Docetaxel CRCA (docetaxel) concentrate for infusions 20 mg/ml. 4 ml. (80 mg.) №1 vial

Description

Docetaxel CRCA Storage
active substance: docetaxel;

1 ml of concentrate for solution for infusion contains 20 mg of docetaxel;

Docetaxel CRCA Excipients: citric acid anhydrous, ethanol anhydrous, polysorbate 80.

Docetaxel CRCA Dosage form
Concentrate for solution for infusion.

Main physical and chemical properties: clear solution from pale yellow to brownish-yellow color, practically without mechanical inclusions.

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

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Docetaxel is an antineoplastic drug, the mechanism of action of which is based on the fact that the drug promotes the accumulation of tubulin in the microtubules of cells and prevents their disintegration, which leads to a significant decrease 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 vital cell functions during both mitosis and interphase.

Pharmacodynamic effects

Clonogenic analysis in vitro showed cytotoxicity of docetaxel against various mouse and human tumor cell lines, 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 in which p-glycoprotein encoded by the drug multidrug resistance gene is expressed. 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 tumors of mice and vaccinated human tumors.

Pharmacokinetics.

Absorption

The pharmacokinetics of docetaxel were studied in phase I studies in cancer patients after administration of 20-115 mg / m2 of the drug. 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 infused over 1 hour, the mean peak plasma concentration of 3.7 μg / ml was obtained with a corresponding AUC of 4.6 μg / ml / h. 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.

Breeding

A 14C-docetaxel radioisotope study was performed in three cancer patients. After oxidative metabolism of the tert-butyl ether group under the action of cytochrome P450, docetaxel was excreted in both urine and feces for 7 days; urinary excretion was 6%, with feces – 75% of the amount of radioisotope administered. About 80% of the isotope contained in the faeces was excreted within the first 48 hours as one major inactive metabolite, three minor metabolites, and a very small amount of the drug unchanged.

Indication
Breast cancer

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

operable breast cancer with lymph node involvement;
operable breast cancer without lymph node involvement.
In patients with operable breast cancer without lymph node involvement, adjuvant therapy should be limited if patients are receiving chemotherapy according to accepted international criteria for primary treatment of early-stage breast cancer.

Docetaxel KRKA in combination with doxorubicin is indicated for the treatment of patients with locally progressive or metastatic breast cancer who have not previously received cytotoxic therapy for this disease.

Docetaxel KRKA 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 agent.

Docetaxel KRKA in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer with increased expression of HER-2 tumor cells, if they have not previously received chemotherapy for metastases.

Docetaxel KRKA in combination with capecitabine is indicated for the treatment of patients with locally progressive or metastatic breast cancer after ineffective cytotoxic therapy, which included anthracyclines.

Non-small cell lung cancer

Docetaxel KRKA is indicated for the treatment of patients with locally progressive or metastatic non-small cell lung cancer after ineffective prior chemotherapy.

Docetaxel KRKA in combination with cisplatin is indicated for the treatment of patients with inoperable locally progressive or metastatic non-small cell lung cancer, if previous chemotherapy for this condition has not been performed.

Prostate cancer

Docetaxel KRKA in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer.

Gastric adenocarcinoma

Docetaxel KRKA in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including gastroesophageal adenocarcinoma, if they have not previously received chemotherapy for metastases.

Head and neck cancer

Docetaxel KRKA in combination with cisplatin and 5-fluorouracil is indicated for the induction therapy of patients with locally advanced squamous cell carcinoma of the head and neck.

Contraindication
Hypersensitivity to the active substance or to any of the excipients. Baseline neutrophil count <1500 cells / mm3. Severe hepatic impairment (see sections “Method and Dosage” and “Specifics”).

Contraindications for the use of other drugs administered in combination with docetaxel should also be considered.