no need to change the dosage regimen of the drug.

    Patients with impaired renal function

    Patients with impaired renal function do not need a dose adjustment. Patients aged 65 years and over

    Patients aged 65 years and older do not need a dose adjustment.

    Side effects:ANDThe safety of the drug was used in clinical trials in 1315 patients within 2 years.

    Serious adverse events, associated with the procedure for the administration of the drug, included endophthalmitis, rheumatogenic retinal detachment and cataracts due to iatrogenic trauma. Other serious adverse eye events observed with Lucentis included intraocular inflammation and increased intraocular pressure. The following adverse events (possibly associated with the use of the drug) were noted at a frequency of at least 2% in patients receiving LUCENTIS at a dose of 0.5 mg, compared with the control group (imitation injection or photodynamic therapy).

    The frequency of development of adverse events was estimated as follows: arising "very often" (> 1/10), "often" (> 1/100; <1/10), "sometimes" > 1/1000; <1/100), "rarely"; (> 1/10000; <1/1000), "very rarely"; (<1/10000).

    Infections and infestations: very often - Nasopharyngitis; often - The flu.

    From the hematopoiesis system: often anemia.

    Mental disorders: often -anxiety.

    From the nervous system: very often - headache.

    From the side of the organ of vision: Often - intraocular inflammation, inflammation of the vitreous, vitreous detachment, retinal hemorrhages, visual disturbances, eye pain, opacity in the vitreous, increased intraocular pressure, conjunctival hemorrhages, eye irritation, feeling of "foreign body" in the eyes, lacrimation, blepharitis, dry eye syndrome, red eyes, itching in the eyes; often - degenerative changes in the retina, retinal damage, retinal detachment, retinal ruptures, retinal pigment epithelial retinal detachment, rupture of pigment epithelium, reduction of visual acuity, vitreous hemorrhage, vitreous damage, uveitis, irit, iridocyclitis, cataract, subcapsular cataract, opacification of the posterior capsule of the lens, point keratitis, corneal erosion, cell opalescence in the anterior chamber of the eye, blurred vision, injection site hemorrhage, ocular hemorrhage, conjunctivitis, allergic conjunctivitis, discharge from the eyes, photopsy, photophobia, a feeling of discomfort in the eyes, swelling of the eyelids, tenderness of the eyelids, hyperemia of the conjunctiva; sometimes - blindness, endophthalmitis, hypopion, hyphema, keratopathy, adhesions of the iris, deposits in the cornea, corneal edema, striae of the cornea, pain and irritation at the injection site, atypical sensations in the eye and irritation of the eyelids.

    From the respiratory system: often - cough.

    From the digestive system: often - nausea. Dermatological disorders: often - allergic reactions (rash, hives, itching).

    From the musculoskeletal system: very often - arthralgia.

    Overdose:

    In clinical trials and with the use of the drug in clinical practice, there have been cases of unintentional drug overdose. In these cases, with an overdose of Lucentis, the most frequent increase in intraocular pressure and pain in the eye.

    In case of drug overdose, it is necessary to monitor intraocular pressure; if necessary, the patient should be under the supervision of a doctor.

    Interaction:The interaction of Lucentis with other medications has not been studied.

    The drug should not be confused with with any other medicinal preparations or solvents.

    There are no data on the use of Lucentis in conjunction with cDDT in patients with a decrease in 03 caused by CNV caused by PM.

    Special instructions:

    Only the ophthalmologist who has the experience of performing intravitreal injections should administer the drug.

    The administration of Lucentis should always be carried out under aseptic conditions. In addition, within 1 week after the injection of the drug, it is necessary to observe the patient in order to identify a possible local infectious process and conduct timely therapy. Patients should be informed of the need to report promptly to the doctor all the symptoms that may indicate the development of endophthalmitis.

    The drug has immunogenic properties. Since patients with DMO have a higher risk of systemic exposure to the drug, it is necessary to remember the higher risk of development of hypersensitivity reactions in this category of patients.

    Patients should be aware of the signs indicating the development of intraocular inflammation, which may indicate intraocular formation of antibodies to the drug.

    When vitreous injection of endothelial growth factor inhibitors A (VEGF-A) possibly the development of arterial thromboembolic complications.

    The risk of stroke may be higher if patients have risk factors, including a history of stroke or transient cerebral circulatory disorders.

    In patients after the administration of the drug Lucentis, there was a temporary increase (within 60 min after injection) of IOP. There have also been cases of a sustained increase in IOP. Against the background of the use of the drug Lucentis, it is recommended to monitor IOP and perfusion of the optic disc. The drug Lucentis is not recommended to be administered simultaneously in both eyes (safety and efficacy of this introduction have not been studied). This can lead to an increase in the systemic impact of Lucentis and the risk of side effects.

    The experience of using Lucentis is limited in patients with DMO due to CD type 1, in patients previously treated with intraocular preparations, in patients with active systemic infections, with proliferative diabetic retinopathy, or in patients with concomitant non-infectious eye diseases, such as retinal detachment, including in the macula.Also, there is no experience of using Lucentis in patients with diabetes with a glycated hemoglobin level of more than 12% and uncontrolled hypertension.

    The experience of using the drug Lucentis is limited in patients with PM, previously unsuccessfully exposed to the PDDT. Despite the fact that patients with subfoveal and juxtafoveal lesion localization had a similar effect, there is insufficient data for the conclusions concerning

    efficacy of Lucentis in patients with PM with extrafoveal localization

    defeat.

    When the drug is administered to women of childbearing age, reliable methods of contraception should be used.

    Effect on the ability to drive transp. cf. and fur:

    Against the background of the use of the drug Lucentis, it is possible to develop temporary visual impairments that adversely affect the ability to control vehicles and work with mechanisms. If such symptoms occur, patients should not drive or work with mechanisms until the temporal visual impairment is reduced.

    Form release / dosage:

    Solution for intraocular administration with ranibizumab 10 mg / ml.

    1. To 0.23 ml in a bottle of colorless glass, corked with a rubber stopper, coated with an aluminum cap with a snap-off lid.

    By one a vial complete with a needle equipped with a filter to extract the contents from the vial, a syringe, an injection needle along with an instruction for medical application in a cardboard box.

    1. For 0.165 ml of the drug in pre-filled glass syringe, sealed with a rubber stopper with a white polypropylene cover to control the first opening. One by one in advance filled syringe in a blister equipped with a label, along with instructions for medical use in a cardboard box.

    Packaging:

    1. To 0.23 ml in a bottle of colorless glass, corked with a rubber stopper, coated with an aluminum cap with a snap-off lid.

    By one a vial complete with a needle equipped with a filter to extract the contents from the vial, a syringe, an injection needle along with an instruction for medical application in a cardboard box.


    1. For 0.165 ml of the drug in pre-filled glass syringe, sealed with a rubber stopper with a white polypropylene cover to control the first opening. One by one in advance filled syringe in a blister equipped with a label, along with instructions for medical use in a cardboard box.

    Storage conditions:

    In the dark place at a temperature from 2 to 8 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:Flacons - 3 years.

    Pre-filled

    syringes - 2 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-004567/08
    Date of registration:16.06.2008
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp10.10.2014
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