Taxotere side effects. Taxotere - description of the drug, instructions for use, reviews. Special instructions for admission

A drug based on docetaxel, one of the many anticancer drugs, the alkaloid Taxotere is a concentrated liquid for intravenous infusion. Often this drug used for second-line chemotherapy, for various cancerous processes in the body.

Taxotere is sold in pharmacies only with a prescription from a doctor.

ATX code

L01CD02 Docetaxel

Active ingredients

Docetaxel

Pharmacological group

Anticancer drugs plant origin

pharmachologic effect

Anticancer drugs

Cytostatic drugs

Indications for use Taxotere

Taxotere may be prescribed in the following situations:

• as an adjuvant treatment for a cancerous process in the mammary gland, involving the nearest lymph nodes. Treatment is supplemented with drugs Doxorubicin and Cyclophosphamide;
• with a localized cancerous process in the mammary gland, with metastasis, in combination with the drug Doxorubicin and as an initial chemotherapeutic regimen. Chemotherapy, both first and second line, is possible. A unilateral treatment regimen may be combined with capecitabine if the initial therapy consisted of anthracyclines and alkylating drugs and was found to be ineffective;
• as an initial chemotherapeutic regimen for breast cancer with the presence of metastases and oncoexpression of HER2 in combination with Trastuzumab;
• in localized or metastatic non-small cell lung cancer (in combination with Cisplatin and Carboplatin), as a baseline chemotherapy regimen, or re-treatment in the absence of the effect of the previous regimen, including medicines based on platinum;
• with a metastatic cancerous process in the ovaries, if the previous type of chemotherapy was found to be ineffective;
• with an inoperable localized squamous cell carcinoma in the head and cervical, in combination with cisplatin and 5-fluorouracil, as initial treatment;
• with metastatic squamous cell carcinoma in the head and cervical region as a second-line chemotherapy regimen;
• with a metastatic hormone-dependent malignant process in combination with medications Prednisolone and Prednisone;
• with a metastatic malignant tumor process in the stomach (including the cardiac section), as an initial treatment in conjunction with the medications Cisplatin and 5-fluorouracil.

Release form

Taxotere is a concentrated substance intended for the manufacture of an infusion liquid.

Taxotere consists of the active ingredient docetaxel and the additional ingredient polysorbate 80. The package includes a solvent liquid in the form of 13% ethyl alcohol diluted with water for injection.

The drug has the appearance of a colorless oily liquid, the color of which varies from yellowish to brownish. The concentrated medicine is poured into bottles:

• 20 mg/0.5 ml;
• 80 mg/2 ml.

Vials are glass, transparent. Rubber stopper with aluminum protection and green or red plastic cap.

One package contains 1 vial of concentrated medicine and 1 vial of dissolving liquid. Cell packaging sealed with polyethylene. Additionally, an information annotation to the medication is included in the pack.

name analysis of analogues of the drug Taxotere

Pharmacodynamics

Taxotere is a natural-based antitumor chemotherapeutic agent (taxoid group). The action of the drug is due to the stimulation of the accumulation of tubulin in resistant microtubules, as well as in the prevention of their decomposition, which leads to a decrease in the amount of freely existing tubulin. The connection of the active component and microtubules does not affect the number of protofilaments.

Laboratory testing indicates that Taxotere alters the microtubular network, which has great importance in the cellular phase of mitosis and interphase.

The drug exhibits toxicity to various malignant cells. At the same time, the effect of Taxotere may not depend on the frequency of use of the agent and manifest itself with an extensive spectrum of anticancer activity.

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Pharmacokinetics

The kinetic properties of Taxotere depend on the amount of drug administered. Communication with plasma proteins is more than 95%.

During the week, the active metabolite is excreted in the urinary fluid and stool(approximately 6% and 75% respectively). Most of the drug, which is excreted in the feces, can be detected within 2 days as an inactive product.

At small functional disorders liver indicators of total clearance are reduced by 27%, compared with the average.

Clearance indicators of the active ingredient of the drug do not change with a small accumulation of fluid in the body.

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Use of Taxotere during pregnancy

The antitumor agent Taxotere is prohibited for use in pregnant and lactating patients.

Before and during treatment with a medication, contraceptives should be used, which are also used 3 months after the end of the course of chemotherapy.

If a woman becomes pregnant during chemotherapy, she must immediately notify the attending doctor.

Clinical trials have shown that Taxotere has a genotoxic effect and can even degrade the quality of male sperm. Therefore, both women and men, during the period of treatment with the drug and within six months after the therapeutic course, it is necessary to take measures to prevent the possible conception of a child. Sometimes, if a couple plans to have children in the future, it is advisable to cryopreserve the sperm before starting a course of chemotherapy.

Contraindications

In some diseases and conditions, treatment with Taxotere may be considered impossible:

• when the level of neutrophils in the peripheral circulation is less than 1500 per μl;
• with significant functional disorders of the liver;
• during the period of gestation and breastfeeding of the baby;
• in childhood and adolescence up to 18 years;
• with a high probability of an allergic reaction in relation to the ingredients of the drug.

During combined treatment with additional drugs it is also necessary to take into account other contraindications that relate to auxiliary medicines.

Side effects of Taxotere

Like all chemotherapy drugs, Taxotere has a long list of side effects:

• severe transient neutropenia occurring against the background of fever, septic complications and pneumonia;
• thrombocytopenia with the possibility of bleeding, anemia;
• allergic manifestations (reddening of the skin, itching, shortness of breath, bronchospasm, rash);
• hair loss, skin rashes, pigmentation of the nail plates, onycholysis;
• swelling of the extremities, accumulation of fluid in abdominal cavity, generalized edema;
• dyspepsia, changes in taste sensations, inflammation of the mucous membrane of the esophagus, stomach, intestines;
• ulcers of the digestive tract, bleeding;
• limb numbness, peripheral neuropathy, convulsive syndrome;
• arrhythmias, changes in blood pressure, increased thrombus formation, pre-infarction and infarction conditions;
• hepatitis, pneumonia, development of pulmonary fibrosis;
• pain in the joints and muscles, myasthenia gravis;
• conjunctivitis, lacrimation, transient visual disturbances;
• deterioration of the skin condition, increased pigmentation, pinpoint hemorrhages on the skin, inflammatory lesions of the veins;
• chest pain, redness of the palms and feet, dehydration.

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Dosage and administration

To prevent allergic processes and accumulation of fluid in the tissues, all patients (excluding patients with prostate adenocarcinoma) are premedicated with glucocorticosteroid drugs before starting chemotherapy. An example of a premedication scheme:

• Dexamethasone 8 mg orally twice a day for 3 days;
• the initial dose of the drug should be taken the day before the start of chemotherapy.

