Docetaxel Sandoz, concentrate for infusion solution 10mg/ml 16ml fl. 1pc

Composition

Concentrate for preparing an infusion solution in the form of a clear liquid, from colorless to light yellow.

1 ml docetaxel (anhydrous)10 mg

Auxiliary substances:

polysorbate 80-80 mg,

macrogol 300-648 mg,

citric acid anhydrous-4 mg,

ethanol 96% – 275.9 mg

Pharmacological action

Antitumor agent-alkaloid

Indications

Breast cancer (BC)

Adjuvant therapy:

– operable breast cancer (drug Docetaxel Sandoz® in combination with doxorubicin and cyclophosphamide);

– resectable breast cancer with lesions of the regional lymph nodes;

– operable breast cancer without damage to the regional lymph nodes in patients who are chemotherapy according to the established international criteria for the selection of primary chemotherapy for early-stage breast cancer (if you have one or more risk factors for the development of recurrence: tumor size greater than 2 cm, negative, estrogen receptor progesterone, high degree of malignancy of the tumor (grade 2-3), age less than 35 years);

– resectable breast cancer with tumor HER2 overexpression (doxorubicin and cyclophosphamide followed by drug Docetaxel Sandoz® in combination with trastuzumab scheme (as-T));

Neoadjuvant therapy:

– operable and locally advanced breast cancer (doxorubicin and cyclophosphamide, followed by Docetaxel Sandoz).

Metastatic and / or locally advanced breast cancer:

– locally advanced or metastatic breast cancer (Docetaxel Sandoz® in combination with doxorubicin, first-line therapy); – metastatic breast

cancer with tumor overexpression of HER2 (Docetaxel Sandoz® in combination with trastuzumab, first-line therapy);

– locally advanced or metastatic breast cancer with the ineffectiveness of previous chemotherapy, including anthracyclines or alkylating agents (Docetaxel Sandoz® in monotherapy);

– locally advanced or metastatic breast cancer with the ineffectiveness of previous chemotherapy, including anthracyclines (the drug Docetaxel Sandoz® in combination with capecitabine);

Non-small cell lung cancer (NSCLC)

– inoperable locally advanced or metastatic NSCLC in combination with cisplatin or carboplatin as first-line therapy;

– locally advanced or metastatic NSCLC in monotherapy as second-line therapy if previous chemotherapy is ineffective;

Ovarian cancer

– metastatic ovarian cancer as a second-line therapy if the previous first-line therapy is ineffective.

Head and neck cancer

– inoperable locally advanced squamous cell carcinoma of the head and neck (in combination with cisplatin and fluorouracil) as induction therapy.

Prostate cancer

is a metastatic, hormone-resistant prostate cancer (in combination with prednisone or prednisone).

Gastric cancer

– metastatic gastric cancer, including gastroesophageal junction adenocarcinoma (in combination with cisplatin and fluorouracil), as a first-line therapy.

Recommendations for use

Intravenous infusion (within 1 hour) 1 time in 3 weeks.

To prevent hypersensitivity reactions, as well as to reduce fluid retention, all patients (with the exception of patients with prostate cancer – see below) before docetaxel use, if there are no contraindications, are premedicated with glucocorticosteroids (corticosteroids), for example, dexamethasone orally at a dose of 16 mg/day (8 mg 2 times a day) for 3 days, starting one day before docetaxel use.

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

Prophylactic use of granulocyte colony-stimulating factor (G-CSF) is recommended to reduce the risk of hematological complications.

Breast cancer (BC)

In adjuvant therapy of non-metastatic operable breast cancer with or without regional lymph node involvement, the recommended dose is 75 mg / m2 1 hour after use of doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 3 weeks. The course of treatment is 6 cycles.

For locally advanced or metastatic breast cancer, the first-line dose of docetaxel is 75 mg / m2 (administered in combination with doxorubicin (50 mg/m2)); as a second-line therapy, the recommended dose of docetaxel in monotherapy is 100 mg/m2.

The following doses are recommended for neoadjuvant therapy in patients with operable and locally advanced breast cancer:

– AS (cycles 1-4): doxorubicin (A) 60 mg/m2, followed by cyclophosphamide (C) 600 mg/m2 every 3 weeks,4 cycles;

– T (cycles 5-8): docetaxel (T) 100 mg/m2 1 time in 3 weeks,4 cycles.

