Docetaxel Amaxa (docetaxel) concentrate for solution for infusions 20 mg/ml. 4 ml. (80 mg.) vial

Description

Docetaxel 4 ml. Storage
active substance: docetaxel;

1 ml of concentrate contains 20 mg of docetaxel;

Docetaxel 4 ml. excipients: polysorbate 80, povidone, anhydrous citric acid, anhydrous ethanol.

Docetaxel 4 ml. Dosage form
Concentrate for solution for infusion.

Main physical and chemical properties: clear, oily, pale yellow solution.

Pharmacotherapeutic group
Antineoplastic agents. Taxanes. ATX code L01C D02.

Pharmacological properties

Pharmacodynamics.

Docetaxel is an antineoplastic drug whose mechanism of action is based on promoting the aggregation of tubulin into stable microtubules and inhibiting their disintegration, which leads to a significant reduction in the level of free tubulin. Binding of docetaxel to microtubules does not alter the number of protofilaments.

In vitro studies have shown that docetaxel disrupts the microtubular network, which plays an important role in the realization of cell vital functions both during mitosis and in the interphase.

Clonogenic analysis in vitro showed the cytotoxicity of docetaxel against different lines of animal and human tumor cells, as well as to cells of newly removed human tumors. Docetaxel reaches significant concentrations in the intercellular fluid and provides a long cell life. In addition, docetaxel is active against some (though not all) cell lines that express p-glycoprotein encoded by the drug multidrug resistance gene. In vivo studies have shown that the effect of docetaxel is independent of the mode of administration and is manifested in experiments with a wide range of antitumor activity against common tumors: both experimental animal tumors and vaccinated human tumors.

Pharmacokinetics.

Absorption The pharmacokinetics of docetaxel have been studied in phase I studies in cancer patients after administration of 20-115 mg / m2. The pharmacokinetic profile of docetaxel is dose-independent and corresponds to a three-chamber pharmacokinetic model with half-lives for α-, β- and γ-phases of 4 min, 36 min and 11.1 hours, respectively. This duration of this indicator in the last phase is partly due to the relatively slow outflow from the peripheral chamber.

Distribution. After administration of a dose of 100 mg / m2, which was administered by infusion over 1 hour, the mean maximum concentration of the drug in blood plasma (Cmax) – 3.7 μg / ml – was obtained with the corresponding area under the pharmacokinetic curve “concentration – time” (AUC) 4 , 6 μg / ml / hour. The mean total clearance and equilibrium volume of drug distribution were 21 l / m2 / h and 113 l, respectively. Interindividual differences in total clearance reached approximately 50%. Docetaxel is more than 95% bound to plasma proteins.

Indication
Breast cancer

Docetaxel in combination with doxorubicin and cyclophosphamide is intended for adjuvant therapy in patients with:

operable breast cancer with lymph node involvement;
operable breast cancer without lymph node involvement.
Adjuvant therapy should be given to patients with operable breast cancer without lymph node involvement if patients are receiving chemotherapy according to accepted international criteria for primary therapy for early-stage breast cancer. Docetaxel in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for the disease.

Docetaxel as monotherapy is indicated for the treatment of patients with locally progressive or metastatic breast cancer after ineffective cytotoxic therapy, which included anthracyclines or an alkylating drug.

Contraindication
Docetaxel is contraindicated in patients with a history of severe hypersensitivity reactions to docetaxel or polysorbate 80; patients with neutrophil count less than 1500 / mm3; patients with severe liver dysfunction.

Contraindications to other drugs should be considered in combination with docetaxel.