Index of drugs

Breast cancer. In combination with doxorubicin and cyclophosphamide in adjuvant therapy in patients with lymph node metastatic or lymph node metastatic breast cancer (adjuvant therapy in patients with lymph node-induced nodal tumor surgery should be limited to patients eligible for lymph node to receive chemotherapy in accordance with international criteria for the treatment of early breast cancer). In combination with doxorubicin in the treatment of locally advanced or metastatic breast cancer in patients who have not previously received cytotoxic medicines in this indication. Monotherapy in patients with locally advanced or metastatic breast cancer after failure of previous treatment with 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 metastatic disease. In combination with capecitabine in the treatment of patients with locally advanced or metastatic breast cancer after failure of previously used chemotherapy (previous treatment should contain anthracyclines).Non-small cell lung cancer. Treatment of locally advanced or metastatic non-small cell lung cancer after failure of previously used chemotherapy. In combination with Cisplatin in the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not received prior chemotherapy for this condition.Prostate cancer. In combination with prednisone or Prednisolone in the treatment of patients with hormone-dependent metastatic 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 gut in patients who have not received prior chemotherapy for the treatment of metastases.Head and neck cancer. In combination with cisplatin and 5-fluorouracil in the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

1 vial of concentrate contains 20 mg or 80 mg docetaxel. The concentrate is reconstituted with a solvent to obtain a docetaxel concentration of 10 mg / ml.

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 duration of the 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. It is metabolized with the participation of cytochrome P-450 by oxidation of tert-butyl ester groups and then excreted in both urine (6%) and faeces (75%) within 7 days.

Hypersensitivity to docetaxel or to any of the excipients. The number of neutrophils before drug administration <1500 cells / mm³. Severe liver dysfunction. There are also contraindications to the use of other drugs administered in combination with docetaxel.

During treatment with docetaxel, the blood count and liver function should be frequently monitored and the dose adjusted during treatment depending on the results of these tests. During treatment with docetaxel, attention should be paid to the possible occurrence of: neutropenia (it may be necessary to reduce the dose in subsequent cycles of treatment, delay the Next course of treatment or initiate appropriate symptomatic treatment), hypersensitivity reactions,especially during the 1st or 2nd intravenous infusion (discontinuation of treatment and initiation of appropriate symptomatic treatment may be necessary, patients with severe hypersensitivity reactions should not be re-administered doectaxel), skin reactions (may be severe and lead to discontinuation or discontinuation of docetaxel), neuropathy (dose reduction may be necessary), fluid retention (closely monitor patients with severe fluid retention), gastrointestinal toxicity (if necessary, appropriate treatment), heart failure (especially when administering the drug in combination with trastuzumab, especially after using anthracycline-containing chemotherapy). Patients who are candidates for combination therapy with docetaxel and trastuzumab should be subjected to a basic cardiac evaluation and then evaluated during the course of treatment for cardiac function (eg every 3 months) so as to detect possible developing cardiac dysfunction. In patients treated with TAC (docetaxel, doxorubicin, cyclophosphamide), the risk of delayed myelodysplanis or myeloid leukemia requires performing a control test. The benefit / risk ratio for patients with 4+ seizure numbers treated with TAC has not been fully defined. Exercise caution in patients with hepatic impairment (dose modification recommended). Elderly patients should be closely monitored because of the higher risk of side effects. No data are available in patients> 70 years of age who have received the TAC regimen. The use of docetaxel in children and adolescents is not appropriate for the following indications: breast cancer, non-small cell lung cancer, prostate cancer, gastric adenoma and head and neck cancer, including low-grade nasopharyngeal cancer type II and III.

Do not use during pregnancy unless the clinical condition of the woman requires docetaxel (the medicine may cause fetal harm). Women of childbearing potential must use effective contraception during docetaxel treatment. Docetaxel is genotoxic and may affect fertility in men - men treated with docetaxel should avoid conceiving a child during treatment and up to 6 months after the end of treatment, and should receive advice on the conservation of semen before starting treatment. Breast-feeding should be discontinued during docetaxel treatment.