In adjuvant therapy of operable breast cancer with tumor overexpression of HER2, the following doses of docetaxel are recommended (chemotherapy according to the AS-TN scheme): :

– AC (cycles 1-4): doxorubicin (A) 60 mg/m 2 followed by use of cyclophosphamide (C) 600 mg/m 2 every 3 weeks, for 4 cycles;

– TN (cycles 5-8): docetaxel (T) 100 mg/m 2 1 3 times in a fortnight,4 cycles, and trastuzumab (H) administered weekly in accordance with the following scheme:

• cycle 5 (starts 3 weeks after the last cycle as): day 1 – trastuzumab 4 mg/kg (loading dose); day 2 docetaxel 100 mg/m2; day 8, and 15: trastuzumab 2 mg/kg;
• 6-8 cycles: day 1 – docetaxel 100 mg/m 2 and trastuzumab 2 mg/kg; day 8-15 – trastuzumab 2 mg/kg;

– three weeks after day 1 of cycle 8 – trastuzumab 6 mg/ml every 3 weeks.

Trastuzumab is administered for a total of 1 year.

For combination with trastuzumab in the treatment of patients with locally advanced or metastatic breast cancer with tumor overexpression of HER2, the recommended dose of docetaxel is 100 mg / m2 every 3 weeks with weekly use of trastuzumab.

The initial infusion of docetaxel is performed the day after the first dose of trastuzumab is administered.

Subsequent doses of docetaxel are administered immediately after the end of the trastuzumab infusion (if the previous dose of trastuzumab is well tolerated). For the dose of trastuzumab and the method of use, see the instructions for use of trastuzumab.

When combined with capecitabine (1250 mg/m2 orally 2 times a day for 2 weeks, followed by a weekly break), the recommended dose of docetaxel is 75 mg / m2 every 3 weeks.

Non-small cell lung cancer

In patients who have not previously received chemotherapy, the following treatment regimen is recommended: docetaxel 75 mg / m2, immediately followed by cisplatin (75 mg / m2 for 30-60 minutes) or carboplatin (AUC 6 mg / ml / min for 30-60 minutes).

For treatment after the failure of platinum-based chemotherapy, docetaxel monotherapy at a dose of 75 mg/m2 is recommended.

Metastatic ovarian cancer

For second-line treatment of ovarian cancer, a dose of docetaxel of 100 mg/m2 is recommended every 3 weeks.

Prostate cancer

The recommended dose of docetaxel is 75 mg / m2 once every 3 weeks. Prednisone or prednisolone is prescribed for a long time at 5 mg orally 2 times a day.

Gastric cancer, including gastroesophageal junction adenocarcinoma

For the treatment of gastric cancer, the recommended dose of docetaxel is 75 mg / m2 in a 1-hour infusion followed by a cisplatin infusion of 75 mg / m2 for 1-3 hours (both drugs only on day 1). Upon completion of cisplatin use, a 24-hour fluorouracil infusion of 750 mg/m2/day is performed for 5 days. The treatment is repeated every 3 weeks. Patients should receive premedication with antiemetics and appropriate hydration for cisplatin use. To reduce the risk of hematological toxicity (see dose adjustment), use of granulocyte colony-stimulating factor (G-CSF) is indicated as a preventive measure.

Head and neck cancer

Induction chemotherapy followed by radiation therapy

For induction therapy in locally advanced inoperable squamous cell carcinoma of the head and neck, the recommended dose of docetaxel is 75 mg / m2 as a 1-hour infusion, followed by a 1-hour cisplatin infusion (75 mg/m2 ) on day 1, followed by a 24-hour continuous infusion of fluorouracil (750 mg / m2) for 5 days. This pattern is repeated every 3 weeks for 4 cycles. After chemotherapy, patients should receive radiation therapy.

Induction chemotherapy followed by chemoradiotherapy

For induction therapy of locally advanced squamous cell unresectable cancer of the head and neck (with a low probability of surgical cure or when deciding to save the organ), the recommended dose of docetaxel is 75 mg/m2 as a 1-hour intravenous infusion on day 1, followed by a 0.5 – 3-hour cisplatin infusion (100 mg/m2) and followed by a continuous infusion of fluorouracil (1000 mg/m2) from day 1 to day 4. This treatment regimen is repeated every 3 weeks, the course of treatment is 3 cycles. After chemotherapy, patients should receive chemoradiotherapy.

Patients should receive premedication with antiemetics and appropriate hydration (before and after cisplatin use). Neutropenic infections should be prevented with antibiotics.

Dose adjustment

General principles

Docetaxel should be administered when the number of neutrophils in the peripheral blood is ≥1500/µl. In the case of febrile neutropenia, a decrease in the number of neutrophils

Adjuvant therapy for breast cancer

Patients with non-metastatic breast cancer receiving adjuvant docetaxel therapy in combination with doxorubicin and cyclophosphamide should be treated with G-CSF. Patients who have developed febrile neutropenia or neutropenic infection should reduce the dose of docetaxel to 60 mg/m2 in all subsequent cycles. In patients who have developed grade 3 or 4 stomatitis, the dose of docetaxel should be reduced to 60 mg/m2.