In case of adenocarcinoma of the prostate during therapy with prednisolone (or prednisone), premedication with Dexamethasone at a dosage of 8 mg is carried out 12 hours, three hours and 60 minutes before the start of chemotherapy.

Preventive administration of G-CSF may be given to reduce the risk of blood complications.

Taxotere is administered intravenously-drip, for one hour, once every 21 days.

• In the adjuvant treatment of a cancerous process in the breast, the standard dosage of Taxotere can be 75 mg / m² 60 minutes after the use of Doxorubicin (50 mg / m²) and Cyclophosphamide (500 mg / m²), once every 21 days. Treatment includes 6 injections.

As self-treatment Taxotere is administered at a dose of 100 mg/m² once every 21 days. In combination with the drugs Doxorubicin (50 mg/m²) and Capecitabine (1250 mg/m²), Taxotere is administered in an amount of 75 mg/m² once every 21 days.

In combination with Trastuzumab, the amount of Taxotere is 100 mg/m² once every 21 days.

• For non-small cell lung cancer, Taxotere is used at 75 mg/m², either alone or in combination with platinum-based drugs, once every 21 days.
• With metastatic cancerous process in the ovaries, Taxotere is used at a dosage of 100 mg / m² once every 21 days.
• With locally localized squamous cell tumors of the head and cervical region, Taxotere is administered in an amount of 75 mg / m². On the same day with the medication, Cisplatin is administered in an amount of 75 mg / m² for 60 minutes, followed by a drip of 5-fluorouracil 750 mg / m² per day, for five days. This scheme is applied once every 21 days and can be repeated up to 4 times.
• In metastatic squamous cell carcinoma of the head and cervical region, Taxotere is administered in an amount of 100 mg/m² once every 21 days.
• In case of a metastatic hormone-independent cancerous process in the prostate gland, Taxotere is administered in an amount of 75 mg / m² once every 21 days. Prednisolone is taken orally at 5 mg twice a day during the entire course of chemotherapy.
• In case of a metastatic cancer process in the stomach (including in the cardiac region), Taxotere is administered in an amount of 75 mg / m² once every 21 days. On the same day, Cisplatin should be instilled in an amount of 75 mg / m², over a 1-3 hour infusion, followed by the introduction of 5-fluorouracil in an amount of 750 mg / m² (daily infusion for 5 days).

(used in the form of docetaxel trihydrate), the excipient is polysorbate 80 - in a volume of 0.5 ml. Attached solvent: 191.1 mg of ethanol, as well as 1.5 ml of water for injection.

In vial of conc. 80 mg 2 ml contains 80 mg of active substance - docetaxel (used in the form of docetaxel trihydrate), the excipient is polysorbate 80 - 2 ml. The solvent is attached: 764.4 mg of ethanol, as well as 6 ml of distilled water for injection.

In vial of conc. docetaxel 160 mg(used as docetaxel trihydrate), vial volume 8 ml excipients are ethanol - 3.2 g and polysorbate 80 - 4.3 g.

Release form

Concentrate for mixing infusions. solution (20 mg per 0.5 ml or 80 mg per 2 ml) is an oily solution with a yellow or brownish-yellow color. A clear, colorless solvent is used for preparation. The drug is produced with a solvent in vials of colorless glass of the first type, corked with rubber stoppers and crimped with aluminum caps with flip-off plastic caps that are green (conc. 20 mg) or red (conc. 80 mg).

Concentrate for mixing infusions. solution (20 mg in 1 ml) is a solution that has a yellow or brown-yellow color. Depending on the concentration active ingredient the color of the plastic flip-off cap is different:

• 20 mg in 1 ml vials have green caps;
• 80 mg in 4 ml vials highlighted in pink;
• 160 mg in 8 ml vials - blue.

The vials are sealed in PVC blisters, sealed with PE film and placed in cardboard boxes.

pharmachologic effect

It has cytostatic and antitumor activity.

Pharmacodynamics and pharmacokinetics

This anticancer drug is of plant origin and belongs to the group taxoid . The mechanism of action is based on the accumulation tubulin in microtubules and preventing their decay to disrupt the process of tumor cell division. Active substance predominantly exhibits activity against cells that produce an excess amount of P-glycoprotein (abbr. Р-gР), which is encoded by the gene of multiresistance to chemotherapeutic drugs.

In vivo studies have shown that Taxotere has a broad spectrum of activity against tumors in laboratory mice (transplanted human tumor cells). Efficiency has been established for , ovarian cancer , stomach , heads and neck, non-small cell lung cancer , hormone resistant prostate cancer .

Characterization of pharmacokinetics docetaxel : Dose-dependent, triphasic model with α, β, γ phase half-lives of 4 minutes, 36 minutes, and 11 hours, respectively.

The active substance binds to blood plasma proteins by ≥95%. Tertbutyl ether group docetaxel undergoes oxidation by the P450 isoenzyme system. During the week, excretion occurs: by the kidneys with urine (from 6% of the dose), through the gastrointestinal tract along with feces (75%), 80% of the administered dose in the first two days is excreted in the form of inactive metabolites with feces.

Carrying out combination therapy docetaxel in combination with does not lead to a change in their pharmacokinetic parameters.

Indications for use

Taxotere is used in the treatment of tumors and other neoplasms in combination with various drugs:

• breast cancer (operable): Taxotere is used in combination with, at adjuvant ) may be without or with damage to regional lymph nodes;
• Breast cancer (operable) with overexpression of HER 2 in combination with Doxorubicin and Cyclophosphamide and subsequent therapy with Taxotere with trastuzumab );
• breast cancer locally widespread or metastatic in combination with Doxorubicin as first-line treatment, monotherapy, or with;
• metastatic breast cancer overexpression of HER 2 (in combination with trastuzumab , LS 1st line).

• locally advanced type or metastatic non-small cell type of lung cancer in case of failure of chemotherapy as a monotherapy drug;
• unresectable locally advanced type or metastatic non-small cell in combination with Cisplatin or with as an alternative treatment for cisplatin therapy - as a drug of the 1st line.

Malignant neoplasms of the ovaries

• metastatic malignant neoplasm Ovarian: Taxotere is used when previous first-line chemotherapy has failed and is used as monotherapy or second-line drug.

• hormone-resistant metastatic (androgen-independent AI) prostate cancer in combination with or .

• at metastatic stomach cancer , including neoplasms of the transition area of ​​the esophagus to the stomach - in combination with Cisplatin , Fluorouracil as first line treatment.

Malignant neoplasms of the head and neck

• in locally advanced squamous cell carcinoma of the head , as well as neck Taxotere is used in combination with Cisplatin , Fluorouracil - as an induction therapy.

