LUCENTIS
Active material: Raniʙizumaʙ
When ATH: S01LA04
CCF: Preparation, used when age-related macular degeneration. Monoclonal antibodies to endothelial growth factor A (VEGF-A)
ICD-10 codes (testimony): H35.3
When CSF: 14.02.02
Manufacturer: NOVARTIS PHARMA AG (Switzerland)
Pharmaceutical form, composition and packaging
The solution for ocular administration clear or slightly opalescent, colorless.
| 1 ml | 1 fl. | |
| raniʙizumaʙ | 10 mg | 2.3 mg |
Excipients: a,a-трегалозы дигидрат, L-histidine hydrochloride monohydrate, L-histidine, polysorbate 20, water d / and.
0.23 ml – colorless glass vials (1) complete with needle, equipped with a filter, d needle / syringe and and – cardboard boxes.
* international non-proprietary name, recommended by the WHO – raniʙiцumaʙ.
Pharmacological action
The drug for the treatment of exudative-hemorrhagic form of age-related macular degeneration (SHC). Ranibizumab fragment is a human monoclonal antibodies to endothelial growth factor A (VEGF-A) and is expressed by a recombinant Escherichia coli strain.
Ranibizumab binds selectively to isoforms of vascular endothelial growth factor, VEGF-А (VEGF110, VEGF121, VEGF165), and prevents the interaction of VEGF-A to its receptors on the surface of endothelial cells (Victory1and VEGR2), which leads to a suppression of neovascularization and vascular proliferation. Inhibiting the growth of new vessels in the retina, choroid, ranibizumab stops the progression of exudative-hemorrhagic form of age-related macular degeneration (SHC).
Results from clinical studies
The efficacy and safety of Lucentis in patients with AMD has been shown in randomized, double-blind controlled studies (with simulated injection or in comparison with photodynamic therapy). When applying for Lucentis 24 months in patients with AMD with minimal intensity and classic subfoveal choroidal neovascularization hidden (KhNV) In most cases (90%) significantly reduces the risk of loss of visual acuity (loss less 15 letters on a scale ETDRS visual acuity or 3 lines of Snellen table), a third of patients (33%) an improvement in visual acuity 15 letters and more on the ETDRS scale (p<0.01). Patients with simulated injections loss less 15 letters ETDRS scale (3 lines of Snellen table) and improvement of visual acuity over 15 letters ETDRS scale occurred in 53% and 4% of cases, respectively.
In most patients (96%), suffering from AMD with predominantly classic subfoveal CNV, during treatment with Lucentis for 12 months decreased incidence of significant decrease of (more than 3 lines), a third of patients (40%) showed improvement in visual acuity (more than 3 lines). In the group of patients, receiving photodynamic therapy with verteporfin, reducing the risk of loss of visual acuity (more than 3 lines) and improvement of visual acuity (more than 3 lines) We observed respectively 64% and 6% cases.
Through 12 Months use Lucentis in patients with AMD with a minimum expressed classic subfoveal CNV and latent mean change in visual acuity at near and distance compared to baseline ranged from +10.4 and + 7.0 letters, respectively (p<0.01). In the control group of patients with simulated injections mean change in visual acuity at near and distance compared to baseline was: -2.6 and -5.9 letters (p<0.01). Patients, treated with Lucentis, increased rate of capacity, related vision, on +6.8 points, and in patients, received sham injections, this figure fell to 4.7 item (p<0.01). When using Lucentis in patients with AMD with a minimum expressed classic subfoveal CNV and hidden improvement in visual acuity was maintained during 24 Months.
In most patients, suffering from AMD with predominantly classic subfoveal CNV, during treatment with Lucentis for 12 months mean change in visual acuity at near and distance compared to baseline ranged from +9.1 and + 9.3 letters, respectively (p<0.01). In the control group of patients, treated with verteporfin photodynamic therapy, Mean change in visual acuity at near and distance compared to baseline was +3.7 and +1.7 letters (p<0.01). Patients, treated with Lucentis, increased rate of capacity, related eye on +8.9 points, and in patients, received sham injections, This represents an improvement on the 1.4 item (p<0.01).
