Lucentis, 10 mg/ml 0.23 ml

Lucentis is an angiogenesis inhibitor.

Pharmacodynamics

Ranibizumab is a fragment of humanized antibody to endothelial growth factor A (VEGF-A) and is expressed by a recombinant Escherichia coli strain.

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

. Administration of ranibizumab for 24 months in patients with TMD with minimally severe classic and occult subfoveal chorioidal neovascularization (CNV) significantly reduced the risk of visual acuity (VA) reduction in most cases (90%) (loss of less than 15 letters on the ETDRS VA definition scale or 3 lines on the Snellen table), One-third of patients (33%) showed an improvement in OZ of 15 letters or more on the ETDRS (3 lines on the Snellen Table) and an improvement in OZ of more than 15 letters on the ETDRS were observed in 53 and 4% of cases, respectively.

The majority of patients (90%) suffering from TMD with predominantly classical subfoveal CV, on the background of treatment with ranibizumab within 24 months reduced the frequency of development of marked visual impairment (by more than 3 lines), one third of patients (41%) had improvement of OZ (by more than 3 lines). In the group of patients receiving photodynamic therapy with verteporfin (vFDT), a decrease in the risk of OZ reduction (by more than 3 lines) and improvement of OZ (by more than 3 lines) were observed in 64 and 6% of cases, respectively. According to the NEI – VFQ (National Eye Institute – Visual Function Questionnaire), after 12 months of using ranibizumab in patients with TMD with minimally severe classical and occult subfoveal CVD, the mean improvement in near and far vision compared to baseline was 10.4 and 7 letters, respectively (p

The majority of patients with TMD with predominantly classical subfoveal CVD had a mean change in near and far vision over 12 months compared to baseline of +9.1 and +9.3 letters, respectively (p

In most patients with a decrease in near and far vision compared to baseline of +9.1 and +9.3 letters, respectively. In patients with decreased OZ associated with diabetic macular edema (DME), the change in OZ after 12 months of therapy compared with baseline was +6.8 letters on ranibizumab monotherapy, +6,4 letters – when combining ranibizumab with laser photocoagulation (LC) and 0.9 letters – with LC only (p

DRS was observed in 22.6, 22.9 and 8.2 patients receiving ranibizumab alone, the drug in combination with LC and LC only, respectively (p

)./p>

When ranibizumab was used for 12 months (if needed in combination with LC) in patients with DMO-related OZ reduction, the mean change in OZ from baseline was +10.3 letters compared with -1.4 letters for simulated injection. Improvements in OZ of more than 10 and 15 letters on the ETDRS scale were seen in 60.8 and 32.4% of patients treated with ranibizumab, compared with 18.4 and 10.2% with simulated injection (p

Stopping the drug was possible when stable OZ scores were achieved at three consecutive examinations. If resumption of treatment with ranibizumab was necessary, at least 2 consecutive monthly injections of the drug were performed.

With the use of ranibizumab, there was a marked persistent reduction in the thickness of the central zone of the retina as measured by optical coherence tomography. After 12 months of therapy with ranibizumab, retinal thickness in the central zone decreased by 194 μm compared to 48 μm when using simulated injection. The safety profile of the drug in patients with DMD was similar to that of wet AMD treatment.

In patients with decreased OZ caused by macular edema due to retinal vein occlusion, the change in OZ after 12 months of therapy compared with baseline was +18.3 letters with ranibizumab therapy in combination with LC, +12.1 letters with ranibizumab therapy after 6 months of simulated injection in combination with LC. Improvement of OZ by more than 15 letters on the ETDRS scale was seen in 60.3 and 43.9% of patients treated with ranibizumab or ranibizumab after use of simulated injection. When both therapies were administered for one day, ranibizumab was administered at least 30 minutes after LC.

In patients with decreased OZ caused by macular edema due to central retinal vein occlusion (CRV), the change in OZ after 12 months of therapy compared with baseline was +13.9 letters with ranibizumab monotherapy and +7.3 letters with ranibizumab therapy after 6 months using simulated injection.

OH improvement of more than 15 letters on the ETDRS scale was seen in 50.8 and 33.1% of patients treated with ranibizumab or ranibizumab after use of simulated injection.

The use of ranibizumab in both cases showed a pronounced persistent reduction in central retinal thickness.

In patients with CNS-induced decreased OZ caused by pathological myopia (PM), the change in OZ after 1-3 months of therapy compared to the initial value was +10.5 letters with ranibizumab therapy depending on the achievement of OZ stabilization criteria, +10.6 letters with ranibizumab therapy depending on disease activity; change in OZ after 6 months of therapy compared to the initial value was +11.9 letters and + 11.7 letters, respectively; after 12 months – +12.8 and +12.5 letters, respectively. In assessing the dynamics of the average OZ changes from the baseline value over 12 months, rapid achievement of the results was recorded, with the maximum improvement already achieved by the 2nd month. Improvement in OZ was maintained throughout the 12-month period.

