Ranibizumab - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Ophthalmic products

Included in the formulation

Lucentis®

solution d / eye

Novartis Pharma AG Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

S.01.L.A Preparations preventing neovascularization

S.01.L.A.04 Ranibizumab

Pharmacodynamics:

Means for treatment of exudative hemorrhagic form of age-related macular degeneration (AMD).

A fragment of a humanized recombinant monoclonal antibody is expressed by a recombinant strain of Escherichia coli. directed against vascular endothelial growth factor A (VEGF-A). Strongly binds to the isoforms of VEGF-A (including VEGF110, VEGF121 and VEGF165), which prevents its binding to its own receptors (VEGFR-1 and VEGFR-2).

It causes inhibition of endothelial proliferation, neovascularization and decreased sweating of fluid through the vessels: slowing the progression of age-related macular degeneration.

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 and macular edema in patients with diabetes mellitus.

Pharmacokinetics:

When ranibizumab is administered to the vitreous body (once a month), patients with neovascular form age-related macular degeneration, the maximum concentration of ranibizumab in blood 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 administered to the vitreous humor at a dose range of 0.05 to 1 mg, the maximum plasma concentration was proportional to its dose.

Based on the results of the pharmacokinetic analysis and taking into account the removal of ranibizumab from blood plasma, the mean 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 0.79-2.9 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 the serum is approximately 90,000 times lower than that in the vitreous.

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 of patients in whom it was previously performed.
Treatment of visual acuity reduction caused by edema of the macula due to retinal vein occlusion (the central vein of the retina or its branches).
Treatment of visual acuity reduction caused by choroidal neovascularization caused by pathological myopia.

ICD-10

VII.H30-H36.H35.3 Degeneration of the macula and posterior pole

VII.H30-H36.H36.0 * Diabetic retinopathy (E10-E14 + with common fourth sign .3)

VII.H30-H36.H34 Vascular occlusion of the retina

VII.H43-H45.H44.2 Degenerative myopia

VII.H49-H52.H52.1 Myopia

VII.H55-H59.H58.1 * Visual impairment in diseases classified elsewhere

Contraindications:

Hypersensitivity to ranibizumab or any other component of the drug.
Proven or suspected eye infections or infectious processes of periocular localization.
Intraocular inflammation.
Pregnancy.
Lactation period.
Children under 18 years of age (efficacy and safety of the drug in this category of patients has not been studied).

Carefully:

Patients with a known 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.The use of VEGF inhibitors in patients with diabetic macular edema and macular edema due to retinal vein occlusion and choroidal neovascularization due to pathological myopia, with a history of stroke or transient ischemia of the brain, should be performed with caution because of the risk of developing thromboembolic events. The drug should not be used concurrently with other drugs that affect the endothelial growth factor of the vessels (local or systemic application).

Clinical conditions in which ranibizumab therapy should be discontinued and should not be resumed:

- Reducing visual acuity by ≥30 letters compared to the last definition;

- intraocular pressure ≥ 30 mm Hg. p.

- rupture of the retina;

- subretinal hemorrhages affecting the central fossa, or lesion area ≥ 50%;

- condition after intraocular surgery or until planned in the next 28 days.

It is necessary to observe aseptic conditions during the injection of ranibizumab to prevent the development of complications such as endophthalmitis, retinal rupture, iatrogenic traumatic cataract.

Caution should be exercised when using the drug in patients with age-related macular degeneration and with the revealed extensive detachment of pigment epithelium, as they have an increased risk of development of pigment epithelial ruptures.

The drug should be used with caution in patients at risk of developing rheumatogenic retinal detachment. In patients with rheumatogenic retinal detachment or rupture of the macula of the 3rd, 4th stages of treatment with ranibizumab should be discontinued.

The experience with ranibizumab in patients with retinal vein occlusion in history and in patients with ischemic occlusion of the central vein of the retina or its branches is limited. In patients with retinal vein occlusion, in which there are clinical manifestations of irreversible ischemic loss of visual function, the drug is not recommended.