For operable and locally advanced breast cancer after an episode of febrile neutropenia or infection with neoadjuvant therapy, G-CSF should be used as a preventive measure on all subsequent cycles, and the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2.

In operable breast cancer with tumor overexpression of HER2 after an episode of febrile neutropenia or infection on the background of neoadjuvant therapy according to the AS TN scheme, G-CSF should be used for preventive purposes on all subsequent cycles, and the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2.

In combination with cisplatin or carboplatin

In patients who initially received docetaxel at a dose of 75 mg/m2 in combination with cisplatin or carboplatin and whose platelet counts in the previous cycle was reduced to 25,000/µl, or in patients who have developed febrile neutropenia, or in patients with serious non-hematologic toxicities, the docetaxel dose in subsequent cycles should be reduced to 65 mg/m2.

In combination with capecitabine

At the first occurrence of grade 2 toxicity, which persists until the beginning of the next docetaxel/capecitabine cycle, the next treatment cycle can be postponed until the toxicity decreases to grade 0-1, while 100% of the initial dose is administered during the next treatment cycle. In patients with repeated development of grade 2 toxicity or first development of grade 3 toxicity at any time of the cycle, treatment is postponed until toxicity decreases to grade 0-1, then treatment with docetaxel is resumed at a dose of 55 mg / m2.

In case of any subsequent manifestations of toxicity or the appearance of any types of grade 4 toxicity, docetaxel use should be discontinued.

Recommendations for dose adjustment of capecitabine are given in the instructions for use of the drug.

Docetaxel in combination with cisplatin and fluorouracil

Patients receiving docetaxel in combination with cisplatin and fluorouracil should receive antiemetics and adequate hydration in accordance with current generally accepted guidelines. To reduce the risk of complicated neutropenia should be used with G-CSF.

If, despite the use of G-CSF, there are episodes of febrile neutropenia, prolonged neutropenia or neitropeniceskih infection, the dose of docetaxel reduced from 75 to 60 mg/m 2. In the subsequent development of episodes of complicated neutropenia, the dose of docetaxel reduced from 60 mg/m2 to 45 mg/m 2. With the development of grade 4 thrombocytopenia, the dose of docetaxel is reduced from 75 mg / m2 to 60 mg/m2. Subsequent cycles using docetaxel are possible if the neutrophil count is >1500/µl and the platelet count is >100,000/µl. If toxic symptoms persist, treatment should be discontinued.

Recommendations for dose adjustment in case of toxicity in patients receiving docetaxel in combination with cisplatin and fluorouracil (FU)

Toxicity

Correction of the dosage regimen

Grade 3 diarrhea

First episode: reduce the dose of FU by 20%

Repeat episode: Reduce docetaxel dose by 20%

Grade 4 diarrhea

First episode: Reduce docetaxel and FU doses by 20%

Recurrent episode: stop treatment

Stomatitis/mucositis of 3 degrees

First episode: reduce the dose of FU by 20%

Repeat episode: stop only taking FU in all subsequent courses

Third episode: Reduce docetaxel dose by 20%

Stomatitis/mucositis of 4 degrees

First episode: Stop taking only FU on subsequent cycles

Repeat episode: Reduce docetaxel dose by 20%

Special patient groups

Patients with impaired liver function

When the activity of “hepatic” transaminases in blood plasma exceeds more than 1.5 times the upper limit of normal (ULN), or alkaline phosphatase exceeds more than 2.5 times ULN, the recommended dose of Docetaxel Sandoz® is 75 mg/m2. In patients with increased bilirubin concentration and/or activity of “hepatic” transaminases (>3.5 ULN) in combination with an increase in alkaline phosphatase activity more than 6 times ULN, use Docetaxel Sandoz® is not recommended, except for strict indications.

Elderly patients

There are no specific instructions for the use of docetaxel in elderly patients. When combined with capecitabine in patients over 60 years of age, it is recommended to reduce the starting dose of capecitabine in accordance with the instructions for the drug.

When combining docetaxel with other antitumor drugs, the dose (including dose adjustment), the method of use should be selected according to the instructions for the medical use of these drugs.

Preparation of the infusion solution

Docetaxel Sandoz®, a concentrate for preparing an infusion solution, does not need to be pre-diluted with a solvent and is already ready to be added to the infusion solution.

If the vials are stored in the refrigerator, the required number of packages of the drug with the concentrate for preparing the infusion solution should be kept at room temperature (no higher than 25 °C) for 5 minutes before using it to prepare the infusion solution.