The proportion of patients with an increase in OZ of 10 letters or more or reaching a value of ≥84 letters was higher with ranibizumab compared to wFDT. After 3 months of therapy, an increase in OZ by 10 letters or more (or achieving an OZ value ≥84 letters) compared to the baseline value was observed in 61.9% of patients against ranibizumab therapy, depending on the achievement of OZ stabilization criteria, and in 65.5% of patients against ranibizumab therapy depending on disease activity; after 6 months – in 71.4 and 64.7% of patients, respectively; after 12 months – in 69.5 and 69% of patients, respectively.

The increase in OZ by 10 letters or more (or achievement of OZ ≥84 letters) in the vFDT group after 3 months of therapy was observed in only 27.3% of patients.

In 3 months of therapy, an increase in OZ of 15 letters or more (or achievement of OZ ≥84 letters) compared with baseline was observed in 38.1% of patients on ranibizumab therapy depending on achievement of OZ stabilization criteria and in 43.1% of patients on ranibizumab therapy depending on disease activity; after 6 months, in 46.7 and 44.8% of patients, respectively; after 12 months, in 53.3 and 51.7% of patients, respectively.

A 15-letter or greater increase in OZ (or achievement of an OZ ≥84 letters) in the vFDT group after 3 months of therapy was observed in only 14.5% of patients.

It should be noted that patients who were monitored and resumed therapy based on disease activity criteria had, on average, one fewer injection per 12-month period than patients who received therapy based on achieving OZ stabilization criteria.

No adverse effect on OZ was detected immediately after suspension of therapy. After resumption of therapy, there was a recovery of lost OZ within one month.

There was a decrease in the proportion of patients with subretinal fluid, intraretinal edema and/or intraretinal cysts from baseline and an improvement in the overall NEI – VFQ-25 score.

Pharmacokinetics

Injecting ranibizumab into the vitreous (once a month) in patients with neovascular TMD C_max of ranibizumab in plasma was low and insufficient to inhibit the biological activity of VEGF-A by 50% (11-27 ng/mL according to in vitro cell proliferation studies). When ranibizumab was injected into the vitreous in the dose range of 0.05 to 1 mg C_max in plasma was proportional to its dose.

Based on the results of the pharmacokinetic analysis and considering the plasma excretion of ranibizumab, the average T_1/2 of ranibizumab (0.5 mg dose) from the vitreous averaged about 9 days.

Injection of ranibizumab into the vitreous body (once a month), the plasma concentration of ranibizumab reaches a maximum value within 24 hours after injection and ranges from 0.79-2.9 ng/mL. C_min of ranibizumab in plasma is in the range of 0.07-0.49 ng/ml. The serum concentration of ranibizumab is approximately 90,000 times lower than that in the vitreous.

Particular patient groups

In patients with impaired renal function. No specific pharmacokinetic studies on the use of ranibizumab have been performed in patients with impaired renal function. Sixty-eight percent (136 of 200) of the TMD patients included in the pharmacokinetic analysis had impaired renal function (46.5% mild, 20% moderate, and 1.5% severe). Kidney dysfunction was present in 48.2% (253 of 525) of the patients with retinal vein occlusion (RVC) (36.4% mild, 9.5% moderate, and 2.3% severe). In patients with impaired renal function, there was a minimal decrease in clearance of ranibizumab with no clinical significance during treatment with the drug.

Hepatic impairment. No specific pharmacokinetic studies on the use of ranibizumab have been performed in patients with impaired liver function.

Indications

Active ingredient

Composition

Active ingredient:

Ranibizumab;

Associates:

α,α-trehalose dihydrate;

L-histidine hydrochloride monohydrate;

L-histidine; polysorbate 20;

water for injection

How to take, the dosage

Intravitreal.

Lucentis is used only as an injection into the vitreous body.

The contents of one vial of Lucentis should be used for only one intravitreal injection. Only an ophthalmologist experienced in intravitreal injections should administer ranibizumab (under aseptic conditions). An interval of at least 1 month should be observed between two doses of the drug.

The recommended dose of Lucentis is 0.5 mg (0.05 ml) once a month by injection into the vitreous body.

Monthly OZ monitoring is performed during treatment with the drug.

Wet AMD treatment

Lucentis injections are given monthly and continue until maximum stable OZ is reached, determined at three consecutive monthly visits with Lucentis injections.

Lucentis treatment is resumed if OZ decreases by 1 or more lines (≥5 letters) associated with a monitored TMD and is continued until stable OZ is achieved at three consecutive monthly visits as well.