Contraindications

Contraindications must be taken into account when using Taxotere both in monotherapy and in combination with other drugs:

• hypersensitivity reactions to active docetaxel or polysorbate 80 ;
• a similar number of neutrophils - within 1500 / μl in peripheral blood;
• pronounced functional disorders liver;
• pregnant or breastfeeding patients;
• children's age group up to 18 years.

With caution, Taxotere is used with drugs that can induce or inhibit isoenzymes 3A of cytochrome P450, as well as be metabolized with their help. These include various antifungal agents from imidazoles (for example, ), Troleandomycin , Ritonavir and inhibitors of enzymes - proteases.

Side effects

Development frequency adverse reactions specified using the WHO NDP classification:

• very often there were adverse reactions if ≥10%;
• often 1-10% of cases;
• infrequently, when 0.1 - 1%;
• rarely occurred 0.01 - 0.1%;
• very rarely observed - less than 0.01%.

Taxotere monotherapy

The following reactions may occur from various systems, organs of the human body:

• Blood and lymphatic system: ≥10% reversible or non-cumulative neutropenia , infections; 1-10% - the development of severe infections against the background of a decrease in the number of neutrophils in the peripheral blood volume, sepsis , pneumonia , possibly fatal thrombocytopenia , anemia , .
• Immune system: in ≥10% of cases, mild or moderate allergic reactions occurred in the first minutes of intravenous infusion and manifested as flushing of the skin, rash, itching, chest tightness, back pain, shortness of breath, drug fever, chills; "often" more severe allergic reactions were observed in the form of reduced blood pressure, bronchospasm,.
• Skin and subcutaneous tissues: "very often" reversible skin reactions of mild to moderate severity were observed in the form of localized rashes with itching on the hands, feet, face, chest, as well as hypo- or hyperpigmentation of the nails, pain and onycholysis (loss of a nail), ; 1-10% developed severe skin reactions: rashes with desquamation , severe manifestations of the syndrome of lesions of the palms.
• Gastrointestinal: "very often" adverse reactions occurred in the form of nausea, vomiting, diarrhea, anorexia , ; often - esophagitis , epigastric pain, severe bleeding gastrointestinal tract.
• Liver and biliary tract: ≥10% - increase in serum activity enzymes AST, ALT, alkaline phosphatase , quantity .
• Nervous system: ≥10% - , dysesthesia , burning sensation, muscle weakness, taste disturbance; 1-10% - severe manifestations of neurosensory, neuro motor reactions; 0.1-1% - severe violations of taste sensations.
• Heart: "often" there were violations of the heart rhythm; infrequent occurrences heart failure .
• Vessels: 1-10% experienced an increase or decrease in blood pressure and bleeding.
• Respiratory system: shortness of breath.
• Support device: myalgia , arthralgia .
• General: edema , body weight gain.

Taxotere in combination therapy

• C : increased frequency of occurrence anemia , neutropenia , thrombocytopenia , infections , including severe forms, nausea, vomiting, diarrhea, stomatitis , heart failure , hair loss, with a decrease in the frequency of development allergic reactions(on the part of the skin, nails, fluid retention), the development of anorexia, neurosensory and motor reactions, hypotension , myalgia , asthenia .
• With Doxorubicin and Cyclophosphamide (according to the scheme TAS ): decrease in the frequency of occurrence neutropenia , anemia , infections, allergic reactions, edema, adverse reactions nervous system, diarrhea, arrhythmias, but an increase in the frequency of anemia, thrombocytopenia , stomatitis , nausea, vomiting, constipation, taste disorders, arthralgia and . Additional adverse reactions: myeloid , myelodysplastic syndrome . Moreover, G-CSF able to reduce the incidence of neutropenia and subsequent neutropenic infections by 60%.
• With Capecitabine : more frequent side effects from the gastrointestinal tract, arthralgia , heavy thrombocytopenia and anemia , hyperbilirubinemia , hand and foot syndrome , however, more rare cases neutropenia , alopecia , onycholysis , asthenia and myalgia , anorexia and decreased appetite. Additional adverse reactions:, dryness and mouth, dermatitis and erythematous rashes, pyrexia , pain in the extremities, in the back, manifestations lethargy (drowsiness, numbness, lethargy), shortness of breath and cough, nosebleeds, paresthesia , dizziness, peripheral neuropathy, dehydration.
• With trastuzumab : nausea occurs more often, and other disorders of the gastrointestinal tract described above against the background of Taxotere, as well as neutropenia , arthralgia , develops anorexia , severe toxic manifestations of the 4th degree, heart failure (in combination with prior adjuvant therapy with anthracyclines ). More rare cases neutropenia 3 and 4 degrees, asthenia, alopecia, nail lesions, skin rashes, vomiting, stomatitis and myalgia. Additional side effects: lacrimation, conjunctivitis and inflammation of the mucous membranes, erythema , nasopharyngitis , nosebleeds, rhinorrhea flu-like symptoms, cough, fever, chills, lethargy or insomnia , shortness of breath, indigestion , paresthesia , headaches.
• Scheme AC-TN leads to an increase in the incidence of most adverse reactions, for example, alopecia , anemia , thrombocytopenia feeling of nausea, myalgia , arthralgia , heart failure, etc. Less common: severe and febrile neutropenia , fluid retention, manifestations of neurosensory, neuromotor reactions, rash with desquamation, allergic reactions. Additionally: insomnia an increase in the amount of creatinine in the blood.
• With either Carboplatin : increased frequency of occurrence thrombocytopenia , nausea, diarrhea, anorexia, local reactions. Decrease in cases neutropenia , anemia, infections, skin reactions and nail lesions, edema, stomatitis, neurosensory and, to a lesser extent, neuromotor reactions, alopecia , asthenia , myalgia . Additionally, it may occur, incl. in the absence of infection, as well as pain.
• With or Prednisone : a significant decrease in the frequency of adverse events in the form of anemia, infection, neutropenia , thrombocytopenia , allergic reactions, myalgia , arthralgia , neurosensory, neuromotor reactions, hair loss, rash with desquamation, anorexia, fluid retention, the above gastrointestinal reactions against the background of Taxotere, except for taste disturbances and heart failure , the cases of which are increasing. Additionally: nosebleeds, cough, lacrimation, shortness of breath.
• With Cisplatin and Fluorouracil anemia is more common thrombocytopenia , febrile type neutropenia and the development of neutropenic infections (including when using G-CSF ), may cause nausea with vomiting, the development anorexia , stomatitis , diarrhea, esophagitis/dysphagia and pain when swallowing. At the same time, infections and allergic manifestations, edema, neuropathies, myalgia , as well as alopecia . Additional list of adverse reactions: fever , lethargic manifestations, hearing change, dizziness, tearfulness, heartburn, myocardium, conjunctivitis , weight loss.