The required volume of docetaxel concentrate for the preparation of an infusion solution,10 mg / ml, in accordance with the required dose under aseptic conditions, is extracted from vials using a single graduated syringe connected to a needle, and inserted into an infusion bag or bottle with 5% dextrose solution or 0.9% sodium chloride solution to a docetaxel concentration of no more than 0.74 mg/ml (use is carried out by a single injection of the entire required dose into the infusion container). The resulting infusion solution should be mixed by slowly turning the infusion bag or vial over. The resulting solution should be used for 4 hours (including a 1-hour infusion) at room temperature and normal light conditions.

The infusion solution should be examined before use; if any sediment is present, the solution should be destroyed.

Contraindications

Increased individual sensitivity to docetaxel or other components of the drug;

– neutropenia (initial number of neutrophils in peripheral blood < 1500 / µl);

– severe liver function disorders;

– pregnancy;

– breast – feeding period;

– children under 18 years of age.

When using Docetaxel Sandoz® in combination with other drugs, contraindications to their use should also be taken into account.

With caution:

Concomitant use of drugs that induce or inhibit cytochrome P 450-3 A isoenzymes, or that are metabolized by cytochrome P 450-3 A isoenzymes, such as cyclosporine, terfenadine, imidazole antifungal agents (ketoconazole, itraconazole, voriconazole), erythromycin, troleandomycin, clarithromycin, telithromycin, protease inhibitors (ritonavir, indinavir, nelfinavir, saquinavir), as well as nefadozone.

Side effects

According to the World Health Organization (WHO), adverse events are classified according to their frequency as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), and very rare (

Monotherapy (75 mg / m2 and 100 mg/m2)

From the blood and lymphatic system

very often: reversible neutropenia after an average of 7 days (in patients who have previously received chemotherapy, this period may be shorter), the average duration of severe neutropenia (less than 500 cells/µl) – 7 days; febrile neutropenia, anemia, thrombocytopenia, infections;

often: severe infections, combined with a reduction in the number of neutrophils in the peripheral blood of less than 500/µl; severe infections, including sepsis and pneumonia, including fatality; thrombocytopenia less than 100,000/µl, bleeding, combined with thrombocytopenia less 50000/µl and anemia (hemoglobin less than 11 g/DL), including severe (hemoglobin less than 8 g/DL);

infrequently: severe thrombocytopenia;

frequency unknown: inhibition of bone marrow hematopoiesis and other hematological side effects; development of disseminated intravascular coagulation syndrome (DIC), often in combination with sepsis and multi-organ failure.

From the immune system

very often: allergic reactions that usually occur within a few minutes of starting the infusion (“hot flashes” of blood to the face, rash with or without itching, chest tightness, back pain, shortness of breath, drug fever or chills);

often: severe allergic reactions characterized by low blood pressure and / or bronchospasm or generalized rash / erythema;

frequency unknown: anaphylactic shock, sometimes fatal (in patients who received premedication, these cases ended in a fatal outcome very rarely).

From the skin and subcutaneous tissue

very often: reversible cutaneous reactions are usually mild or moderately severe localized rash, mainly on the hands and feet, as well as on the face and chest, often accompanied by itching, rashes usually occurred within one week after the infusion of docetaxel; violations of the nails characterized by Hypo – and hyperpigmentation, pain and onycholysis; alopecia;

often: severe skin reactions, including rash followed by desquamation, including severe palm and foot syndrome, which may require discontinuation or discontinuation of docetaxel treatment;

infrequently: severe alopecia;

very rare: cutaneous lupus erythematosus, bullous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (in some cases, several factors have contributed to the development of these conditions, such as concomitant infections, concomitant medications and concomitant diseases), scleroderma-like changes preceded by lymphangiectatic edema.

From the side of water-electrolyte metabolism

very often: fluid retention;

often: severe fluid retention. Peripheral edema has been reported, and less frequently pleural and pericardial effusion, ascites, and weight gain. The frequency and severity of fluid retention increases with repeated use of docetaxel;

the frequency is unknown: Hyponatremia has been reported, mainly in combination with dehydration, vomiting and pneumonia.

From the gastrointestinal tract

very often: nausea, vomiting, diarrhea, anorexia, stomatitis, taste disorders;

often: severe nausea and vomiting, severe diarrhea, constipation, severe stomatitis, esophagitis, epigastric pain (including severe), gastrointestinal bleeding;

infrequently: severe gastrointestinal bleeding, severe constipation and esophagitis, severe taste disorders;

rarely: dehydration due to the development of gastrointestinal reactions, perforation of the stomach or intestines, colitis, including ischemic, neutropenic enterocolitis, ileus (intestinal obstruction), intestinal obstruction.

