Expiration date: 01/2026

Release form

Lyophilisate for preparation of solution for p/to the introduction

Packaging

In vials of 100,000 UNITS. In a carton box 5 bottles.

Pharmacological action

The drug Refnot® has direct antitumor activity in vitro and in vivo on different tumor cell lines. The spectrum of cytotoxic and cytostatic effect on the tumor cells of the drug corresponds to the tumor necrosis factor ? (TNF) man, however, Refnot® has more than 100 times lower General toxicity than TNF.

The mechanism of antitumor action in vivo includes several ways to destroy tumors or stop its growth:

• the immediate impact of the protein tumor necrosis factor-thymosin alpha 1 (TNF-T) on the tumor cell target via appropriate receptors on its surface, resulting in apoptosis of the cells (cytotoxic effect) or cell cycle arrest (zitostaticescoe action). In the case of the latter event, the cell becomes more differentiated and expresses a number of antigens;
  
• the chemical cascade that includes activation of coagulation blood system and local inflammatory responses due to activated drug action of endothelial cells and lymphocytes and leading to a "hemorrhagic" tumor necrosis;
  
• the blocking of angiogenesis, leading to reduction in sprouting new vessels the fast-growing tumours and, as consequence, to reduction of blood supply until the necrotic center of the tumor;
  
• impact of immune system cells, the cytotoxicity of which were closely related to the presence of molecules of the TNF-T on their surface, or the process of maturation/activation of these cells is associated with response to TNF-T.
  

Combination drug Refnot® ?2 - and ?-interferons have a synergistic cytotoxic effect. The drug enhances the antiviral activity of recombinant interferon gamma in 100-1000 times (against vesicular stomatitis virus).

Refnot® increases the effectiveness of chemotherapy: actinomycin D, Cytosar, doxorubicin against tumor cells, weakly sensitive to them, eliminating this resistance. This allows us to consider Refnot® as a modifier of antitumor action of chemical drugs in cases of multi-drug resistance of tumor cells.

Refnot® has no cytotoxic effect on normal cells and in high concentrations in vitro stimulates the cell proliferation of the spleen and lymph nodes. It increases the production of antibodies to T-dependent antigens, has a stimulating effect on the cytotoxic activity of natural killer cells, has a stimulating effect on phagocytosis, increases the expression of antigens GCHS class I H-2K, CD-4 and CD-8 as a factor of differentiation of T-helpers and T-killers.

Testimony

Breast cancer in the combined therapy with chemotherapy.

Contraindications

• Pregnancy;
  
• lactation (breastfeeding);
  
• increased sensitivity to tumor necrosis factor-thymosin alpha 1 or any component of the drug.
  

Application of pregnancy and breastfeeding

The use of the drug Refnot® is contraindicated during pregnancy and lactation.

Composition

1 vial contains:

Active substance: tumor necrosis factor - thymosin ?-1 recombinant 100 thousand UNITS.

Excipients: mannitol (mannitol), sodium chloride, sodium phosphate dihydrate (sodium phosphate odnosemjannyj 2 water), sodium phosphate dodecahydrate (sodium disodium phosphate 12-water).

Method of application and doses

For the treatment of breast cancer in combination with chemotherapy the average daily dose is 200 000 UNITS. The drug is injected p/to a day of chemotherapy (30 minutes) and for 4 days after chemotherapy, 1 time/day.

Immediately before use the contents of bottle dissolved in 1 ml of water for injection.

Side effects

It was noted the development of reactions of individual hypersensitivity.

Some patients have observed short-term (several hours) rise in body temperature of 1-2°C, chills.

To reduce the intensity of side effects, we recommend taking indomethacin or ibuprofen have no effect on the cytotoxic action of the drug.

Drug interactions

Drug interactions drug Refnot® is not known

Overdose

Data on overdose of the drug Refnot® is not available.

Storage conditions

Store in a dry, dark, inaccessible to children place at temperature from 2° to 10°C. do Not freeze.

The dissolved drug must not be stored.

Shelf life

2 years.

Analogues

To analogues of this medicine include:

Ingaron

Vero-Ifosfamide

Leakage

Mielosan