When administered intravitreally ranibizumab (1 per month) in patients with neovascular AMD maximum drug concentration (Cmax) in plasma was low and insufficient to inhibit the biological activity of VEGF-A by 50% (11 -27 ng / ml as studies of cell equipoise dosage proliferation in vitro). When administered drug in the vitreous humor in a dose range from 0.05 to 1.0 mg Cmax ranibizumab plasma was proportional to the dosage.
Based on the results of pharmacokinetic analysis and considering excretion ranibizumab from blood plasma, the average half-life of the drug (dose 0.5 mg) of vitreous average It was about 9 days.
When administered intravitreally Lucentis (1 per month) ranibizumab plasma concentration reaches the maximum value within one day after injection, and is in the range 0.79-2.90 ng / ml. Ranibizumab minimum concentration in plasma is in the range of 0.07-0.49 ng / mL. The concentration of serum ranibizumab approximately 90,000 times lower than that of the vitreous body. Patients with impaired renal function In patients with impaired renal function specific pharmacokinetic studies on the use of the drug have not been conducted. In 68% (136 of 200) of patients included in the pharmacokinetic analysis had renal impairment (46.5% – mild, 20% – moderate and 1.5% -Heavy degree). In patients with impaired renal function on the background of treatment with minimal observed decrease in clearance of ranibizumab, has no clinical significance. Patients with hepatic impairment In patients with impaired hepatic function on the application of specific pharmacokinetic studies have not been conducted ranibizumab.
Neovascular (wet) form of age-related macular degeneration in adults.
- Hypersensitivity to ranibizumab or any other component of the formulation.
- Confirmed or suspected infection of the eye or periocular infections processes of localization.
- Intraocular inflammation.
- Children under 18 years of age (efficacy and safety of the drug in these patients has not been studied).
- Pregnancy and lactation.
Patients with a known history of hypersensitivity, the presence of stroke risk factors, the drug should be administered only after a careful assessment of risk / benefit ratio.
DOSAGE AND ADMINISTRATION
Lucentis is used only as an injection into the vitreous body.
The recommended dose of Lucentis is 0.5 mg (0.05 mL) 1 time a month as an injection into the vitreous body.
The first three Lucentis injections performed at a frequency of 1 time per month consistently for 3 -x months after drug treatment is stopped (stabilization phase) and regularly (at least 1 time per month) check visual acuity. By reducing the visual acuity of more than 5 letters on the ETDRS cupboard (1 line on the Snellen chart) treatment Lucentis resume.
Between the introduction of two doses of the drug should be observed interval of at least 1 month.
Before the introduction of Lucentis should monitor the quality of solution and the solution color. The drug should not be used when the color of the solution change and the emergence of insoluble visible particles.
The injection of the drug into the vitreous body should be carried out under aseptic conditions, including treatment of the hands of health professionals, the use of sterile gloves, napkins, blepharostat (or its equivalent) and, if necessary tools for paracentesis.
Before the introduction of the drug necessary to carry out proper disinfection of the skin of eyelids and around the eyes, anesthesia of the conjunctiva and therapy antimicrobials wide spectrum.
antimicrobial drugs should be instilled into the conjunctival sac 3 times a day for 3 days before and after drug administration.
Lucentis should be administered into the vitreous body at 3.5-4 mm posterior to the limbus, avoiding the horizontal meridian and directing the needle toward the center of the eyeball. The volume of drug administered is 0.05 ml.
Next injection of a drug into the other half of the sclera.
As for 60 min after injection Lucentis may increase intraocular pressure (IOP), must be controlled IOP perfusion of the optic nerve n apply appropriate treatment, if necessary.
One session administering Lucentis is performed only in one eye. patients with hepatic impairment Use of the drug in patients with hepatic impairment has not been studied. Given the small concentration of Lucentis in plasma, does not require changes in drug dosing regimen. Patients with impaired renal function, patients with impaired renal function does not require dose adjustment. Patients aged 65 years and older patients aged 65 years and older did not require dose adjustment .
safety study of the drug was carried out in the course of clinical trials in 1315 patients within 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 with the use of the drug) were observed in the frequency of at least 2% of patients treated with Lucentis 0.5 mg, compared with the equipoise dosage control group (simulated injection or photodynamic therapy).
The incidence of adverse events was estimated as follows: emerging “very often” ( > 1 / 10), “often” ( > 1/100, <1/10), “sometimes” ( > 1/1000, <1/100), “rare”; ( > 1/10000, <1/1000), “very rare”; . (<1/10000)Infections and infestations : very often -nazofaringit; often – flu. From the hematopoietic system : often – anemia. Psychiatric disorders : often – anxiety. From the nervous system : very often – headache, sometimes – a stroke. From a sight organ : very often -intraokulyarnoe inflammation, inflammation of the vitreous, vitreous detachment, retinal haemorrhage, visual disturbances, eye pain, turbidity in the vitreous body, increased intraocular pressure, conjunctival hemorrhage, eye irritation, a feeling of “foreign body” in the eyes, lacrimation, blepharitis, a syndrome of “dry” eyes, eye redness, itching sensation in the eyes, often degenerative changes in the retina, retinal damage, retinal detachment, retinal tears, detachment of the retinal pigment epithelium, RPE tear, reduced visual acuity, vitreous hemorrhage, vitreous loss, uveitis, iritis, iridocyclitis, cataract, subcapsular cataracts, clouding of the posterior lens capsule, punctate keratitis, corneal erosion, cell opalescence in the anterior chamber of the eye, blurred vision, bleeding at the injection site, eye haemorrhage, conjunctivitis, allergic conjunctivitis, eye discharge, photopsia, photophobia, discomfort in the eyes, swelling of the age, tenderness eyelids, conjunctival hyperemia, sometimes – blindness, endophthalmitis, hypopyon, hyphema, keratopathy, adhesions of the iris, the deposits in the cornea, corneal edema, striae cornea, pain or irritation at the site of injection, abnormal sensation in the eye and irritation century. From the respiratory system : often – cough. From the digestive system : often – nausea. Dermatological disorders : often -allergicheskie reactions (rash, hives, itching. On the part of the musculoskeletal system : very often -artralgii.
INTERACTION WITH OTHER DRUGS
Lucentis interaction with other drugs has not been studied.
Lucentis should not be mixed with any other drugs or solvents.
Overdose In clinical trials and use of the drug in clinical practice, there were cases of unintentional overdose. In these cases, an overdose of Lucentis most frequently observed increased intraocular pressure and pain in the eye . In case of overdose should be sure to monitor the intraocular pressure; if necessary, the patient must remain under medical supervision.
provide treatment Lucentis should only ophthalmologist who has experience performing intravitreal injection.
The introduction of Lucentis must always be carried out under aseptic conditions. In addition, within I week after injection of the drug should be monitored in patients with a view to identifying possible local infection and of timely treatment. It is necessary to inform patients about the need to immediately tell your doctor about all of the symptoms that may indicate the development of endophthalmitis.
When intravitreal injection of inhibitors of endothelial growth factor A (VEGF-A) may develop arterial thromboembolic events.
When intravitreal injection of VEGF inhibitors A (VEGF-A) may develop arterial thromboembolic events. The risk of stroke can be higher in the presence of risk factors in patients, including equipoise dosage previous myocardial stroke or transient cerebrovascular accidents in history. during the therapy with women of childbearing age should use reliable methods of contraception.
Effects on ability to drive vehicles and use machines
On the background of Lucentis may develop temporary visual impairment, adversely affecting the ability to drive vehicles and use machines. If you have these symptoms, patients should not drive vehicles or operate machinery to reduce the severity of temporary visual impairment.