Treatment of DMD-related OD reduction

Lucentis injections are given monthly and continue until maximum stable OD, as determined at three consecutive monthly visits, is achieved with Lucentis injections.

Lucentis treatment is resumed if there is a decrease in OZ associated with DME as determined by monitoring and is continued until stable OZ is achieved at three consecutive monthly visits as well.

Lucentis therapy may be combined with the use of LC in patients with DME (including those with prior LC use). If both therapies are administered on the same day, Lucentis should be administered at least 30 minutes after LC.

The treatment of decreased OD caused by macular edema due to TIA (CBC or its branches)

Lucentis injections are given monthly and continue until maximum OD is achieved, determined at three consecutive monthly visits with Lucentis.

Lucentis treatment is resumed as monthly injections if the OD associated with OIA decreases as determined by monthly monitoring and is continued until stable OD is achieved at three consecutive monthly visits. Lucentis therapy may be combined with the use of LC in patients. When both therapies are administered on the same day, Lucentis should be administered at least 30 min after LC. Lucentis may also be used in patients with prior use of LC.

Lucentis treatment for PD-induced OD reduction

Lucentis treatment starts with a single injection. If there is evidence of disease activity as assessed by periodic monitoring, which may include clinical examination, optical coherence tomography (OCT), or fluorescence angiography (FA), renewal of treatment with Lucentis is recommended.

In most cases, 1 or 2 injections of Lucentis are required during the 1st year of therapy. However, some cases may require more frequent injections. Therefore, monthly monitoring is recommended for the first 2 months and at least once every 3 months thereafter during the 1st year of treatment with Lucentis. Thereafter the frequency of monitoring is determined by the treating physician.

The dissolution and color of the Lucentis solution should be monitored before the drug is administered. The drug should not be used if the color of the solution changes and insoluble visible particles appear.

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

Before the drug is administered, appropriate disinfection of the eyelid skin and eye area, anesthesia of the conjunctiva and therapy with broad-spectrum antimicrobials should be performed. Antimicrobials should be injected into the conjunctival sac 3 times a day for 3 days before and after injection.

Lucentis should be injected into the vitreous body 3.5-4 mm posterior to the limbus, avoiding the horizontal meridian and pointing the needle toward the center of the eyeball. The volume of the injected drug is 0.05 ml. The next injection of the drug is made into the other half of the sclera.

As IOP may rise temporarily within 60 minutes after injection of Lucentis, IOP and optic disk perfusion should be monitored and appropriate treatment applied if necessary. There have also been cases of persistent IOP elevation after Lucentis injection.

Lucentis is injected into only one eye per session.

Patient special groups

Liver dysfunction. The use of the drug in patients with impaired liver function has not been studied. Taking into account the low concentration of the drug Lucentis in blood plasma, it is not required to change the dosing regimen of the drug.

Renal dysfunction. Patients with impaired renal function do not need to adjust the dose of the drug.

Patients 65 years and older. Patients 65 years of age and older do not require a dose adjustment of the drug.

Interaction

The interaction of the drug Lucentis with other medicinal products has not been studied.

Lucentis should not be mixed with any other drugs or solvents.

Special Instructions

Treatment with the drug should only be performed by an ophthalmologist experienced in intravitreal injections. Injection of Lucentis should always be performed under aseptic conditions. Besides, within 1 week after the drug injection the patient must be monitored in order to detect possible local infection and timely treatment. Patients should be informed about the necessity to immediately inform the physician about all symptoms that may be indicative of endophthalmitis development.

The drug has immunogenic properties. Because patients with DME have a higher risk of systemic exposure to the drug, we must also be aware of the higher risk of hypersensitivity reactions in this patient population.

Patients should be aware of signs that suggest the development of intraocular inflammation, which may indicate intraocular antibody formation to the drug.

Injection of endothelial growth factor A (VEGF-A) inhibitors into the vitreous may result in arterial thromboembolic complications. The risk of stroke may be higher in patients with a history of risk factors, including a history of previous stroke or transient cerebrovascular events.

There were temporary (within 60 minutes after the injection) increase of IOP in patients after injection of Lucentis. There were also cases of steady increase of IOP. It is recommended to monitor IOP and optic disk perfusion during the use of Lucentis drug.

Lucentis is not recommended to be injected simultaneously in both eyes (safety and efficacy of this injection has not been studied). This may increase the systemic effect of Lucentis and the risk of side effects.

Lucentis has limited experience with DMO due to diabetes mellitus (DM) type 1 in patients previously treated with intraocular injectable drugs, in patients with active systemic infections, with proliferative diabetic retinopathy or with concomitant non-infectious eye diseases such as retinal detachment, including in the macula. There is also no experience with the use of Lucentis in patients with diabetes with a glycated hemoglobin level greater than 12% and uncontrolled arterial hypertension.