From the side of the liver and biliary tract

often: increased serum activity of ACT, ALT, alkaline phosphatase and bilirubin concentration in the blood (more than 2.5 times the ULN);

very rare: hepatitis (fatal outcome was observed in patients with a history of liver disease).

From the nervous system

very often: mild to moderate sensorineural reactions: paresthesia, dysesthesia, pain, including burning sensation; and neuromotor reactions, mainly manifested by muscle weakness; often: severe sensorineural and neuromotor reactions; rarely: convulsions, transient loss of consciousness, sometimes developing during infusion of the drug.

From the cardiovascular system

often: arrhythmia, increased or decreased blood pressure; bleeding;

infrequently: heart failure;

rarely: venous thromboembolism and myocardial infarction were rarely reported.

From the side of the organ of vision

rarely: lacrimation in combination with conjunctivitis (or without it), transient visual disturbances (flashes of light in the eyes, appearance of cattle), usually occurring during the use of the drug and combined with the development of hypersensitivity reactions, which usually disappear after stopping the infusion;

very rare: occlusion of the lacrimal canal, leading to excessive lacrimation.

Hearing disorders and labyrinth disorders

are rare: ototoxic effect of the drug, hearing impairment and / or hearing loss.

Respiratory, thoracic and mediastinal

disorders very common: shortness of breath;

often: severe shortness of breath;

rarely: acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, respiratory failure, which could lead to death; with simultaneous radiation exposure, rare cases of radiation pulmonitis occurred; pulmonary fibrosis, pulmonary edema;

From the musculoskeletal system

very often: myalgia;

often: arthralgia.

General disorders and reactions at the injection

site are very common: asthenia, including severe; generalized and localized pain syndrome, including chest pain of non-cardiac origin;

often: reactions at the injection site, usually mild: hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, hemorrhage from a punctured vein or edema of the vein; pronounced generalized and localized pain syndrome, including chest pain of non-cardiac origin.

Other

very rare: acute myeloid leukemia and myelodysplatic syndrome, macular edema, the phenomenon of the return of local radiation reaction in the previously irradiated area, deterioration of renal function, the development of renal failure, in most cases associated with the simultaneous use of nephrotoxic drugs.

Docetaxel Sandoz® in combination with other medications Docetaxel Sandoz® in combination with doxorubicin

When Docetaxel Sandoz® was used in combination with doxorubicin compared to Docetaxel Sandoz® monotherapy, there was a higher incidence of neutropenia, including severe neutropenia; febrile neutropenia; thrombocytopenia, including severe thrombocytopenia; anemia; infections, including severe infections; nausea; vomiting; diarrhea, including severe diarrhea; constipation; stomatitis, including severe stomatitis; heart failure; alopecia; but a lower frequency of allergic reactions; skin reactions, including severe; nail damage, including severe; fluid retention, including severe; anorexia, sensorineural and neuromotor reactions, including severe forms; hypotension; rhythm disorders; increased activity of hepatic transaminases, alkaline phosphatase, bilirubin content in the blood; myalgia; asthenia.

Docetaxel Sandoz® in combination with doxorubicin and cyclophosphamide (TAC scheme)

When using this chemotherapeutic regimen, compared with Docetaxel Sandoz monotherapy, there was a lower incidence of neutropenia, severe anemia, febrile neutropenia, infections, allergic reactions, peripheral edema, sensorineural and neuromotor reactions, nail damage, diarrhea, arrhythmia, but there was a higher incidence of non-severe anemia, thrombocytopenia, nausea, vomiting, stomatitis, taste disorders, constipation, asthenia, arthralgia, alopecia, colitis, enterocolitis, myelodysplatic syndrome.

In addition, the following cases were observed: perforation of the large intestine without fatal outcomes, acute myeloid leukemia, and acute leukemia. Prophylactic use of G-CSF reduced the incidence of neutropenia (by 60%) and neutropenic infections of 3-4 degrees of severity.

Doxorubicin and cyclophosphamide) with subsequent use of Docetaxel Sandoz® in combination with trastuzumab (AS-TN scheme)

When using these chemotherapy regimens compared to monotherapy with the drug Alopecia; anemia, including grade 3-4 anemia; thrombocytopenia, including grade 3-4 thrombocytopenia; nausea, including grade 3-4 nausea; stomatitis; vomiting; diarrhea; constipation; anorexia; abdominal pain; increased ACT activity, ALT and alkaline phosphatase; myalgia; nail damage; arthralgia; infections of 3-4 degrees of severity; heart failure.

There was no increase in febrile neutropenia.

Less common were grade 3-4 neutropenia, fluid retention, sensorineural and neuromotor reactions, rash and desquamation, and allergic reactions.