Information about the use of Taxotere after registration

It was found that against the background docetaxel and chemotherapeutic agents and / or radiation "very rarely" occurred acute form myeloid leukemia and myelodysplastic syndrome . In addition, the following data were obtained from individual organs and systems:

• Blood and lymphatic system: cases of oppression of hematopoiesis in the bone marrow, development DIC syndrome(disseminated within vascular coagulation ) is most often combined with sepsis or poly organ failure .
• Immune system: "rarely", up to a lethal outcome (the probability is greater in the absence of premedication).
• Nervous system: "rarely" convulsions or transient loss of consciousness, sometimes occurring directly with intravenous infusions.
• Organs of vision: "rarely" lacrimation, conjunctivitis , visual disorders, "very rarely" obstruction of the lacrimal canal, up to its rupture.
• Organs of hearing: "rarely" cases of ototoxic effects of the drug, impaired and / or loss of hearing.
• CCC: venous thromboembolic complications, .
• Respiratory system: acute respiratory distress syndrome , interstitial pneumonia or lung disease, respiratory failure, pulmonary fibrosis and other complications that can lead to death.
• Gastrointestinal: "rarely" perforation , colitis , intestinal obstruction , obstruction .
• Liver and bile ducts: hepatitis may be fatal in patients with liver disease.
• Epidermis: , erythema multiforme , Stevens-Johnson syndrome , toxic necrolysis . Lymphangiectatic edema can lead to similar scleroderma changes.
• Local reactions: rare cases of the phenomenon of the return of the local radiation effect in the area previously irradiated, as well as the development of pulmonary edema.
• Kidneys and urinary tract: deterioration of the functional state of the kidneys, up to kidney failure due to the nephrotoxic effect of the drug.
• Metabolism: hyponatremia caused by dehydration, pneumonia and vomiting.

Taxotere, instructions for use (Method and dosage)

Taxotere must be administered intravenously over 1 hour once every three weeks.

Premedication GCS

To prevent hypersensitivity reactions and reduce fluid retention in the absence of contraindications, premedication is started before Taxotere therapy (1 day in advance). GKS , for example, Dexamethasone . It is taken: inside 16 mg in two doses during the day for 3 days.

In order to reduce the risk of hematological complications, prophylactically administered granulocyte colony stimulating factor (abbr. G-CSF) .

Different types of breast cancer (BC)

Use of adjuvant therapy: resectable breast cancer with and without lesions of regional lymph nodes, the dosage is 75 mg per square meter. 1 hour after the injection Doxorubicin at a dose of 50 mg/sq.m. and Cyclophosphamide at a dose of 500 mg/sq.m. every three weeks (according to the TAC scheme). It is recommended to carry out 6 cycles. Dosage for operable breast cancer with HER 2 overexpression:

• Chemotherapy AC-TN : AC (1st–4th cycle) Doxorubicin 60 mg per sq. m. followed by the introduction Cyclophosphamide 600 mg per sq. m. repeating after 21 days;
• TN (5th–8th cycle): Docetaxel 100 mg per m2 once every three weeks 4 cycles + Trastuzumab every week (3 weeks after AS on the 1st day, a loading dose of Trastuzumab is administered - 4 mg per kg, 2nd - 100 mg / m sq. docetaxel; 8th, and also and 15, 2mg/kg Trastuzumab.Cycles 6-8: Day 1, 100mg/m2 docetaxel and 2mg/kg Trastuzumab, 8th and 15th, 2mg/kg Trastuzumab. After 3 weeks from day 1 of cycle 8, trastuzumab 6 mg/kg is administered every 3 weeks Trastuzumab is recommended to be administered throughout the year.

Locally advanced or metastatic breast cancer

• First line therapy: inject docetaxel 75 mg per m2 entered from Doxorubicin at a dose of 50 mg per square meter.
• Second line therapy: dose docetaxel as a monotherapy drug - 100 mg per square meter. When combined with trastuzumab Taxotere is administered weekly at a dose of 100 mg per square meter. every three weeks (starting after the 1st dose trastuzumab and continue immediately after its introduction).
• Combination therapy with Capecitabine : standard dose docetaxel 75 mg per m2 every three weeks + 1250 mg per square meter. Capecitabine is taken orally twice a day 0.5 hours after meals for 2 weeks, then a weekly rest period.

Varieties of non-small cell lung cancer

If chemotherapy has not been received before, the recommended treatment regimen includes: 75 mg per square meter. docetaxel , then immediately - the introduction of 75 mg per square meter. Cisplatin introduction for 0.5-1 hour or 6 mg per ml in 1 minute Carboplatin (AUC) for 0.5-1 hour. If chemotherapy fails, monotherapy is recommended. docetaxel , dosage: 75 mg per square meter.

Metastatic malignant neoplasms of the ovaries

Carry out second-line therapy using monotherapy docetaxel at a dose of 100 mg per square meter every three weeks.

Malignant neoplasms of the prostate gland

The prescribed dosage of Taxotere is 75 mg per square meter. once every three weeks. Long term recommended Prednisone or Prednisolone 5 mg orally 2 times a day.

Cancer of the stomach and esophagogastric junction

The recommended dose of Taxotere is 75 mg per square meter. + follow-up IV infusion (1-3 hours) Cisplatin at a dose of 75 mg per square meter, exclusively on the 1st day of subsequent cycles of chemotherapy. After infusion Cisplatin daily intravenous infusion with Fluorouracil at a dose of 750 mg per square meter. for 5 days. Treatment must be repeated every three weeks. Additionally, premedication with antiemetics and appropriate hydration for therapy is recommended. Cisplatin .

Malignant neoplasms of the head, neck

Premedication should be carried out using antiemetics with appropriate hydration before and after drug administration. Cisplatin , as well as the prevention of neutropenic infections (use).

Induction chemotherapy and subsequent radiotherapy

On the first day of chemotherapy cycles, the recommended dose of Taxotere is 75 mg per square meter. one-hour intravenous infusion + subsequent administration of 75 mg per square meter. Cisplatin 1 hour. Then it is necessary to continuously inject / infusion Fluorouracil - 750 mg per square meter. per day for 5 days. Repeat the scheme every three weeks for 4 cycles, then - conduct radiation therapy.

Induction chemotherapy and subsequent chemoradiotherapy

On the first day of chemotherapy cycles, the recommended dose of Taxotere is 75 mg per square meter. IV infusion + subsequent 0.5–3-hour IV infusion Cisplatin at a dose of 100 mg per square meter. Then it is necessary to continuously inject / infusion Fluorouracil - 1000 mg per square meter. per day for 4 days. Repeat the regimen every three weeks for a total of 3 cycles, then chemoradiotherapy.