Lucentis has limited experience in patients with DM who have previously undergone vFDT without success. Although patients with subfoveal and juxtafoveal lesions have had similar effects, there is insufficient data to draw conclusions regarding the efficacy of Lucentis in patients with extrafoveal TM.

Women of childbearing age should use reliable contraception during therapy with the drug.

Impact on the ability to drive vehicles and operate machinery. During the use of the drug Lucentis temporary visual impairment may occur, which negatively influences the ability to drive vehicles and operate mechanisms. In case of such symptoms patients should not drive motor transport or operate mechanisms until the degree of temporary visual impairment reduces.

Instructions for use

The contents of one vial of Lucentis should be used for only one intravitreal injection.

The Lucentis kit includes a needle with a filter to remove the contents from the vial, a syringe and an injection needle (yellow).

Lucentis solution for intravitreal injection should be prepared as follows:

1. The surface of the rubber stopper should be disinfected before opening the vial with the drug.

(2) Under aseptic conditions, connect the included syringe (1 ml capacity) with a needle equipped with a filter (pore size – 5 microns). Insert the filtered needle into the vial through the central part of the rubber stopper (the end of the needle must reach the bottom of the vial).

3. Draw the entire contents of the vial into the syringe while holding the vial upright and tilting it slightly (to extract the solution completely).

4 After removing the medication from the bottle, the syringe piston should be pulled back (to the 0.8-0.9 ml mark) to allow the solution to fully pass from the filtered needle into the syringe.

5. Then disconnect the filter needle from the syringe and leave it in the vial. After removing the solution from the vial into the syringe, dispose of the filtered needle appropriately.

Please note: The filtered needle must not be used for intravitreal injection.

6. Connect the syringe tightly to the injection needle under aseptic conditions.

7. Carefully remove the cap from the injection needle (the needle must remain attached to the syringe).

Please note: When removing the cap from the intravitreal injection needle, only touch the cannula of the intravitreal injection needle.

8 Carefully remove the air from the syringe and set the plunger to the 0.05 ml mark. Only then can the drug be injected into the vitreous body.

Please note: Do not touch the injection needle and do not pull back on the plunger (after the 0.05 ml setting).

If an unused solution of the product remains in the bottle after a single injection into the vitreous, it must be disposed of appropriately (the unused solution must not be reused).

Contraindications

Side effects

Infections and invasions: very common – nasopharyngitis; common – influenza, urinary tract infection (observed only in patients with DME).

Hematopoietic system: often – anemia.

Mental disorders: often – anxiety.

Nervous system disorders: very common – headache; infrequent – stroke.

Visual organ disorders: very common – intraocular inflammation, vitreous inflammation, vitreous detachment, retinal hemorrhages, visual disturbances, eye pain, opacity in the vitreous, increased IOP, conjunctival hemorrhages, eye irritation, feeling of foreign body in the eye, lacrimation, blepharitis, dry eye syndrome, eye redness, feeling of itching in the eye; common – degenerative retinal changes, retinal lesions, retinal detachment, retinal tears, retinal pigment epithelium detachment, pigment epithelium rupture, decreased OZ, vitreous hemorrhage, vitreous body lesions, uveitis, iritis, iridocyclitis, cataract, subcapsular cataract, lens posterior capsule opacities, pitting keratitis, corneal erosions, cellular opalescence in the anterior chamber of the eye, blurred vision, bleeding at the injection site, ocular hemorrhages, conjunctivitis, allergic conjunctivitis, eye discharge, photopsia, photophobia, photophobia, feeling of discomfort in the eyes, eyelid edema, painful eyelids, conjunctival hyperemia; infrequent – blindness, endophthalmitis, hypopyon, hyphema, keratopathy, iris adhesions, corneal deposits, corneal edema, corneal striae, pain and irritation at the injection site, atypical eye sensations and eyelid irritation.

Respiratory system: often – cough.

The digestive system: often – nausea.

Dermatological disorders: often – allergic reactions (rash, urticaria, pruritus, erythema).

Muscular system disorders: very common – arthralgia.

Overdose

Symptoms: in clinical trials and during use of the drug in clinical practice there were cases of unintentional overdose of the drug. In these cases of overdose of the drug Lucentis the most common were increased IOP and pain in the eye.

Treatment: If there is an overdose of the drug the IOP should always be controlled; the patient should be under medical supervision if necessary.

Pregnancy use

The use in pregnancy and during breastfeeding is not recommended.

The systemic effects of ranibizumab after its intraocular administration are 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 are advised to use contraception when using Lucentis.

The interval between the end of treatment with Lucentis and conception should be at least 3 months.