Additionally, insomnia and increased blood creatinine concentrations were recorded.

Docetaxel Sandoz® in combination with capecitabine

When using Docetaxel Sandoz® in combination with capecitabine, there is a more frequent development of adverse events from the gastrointestinal tract (stomatitis, diarrhea, vomiting, constipation, abdominal pain, impaired taste perception); arthralgia; severe thrombocytopenia and anemia; hyperbilirubinemia; palmar-plantar syndrome (hyperemia of the skin of the extremities (palms and feet) with subsequent edema and desquamation); but more rare development of severe thrombocytopenia and anemia. neutropenia; alopecia; nail disorders, discoloration of the nails, including onycholysis, dyspnea, paresthesia, dehydration, lacrimation; asthenia; myalgia; decreased appetite and anorexia.

Additionally, dyspepsia, dry mouth, sore throat, oral candidiasis, dermatitis, erythematous rash, pyrexia, limb pain, back pain, lethargy (drowsiness, lethargy, numbness), cough, nosebleeds, dizziness, headache, peripheral neuropathy, and weight loss were observed.

Compared to younger patients, patients 60 years and older who received a combination of Docetaxel Sandoz® and capecitabine were more likely to develop grade 3-4 toxicity.

Docetaxel Sandoz® in combination with trastuzumab

Patients receiving a combination of Docetaxel Sandoz® and trastuzumab (compared to Docetaxel Sandoz® monotherapy) were more likely to experience nausea, diarrhea, constipation, abdominal pain, taste disorders, febrile neutropenia, arthralgia, anorexia, grade 4 toxic events, and cases of heart failure, especially in patients previously treated with anthracyclines as adjuvant therapy, but less frequently observed neutropenia of 3-4 degrees of severity, asthenia, weakness, alopecia, nail damage, skin rashes, vomiting, stomatitis and myalgia. Additionally, lacrimation, conjunctivitis, pain, shortness of breath, paresthesia, mucosal inflammation, nasopharyngitis, pharyngeal and laryngeal pain, nosebleeds, rhinorrhea, flu-like illnesses, cough, pyrexia, chills, chest pain, limb pain, back pain, bone pain, lethargy (drowsiness, lethargy, numbness), insomnia, erythema, dyspepsia, headache pain, hypesthesia.

Compared with docetaxel monotherapy, there was an increase in the incidence of severe adverse reactions.

Combination of Docetaxel Sandoz with cisplatin or carboplatin

Thrombocytopenia, including grade 3-4 thrombocytopenia; anemia, including grade 3-4 anemia; nausea, including grade 3-4 nausea; grade 3-4 diarrhea; anorexia, including grade 3-4 diarrhea; and injection site reactions were more common with these chemotherapy regimens compared to Docetaxel Sandoz monotherapy. However, neutropenia, including grade 3-4 neutropenia; infections; febrile neutropenia; allergic reactions; skin reactions; nail damage; fluid retention, including grade 3-4 fluid retention; stomatitis, sensorineural and to a lesser extent neuromotor neuropathies; alopecia; asthenia and myalgia.

Additionally observed: fever in the absence of infection, including 3-4 degrees of severity; pain.

Combination of Docetaxel Sandoz with prednisone or prednisone

When using Docetaxel Sandoz® in combination with prednisone or prednisone, compared with Docetaxel Sandoz® monotherapy, the incidence of side effects was significantly reduced: anemia, including 3-4 degrees of severity; infections; neutropenia, including 3-4 degrees of severity; thrombocytopenia; febrile neutropenia; weakness; allergic reactions; sensorineural and neuromotor reactions; alopecia; rash; desquamation; nausea diarrhoea; stomatitis; vomiting; anorexia; myalgia; arthralgia; fluid retention; but more often taste disorders and heart failure were observed.

Additionally observed: nosebleeds, cough, weakness, lacrimation.

Combination of Docetaxel Sandoz with cisplatin and fluorouracil

When using this combination, compared with Docetaxel Sandoz® monotherapy, anemia, including 3-4 degrees of severity; thrombocytopenia, including 3-4 degrees of severity; febrile neutropenia; neutropenic infections (even with G-CSF); nausea; vomiting; anorexia; stomatitis; diarrhea; esophagitis/dysphagia/pain when swallowing; but less often infections; allergic reactions; fluid retention; neurosensory and neuromotor reactions; myalgia; alopecia; rash; pruritus; nail damage; skin desquamation; rhythm disorders.

In addition, fever was observed in the absence of infection; lethargy (drowsiness, lethargy, numbness); hearing changes; dizziness; lacrimation; dry skin; heartburn; myocardial ischemia; stressed venous pattern; cancer pain; weight loss. Prophylactic use of G-CSF reduces the incidence of febrile neutropenia and / or neutropenic infectious complications.