Instructions for the preparation of Taxotere infusion solution

To prepare a premixed concentration solution docetaxel at 10 mg per ml should be a concentrate for the preparation of inf. pre-diluted solution in the solvent available in the package. To do this, draw the entire contents of the vial together with the solvent, under aseptic conditions, with a needle into the syringe, placing the vial slightly at an angle and inject into the vial with Taxotere. Next, mix the resulting mixture by turning, but not shaking the bottle, up and then down for 45 seconds. Leave the mixture for 5 minutes at room temperature and check the homogeneity, transparency, foam in the resulting solution. Check for sediment: if found, destroy.

The next stage of using the prepared inf. solution involves preliminary mixing of the solution in accordance with the required dose and further introduction into inf. bag or bottle (provided it contains 250 ml of a 5% solution or 0.9% ). Mix inf. bag or vial with rotational movements. Infusion should be carried out no later than 4 hours after preparation (1 hour of administration inclusive) while maintaining 25 ° C storage temperature and standard lighting conditions.

Overdose

Symptoms: Suppressed bone marrow function, mucositis , peripheral neurotoxicity.

Method of treatment: docetaxel is unknown, therefore, in case of an overdose, the patient is hospitalized, prescribed G-CSF , spend symptomatic therapy with constant monitoring of vital functions.

Interaction

• leads to lower ground clearance docetaxel by 50%.
• Co-administration of docetaxel with Carboplatin leads to an increase in the clearance of Carboplatin by 50% in comparison with the indicators for monotherapy with Carboplatin.

Terms of sale

A prescription is required to purchase the anticancer drug Taxotere.

Storage conditions

It is necessary that the place is protected from the rays of light, and the temperature is within 2–25 ° Celsius. It is recommended to restrict access to children.

If the packaged preparation with the solvent was stored in the refrigerator, then they should be kept at room temperature for about 5 minutes before mixing.

Shelf life

Do not use after 36 months from the date indicated on the package.

special instructions

Treatment with Taxotere should be carried out exclusively in a hospital, supervised an experienced doctor specializing in cancer chemotherapy. Careful monitoring of clinical blood counts is necessary.

Docetaxel has genotoxic action and is able to disrupt the male, therefore, in the treatment docetaxel and 6 months. after the end, you should refrain from conceiving a child. Patients are advised to conserve before starting treatment. sperm .

Analogues

• Docet;
• Docetax;
• Docetaxel;
• docetactin;
• Taxolik.

Taxotere: instructions for use and reviews

Latin name: Taxotere

ATX code: L01CD02

Active substance: Docetaxel (Docetaxel)

Producer: Aventis Pharma (Dagenham) (Great Britain), Sanofi-Aventis Deutschland GmbH (Germany)

Description and photo update: 07.08.2019

Taxotere - an updated description of the medication, you can read contraindications, indications for use, dosage of Taxotere. Useful reviews about Taxotere -

Antitumor cytostatic drug of plant origin from the group of taxoids.
Preparation: TAXOTHER®
The active substance of the drug: docetaxel
ATX encoding: L01CD02
CFG: Anticancer drug
Registration number: P No. 013044/01
Date of registration: 20.03.07
The owner of the reg. honor.: AVENTIS PHARMA S.A. (France)

Taxotere release form, drug packaging and composition.

0.5 ml

20 mg

Solvent: 13% solution of ethanol in water for injection (1.98 ml).

0.61 ml - colorless glass bottles (1) complete with a solvent (vial. 1 pc.) - blister packs contour (1) - packs of cardboard.

Concentrate for solution for infusion in the form of a clear, yellow to brownish-yellow oily solution; the applied solvent is transparent, colorless.

2 ml
docetaxel (as docetaxel trihydrate)
80 mg

Excipients: polysorbate 80.

Solvent: 13% solution of ethanol in water for injection (7.33 ml).

2.36 ml - colorless glass bottles (1) complete with a solvent (vial. 1 pc.) - blister packs (1) - cardboard packs.

The description of the drug is based on the officially approved instructions for use.
PHARMACHOLOGIC EFFECT

Antitumor cytostatic drug of plant origin from the group of taxoids. The active substance of the drug - docetaxel - accumulates tubulin in microtubules, prevents their decay, which leads to disruption of the mitosis phase and interfacial processes in tumor cells. Docetaxel is retained for a long time in cells where its high concentrations are reached. Docetaxel is active against some (but not all) cells that overproduce P-glycoprotein, which is encoded by the multiple resistance gene.

In vivo, docetaxel has wide range activity against mouse tumors and transplanted human tumor cells.

Pharmacokinetics of the drug.

Pharmacokinetics of the drug.

docetaxel is dose-dependent and corresponds to a three-phase pharmacokinetic model with T1 / 2 4 min, 36 min and 11.4 h, respectively.

Plasma protein binding is over 95%.

Metabolism and excretion

Within 7 days, docetaxel is excreted in the urine and feces after oxidation of the tert-butyl ether group with the participation of cytochrome P450. Excretion with urine is 6% of the radioactive dose, with feces - 75%. Approximately 80% of the radioactive drug excreted in the feces was found within 48 hours as the main inactive metabolite and three less significant inactive metabolites and, in a very small amount, unchanged.

Pharmacokinetics of the drug.

in special clinical situations

Pharmacokinetics of the drug.

docetaxel does not depend on the age and sex of the patient.

With mild liver dysfunction (AST and ALT1.5 ULN in combination with an increase in the activity of ALP2.5 ULN), the total clearance is reduced by 27% compared with the average.

Clearance of docetaxel did not change in patients with mild to moderate fluid retention. There are no data on the clearance of the drug in patients with severe fluid retention.

Indications for use:

Adjuvant therapy for operable breast cancer with damage to regional lymph nodes in combination with doxorubicin and cyclophosphamide;

Locally advanced or metastatic breast cancer (in combination with doxorubicin as primary chemotherapeutic treatment as a 1st-line drug; or as a 2nd-line therapy - in monotherapy, in case of failure of previous treatment, including anthracyclines or alkylating agents, and in combinations with capecitabine if previous therapy included anthracyclines);

Metastatic breast cancer with tumor expression of HER2 in combination with trastuzumab, in the absence of previous chemotherapy;

Unresectable, locally advanced, or metastatic non-small cell lung cancer (in combination with cisplatin or carboplatin) as 1st-line therapy or as monotherapy as 2nd-line therapy with failure of platinum-based chemotherapy;

Metastatic ovarian cancer with the ineffectiveness of previous 1st line therapy (2nd line therapy);

Unresectable locally advanced squamous cell carcinoma of the head and neck (in combination with cisplatin and 5-fluorouracil) as 1st line therapy;

Metastatic squamous cell carcinoma of the head and neck with the ineffectiveness of previous therapy (2nd line therapy);

Metastatic, hormone-resistant prostate cancer (in combination with prednisone or prednisolone);

Metastatic gastric cancer, including the cardia (in combination with cisplatin and 5-fluorouracil) as 1st line therapy.

