Index of drugs

Breast cancer: in combination with doxorubicin and cyclophosphamide in adjuvant treatment in patients with operable breast cancer with lymph node metastases; in combination with doxorubicin for the treatment of locally advanced or metastatic breast cancer in patients who have not previously received cytotoxic medicines in this indication; as monotherapy in the treatment of patients with locally advanced or metastatic breast cancer, after failure of previously used cytotoxic drugs, previous treatment should contain an anthracycline or alkylating agent; in combination with trastuzumab in the treatment of metastatic breast cancer in patients whose tumors overexpress the HER2 gene and who have not previously received chemotherapy for the treatment of metastases; in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer, after failure of previous chemotherapy, previous treatment should contain anthracyclines. Non-small cell lung cancer: for the treatment of locally advanced or metastatic non-small cell lung cancer after failure of previously administered chemotherapy; in combination with Cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not previously received chemotherapy for this condition. Prostate cancer: in combination with prednisone or Prednisolone to treat patients with metastatic hormone-dependent prostate cancer. Gastric adenocarcinoma: in combination with cisplatin and 5-fluorouracil in the treatment of metastatic adenocarcinoma of the stomach, including adenocarcinoma of the gastric gland in patients who have not received chemotherapy before for the treatment of metastases. Head and neck cancer: in combination with cisplatin and 5-fluorouracil for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

1 vial contains 1 ml concentrate equivalent to 20 mg docetaxel.

An anti-cancer drug. It works by stimulating tubulin binding into stable microtubules and inhibiting their breakdown, which results in a significant reduction in the amount of free tubulin. docetaxel disrupts the microtubular network in cells, which is essential for vital cell functions in the phase of mitosis and interphase. Docetaxel is active in many cell lines expressing excessive expression of the p-glycoprotein encoded by the multidrug resistance gene. The kinetics of the drug are independent of the dose and correspond to the pharmacodynamic three-compartment model with T_0,5 for alpha, beta and gamma phases, respectively 4 min, 36 min and 11.1 h. The long period of late phase is partly due to the relatively slow release of docetaxel from the peripheral compartment. Docetaxel is more than 95% bound to plasma proteins. The total clearance is 21 l / h / m²and steady-state volume of distribution averaging 113 l. In hepatic insufficiency (transaminase transaminase 1.5-fold higher, and alkaline phosphatase 2.5-fold higher than the upper normal limit), the total clearance of the drug was reduced by 27%. It is metabolized with cytochrome P-450 and excreted within 7 days in urine and faeces. About 80% of the radioactive material in the faeces was excreted in the first 48 hours as inactive metabolites.

Hypersensitivity to docetaxel or to any of the excipients. Neutrophil count <1500 cells / mm³ marked before starting the drug. Severe hepatic failure. There are also contraindications for the use of other medicinal products administered in combination with docetaxel.