Interaction

In vitro studies have shown that the biotransformation of the drug can change with the simultaneous use of other drugs that induce, inhibit or are metabolized by the cytochrome CYP3A isoenzyme, such as cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. In this regard, caution should be exercised when using such drugs simultaneously, taking into account the possibility of pronounced interaction.

Concomitant use of docetaxel with inhibitors of the CYP3A4 isoenzyme may increase the risk of side effects. If concomitant use of docetaxel with strong inhibitors of the CYP3A4 isoenzyme (ketoconazole, itraconazole, clarithromycin, indinavir, nefadosone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) is necessary, caution should be exercised, dose adjustment of docetaxel is required.

Studies conducted in patients treated simultaneously with docetaxel and ketoconazole showed that the clearance of docetaxel decreased by 49%, apparently due to the fact that the main route of docetaxel metabolism is its metabolism using the CYP3A4 isoenzyme. In this case, even with the use of lower doses of docetaxel, its tolerability may worsen.

In vitro, drugs that bind strongly to plasma proteins, such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylates, sulfamethoxazole, and valproic acid, did not affect the binding of docetaxel to plasma proteins. Dexamethasone also does not affect the degree of binding of docetaxel to plasma proteins. Docetaxel does not affect the binding to plasma proteins of digitoxin. The pharmacokinetics of docetaxel, doxorubicin, and cyclophosphamide did not change when they were co-administered.

The pharmacokinetics of docetaxel in the presence of prednisone were studied in patients with metastatic prostate cancer, despite the fact that docetaxel is metabolized by the CYP3A4 isoenzyme, and prednisone is an inducer of the CYP3A4 isoenzyme, there was no statistically significant effect of prednisone on the pharmacokinetics of docetaxel.

There is information about the interaction of docetaxel and carboplatin. When using a combination of carboplatin and docetaxel, the clearance of carboplatin increases by 50% compared to carboplatin monotherapy.

Special instructions

Treatment with Docetaxel Sandoz® is carried out only under the supervision of a doctor who has experience in the use of antitumor drugs, in a specialized hospital.

Neutropenia

A general blood test should be monitored periodically. With the development of severe neutropenia (neutrophil count less than 500 / µl for 7 days or more) during the course of Docetaxel Sandoz therapy, it is recommended to reduce the dose of the drug (see Dosage and use) in subsequent courses or use adequate symptomatic measures. It is possible to continue treatment with Docetaxel Sandoz® after the neutrophil count has been restored to 1500 / µl.

Patients receiving docetaxel in combination with cisplatin and fluorouracil are less likely to develop febrile neutropenia and /or neutropenic infections when receiving G-CSF. Therefore, when using this combination, it is necessary to prescribe G-CSF for preventive purposes to reduce the risk of developing complicated neutropenia (febrile neutropenia, long-term neutropenia, neutropenic infection). The condition and laboratory parameters of patients receiving this chemotherapeutic regimen should be carefully monitored.

Hypersensitivity reactions

Patients should be carefully monitored for hypersensitivity reactions, especially during the first and second infusions. The development of hypersensitivity reactions is possible in the very first minutes of infusions of the drug. Hypersensitivity reactions, such as redness of the face or localized skin reactions, do not require interruption of the drug use. Severe hypersensitivity reactions (low blood pressure, bronchospasm, or generalized rash / erythema) require immediate discontinuation of Docetaxel Sandoz and appropriate treatment measures. Repeated use of Docetaxel Sandoz in such patients is not permitted.

Patients with hepatic insufficiency

Patients receiving docetaxel monotherapy at a dose of 100 mg / m%^%2 and with a high activity of “hepatic” transaminases, more than 1.5 times the ULN, in combination with an increase in alkaline phosphatase activity more than 2.5 times the ULN, are extremely at risk of developing severe side effects, such as sepsis, gastrointestinal bleeding, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia. In this regard, liver function tests should be determined before the start of therapy and before each subsequent cycle of therapy with Docetaxel Sandoz®. In patients with elevated bilirubin concentrations and/or hepatic transaminase activity (>3.5 ULN) in combination with an increase in alkaline phosphatase activity more than 6 times the ULN, Docetaxel Sandoz® is not recommended.

Currently, there are no data on the use of docetaxel in combination with other drugs in patients with impaired liver function.

Fluid retention

Due to the possibility of fluid retention, patients with pleural effusion, pericardium, or ascites should be carefully monitored. If edema occurs, it is necessary to limit the salt and drinking regime and prescribe diuretics.