Dosage and method of application of the drug.

To prevent hypersensitivity reactions, as well as to reduce fluid retention, all patients (excluding patients with prostate cancer) before the administration of Taxotere, glucocorticosteroids are premedicated, for example, dexamethasone at a dose of 16 mg / day (8 mg 2 times / day) orally, in within 3 days, starting 1 day before the introduction of Taxotere.

In patients with prostate cancer receiving concomitant treatment with prednisone or prednisolone, premedication with dexamethasone at a dose of 8 mg is performed 12, 3 and 1 hour before the start of Taxotere administration.

To reduce the risk of developing hematological complications, prophylactic administration of granulocyte colony-stimulating factor (G-CSF) is recommended.

Taxotere is given as a one-hour IV infusion every 3 weeks.

Mammary cancer

In adjuvant therapy of patients with operable breast cancer, the recommended dose of Taxotere is 75 mg/m2 1 hour after administration of doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 3 weeks. Only 6 cycles.

In monotherapy, Taxotere is administered at a dose of 100 mg/m2 every 3 weeks. When combined with doxorubicin (50 mg/m2) or capecitabine (1250 mg/m2 orally twice a day for 2 weeks followed by a week break), Taxotere is administered at a dose of 75 mg/m2 every 3 weeks.

In non-small cell lung cancer, Taxotere is administered at a dose of 75 mg/m2 as monotherapy and 75 mg/m2 in combination with platinum preparations every 3 weeks. With the ineffectiveness of combination with platinum preparations, Taxotere is used as monotherapy.

In metastatic ovarian cancer, Taxotere is administered at a dose of 100 mg/m2 every 3 weeks.

For locally advanced squamous cell carcinoma of the head and neck, Taxotere is administered at a dose of 75 mg/m2. After Taxotere infusion, on the same day, cisplatin infusion is performed at a dose of 75 mg/m2 for 1 hour, followed by an infusion of 5-fluorouracil at a dose of 750 mg/m2/day as a 24-hour infusion for 5 days. This mode is prescribed 1 time in 3 weeks and repeated up to 4 cycles. After a course of chemotherapy, radiation therapy is prescribed.

In metastatic squamous cell carcinoma of the head and neck tissues, Taxotere is administered at a dose of 100 mg/m2 every 3 weeks.

In metastatic hormone-resistant prostate cancer, Taxotere is administered at a dose of 75 mg/m2 once every 3 weeks. Prednisone or prednisolone is prescribed orally at 5 mg 2 times / day for a long time for the entire period of course treatment.

In case of metastatic cancer of the stomach, including the cardiac region, Taxotere is administered at a dose of 75 mg/m2 once every 3 weeks. After Taxotere infusion, on the same day, infusion of cisplatin at a dose of 75 mg/m2 for 1-3 hours is carried out, followed by an infusion of 5-fluorouracil at a dose of 750 mg/m2/day as a 24-hour infusion for 5 days, starting from the end of the cisaplatin infusion.

Dose adjustment

Taxotere is administered at a neutrophil count of 1500/µl. When the number of neutrophils falls<500/мкл, которое наблюдалось более недели, или развитии фебрильной нейтропении, или развитии выраженных кожных реакций, или выраженной периферической невропатии во время терапии доцетакселом дозу этого препарата для следующих введений следует снизить со 100 до 75 мг/м2 и/или с 75 до 60 мг/м2. Если подобные осложнения возникают и при применении доцетаксела в дозе 60 мг/м2, лечение следует прекратить.

Patients with resectable breast cancer receiving adjuvant therapy who develop febrile neutropenia should receive G-CSF in all subsequent cycles. If febrile neutropenia persists, the dose of Taxotere should be reduced to 60 mg/m2 and G-CSF should be continued. If G-CSF is not used, the dose of Taxotere should be reduced from 75 mg/m2 to 60 mg/m2. In patients with grade 3 or 4 stomatitis, a dose reduction to 60 mg/m2 is necessary.

At the first appearance of grade 2 toxicity, which persists until the time of the next Taxotere/capecitabine treatment cycle, the next treatment cycle may be delayed until the toxicity is reduced to grade 0-1, while 100% of the original Taxotere dose is administered during the next treatment cycle.

In patients with recurrence of grade 2 toxicity or first development of grade 3 toxicity at any time in the therapy cycle, treatment is delayed until toxicity is reduced to grade 0-1, then Taxotere is resumed at a dose of 55 mg/m2.

With any subsequent manifestations of toxicity or the appearance of any types of toxicity of the 4th degree, the administration of Taxotere should be discontinued.

Correction of the dose of capecitabine when combined with Taxotere is carried out according to the instructions for use of capecitabine.

In combination therapy for non-small cell lung cancer, for patients who initially receive Taxotere 75 mg/m2 in combination with cisplatin or carboplatin, in whom the platelet count in the previous treatment cycle decreased to<25 000/мкл (с цисплатином) и до <75 000/мкл (с карбоплатином), или у пациентов, у которых развилась фебрильная нейтропения, или у пациентов с серьезными проявлениями негематологической токсичности доза Таксотера в следующем цикле должна быть снижена до 65 мг/м2. При коррекции дозы цисплатина необходимо следовать инструкции по применению цисплатина.

When Taxotere is combined with cisplatin and 5-fluorouracil (5-FU), in the event of febrile neutropenia or infection, despite the use of G-CSF, the dose of Taxotere should be reduced to 60 mg / m2. With the subsequent development of episodes of complicated neutropenia, it is recommended to reduce the dose of Taxotere from 60 mg/m2 to 45 mg/m2. With the development of thrombocytopenia of the 4th degree, it is recommended to reduce the dose of Taxotere from 75 mg/m2 to 60 mg/m2. Subsequent cycles with docetaxel are possible with neutrophil counts > 1500/mcL and platelets > 100,000/mcL. If toxicity persists, treatment should be discontinued.

With the development of other types of toxicity, dose adjustment of Taxotere is carried out in accordance with the recommendations given in the table.
Toxicity
Dose adjustment
Diarrhea grade 3


Diarrhea grade 4
First episode: reduce the dose of Taxotere and 5-FU by 20%
Re-episode: stop treatment
Stomatitis 3 degrees
First episode: reduce the dose of 5-FU by 20%
Re-episode: stop 5-FU alone on subsequent cycles
Third episode: reduce the dose of Taxotere by 20%
Stomatitis 4 degrees
First episode: stop 5-FU only on subsequent cycles
Re-episode: Reduce Taxotere dose by 20%

Dose adjustment of cisplatin is carried out according to the instructions for use of cisplatin.