The drug is not recommended in children (no data on safety and efficacy). During therapy, attention should be paid to the possibility of neutropenia (treatment cycle should not be initiated if the neutrophil count does not reach ≥ 1500 cells / mm³). In case of severe neutropenia (<500 cells / mm³ for 7 days or more) during treatment with docetaxel it is recommended to reduce the dose of the drug in subsequent treatment cycles or to start appropriate symptomatic treatment.The incidence of febrile neutropenia and neutropenic infection was lower in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil when prophylactically treated with G-CSF. Patients treated with docetaxel with cisplatin and 5-fluorouracil should receive prophylactic G-CSF to reduce the risk of neutropenia with complications and should be closely monitored. The patient should be monitored for hypersensitivity reactions, especially during the first or second infusion. In case of severe symptoms of hypersensitivity (hypotension, bronchospasm, generalized rash or erythema), the drug should be immediately discontinued and appropriate treatment should be instituted (the drug should not be re-administered). Patients with severe fluid retention, such as pleural effusion, pericardial effusion or ascites should be carefully monitored. In patients treated with docetaxel monotherapy at a dose of 100 mg / m² have increased transaminase (ALT and / or AST) levels above 1.5 times the upper limit of normal (ULN) with increased alkaline phosphatase - more than 2.5 times ULN, the risk of serious adverse reactions such as: life-threatening sepsis, life-threatening gastrointestinal bleeding, neutropenic fever, infection, thrombocytopenia, stomatitis and weakness. Hence, the recommended dose of docetaxel is 75 mg / m in patients with elevated liver function tests² and liver parameters should be measured before and before each treatment cycle. In patients with elevated serum bilirubin> GGN and / or elevated transaminases> 3.5-fold GGN and with increased alkaline phosphatase> 6-fold ULN, dose reduction is not recommended and docetaxel should not be used, if it is not absolutely necessary. In patients taking docetaxel in combination with cisplatin and 5-fluorouracil in the treatment of gastric adenocarcinoma, transaminase elevation> 1.5-fold GGN, with the simultaneous increase in alkaline phosphatase> 2.5-fold ULN and increased bilirubin> GGN, dose reduction is not recommended and the drug should not be administered except in patients when it is strictly indicated. There are no data on the use of docetaxel in patients with hepatic impairment in combination chemotherapy in other indications. There are no data on the use of the drug in patients with severe renal impairment. In the case of severe symptoms of peripheral nervous system disorders, it is necessary to reduce the dose of the drug. The drug contains ethanol (400 mg ethanol per 1 ml concentrate), which may be harmful for patients with alcoholism and what should be taken into account in children and people at high risk (liver disease, diseases that affect o.u.n.). In patients receiving docetaxel in combination with trastuzumab, particularly after chemotherapy with an anthracycline (doxorubicin or epirubicin), moderate or severe heart failure has been reported (deaths have been reported). Early symptoms such as abdominal pain and tenderness, fever, diarrhea with neutropenia and no neutropenia may be early symptoms of severe gastrointestinal toxicity and therefore should be monitored and treatment promptly instituted. Patients should be monitored during treatment and during follow-up after treatment for symptoms of congestive heart failure. In the group of patients treated with docetaxel with doxorubicin and cyclophosphamide, the risk of delayed myelodysplasia or myeloid leukemia requires performing haematological monitoring tests. There is no data available in patients> 70 years of age who have received docetaxel in combination with doxorubicin and cyclophosphamide. Elderly patients treated with docetaxel in combination with cisplatin and 5-fluorouracil should be monitored.

Docetaxel is embryotoxic and fetotoxic in rabbits and rats and reduces fertility in rats. Like other cytotoxic medicines, docetaxel used in pregnant women may cause fetal damage, therefore docetaxel must not be used during pregnancy unless the clinical condition of the woman requires it.Women of childbearing potential receiving docetaxel should be informed about the need to prevent pregnancy and oblige to immediately inform the treating physician about pregnancy. During treatment should use an effective method of contraception. In non-clinical studies, docetaxel has been found to be genotoxic and may alter fertility in men, therefore it is recommended that men receiving docetaxel will not become fathers during treatment and up to 6 months after treatment and should be advised to store them before starting treatment. seed. During docetaxel treatment, breast-feeding should be discontinued due to the risk of side effects in the child.

The most common were: neutropenia (transient and non-accumulating, with the lowest neutrophil count at day 7, and mean duration of severe neutropenia (<500 cells / mm)³) of 7 days), anemia, alopecia, nausea, vomiting, stomatitis, diarrhea and weakness. In addition, very often it was observed in monotherapy or combination therapy: sensory neuropathy, motor neuropathy, dysgeusia, dyspnoea, skin reactions, changes in the nail, myalgia, loss of appetite, infection (including sepsis and pneumonia, leading to death), detention fluids, asthenia, pain, hypersensitivity, thrombocytopenia, neutropenic fever, weight gain or loss, paresthesia, headache, hypoaesthesia, lachrymation severity, conjunctivitis, nosebleeds, nose and throat pain, inflammation of the nose and throat, cough, watery leakage from the nose, constipation, indigestion, abdominal pain, erythema, rash, joint pain, pain in the limbs, bone pain, backache, swollen edema, peripheral edema, mucositis, flu-like symptoms, chest pain, muscle stiffness, insomnia, pain throat and larynx, hand-foot syndrome, decreased appetite, toxic effects on the skin, vasodilatation, amenorrhea, lethargy, impaired sense of smell, hearing impairment, oesophagitis / dysphagia / pain during swallowing, pruritus rash. Common (monotherapy, combination therapy): increased bilirubin, increased alkaline phosphatase, increased AST, ALT, arrhythmias, gastrointestinal bleeding, hypotension, hypertension, haemorrhage, reactions at the infusion site, pain in the chest without connection to the cardiovascular system or respiratory system, heart failure, hyperbilirubinemia, epigastric pain, dry mouth, dermatitis, erythematous rash, exfoliative rash, pruritus rash, discolored nails, separation of the nail plate from the placenta, dehydration , oral mycosis, left ventricular dysfunction, congestive heart failure, cortical disorders, cerebellar disorders, myocardial ischemia, dry skin, peeling of the skin, pain due to cancer. Uncommon (combination therapy): syncope, colitis / small intestine / perforation of the large intestine, phlebitis, lymphoedema, venous disorders. In addition, rare cases of myocardial infarction, convulsions or transient loss of consciousness, loss of hearing, acute respiratory distress syndrome, interstitial pneumonitis and pulmonary fibrosis have been reported post-marketing (patients receiving concomitant radiation therapy have reported cases of radiation pneumonia), gastric perforation or intestine, ischemic colitis, colitis or bowel inflammation in the course of neutropenia, intestinal obstruction, venous thromboembolic events, the phenomenon of recurrence of radiation symptoms; bone marrow suppression and other hematopoietic side effects have been reported; disseminated intravascular coagulation has been reported, often in combination with sepsis or multi-organ failure, cases of anaphylactic shock (sometimes fatal); very rare transient visual disturbances (flashes, scots) and lupus erythematosus, blister rashes (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), sclerodermal lesions (usually preceded by lymphoedema), acute myelogenous leukemia and myelodysplasia. (associated with the use of other chemotherapeutic and / or radiotherapy), hepatitis (sometimes leading to death,especially in patients with pre-existing liver disease).