Pregnancy and lactation:

Recommendations for FDA - Category C. Qualitative and well-controlled studies in humans have not been conducted. In animals, a high incidence of fetal death and interruption of pregnancy results. The application is permissible if the potential benefit to the mother exceeds the risk to the fetus.

There is no information on the penetration into breast milk, penetrates into the milk of animals. The use is contraindicated.

Dosing and Administration:

Applied only in the form of injections in the vitreous.

The recommended dose is 0.5 mg once a month.

The first three injections are performed at a frequency of once a month consecutively for 3 months, then treatment with ranibizumab is terminated (stabilization phase) and regularly (at least 1 time per month) is checked for visual acuity. With a drop in visual acuity of more than 5 letters on the ETDRS visual acuity scale (1 line in the Snellen table), treatment with ranibizumab is resumed.

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

Side effects:

Infections and infestations: nasopharyngitis; flu.

From the side hematopoiesis system: anemia.

From the side mentality: anxiety.

From the side CNS: headache; stroke.

From the side organ of vision: intraocular inflammation, vitreous inflammation, vitreous humor, retinal hemorrhages, visual disturbances, eye pain, opacity in the vitreous, increased intraocular pressure, conjunctival hemorrhages,eye irritation, foreign body sensation in the eye, 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, decreased visual acuity, vitreous hemorrhage, vitreous damage, uveitis, iritis, iridocyclitis, cataracts, subcapsular cataracts, lens capsules, pinpoint keratitis, corneal erosion, cell opalescence in the anterior chamber of the eye, blurred vision, injection site hemorrhage, eye hemorrhage, conjunctivitis, allergic conjunctivitis, discharge from the eyes, photopsy, photophobia, a feeling of discomfort in the eyes, eyelid edema, tenderness of the eyelids, congestion hyperemia; blindness, endophthalmitis, hypopion, hyphema, keratopathy, iris adhesions, corneal deposits, corneal edema, corneal striae, pain and irritation at the injection site, atypical sensations in the eye and irritation of the eyelids.

From the side respiratory system: cough.

From the side digestive system: nausea.

Allergic reactions: rash, hives, itching.

From the side musculoskeletal system: arthralgia.

Overdose:

Symptoms: increased intraocular pressure, transient blindness, decreased visual acuity, corneal edema, and pain in the eye (including the cornea).

Treatment: Symptomatic, including a decrease in intraocular pressure.

Interaction:

Interaction with other drugs has not been studied.

Do not mix with any other medicines or solvents.

Special instructions:

Only the ophthalmologist who has the experience of performing intravitreal injections should administer the drug. The administration of ranibizumab 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 in patients with diabetic macular edema there is a higher risk of systemic exposure to the drug, it is necessary to remember and a 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.

Injection of endothelial growth factor A (VEGF-A) inhibitors into the vitreous humor may lead to 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 ranibizumab, a temporary increase (within 60 min after injection) of intraocular pressure was noted. There have also been cases of sustained improvement intraocular pressure. Against the background of the recommended monitoring intraocular pressuree and perfusion of the optic disc.

Ranibizumab is not recommended to be administered simultaneously in both eyes (safety and efficacy of thiswere studied). This can lead to increased systemic exposure and the risk of side effects.

The experience with ranibizumab is limited in patients with diabetic macular edema due to Type 1 diabetes mellitus in patients previously treated with intraocular preparations 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. Also, there is no experience of using the drug in patients with diabetes mellitus with a glycated hemoglobin level of more than 12% and uncontrolled hypertension.

The experience with ranibizumab is limited in patients with pathological myopia, previously unsuccessfully exposed photodynamic therapy with verteporfinom (WFDT). Despite the fact that patients with subfoveal and juxtafoveal localization of the lesion had a similar effect, there is insufficient data for the conclusions regarding the effectiveness of the drug in patients with pathological myopia with extrafoveal localization of the lesion.

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

Against the background of the application, it is possible to develop temporary visual impairments that adversely affect the ability to drive vehicles and work with mechanisms. If such symptoms occur, patients should not drive vehicles or work with mechanisms until the severity of temporary visual disturbances is reduced.

Instructions

Ranibizumab (Ranibizumabum)