For patients with impaired liver function with ALT or AST levels greater than 1.5 times the ULN, or ALP levels greater than 2.5 times the ULN, the recommended dose is 75 mg/m2. Taxotere is not recommended in patients with elevated bilirubin levels and/or elevated ALT and AST activity (>3.5 ULN) in combination with an increase in alkaline phosphatase (>6 ULN).

There are currently no data on the use of Taxotere in combination with other medicines in patients with impaired liver function.

Based on the analysis of pharmacokinetic data, there are no special instructions for the use of Taxotere in elderly patients. When combined with capecitabine in patients over 60 years of age, a reduction in the starting dose of capecitabine is recommended (in accordance with the instructions for use of capecitabine).

Rules for the preparation of solutions

Concentrate for the preparation of a solution for infusion 20 mg/0.5 ml: the actual content in the vial is 24.4 mg/0.61 ml, which allows you to compensate for the loss of liquid during the preparation of a pre-mixed solution due to foaming, adhesion to the walls of the vial and the presence of "dead" space. Thus, the excess of the drug in the vial ensures that after dilution of its contents with the supplied diluent, the minimum volume of premixed solution drawn up will be 2 ml, containing 10 mg/ml docetaxel, which corresponds to 20 mg (the dose indicated on the vial label).

Concentrate for solution for infusion 80 mg / 2 ml: actual content in the vial 94.4 mg / 2.36 ml, which allows you to compensate for the loss of fluid in the preparation of a pre-mixed solution due to foaming, adhesion to the walls of the vial and the presence of "dead" space. Thus, an excess of the drug in the vial ensures that after dilution of its contents with the supplied diluent, the minimum volume of premixed solution drawn up will be 8 ml, containing 10 mg/ml docetaxel, which corresponds to 80 mg (the dose is indicated on the vial label).

The concentrate for the preparation of an infusion solution for parenteral use must first be diluted in the supplied solvent.

Preparation of Taxotere Premixed Solution (Docetaxel 10 mg/mL)

Before dilution, the vials with the drug and the solvent must be kept at room temperature for 5 minutes.

The entire contents of the vial with the solvent is collected with a needle into a syringe (the vial is placed slightly at an angle) and injected into the vial with Taxotere.

Turn the bottle with the resulting mixture over for 45 seconds (do not shake!) And leave for 5 minutes at room temperature, after which the solution is checked for homogeneity and transparency (the presence of foam even after 5 minutes is the norm).

Pre-mixed solution is recommended to be used for solution for infusion immediately after its preparation. The premixed Taxotere solution can be stored in the refrigerator (between 2° and 8°C) or at room temperature for up to 8 hours.

Preparation of solution for infusion

The required volume of premixed solution according to the required dose is injected into an infusion bag or vial containing 250 ml of 5% dextrose solution or 0.9% sodium chloride solution. If the required dose of docetaxel exceeds 200 mg, then a larger volume of fluid for infusion should be used so that the concentration of docetaxel is not higher than 0.74 mg / ml.

It is necessary to mix the contents of the infusion bag or vial. The resulting solution should be used within 4 hours for a one-hour intravenous infusion at room temperature and normal light conditions.

Taxotere's premixed solution and infusion solution should be inspected prior to administration; in the presence of sediment, the solution should be destroyed.

Side effects of Taxotere:

On the part of the hematopoietic system: most often - reversible neutropenia (in patients who did not receive G-CSF), in some cases accompanied by fever, infections, and sometimes the development of sepsis and pneumonia. The number of neutrophils decreases to the minimum values ​​after an average of 7 days (in patients who have previously received chemotherapy, this period may be shorter), average duration severe neutropenia (<500/мкл) также составляет 7 дней. Возможно развитие тромбоцитопении и анемии. Редко возникают кровотечения, в основном обусловленные тромбоцитопенией.

Allergic reactions: mild or moderate hypersensitivity reactions usually occur within a few minutes after the start of the infusion (hot flashes, rash, itching, chest tightness, back pain, shortness of breath, drug fever, chills); extremely rare - Lyell's syndrome, Stevens-Johnson syndrome. It is possible to develop severe reactions (arterial hypotension, bronchospasm, generalized rash and erythema), which disappeared after the infusion was stopped and adequate therapy was prescribed.

Dermatological reactions: alopecia, mild and moderate skin reactions; rarely - severe rash accompanied by itching, or limited erythema of the skin of the palms and feet with swelling and subsequent desquamation, as well as swelling of the hands, face and chest, hypo- or hyperpigmentation of the nails, onycholysis.

From the side of metabolism: fluid retention - cases of development of peripheral edema, pleural or pericardial effusion, ascites, weight gain are described. Peripheral edema usually occurs in the lower extremities and then may become generalized, leading to an increase in body weight of 3 kg or more. The frequency and severity of fluid retention increase with repeated administration of the drug; the mean total doses of Taxotere at which fluid retention was observed were 818.9 mg/m2 with premedication and 489.7 mg/m2 without premedication. However, in some cases, edema occurred during the first courses of therapy. Fluid retention was not accompanied by acute episodes of oliguria or arterial hypotension. In rare cases, dehydration and pulmonary edema have been reported.

From the digestive system: nausea, vomiting, diarrhea, anorexia, constipation, stomatitis, taste disturbance, esophagitis, epigastric pain; colitis, including ischemic, enterocolitis, perforation of the stomach or intestines; rarely - gastrointestinal bleeding, intestinal obstruction. In patients receiving monotherapy with Taxotere at a dose of 100 mg / m2, an increase in serum activity of ACT, ALT, alkaline phosphatase and serum bilirubin concentration more than 2.5 times higher than VGN is observed in less than 5% of cases. In some cases, hepatitis (death was observed in patients with a history of liver disease).

From the side of the central nervous system and peripheral nervous system: peripheral neuropathy in the form of mild or moderate paresthesia, hyperesthesia, dysesthesia or pain, including burning. Movement disorders were characterized by weakness. If these symptoms occur, dose adjustment is necessary. If symptoms persist, treatment should be discontinued. Very rarely - convulsions, transient loss of consciousness.

From the side of the cardiovascular system: cardiac arrhythmias (sinus tachycardia, atrial fibrillation), unstable angina pectoris, heart failure, arterial hypo- or hypertension; rarely - venous thromboembolism and myocardial infarction.

From the respiratory system: very rarely - acute respiratory distress syndrome and interstitial pneumonia, pulmonary fibrosis and increased response to radiation.

From the musculoskeletal system: arthralgia, myalgia, muscle weakness.

