PATIENT
PHYSICIANS
Marketing Authorization Number: ЛП-000671
Date of registration: 28.09.2011
Trade Name: Neovasculgen®
INN or Generic Name Deoxyribonucleic acid, plasmid (supercoiled circular double-stranded DNA).
Dosage form: lyophilisate for solution for intramuscular infusion.
Composition per vial: Active substance: plasmid supercoiled deoxyribonucleic acid pCMV-VEGF165 — 1.2 mg; Excipients: dextrose monohydrate — 60.0 mg, disodium hydrogen phosphate dodecahydrate — 3.94 mg, sodium dihydrogen phosphate dihydrate — 0.160 mg.
Appearance: white lyophilized powder.
Pharmacotherapeutic group: Stimulator of tissue reparation.
ATC-code: V03AX
Pharmacological properties: The drug Neovasculgen® is a highly purified supercoiled form of plasmid рCMV-VEGF165 encoding vascular endothelial growth factor (VEGF) under control of a promoter (a regulatory region of DNA). Recombinant plasmid DNA consists of the following components: a regulatory site fragment (22 base pairs) which determines the gene transcription, a mini-gene VEGF, upon expression of which a VEGF isoform consisting of 165 amino acids is synthesized, a splicing signal, a polyadenylation signal, and a transcription terminator SV40, which provides for the synthesis of the gene mature RNA and accessory regions required for effective biosythesis of plasmid DNA in E.coli producer-cells. Incorporation of plasmid DNA into the mammalian cells leads to the production of VEGF, which stimulates cells of the endothelium and results in the growth of blood vessels (vascularization) within the site of administration. The endothelial cells are involved in various processes such as vasoconstriction and vasodilatation, and antigen presentation; they are also the vital elements of all blood vessels, both capillaries, veins, and arteries. Thus, by stimulating the endothelial cells VEGF plays a key role in the process of angiogenesis. There are two different but structurally similar VEGF receptors located on the surface of vascular endothelial cells. These receptors, known as VEGF receptor 1 (Flt-1) and VEGF receptor 2 (DR/Flk-1) are receptor tyrosine kinases, which undergo phosphorylation after making a bond with VEGF ligand. The activation of these receptors leads to switching in numerous intracellular post-receptor signaling cascades triggering angiogenesis. The plasmid incorporation into the cells is a spontaneous process, and plasmid DNA cannot replicate in mammalian cells. A plasmid molecular weight is 2,817,091.85 g/mol. The size is 4,559 bp. The sensitivity to a breakage of one of 9,116 phosphodiester bonds is the specific characteristic of supercoiled circular DNA. A DNA molecule with a single broken bond loses its supercoiling and turns into a relaxed coiled form (a related compound). In an experiment Neovasculgen® stimulated proliferation of human endothelial cells comparable to a recombinant vascular endothelial growth factor; it also significantly stimulated the growth of the murine blood vessels. The drug is developed as a pharmaceutical product to reduce the rate of amputation and mortality in patients with chronic limb ischemia, especially those who cannot undergo standard revascularization procedure for an occlusive peripheral arterial disease.
Pharmakokinetics:No information available
Therapeutic Indications: In combination therapy for revascularization in lower limb ischemia of atherosclerotic genesis (Fontaine-Pokrovsky Stages IIa-III).
Contraindications: Hypersensitivity to the drug components. Age under 18 years.
Administration during pregnancy and breast feeding: the drug is contraindicated.
Route of administration and doses: The drug is given twice as intramuscular injections in a dose of 1.2 mg at an interval of 14 days as close to the ischemic area as possible. The drug solution should be prepared according to the instructions; after the standard skin preparation and in compliance with the aseptic requirements intramuscular injections are made into the affected muscles of the involved segment.
Side effects: Possible allergic reactions.
Overdosage: No information available.
Interaction with other medicinal products: No information available.
Special warnings:Prior to use add 3-5 ml of water for injection to the vial contents. Wait until fully dissolved (for 5-10 min). The solution for injection should be kept at room temperature. The drug must be used under the supervision of a surgeon in an inpatient or outpatient setting.
Effects on the ability to drive or to use machines: : Caution should be taken, as there are no data on the drug effects on the ability to drive or to use machines.
Presentation: Lyophilisate for solution for intramuscular infusion per 1.2 mg.
Storage conditions: Store in a place protected from light at temperature 2ºС — 8 ºС. Keep out of the reach of children.
Shelf life: 2 years. Do not use after the expiration date on the package.
Prescription status: On prescription.
Manufactured by: Federal State Institution « Hematology Research Center» of Ministry of Healcare of the Russian Federation. 4, Novy Zykovsky pr., Moscow, 125167, Russia
