Overview
Bortezomib vita: instructions for use
Koanaa can be harmful to your health.
It is necessary to consult a doctor, as well as read the instructions before use.
1 bottle contains: Active substance: bortezomib - 3.5 mg. Excipients: mannitol - 25 mg white or almost white lyophilized mass or powder; Bortezomib is a reversible, highly selective inhibitor of Bortezomib activity of the 26B proteasome of mammalian cells and is a modified boric acid. 26S - proteasome, is present in the nucleus and cytosol of all eukaryotic cells and is a key component that catalyzes the breakdown of the main proteins involved in the management of cell life cycle. Bortezomib inhibits the chymotrypsin-like action of the proteasome, causes inhibition of proteolysis and leads to apoptosis. Myeloma cells (in vitro) are almost a thousand times more susceptible to apoptosis caused by bortezomib than normal plasma cells. The main factor explaining the ability of a bortezomib proteasome inhibitor to kill myeloma cells is its ability to block NF-kB activation. In Koanaa cells, NF-kB (which exists as the p50-p65 dimer) is bound to the inhibitory protein LkB. which keeps it inactive in the cytosol. Some tumors contain activated forms of NF-kB, and the proteasome plays an important role in this activation, as it catalyzes the proteolytic generation of the subgroup NF-kB p50 from the inactive precursor p50 and the destruction of the inhibitory protein LkB. Activated NF-kB, penetrating the nucleus, helps the cell survive and proliferate. By inhibiting the proteasome and therefore inhibiting the activation of NF-k, bortezomib helps reduce the number of antiapoptotic factors, inflammatory molecules, cell adhesion molecules (which allow connective cells to attach to bone marrow cells) and cytokines (which stimulate the growth of myeloma cells). In vivo, bortezomib has slowed the growth of many experimental models of human tumors, including multiple myeloma.
After a single intravenous administration, the concentration of bortezomib in the blood plasma decreases along a two-phase curve, characterized by a fast initial phase
distribution and a longer final elimination phase. The half-life of the drug in the initial phase of the distribution ranges from 5 to 15 hours.
The systemic effect of bortezomib is dose-dependent in the dose range from 1.45 to 2.0 mg / m2 and in the dose range of 1.0-1.3 mg / m2, the systemic effect increases in proportion to the dose.
After a single or repeated administration in doses of 1.0 and 1.3 mg / m2, the average volume of distribution of bortezomib in patients with multiple myeloma is 1659-3294 l (489-1884 l / m2). This suggests that bortezomib is intensively distributed in peripheral tissues.
At bortezomib concentrations of 100-1000 ng / ml, the binding of the drug to blood plasma proteins averages 82.9%. In vitro, the metabolism of bortezomib is predominantly carried out by cytochrome P450 isoenzymes - CYP3A4, CYP2C19 and CYP1A2. Only a small amount of unchanged substance is excreted in the urine, and unchanged bortezomib is not found in bile and feces.
Ways of excretion of bortezomib in vivo have not been studied.
The drug is intended for the treatment of:
multiple myeloma in patients previously receiving 1st-line treatment of mantle cell lymphoma in patients previously receiving at least 1 line of therapy.
Contraindications
- Hypersensitivity to bortezomib, boron, as well as Bortezomib any of the components that make up the drug;
- period of breastfeeding;
- children's age (lack of experience)
-severe violations of the liver and kidneys.
Dosage and administration
The drug is administered iv in a jet for 3-5 seconds.
The recommended initial dose of bortezomib is 1.3 mg / m2 body surface area 2 times a week for 2 weeks (days 1, 4, 8 and 11) followed by a 10-day break (days 12-21). The treatment cycle is 21 days. Between the introduction of successive doses of Bortezomib-Vita, at least 72 hours should pass.
The degree of clinical response is recommended to be evaluated after 3 and 5 treatment cycles.
If a full clinical response is achieved, 2 additional treatment cycles are recommended.
With a treatment duration of more than 8 cycles, Bortezomib-Vita can be used according to the standard regimen or the maintenance therapy regimen - weekly for 4 weeks (days 1.8, 15, 22) followed by a 13-day rest period (days 23-35).
Recommendations for dose adjustment and administration of Bortezomib-Vita:
Bortezomib the development of any non-hematological toxic effect of the 3rd degree or hematological toxicity of the 4th degree, with the exception of Koanaa, treatment with Bortezomib-Vita should be suspended.
After the symptoms of toxicity disappear, treatment with Bortezomib-Vita can be resumed in a dose reduced by 25% (a dose of 1.3 mg / m2 is reduced to 1 mg / m2, a dose of 1 mg / m2 is reduced to 0.7 mg / m2).
If the symptoms of toxicity do not disappear or reappear at the minimum dose, then the possibility of withdrawal of Bortezomib-Vit should be considered, unless the benefits of its use clearly exceed the risk.
When neuropathic pain and / or peripheral neuropathy associated with the use of Bortezomib-Vit appears, the dose of the drug is changed in accordance with the table. In patients with a history of severe neuropathy, Botezomib-Vita can be used only after a thorough assessment of the risk / benefit ratio.
The degree of impaired renal function does not affect the pharmacokinetics of Bortezomib-Vit. Therefore, for patients with renal failure, dose adjustment is not required. Since dialysis can reduce the concentration of bortezomib in the blood, the Koanaa should be administered after dialysis.
Bortezomib-Vita is administered iv in a stream for 3-5 seconds in combination with melphalan and prednisone taken orally. Spend nine 6-week cycles, as shown in the table. In cycles 1-4, Bortezomib-Vita is used 2 times a week (days 1, 4, 8, 11, 22, 25, 29 and 32), and in cycles 5-9 Bortezomib 1 time per week (days 1, 8, 22 and 29).