On the part of the organ of vision: rarely - the development of lacrimation in combination with conjunctivitis (or without it), transient visual disorders (flashes of light in the eyes, the appearance of cattle), usually occurring during the administration of the drug and combined with the development of hypersensitivity reactions, which usually disappear after discontinuation infusions; very rarely, mainly in patients receiving other anticancer drugs at the same time, it is possible to develop occlusion of the lacrimal canal, leading to excessive lacrimation.

Local reactions: moderate hyperpigmentation, inflammation, redness, dry skin, phlebitis, hemorrhage, swelling of the veins.

Other: asthenia, shortness of breath, generalized or local pain, including chest pain, not associated with heart or lung disease.

When Taxotere was used in combination with capecitabine, there was a more frequent development of adverse events from the digestive system, palmoplantar syndrome (hyperemia of the skin of the extremities / palms and feet / followed by edema and desquamation), dehydration, lacrimation, arthralgia, severe thrombocytopenia and anemia, hyperbilirubinemia , but more rare development of severe neutropenia, alopecia, disorders of the nails, asthenia, myalgia, edema of the lower extremities.

In patients over the age of 60 years who received combination therapy with Taxotere and capecitabine, compared with younger patients, there is a more frequent development of grade 3-4 toxicity.

Patients receiving combined treatment with trastuzumab showed a higher incidence of adverse reactions and more frequent development of grade 4 toxicity, compared with Taxotere monotherapy. Cases of heart failure have been identified, especially when added to anthracycline therapy (doxorubicin or epirubicin).

When Taxotere is used in combination with cisplatin and 5-fluorouracil, febrile neutropenia and / or neutropenic infectious complications occur in a smaller percentage of cases with the prophylactic administration of G-CSF.

Contraindications to the drug:

Initial number of neutrophils<1500/мкл;

Severe liver dysfunction;

Pregnancy;

lactation (breastfeeding);

Hypersensitivity to the components of the drug.

Use during pregnancy and lactation.

Taxotere is contraindicated for use during pregnancy and lactation (breastfeeding).

Women and men of childbearing age should avoid conception by using reliable methods of contraception during the use of the drug and for at least 3 months after its withdrawal.

Special instructions for the use of Taxotere.

Treatment with Taxotere is carried out only with the participation of an experienced specialist in antitumor chemotherapy in a specialized hospital.

With the development of severe neutropenia (<500/мкл в течение 7 дней и более) во время курса терапии Таксотером рекомендуется снизить дозу препарата при последующих курсах или использовать адекватные симптоматические меры. Продолжать последующее лечение Таксотером возможно после восстановления числа нейтрофилов до 1500/мкл.

Patients should be carefully monitored for hypersensitivity reactions, especially during the first and second infusions. The development of hypersensitivity reactions is possible in the first minutes of Taxotere infusion. Mild manifestations of hypersensitivity (facial flushing, localized skin reactions) do not require interruption of therapy. Severe hypersensitivity reactions (arterial hypotension, bronchospasm, generalized rash, erythema) require immediate discontinuation of the drug administration and appropriate therapeutic measures. Re-appointment of Taxotere in such patients is not allowed.

Patients receiving monotherapy with docetaxel at a dose of 100 mg / m2 and having high ALT and / or AST activity, more than 1.5 times the ULN, in combination with an elevated level of alkaline phosphatase more than 2.5 times the ULN, are at an extremely high risk of developing severe side effects. effects: sepsis, gastrointestinal bleeding, febrile neutropenia, infections, thrombocytopenia, stomatitis, asthenia. In this regard, in such patients with elevated liver function, the recommended dose of Taxotere is 75 mg / m2. Liver function tests should be determined prior to initiation of therapy and before each subsequent cycle of Taxotere therapy. Taxotere is not recommended in patients with elevated bilirubin and/or elevated ALT and AST (>3.5 ULN) in combination with elevated ALP (>6 ULN). At the moment, there are no data on the use of Taxotere in combination with other drugs in patients with impaired liver function.

Due to the possibility of developing edematous syndrome, it is necessary to monitor patients with ascites, effusion in pleural cavity or pericardium. With the appearance of edema, restriction of salt and drinking regimen and the appointment of diuretics are shown.

In combination therapy with Taxotere, doxorubicin and cyclophosphamide, the risk of developing acute leukemia is comparable to the risk with treatment regimens containing anthracycline/cyclophosphamide.

As with the use of other potentially toxic substances, care must be taken when using Taxotere and preparing solutions. The use of gloves is recommended. If the concentrate, pre-mixed solution or solution for infusion comes into contact with the skin, immediately wash it with soap and water. If a concentrate, pre-mixed solution or solution for infusion comes into contact with mucous membranes, immediately rinse them with water.

Control of laboratory indicators

It is necessary to systematically monitor the picture of peripheral blood in order to timely detect myelotoxicity.

Pediatric use

The safety and efficacy of Taxotere in children have not been adequately studied. There is limited experience with Taxotere in children.

Drug overdose:

Symptoms: suppression of bone marrow function, peripheral neuropathy, inflammation of the mucous membranes.

Treatment: There is no specific antidote. Hospitalization in a specialized department and careful monitoring of the function of vital organs are indicated. Give G-CSF as soon as possible. If necessary, carry out symptomatic therapy.

Interaction of Taxotere with other drugs.

In vitro studies have shown that the biotransformation of the drug may change with the simultaneous use of substances that induce, inhibit isoenzymes of the cytochrome P450 system or are metabolized by CYP3A isoenzymes (cyclosporine, terfenadine, ketoconazole, erythromycin, troleandomycin). In this regard, care must be taken when prescribing with similar drugs, given the possibility of a pronounced interaction.

In vitro, drugs with high protein binding (such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole, sodium valproate) did not affect protein binding of docetaxel.

Dexamethasone does not affect the degree of binding of docetaxel to plasma proteins.

Docetaxel does not affect the binding of digitoxin to plasma proteins.

Pharmacokinetic interaction

When using docetaxel in combination with doxorubicin, the clearance of docetaxel is increased while maintaining its effectiveness. At the same time, the clearance of doxorubicin and the concentration of doxorubicinol (doxorubicin metabolite) in plasma do not change.

The clearance of carboplatin in combination therapy with docetaxel is increased by 50% compared with carboplatin monotherapy.

There was no effect of docetaxel on the pharmacokinetics (Cmax, AUC) of the main metabolite of capecitabine (5DFUR) and no effect of capecitabine on the pharmacokinetics (Cmax, AUC) of docetaxel.

Conditions of sale in pharmacies.

The drug is dispensed by prescription.

Terms of the storage conditions of the drug Taxotere.

List B. The drug should be stored out of the reach of children, protected from light at a temperature of 2 ° to 25 ° C.

The shelf life of the concentrate for solution for infusion containing 20 mg of docetaxel is 24 months. The shelf life of the concentrate for solution for infusion containing 80 mg of docetaxel is 36 months.