Docetaxel

When ATH:
L01CD02

Characteristic.

Semi-synthetic antitumor agent of plant origin, obtained by chemical synthesis from natural raw materials - European yew needles (Taxus baccata). White or almost white powder, highly lipophilic and practically insoluble in water. Molecular weight 861,9.

Pharmacological action.
Antitumor, cytostatic.

Application.

Locally advanced or metastatic breast cancer as the primary chemotherapy (1-Line) or the ineffectiveness of previous therapy (2-line treatment);

- Locally advanced or metastatic non-small cell lung cancer as a 1st or 2nd line treatment;

- Metastatic ovarian cancer after failure of prior therapy 1st line (2-line treatment).

Contraindications.

Hypersensitivity, neutropenia (<1,5In the treatment of severe infections in patients with a normal white blood cell count in adults - at a dose⁹/l), expressed human liver (increased levels of bilirubin, transaminases, AP - see. Precautions).

Restrictions apply.

Children up to age 16 years (safety and effectiveness of poorly studied, there is limited experience in children).

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding (unknown, Do penetrates docetaxel in breast milk).

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): neutropenia, thrombocytopenia, anemia; abnormal heart rhythm, heart failure, decrease or increase in blood pressure, Cases of venous thromboembolism and myocardial infarction.

From the digestive tract: nausea, vomiting, diarrhea / constipation, anorexia, stomatitis, taste disturbance, esophagitis, pain in the stomach, increase in serum levels of AST, GOLD, Alkaline phosphatase, giperʙiliruʙinemija; cases of gastro-intestinal bleeding.

For the skin: alopecia; skin rash, often accompanied by itching, sometimes followed by desquamation, leading in some cases to the interruption or termination of docetaxel; Hypo- or pigmentation of nails and onycholysis.

Allergic reactions: hypersensitivity reactions of mild or moderate severity (flushing, rash combined with itching, narrowing in Gruda, backache, dyspnoea and drug fever or chills), severe reactions (accompanied by hypotension and / or bronchospasm or generalized rash / erythema) - Cm. Precautions.

Other: peripheral neuropathy (paraesthesia, dysesthesia or pain, weakness), peripheral edema (Original usually appear on the lower extremities), ascites, asthenia, arthralgia and myalgia, injection site reactions (giperpigmentatsiya, inflammation, redness or dryness of the skin, phlebitis, bleeding or swelling of the veins).

Cooperation.

In clinical studies the interaction of docetaxel with other drugs have not been assessed. Studies in vitro shows, that the metabolism of docetaxel may be changed while the application substances, which induce, inhibit or are metabolized with isoenzyme CYP3A: cyclosporine, terfenadine, ketoconazole, erythromycin and other (Care must be taken while the appointment, given the opportunity to express interaction).

Docetaxel is largely associated with a protein (cm. Farmakokinetiku). Although the possible interaction of docetaxel with other drugs live It has not been studied, However in vitro other drugs, It is closely associated with malnutrition, such as erythromycin, difengidramin, propranolol, propafenone, phenytoin, salicilaty, sulfamethoxazole and sodium valproate did not affect the binding of docetaxel with proteins. Docetaxel did not influence the binding of digitoxin.

Overdose.

Symptoms: mielosuprescia, peripheral neurotoxicity, mucositis.

Treatment: hospitalization of the patient to a specialist unit, Careful monitoring of vital functions, simptomaticheskaya therapy. Patients should be as soon as possible to appoint a granulocyte colony stimulating factor. Spetsificheskiy antidote unknown.

Dosing and Administration.

B / slowly (during 1 no), single, every 3 Sun, at a dose of 75-100 mg / m² (depending on indications and regimens).

Precautions.

Treatment is carried out only with the assistance of an experienced specialist in anti-tumor therapy in the presence of conditions, needed for the relief of complications (in a specialized hospital). In order to prevent hypersensitivity reactions, as well as to reduce the fluid retention is recommended for all patients 1 day before treatment assign dexamethasone into a daily dose of 16 mg for a period of 3 day.

Careful monitoring of patients, especially during the first and second infusion of docetaxel because of the possibility of hypersensitivity reactions. Mild symptoms of hypersensitivity (facial flushing or localized skin reactions) do not require interruption of drug administration. With the development of severe hypersensitivity reactions (hypotension and / or bronchospasm, generalized rash / erythema) Necessity of ending the infusion and carrying out relevant measures for relief of medical complications. Repeated use of docetaxel in these patients is not permitted.

All patients in the docetaxel, careful regular monitoring of peripheral blood. With the development of serious adverse reactions (neutropenia <0,5In the treatment of severe infections in patients with a normal white blood cell count in adults - at a dose⁹/l, continuing more 7 days, or febrile neutropenia, or the development of severe skin reactions, or severe peripheral neuropathy) during docetaxel, the dose for the next injections should be reduced to 100 to 75 mg / m² and / or 75 to 60 mg / m². If such complications arise when applying the docetaxel dose 60 mg / m², treatment should be discontinued.

Prior to the start of therapy and before each subsequent cycle of docetaxel should be determined by liver function tests.

Patients, receiving docetaxel monotherapy at a dose of 100 mg / m² and having a high activity of serum transaminase (ALT and / or AST), more than 1,5 times the upper limit of normal (VGN), combined with increased serum levels of alkaline phosphatase in more than 2,5 times the ULN, increased risk of side effects: gastrointestinal bleeding, grade IV neutropenia, febrile neutropenia, infection, vыrazhennaya thrombocytopenia, severe stomatitis,severe skin toxicity, sepsis. Due to such patients with elevated liver function recommended dose of docetaxel is 75 mg / m². Patients with elevated bilirubin levels and / or increased activity of ALT and AST (>3,5 VGN) in conjunction with increased levels of alkaline phosphatase in more than 6 times the ULN, docetaxel is not recommended. At the moment, there are no data on the use of docetaxel in combination with other drugs in patients with impaired hepatic function.

Due to the possibility of fluid retention should be carefully monitored for patients with pleural effusion, pericardium or with ascites.

During treatment and for, at least, 3 months after cessation of therapy must be protected from pregnancy.

Cautions.

Caution must be exercised in applying and preparing docetaxel solutions (as working with other anticancer drugs). In preparing solutions, it is recommended to use gloves. In case of contact with skin or mucous membranes must be thoroughly rinsed with water mucosal, and skin - with soap and water.

Cooperation