Pharmacokinetics
When administered intravitreally ranibizumab (1 times / month) patients with neovascular AMD Cmax ranibizumab in plasma was low and insufficient to inhibit the biological activity of VEGF-A in 50% (11 -27 ng / ml according to studies of cell proliferation in vitro). With the drug into the vitreous in the dose range of 0.05 to 1.0 mg Cmax ranibizumab in plasma was proportional to the dosage.
According to the results of pharmacokinetic analysis and in view of the elimination of ranibizumab average plasma T1/2 (at an application rate 0.5 mg) vitreous averaged about 9 days.
When administered intravitreally Lucentis (1 once a month) FROMmax ranibizumab plasma levels achieved during the days after injection, and is in the range 0.79-2.90 ng / ml. FROMmin ranibizumab plasma ranges 0.07-0.49 ng / ml. Concentration in serum ranibizumab approximately 90 000 times lower than that of the vitreous body.
Pharmacokinetics in special clinical situations
In patients with impaired renal function, special pharmacokinetic studies on the drug were not carried out. In 68% (136 from 200) patients, included in the pharmacokinetic analysis, had impaired renal function (46.5% -mild, 20% – moderate and 1.5% – severe). In patients with impaired renal function during treatment with the drug noted minimal decrease in clearance of ranibizumab, having no clinical significance.
In patients with impaired liver function specific pharmacokinetic studies on the use of ranibizumab were not carried out.
Testimony
- Neovascular (wet) form of age-related macular degeneration in adults.
Dosage regimen
Lucentis is used only as an injection into the vitreous body.
The recommended dose of Lucentis 0.5 mg (0.05 ml) 1 times / month as intravitreal injection.
The first three injections Lucentis operate with frequency 1 X / mo consecutively for 3 months, then drug treatment is stopped (the stabilization phase) regularly (no less 1 times / month) check visual acuity. By reducing the visual acuity over 5 letters ETDRS scale (1 line on the Snellen table) Lucentis treatment is resumed.
Between the introduction of two doses of the drug should be observed interval of at least 1 Months. Before the introduction of Lucentis should control the quality of dissolution and the color of the solution. The drug should not be used when changing the color of the solution and the appearance of insoluble visible particles.
Injection of drugs into the vitreous body should be performed under aseptic conditions, comprises treating the hands of health professionals, the use of sterile gloves, napkins, blepharostat (or an analogue thereof) and, if necessary tools for paracentesis.
Before the introduction of the drug necessary to carry out the proper disinfection of the eyelid skin and eye, conjunctiva and anesthesia therapy antimicrobial broad-spectrum. Antimicrobials should be instilled into the conjunctival sac 3 times / day for 3 days before and after administration.
The kit includes a needle Lucentis, equipped with filter, to extract the contents from the vial, a syringe and needle for injection.
Before opening the vial rubber stopper surface should be disinfected.
The contents of the vial into the syringe capacity gain 1 ml kept upright using a needle, equipped with a filter (pore size 5 m). After dialing the contents of the vial needle, equipped with a filter, It can not be used for intravitreal injection, It should be replaced by a needle for injection. With the introduction of the syringe into the vitreous body of the piston is stopped on mark 0.05 ml.
Lucentis should be administered into the vitreous at 3.5-4 kzadi mm from the limbus, avoiding the horizontal meridian and aiming towards the center of the needle the eyeball. The amount of drug administered is 0.05 ml. The following injections carried out in the other half of the sclera.
As for 60 Lucentis min after injection may increase intraocular pressure (IOP). IOP should be monitored, perfusion of the optic nerve, and if necessary to apply appropriate treatment. During one session administering Lucentis performed only in one eye.
Use of the drug in patients with impaired liver function It has not been studied. Given the low concentrations in blood plasma Lucentis, You do not need to change the dosage of the drug.
Patients with impaired renal function It does not require correction dose.
Patients aged 65 and older It does not require correction dose.
Side effect
The study of the safety of the drug was carried out in the course of clinical trials in 1315 patients for 2 years.