The most common, both monotherapy and combination therapy, were: neutropenia (transient and non-accumulating, with the lowest neutrophil count at day 7, and mean duration of severe neutropenia <500 cells / mm³, 7 days), neutropenic fever, infections (including sepsis and pneumonia, sometimes fatal), anemia, thrombocytopenia, peripheral motor neuropathy, peripheral sensory neuropathy, dysgeusia, lack of appetite, nausea, vomiting, diarrhea, cavity inflammation oral, constipation, alopecia, skin reactions (mild or moderate, including erythema involving local skin eruptions, mainly on the feet, hands, arms, face, chest, often with pruritus, less severe symptoms such as eruptions with subsequent exfoliation), changes in the nails (sometimes can be severe - discoloration, discoloration, sometimes pain, separation of the nail plate from the placenta), weakness, fatigue, fluid retention (including such events as: peripheral edema, less pleural effusion, pericardial effusion, ascites and weight gain), hypersensitivity reactions (mild - redness no, rash with or without pruritus, tightness in the chest, back pain, shortness of breath, drug-induced fever, chills; severe hypersensitivity reactions were characterized by hypotension and / or bronchospasm or generalized rash and / or erythema), reactions at the site of infusion (discoloration, inflammation, redness or dryness of the skin, phlebitis or extravasation at the injection site, swelling of the vein), pain muscles, joint pain, pain, fever. In addition, dyspnoea, gastrointestinal bleeding, increased bilirubin, increased alkaline phosphatase, AST, ALT, cardiac arrhythmias, heart failure, hypotension, hypertension, haemorrhage, chest pain without connection to the cardiovascular system were observed. or respiratory system.The following may also occur: oesophagitis, dysphagia, insomnia, lymphoedema, nosebleeds, nose and throat pain, inflammation of the nose and throat, sore throat and larynx, cough, watery runny nose, mucositis, flu-like symptoms, pain in the limbs, bones and back, muscle stiffness, lethargy, palmar-plantar syndrome, oral candidosis, dizziness, headache, dehydration, weight loss, decreased left ventricular function, myocardial ischemia, fainting, drowsiness, flushing, amenorrhea, venous disorders, phlebitis, olfactory disorders, pain due to cancer. The severity of the side effects of docetaxel may be greater when it is given in combination with other chemotherapeutics. Diabetic disseminated disseminated dissection (DIC) has been reported, often in combination with sepsis or multiple organ dysfunction; cases of anaphylactic shock (sometimes fatal). Rarely observed: convulsions or transient loss of consciousness (sometimes during intravenous infusion), ototoxicity (hearing impairment and / or hearing loss), tearing with conjunctivitis or without conjunctivitis, myocardial infarction, venous thromboembolism, acute syndrome breathing disorders, interstitial pneumonitis and pulmonary fibrosis (rare cases of radiation pneumonia have been reported in patients receiving concomitant radiotherapy), dehydration following gastrointestinal disturbances, gastrointestinal perforation, ischemic colitis, colitis or bowel disease in the course of neutropenia , intestinal obstruction, pulmonary edema. Very rare: cases of acute myeloid leukemia and myelodysplasia associated with the use of docetaxel in combination with other chemotherapeutic agents and / or radiotherapy, transient visual disturbances (flashes, scots) that have occurred during the infusion and have been associated with hypersensitivity reactions, hepatitis ( sometimes leading to death, especially in patients with pre-existing liver disease), lupus erythematosus, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, recurrence of radiation effects. After the use of docetaxel, changes of the sclerodermal type usually described by lymphoedema were described.

