Instructions

The product is mellow or porous white paste, it is hygroscopic.

Antitumor drug.
Immunomodulating drug.
ATC code[LO1ХХ], [LO3АХ]

REFNOT has direct antitumor effect in vitro and in vivo on the different lines of tumor cells. The specter of its cytotoxic and cytostatic effect on tumor cells is equal to human tumor necrosis factor a (TNF), but REFNOT toxic potential is more than 100 times lower, than TNF.
The REFNOT mechanism of antineoplastic action in vivo includes several ways, by which the product destroys the tumor or stops its progress:

• A direct influence of tumor necrosis factor thymosine alpha 1 (TNF-T) protein on the target tumor cell through the corresponding receptors on its surface, the end result of which is the cell apoptosis (cytotoxic effect) or cell cycle arrest (cytostatic effect). In case of the latter event the cell also becomes more differentiated and expresses a variety of antigens;
• A cascade of chemical reactions, including the activation of hemic coagulative system and local inflammatory responses determined by the TNF-TREFNOT-activated endothelium cells and lymphocytes, that leads to the “haemorrhagic” tumor necrosis;
• angiogenesis blocking, due to which the aggressive tumor grows new vessels slower, which results in decrease of blood supply up to the necrosis of the tumor center;
• the influence of the immune system cells, the cytotoxicity of which turned out to be closely connected with the presence of TNF molecules on their surface or the growing process/activation of those cells is connected with the response to TNF-T.

The combinations of REFNOT with а2- or у-interferons have synergistic cytotoxic effect. REFNOT increases antiviral activity of recombinant gamma-interferonby 100-1000 times (against vesicular stomatitis virus). REFNOT increases the efficiency of chemotherapeutic agents: actinomycin D, cytosar, doxorubicine– against tumor cells with low response to them by eliminating their resistance. It allows to consider REFNOT an antitumor action modifier of chemocytostatics in case the tumor cells are resistant to multiple drugs.
REFNOT does not have cytotoxic effect on normal cells, moreover, in high concentration in vitro it even stimulates cell growth in the spleen and lymph nodes. It also amplifies antisubstance production on T-dependent antigens, stimulates the cytotoxic effect of natural killer cells against tumor cells, stimulates phagocytosis, amplifies expression of Н-2К, CD4 and CD8 antigens of I class major histocompatibility complex, being the factor of differentiation between T-helpers and T-killers.

Breast cancer combined with chemotherapeutic agents.
As an immunomodulator for melanoma on the disseminate stage of the disease.

Hypersensitivity to tumor necrosis factor-thymosine alpha 1 recombinant or any other component of the drug.
Pregnancy and breast-feeding.

For breast cancer treatment combined with chemotherapy the daily average dose is 200000 units.
The drug is injected subcutaneously on the day of chemotherapy (30 minutes prior) and during 4 days after chemotherapy 1 time a day.
As an immunomodulator for melanoma on the disseminate stage of the disease Refnot is injected subcutaneously in the dosage of 100,000 units once a day five times a week (then a 2-days pause) or in the dosage of 400,000 units once a day 3 times a week (every other day) during 2-4 weeks prior to chemotherapy. A subcutaneous injection into one or several points is permissible; it is recommended to change the injection points.
When applied without following chemotherapy, Refnot is injected subcutaneously in the dosage of 100,000 units once a day five times a week (then a 2-days pause) during four weeks. If the disease does not progress, the injections may be continued.
The contents of the vial are dissolved in 1 ml of water for injections immediately before use.

Individual hypersensitivity to the drug has been noted. In some patients REFNOT causes short (up to several hours) temperature rise by 1-2°C, and chills.
Side effects can be neutralized by additional intake of indomethacin or ibuprofen, which do not affect cytotoxic impact of the product.

Lyophilisate for preparation of solution, which is injected subcutaneously in vials (100000 units of active substance per 1 vial).
1, 5, 10 or 20 vials of the product are placed in cardboard box along with information leaflet or 1, 5, 10 or 20 vials of the product in blister pack or cartridge pack are placed in cardboard box along with information leaflet.

Store in dry, shadowed, childproof place at a temperature of 2-10 °C.
Do not freeze.
The dissolved product is not subject to storage.

2 years. Do not use after expiry date.

Sold on prescription.

Refnot-Pharm, LLC, Russia (rented manufacturing site of Ferment Firm, LLC), Russia
121069, Russia, Moscow, B. Molchanovka Str., 34, building 2 Phone: +7 (495) 691-00-36, 695-48-72.