Ramilatis (Solution) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Nord, JSC (Russia)

Manufactured By

Qilu Pharmaceutical, Co. Ltd. (China)

Or

Pharmasintez-Nord, JSC (Russia)

ATC Code

S01LA04 (Ranibizumab)

Active Substance

Ranibizumab (Rec.INN registered by WHO)

Dosage Form

Ramilatis

Solution for intraocular administration 10 mg/ml

Dosage Form, Packaging, and Composition

Solution for intraocular administration

0.23 ml – vials – carton packs – Prescription only
0.23 ml – vials – carton packs /in a kit with a filter needle, syringe, injection needle/ – Prescription only
0.23 ml – vials – carton packs /in a kit with a filter needle/ – Prescription only

Clinical-Pharmacological Group

A drug used for age-related macular degeneration. Monoclonal antibodies to vascular endothelial growth factor A (VEGF-A)

Pharmacotherapeutic Group

Drugs used in ophthalmology; drugs used for diseases of the uvea; agents preventing neovascularization

Pharmacological Action

Ramilatis is a treatment for the exudative-hemorrhagic form of age-related macular degeneration (AMD). Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor A (VEGF-A) and is expressed by a recombinant strain of Escherichia coli.

Ranibizumab selectively binds to isoforms of vascular endothelial growth factor, VEGF-A (VEGF₁₁₀, VEGF₁₂₁, VEGF₁₆₅), and prevents the interaction of VEGF-A with its receptors on the surface of endothelial cells (VEGFR₁ and VEGFR₂), which leads to the suppression of neovascularization and vascular proliferation. By inhibiting the growth of new choroidal vessels into the retina, Ranibizumab stops the progression of the exudative-hemorrhagic form of AMD and macular edema in patients with diabetes mellitus.

The use of ranibizumab resulted in a pronounced and persistent decrease in the thickness of the central retinal zone, as measured by optical coherence tomography.

The safety profile of ranibizumab in patients with diabetic macular edema was similar to that in the treatment of the wet form of AMD.

Pharmacokinetics

When ranibizumab was administered intravitreally (once a month) to patients with the neovascular form of AMD, the C_max 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 administered intravitreally in a dose range from 0.05 to 1.0 mg, the C_max of ranibizumab in plasma was proportional to its dose.

Based on the results of pharmacokinetic analysis and taking into account the elimination of ranibizumab from blood plasma, the average T_1/2 (when used at a dose of 0.5 mg) from the vitreous body averaged about 9 days.

When administered intravitreally (once a month), the C_max of ranibizumab in blood plasma is reached within one day after injection and is in the range of 0.79-2.90 ng/ml. The C_min of ranibizumab in blood plasma is in the range of 0.07-0.49 ng/ml.

Indications

Treatment of the neovascular (wet) form of age-related macular degeneration in adults; treatment of visual acuity reduction associated with diabetic macular edema as monotherapy or in combination with laser coagulation in patients who have previously undergone laser coagulation.

ICD codes

Dosage Regimen

It is used only as injections into the vitreous body.

The recommended dose is 0.5 mg once a month.

The first three injections are performed with a frequency of once a month sequentially for 3 months, then treatment with ranibizumab is stopped (stabilization phase) and visual acuity is regularly checked (at least once a month). If visual acuity decreases by more than 5 letters on the ETDRS visual acuity scale (1 line on the Snellen chart), treatment with ranibizumab is resumed.

An interval of at least 1 month should be observed between the administration of two doses.

Adverse Reactions

Infections and infestations very common – nasopharyngitis; common – influenza.

Blood and lymphatic system disorders common – anemia.

Psychiatric disorders common – anxiety.

Nervous system disorders very common – headache; uncommon – stroke.

Eye disorders very common – intraocular inflammation, vitreous inflammation, vitreous detachment, retinal hemorrhages, visual disturbances, eye pain, vitreous opacities, increased intraocular pressure, conjunctival hemorrhages, eye irritation, foreign body sensation in the eye, lacrimation, blepharitis, dry eye syndrome, eye redness, itchy eyes; common – retinal degenerative changes, retinal disorder, retinal detachment, retinal tears, retinal pigment epithelial detachment, pigment epithelial tear, decreased visual acuity, vitreous hemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, cataract, subcapsular cataract, posterior lens capsule opacification, punctate keratitis, corneal erosions, anterior chamber cell flare, blurred vision, injection site hemorrhage, ocular hemorrhage, conjunctivitis, allergic conjunctivitis, eye discharge, photopsia, photophobia, eye discomfort, eyelid edema, eyelid pain, conjunctival hyperemia; uncommon – blindness, endophthalmitis, hypopyon, hyphema, keratopathy, iris adhesions, corneal deposits, corneal edema, corneal striae, injection site pain and irritation, atypical eye sensations and eyelid irritation.

Respiratory, thoracic and mediastinal disorders common – cough.

Gastrointestinal disorders common – nausea.

Immune system disorders common – rash, urticaria, pruritus.

Musculoskeletal and connective tissue disorders very common – arthralgia.

Contraindications

Confirmed or suspected eye infections or periocular infectious processes; intraocular inflammation; children and adolescents under 18 years of age; pregnancy; lactation (breastfeeding) period; hypersensitivity to ranibizumab.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Special Precautions

Use with caution in patients with a history of hypersensitivity reactions, in the presence of risk factors for stroke. In such cases, use is possible only after a thorough assessment of the risk/benefit ratio.

Intravitreal injection of vascular endothelial growth factor A (VEGF-A) inhibitors may lead to the development of arterial thromboembolic complications.

The risk of stroke may be higher in patients with risk factors, including a previous history of stroke or transient ischemic attacks.

Effect on ability to drive vehicles and operate machinery

During treatment with ranibizumab, temporary visual disturbances may develop that adversely affect the ability to drive vehicles and operate machinery. If such symptoms occur, patients should not drive vehicles or operate machinery until the temporary visual disturbances subside.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.