The drug should be administered under the supervision of a doctor who has experience in cancer chemotherapy and only in units specialized in the administration of cytotoxic drugs. Docetaxel is administered as a 1-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) may be used. from day 1 before starting docetaxel). To reduce the risk of haematological toxicity, G-CSF may be prophylactically administered. For prostate cancer, while prednisone or prednisolone is administered concomitantly, the recommended pre-medication regimen is orally administered dexamethasone 8 mg for 12 h, 3 h and 1 h prior to docetaxel infusion.Breast cancer: For complementary treatment of metastatic and metastatic breast cancer, the recommended dose of docetaxel is 75 mg / m² pc, administered 1 h after doxorubicin 50 mg / m² pc. and cyclophosphamide at a dose of 500 mg / m² pc, every 3 weeks for 6 cycles (TAC treatment regimen). For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel is 100 mg / m² pc. in monotherapy. For first-line treatment, docetaxel at a dose of 75 mg / m² pc. it is used in combination with doxorubicin (50 mg / m² pc.). In combination with trastuzumab, the recommended dose of docetaxel is 100 mg / m² pc. every 3 weeks, with trastuzumab administered every 1 week. After the first dose of trastuzumab, the first docetaxel infusion was administered the next day. Subsequent docetaxel doses were administered immediately after completion of trastuzumab infusion, if the previous dose of trastuzumab was well tolerated (dose and route of trastuzumab administration, see SmPC trastuzumab). In combination with capecitabine, the recommended dose of docetaxel is 75 mg / m² pc. every 3 weeks, simultaneously with capecitabine in a dose of 1250 mg / m² pc. 2 times a day (within 30 minutes after a meal) for 2 weeks, and then 1 week break.Non-small cell lung cancer. In patients who have not received chemotherapy before: docetaxel 75 mg / m² pc. simultaneously with cisplatin in a dose of 75 mg / m² for 30-60 min.In patients who have previously failed chemotherapy with platinum: docetaxel 75 mg / m² pc. in monotherapy.Prostate cancer: docetaxel in a dose of 75 mg / m² pc. At the same time, oral 5 mg of prednisone or prednisolone is given twice daily.Gastric adenocarcinoma. The recommended dose of docetaxel is 75 mg / m² pc. in 1-hour infusion, followed by cisplatin in a dose of 75 mg / m² pc. administered in a 1-3-hour infusion (both drugs are given only on the first day). In the following days, 5-fluorouracil is administered at a dose of 750 mg / m², in a continuous infusion lasting 24 hours, for 5 days. The first dose is given after the completion of the cisplatin infusion. The treatment cycle is repeated every 3 weeks. Patients must receive premedication, including antiemetics, and adequately hydrated prior to administration of cisplatin. G-CSF should be prophylactically administered to reduce the risk of blood and hematopoietic toxicity.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 in 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. on 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 day 1, 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 1 to 4 days. This schedule is given every 3 weeks for 3 consecutive cycles. After chemotherapy, patients should receive chemoradiotherapy.Dose adjustment during treatment. Adaptation of the dose of drugs used in combination with docetaxel: see the Summary of Product Characteristics of the corresponding medicine. Docetaxel may be administered if the neutrophil count is ≥ 1500 cells / mm³. In patients who developed febrile neutropenia during treatment with docetaxel, with neutrophil count <500 cells / mm³ for over a week and severe or massive cutaneous reactions or symptoms of severe peripheral neuropathy, the docetaxel dose should be reduced from 100 mg / m² pc. up to 75 mg / m² pc. and (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. these symptoms persist, treatment should be discontinued.In the TAC regimen (docetaxel, doxorubicin and cyclophosphamide): in patients receiving a TAC regimen 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 combination with cisplatin: in patients given an 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 <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.toxicity, delay treatment until return to grade 0-1, and then continue with docetaxel 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 the TCF scheme (docetaxel, 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 (5-FU) 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 docetaxel dose 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 stomatitis / grade 4 mucositis: on 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.Special groups of patients. As monotherapy in patients with hepatic impairment - with increased transaminases (ALT and AST)> 1.5-fold GGN (upper limit of normal) with increased alkaline phosphatase> 2.5-fold ULN, the recommended dose of docetaxel is 75 mg / m² and liver function parameters should be measured before starting docetaxel treatment and before each subsequent treatment cycle. In patients with increased serum bilirubin> GGN and / or elevated transaminases (ALT and AST)> 3.5-fold ULN and with increased alkaline phosphatase> 6-fold ULN, dose reduction is not recommended and do not use docetaxel if it is not absolutely necessary. In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the treatment of gastric adenocarcinoma with 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 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 docetaxel in patients with severe renal impairment. Population pharmacokinetic data analysis shows that there are no specific recommendations regarding the use of docetaxel in elderly patients; in patients ≥ 60 years treated with docetaxel in combination with capecitabine, it is recommended to reduce the starting dose of capecitabine to 75% of the recommended dose.