Damage to the respiratory system

Cases of acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, pulmonary fibrosis, and respiratory failure, including fatal cases, have been reported. Cases of radiation pneumonitis have also been reported in the absence of radiation therapy.

If new or pre-existing respiratory symptoms appear or worsen, patients should be carefully monitored by a doctor, and symptomatic therapy is indicated. Docetaxel treatment should be suspended until the diagnosis is clear. Whether to resume docetaxel treatment should be decided based on a thorough assessment of the benefits of such treatment.

Leukemia

When using a combination of Docetaxel Sandoz® with doxorubicin and cyclophosphamide for non-metastatic operable breast cancer, the risk of developing delayed myelodysplasia and/or myeloid leukemia requires hematological monitoring of patients.

Heart failure

During treatment with docetaxel and in the following follow-up period, it is necessary to monitor the symptoms of chronic heart failure (CHF). A higher risk of developing CHF in patients with breast cancer with lymph node involvement receiving TAS chemotherapy is observed in the first year after completion of treatment.

Patients treated with Docetaxel Sandoz® in combination with trastuzumab for metastatic breast cancer with tumor overexpression of HER2, especially after anthracycline-containing chemotherapy (doxorubicin or epirubicin), may develop heart failure, which may be moderate or severe and lead to death. When a patient is indicated for treatment with Docetaxel Sandoz® in combination with trastuzumab, she should undergo an initial cardiological examination. Cardiac function should be monitored every three months to identify patients who may develop heart failure.

Visual disturbances

Macular edema has been reported in patients taking docetaxel. If visual impairment occurs, patients should undergo a full ophthalmological examination. If macular edema is diagnosed, the drug should be discontinued.

The need for contraception

Since preclinical studies have shown that docetaxel has a genotoxic effect and can interfere with male fertility (the ability to conceive), men receiving docetaxel treatment are advised to refrain from conceiving a child during treatment and for at least 6 months after the end of chemotherapy, and to advise sperm preservation prior to treatment.

Women who become pregnant during treatment should immediately inform their doctor about this.

During and for at least 6 months after discontinuation of therapy, patients of both sexes should use reliable methods of contraception.

Neurotoxicity

The development of severe sensory neuropathy requires a reduction in the dose of Docetaxel Sandoz.

Elderly patients

Compared with patients younger than 60 years of age, patients aged 60 years and older receiving docetaxel+capecitabine combination chemotherapy experienced an increase in the incidence of treatment-related grade 3 and 4 adverse events associated with the treatment of serious adverse reactions (NRS) and early discontinuation of treatment due to the development of NRS.

There are limited data on the use of a combination of docetaxel with doxorubicin and cyclophosphamide in patients over 70 years of age.

In patients 65 years and older treated with the drug every 3 weeks for prostate cancer, the frequency of nail changes was ≥ 10% higher than in younger patients, and in patients 75 years and older, the frequency of fever, diarrhea, anorexia and peripheral edema was ≥ 10% higher than in younger patients.

When using a combination of docetaxel with cisplatin and fluorouracil, the following adverse reactions (of all degrees of severity)were observed:: lethargy (drowsiness, lethargy, numbness), stomatitis, and neutropenic infections were ≥10% more common in patients over 65 years of age than in younger patients. Therefore, patients over 65 years of age receiving this combination should be closely monitored.

Ethanol content

Docetaxel Sandoz® contains ethanol at a concentration of 27 volume% (10 mg / ml contains 0.28 g of ethanol in terms of the main substance). This should be taken into account when using the drug in patients with alcoholism and patients at risk (patients with liver disease and epilepsy).

Handling and precautions for handling the product

Caution should be exercised when using and preparing solutions of Docetaxel Sandoz®. It is recommended to use gloves. If the concentrate or infusion solution gets on the skin, it should be immediately washed thoroughly with soap and water. In case of contact with the mucous membranes, they should be immediately thoroughly rinsed with water.

Special precautions for disposal of unused medicinal products

Drug residues, all tools and materials used for the preparation of solutions for intravascular and intravesical use of Docetaxel Sandoz® should be disposed of in accordance with the standard hospital procedure for the disposal of cytotoxic substance waste, taking into account the current regulations for the disposal of hazardous waste.

Influence on the ability to drive vehicles and mechanisms:The drug is used in a hospital setting. No special studies were conducted. However, the development of adverse reactions from the nervous system and the visual organ, as well as the presence of ethanol in the preparation, can lead to a decrease in the speed of psychomotor reactions and attention. In this regard, it is not recommended to drive a car or engage in other potentially dangerous activities during treatment with Docetaxel Sandoz®.

Active ingredient

Docetaxel

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Breast Cancer, Cancer