Serious adverse events, related to the procedure of administration, included endophthalmitis, rhegmatogenous retinal detachment and cataract due to iatrogenic injury. Other serious adverse events from the eyes, seen with Lucentis, included intraocular inflammation and increased intraocular pressure.
The following adverse events (possibly related to the use of the drug) occurred at a frequency of at least 2% patients, received a dose of Lucentis 0.5 mg, compared with the control group (simulation of injection or photodynamic therapy).
The incidence of adverse events was estimated as follows:: arise very often (≥1/10), often (≥1/100; <1/10), sometimes (≥1/1000; <1/100), rarely (≥1/10 000; <1/1000), rarely (<1/10 000).
Infections and infestations: Often – nazofaringit; often – flu.
From the hematopoietic system: often – anemia.
CNS: Often – headache; often – alarm.
On the part of the organ of vision: Often – intraocular inflammation, inflammation vitreous, vitreous detachment, retinal hemorrhage, visual impairment, sore eyes, turbidity in the vitreous, increased intraocular pressure, conjunctival hemorrhage, eye irritation, foreign body sensation in the eye, lacrimation, .Aloe, dry eye syndrome, red eyes, itching sensation in the eyes; often – degenerative changes of the retina, retinal damage, retinal disinsertion, retinal tears, detachment of the retinal pigment epithelium, gap pigment epithelium, reduced visual acuity, vitreous hemorrhage, the defeat of the vitreous, uveitis, Irit, iridocyclitis, Cataract, subkapsulyarnaya cataracts, PCO lens, punctate keratitis, corneal erosion, Opalescence cell in the anterior chamber, blurred vision, hemorrhage at the injection site, eye hemorrhage, conjunctivitis, allergic conjunctivitis, discharge from the eyes, photopsia, photophobia, discomfort in the eyes, swelling of the eyelids, soreness century, conjunctival hyperemia; sometimes – blindness, endophthalmitis, gipopion, gifema, keratopathy, adhesions of the iris, deposition in the cornea, corneal edema, corneal striae, pain or irritation at the injection site, abnormal sensation in the eye and irritation century.
The respiratory system: often – cough.
From the digestive system: often – nausea.
Allergic reactions: often – rash, hives, itch.
On the part of the musculoskeletal system: Often – artralgii.
Contraindications
- Confirmed or suspected eye infection or infectious processes periocular localization;
- Intraocular inflammation;
- Childhood and adolescence up 18 years (the efficacy and safety of the drug in these patients has not been studied);
- Pregnancy;
- Lactation;
- Hypersensitivity to ranibizumab or any other component of the drug.
FROM caution should be administered to patients with known history of hypersensitivity (Only after careful assessment of risk / benefit ratio).
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation (breast-feeding).
During the therapy with women of childbearing age should use reliable methods of contraception.
Cautions
Provide treatment Lucentis should only ophthalmologist, having experience in intravitreal injections.
Introduction Lucentis should always be carried out under aseptic conditions. Besides, during 1 weeks after the injection of the drug should be monitored for patients with a view to identifying possible local infection and timely treatment of. Should inform patients about the need to immediately tell your doctor about all the symptoms, which may indicate the development of endophthalmitis.
When injected into the vitreous inhibitors endothelial growth factor A (VEGF-A) theoretically may develop arterial thromboembolic events. However, in clinical studies in patients, treated with Lucentis, incidence of thromboembolic events was low and similar to that in the control group.
Effects on ability to drive vehicles and management mechanisms
Against the background of Lucentis may develop temporary visual impairment, adversely affect the ability to drive vehicles and use machines. If you experience symptoms such patients should not drive vehicles or operate machinery to reduce the severity of temporary visual impairment.
Overdose
In clinical trials and use of the drug in clinical practice, there were cases of unintentional drug overdose. In these cases, the most frequently observed increase in intraocular pressure and pain in the eye.
Treatment: In case of overdosing, be sure to control the IOP; if necessary, the patient must be under the supervision of a physician.
Drug Interactions
Lucentis interaction with other drugs has not been studied.
Lucentis should not be confused with any other drugs or solvents.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored in the dark, inaccessible to children at 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year. The drug should not be used after the expiration date.