The drug should be administered under the supervision of a doctor who has experience in cancer chemotherapy and only in a hospital setting. Docetaxel is given as a one-hour infusion, once every 3 weeks. In the case of breast cancer, non-small cell lung cancer, stomach cancer and head and neck cancer, premedication (oral corticosteroid, eg Dexamethasone 16 mg / day for 3 days, from the first day before docetaxel administration) may be used. To reduce the risk of haematological toxicity, G-CSF may be prophylactically administered. In the case of prostate cancer, with prednisone or prednisolone administered, the recommended pre-medication regimen is orally administered dexamethasone 8 mg for 12 hours, 3 hours and 1 hour prior to docetaxel infusion.Breast cancer: complementary treatment of surgical breast cancer with lymph node metastases: 75 mg / m² pc. in 1 h after administration of 50 mg / m doxorubicin² pc. and cyclophosphamide at a dose of 500 mg / m² pc, every 3 weeks for 6 cycles (TAC scheme); locally advanced breast cancer or metastatic breast cancer: 100 mg / m² as monotherapy, docetaxel is administered at a dose of 75 mg / m for the first-line treatment² pc. in combination with doxorubicin (50 mg / m² pc.); in combination with trastuzumab: docetaxel in a dose of 100 mg / m² pc. every 3 weeks, with trastuzumab given once a week; in combination with capecitabine: docetaxel in a dose of 75 mg / m² pc. every 3 weeks, (capecitabine 1250 mg / m² pc. 2 times a day for 30 minutes after eating, for 2 weeks, then a week break).Non-small cell lung cancer: in patients who have not received chemotherapy before - 75 mg / m² pc. simultaneously with cisplatin in a dose of 75 mg / m² for 30-60 min .; after failure of previously used chemotherapy with platinum preparations: 75 mg / m² pc. in monotherapy.Prostate cancer: 75 mg / m² at the same time, oral 5 mg of prednisone or prednisolone is administered orally 2 times a day.Gastric adenocarcinoma: 75 mg / m² pc. in a 1-hour infusion, followed by cisplatin in a dose of 75 mg / m² pc. administered in a 1-hour infusion (both medicines are given only on the first day); then 5-fluorouracil administered at a dose of 750 mg / m², continuous infusion lasting 24 hours, for 5 days, after cisplatin has been administered at a daily dose; the therapy cycle is repeated every 21 days.Head and neck cancer: patients must receive antiemetics as premedication. It is also necessary to properly hydrate (before and after administration of cisplatin). The prophylactic use of G-CSF is recommended to reduce the risk of hematopoietic toxicity. All patients participating in clinical trials TAX 323 and TAX 324 received prophylactic antibiotics.Induction chemotherapy followed by radiotherapy (TAX 323): the recommended dose of docetaxel for the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN) is 75 mg / m² pc. as an infusion lasting 1 hour, followed by cisplatin 75 mg / m² pc. in the first day of the therapy cycle. Then 5-fluorouracil is administered as a continuous infusion at a dose of 750 mg / m² pc. daily, for 5 days. This schedule is given every 3 weeks for 4 consecutive cycles. After chemotherapy, patients should receive radiotherapy.Induction chemotherapy followed by chemoradiotherapy (TAX 324): in the induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg / m² pc. in the form of an infusion lasting 1 hour on the first day, followed by cisplatinum at a dose of 100 mg / m² pc. in an infusion lasting from 30 minutes to 3 hours. Then 5-fluorouracil is administered as a continuous infusion at a dose of 1000 mg / m² pc. daily, from the first to the fourth day. This schedule is given every 3 weeks for 3 consecutive cycles. After chemotherapy, patients should receive chemoradiotherapy. Dose adjustments for cisplatin and 5-fluorouracil are presented in the respective product characteristics.Dose adjustment