Docetaxel (docetaxel) concentrate for solution for infusions 10 mg/ml. 8 ml. (80 mg.) vial №1

Description

Docetaxel №1 Composition
active substance: docetaxel;

1 ml of concentrate contains 10 mg of docetaxel;

Docetaxel №1 excipients: citric acid, polyethylene glycol 300, polysorbate 80, ethanol 96%.

Docetaxel №1 Dosage form
Concentrate for preparation of solution for infusion.

Basic physical and chemical properties: transparent, colorless or pale yellow solution.

Docetaxel №1 Pharmacotherapeutic group
Antineoplastic drugs. Plant alkaloids and other natural products. Taxanes. ATX code L01C D02.

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 breakdown, 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 implementation of vital cell functions both during mitosis and in interphase.

Pharmacodynamic effects

An in vitro clonogenic assay has shown the cytotoxicity of docetaxel against various murine and human tumor cell lines, as well as against cells from only remote human tumors. Docetaxel reaches significant concentrations in the extracellular fluid and ensures a long cell life. In addition, docetaxel is active against some (although not all) cell lines in which the expression of the p-glycoprotein encoded by the drug multidrug resistance gene takes place. In in vivo studies, it turned out that the effect of docetaxel does not depend on the mode of use and is manifested in experiments by a wide spectrum of antitumor activity types on common tumors – both experimental tumors of mice and grafted human tumors.

Pharmacokinetics
Absorption

The pharmacokinetics of docetaxel was studied in phase I studies in patients with cancer after administration of 20-115 mg / m2 of the drug. The pharmacokinetic profile of docetaxel is independent of dose and corresponds to a three-chamber pharmacokinetic model with elimination half-lives for the α-, β- and γ-phases of 4 minutes, 36 minutes 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 taking 100 mg / m2, which was infused over 1 hour, the average peak plasma concentration – 3.7 μg / ml – was obtained from the corresponding AUC of 4.6 μg / ml / hour. The average values ​​of the total clearance and the equilibrium volume of distribution of the drug were 21 l / m2 / year and 113 l, respectively. Interindividual differences in total clearance reached 50%. Docetaxel binds to plasma proteins by more than 95%.

Withdrawal

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

Indications
Mammary cancer

Docetaxel Ebeve in combination with doxorubicin and cyclophosphamide is intended for the adjuvant treatment of patients with:

operable breast cancer with lymph node involvement;
operable breast cancer without affecting the lymph nodes.
In patients with resectable breast cancer without lymph node involvement, adjuvant therapy should be limited if patients are to be treated with chemotherapy according to internationally accepted criteria for primary therapy for early-stage breast cancer.

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

Docetaxel Ebeve as monotherapy is indicated for the treatment of patients with locally or metastatic breast cancer following ineffective cytotoxic therapy, which included an anthracycline or an alkyluvalue agent.

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

Docetaxel Ebeve in combination with capecitabine is indicated for the treatment of patients with local or metastatic breast cancer after ineffective cytotoxic therapy that includes anthracycline.

Non-small cell lung cancer

Docetaxel Ebeve is indicated for the treatment of patients with locally or metastatic non-small cell lung cancer following ineffective previous chemotherapy.

Docetaxel Ebeve in combination with cisplatin is indicated for the treatment of patients with locally inoperable or metastatic non-small cell lung cancer who have not received previous chemotherapy for the condition.

Prostate cancer

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

Adenocarcinoma of the stomach

Docetaxel Ebeve 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 Ebeve in combination with cisplatin and 5-fluorouracil is intended for induction therapy of patients with local squamous clitin carcinoma of the head and neck.

Contraindications
Hypersensitivity to the active substance or to any of the excipients.
The initial level of neutrophils <1500 cells / mm 3. The period of pregnancy and lactation. Severe liver dysfunctions (see Sections “Dosage and Administration” and “Application Features”). Consideration should be given to contraindications to other drugs that are used in combination with docetaxel.