during treatment. Patients who develop febrile neutropenia during treatment with neutrophil counts are less than 500 cells / mm³ for more than a week, severe or massive cutaneous reactions or symptoms of severe peripheral neuropathy, the dose should be reduced from 100 mg / m² pc. up to 75 mg / m² pc. or with 75 mg / m² pc. up to 60 mg / m² pc. If, despite reducing the dose of the drug to 60 mg / m² pc. the above symptoms persist, docetaxel should be discontinued. In patients receiving docetaxel, doxorubicin and cyclophosphamide (TAC) in the adjuvant treatment of breast cancer, primary G-CSF prophylaxis should be considered. Patients who develop febrile neutropenia and / or neutropenic infection should have their docetaxel dose reduced to 60 mg / m² pc. in all subsequent cycles. In patients who have had Grade 3 or 4 stomatitis, the dose should be reduced to 60 mg / m² pc. In patients given the initial dose of docetaxel 75 mg / m² pc.in combination with cisplatin and for whom the smallest number of platelets determined during the previous course of chemotherapy was below 25,000 cells / mm³ or in patients who have experienced neutropenia-associated fever or in patients with severe non-haemolytic toxicities in later cycles, the docetaxel dose should be reduced to 65 mg / m² pc. In combination with capecitabine: in patients who experienced the first grade of toxicity that persisted during the Next docetaxel / capecitabine treatment cycle, treatment should be delayed until recovery to grade 0-1 and treatment should be continued at baseline; in patients who have experienced a second grade of toxicity or for the first time 3. degree of toxicity, treatment should be delayed until return to grade 0-1, followed by continued docetaxel treatment at a dose of 55 mg / m² pc .; in the event of once again any degree of toxicity or if grade 4 toxicity occurs, docetaxel should be discontinued. In combination with cisplatin and 5-fluorouracil in case of febrile neutropenia, prolonged neutropenia or neutropenic infection, despite administration of G-CSF, the dose of docetaxel should be reduced from 75 to 60 mg / m² pc. If further neutropenic episodes occur with complications, the docetaxel dose should be reduced from 60 to 45 mg / m² pc. If grade 4 thrombocytopenia is diagnosed, the docetaxel dose should be reduced from 75 to 60 mg / m² pc. In the following cycles, patients should not be administered docetaxel until the neutrophil count does not increase to> 1500 / mm³ and tiles up to> 100,000 / mm³. If hematopoietic toxicity persists, docetaxel should be completely discontinued. In combination with cisplatin and 5-fluorouracil in the event of Grade 3 diarrhea: at the first episode, reduce the dose of 5-FU by 20%, at the second episode, reduce the dose of docetaxel by 20%; Grade 4 diarrhea: at the first episode, reduce the dose of docetaxel and 5-FU by 20%, stop the therapy on the second episode; in case of stomatitis / mucositis grade 3: at the first episode, reduce the dose of 5-FU by 20%, on the second episode, stop only 5-FU administration in all subsequent cycles, reduce the docetaxel dose by 20% on the third episode ; in the event of oral inflammation / grade 4 mucositis at the first episode, only interrupt 5-FU administration in all subsequent cycles, reduce the docetaxel dose by 20% on the second episode. In patients with complicated neutropenia (including long-term neutropenia, febrile neutropenia or infection), G-CSF is recommended for best protection (eg 6-15 days) in all subsequent cycles. In patients whose blood transaminase levels exceed 1.5-fold GGN and alkaline phosphatase in the blood exceeds 2.5-fold GGN, the recommended dose is 75 mg / m² pc. In patients aged 60 years and older treated with docetaxel in combination with capecitabine, a reduction of the initial dose of capecitabine to 75% of the recommended dose is recommended.