Index of drugs

The drug, in combination with prednisone or Prednisolone, is indicated for the treatment of patients with hormone refractory metastatic prostate cancer who have previously been treated with docetaxel chemotherapy.

1 vial (1.5 ml) with concentrate contains 60 mg cabazitaxel. After initial dilution with the entire volume of solvent, 1 ml of solution contains 10 mg of cabazitaxel. The solvent vial contains 573.3 mg ethanol 96%.

An anti-cancer drug. It works by disrupting the network of microtubule connections in cells, binds tubulin and stimulates the process of tubulin deposition to microtubules, while at the same time inhibiting their disintegration. It leads to the stabilization of microtubules, which causes the inhibition of mitotic and interphase cell divisions. Cabazitaxel has a broad spectrum of antitumor activity against advanced human tumors implanted in mice. It shows activity towards tumors susceptible to docetaxel and not sensitive to chemotherapy containing docetaxel. It is metabolised in the liver (> 95%), mainly mediated by CYP3A4 isoenzyme (80-90%). Excreted mainly in the faeces in the form of numerous metabolites (76% of the dose, excretion through the kidneys is less than 4% of the dose). It binds to serum proteins in 89-92%. T_0,5 in the elimination phase is 95 hours.

Hypersensitivity to cabazitaxel, other taxanes or any of the excipients of the drug, including polysorbate 80. Number of neutrophils below 1500 / mm³. Hepatic impairment (bilirubin ≥1 x upper limit of normal (ULN) or AST (or) ALT ≥ 1.5 x ULN). Simultaneous vaccination against yellow fever vaccine.

All patients should receive premedication before the start of the cabazitaxel infusion. Patients should be monitored for hypersensitivity reactions (especially during the first and second infusions, severe hypersensitivity reactions - generalized rash, erythema, hypotension, bronchospasm); if hypersensitivity reactions occur, the drug should be discontinued. Patients treated with cabazitaxel may receive prophylactic G-CSF according to the recommendations of the American Association of Clinical Oncology and / or the current guidelines of the treatment center to reduce the risk or manage the complications of neutropenia. Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features (age> 65 years, poor functional status, previous neutropenic febrile episodes, extensive pre-irradiated areas of the body, poor nutritional status or other severe comorbidities) that predispose to increase the complications resulting from prolonged neutropenia. The use of G-CSF has been shown to reduce the incidence and severity of neutropenia. Complete blood counts should be performed every week during the first course of treatment and before each subsequent cycle so that the dose can be adjusted if necessary. The dose should be reduced in case of febrile neutropenia or prolonged neutropenia, despite adequate treatment. Re-treatment of patients can only be started if the neutrophil count returns to ≥ 1500 / mm³. If patients experience diarrhea, they can be treated with commonly used antidiarrheal medications. A greater risk of diarrhea occurs in patients who have previously undergone irradiation of the abdominal and pelvic area. Dehydration is more common in patients ≥ 65 years of age. Actions should be taken to restore the hydration status of the patient and to monitor and correct serum electrolytes, especially potassium. In case of grade ≥3 diarrhea. it may be necessary to postpone the treatment or reduce the dose of the drug. If patients experience nausea or vomiting, they can be treated with commonly used antiemetics. The presence or worsening of neuropathy should be assessed before each treatment; treatment should be postponed until the symptoms improve and in the case of persistent peripheral neuropathy> 2.reduce the dose of the drug. Serum creatinine should be measured before initiation of treatment, during all blood counts, and each time a patient reports a change in urine volume. If CTCAE 4.0 grade ≥3 renal failure occurs, treatment should be discontinued. Caution should be exercised in elderly patients (≥ 65 years) due to the increased risk of adverse reactions, including neutropenia and febrile neutropenia, and in patients with hemoglobin <10 g / dl. The safety and efficacy of the medicine in children and adolescents under 18 has not yet been established. The solvent contains 573.3 mg ethanol 96% (15% v / v), equivalent to 14 ml of beer or 6 ml of wine - this should be taken into account in people with alcoholism and patients with liver disease or epilepsy.

There are no data on the use of cabazitaxel in pregnant women. Animal studies have shown reproductive toxicity after using toxic doses for pregnant females and passing of cabazitaxel across the placental barrier, hence cabazitaxel may cause fetal damage in exposed pregnant women - do not use during pregnancy and in women of childbearing potential not using effective contraception. The drug should not be used during breastfeeding. The effect of cabazitaxel on fertility can not be ruled out in men, therefore effective contraception should be used during treatment and up to 6 months after the last dose. Men receiving cabazitaxel should prevent other people from contacting their ejaculate during treatment and should consider the possibility of storing their sperm prior to treatment.

Adverse reactions and haematological abnormalities in patients receiving the preparation in combination with prednisone or prednisolone. Very common: neutropenia, anemia, leukopenia, thrombocytopenia, anorexia, dysphoria, dyspnoea, cough, diarrhea, nausea, vomiting, constipation, abdominal pain, alopecia, back pain, joint pain, hematuria, fatigue, asthenia, fever. Common: septic shock, sepsis, cellulitis, urinary tract infection, influenza, cystitis, upper respiratory infection, shingles, athlete's foot, febrile neutropenia, hypersensitivity, dehydration, hyperglycemia, hypokalaemia, anxiety, confusion, peripheral neuropathy, peripheral sensory neuropathy, central dizziness, headache, paresthesia, lethargy, hypoesthesia, sciatica, conjunctivitis, increased tearing, tinnitus, diarrheal vertigo, atrial fibrillation, tachycardia, hypotension, deep vein thrombosis, hypertension, orthostatic hypotension , hot flushes, paroxysmal redness of the skin, mouth and throat pain, pneumonia, indigestion, epigastric pain, hemorrhagic nodules, esophageal reflux disease, rectal bleeding, dry mouth, bloating, dry skin, erythema, limb pain, muscle contraction , ache muscle pain, musculoskeletal pain, side-body pain, acute renal failure, renal failure, urinary problems, renal colic, pollakiuria, hydronephrosis, urinary retention, urinary incontinence, ureteral obstruction, pelvic pain, peripheral edema , mucositis, pain, chest pain, swelling, chills, malaise, weight loss, increased AST, elevated transaminases. In a clinical study, 18.3% of patients discontinued treatment due to adverse reactions; the most common adverse reaction leading to discontinuation of treatment was neutropenia (2.4%). The incidence of grade ≥3 neutropenia. based on the results of laboratory tests, it was 81.7%. The incidence of clinical neutropenia and grade 3 neutropenic fever was 21.3% and 7.5%, respectively. Neutropenic complications included neutropenic infections, neutropenic sepsis and septic shock, which in some cases led to death. The incidence of grade 3 anemia, increased AST, ALT and bilirubin based on laboratory tests was 10.6%, 0.7%, 0.9% and 0.6%, respectively.The following adverse reactions occurring at a frequency of ≥5% have been reported more frequently in patients ≥65 years compared to younger patients: fatigue, clinical neutropenia, asthenia, fever, central dizziness, urinary tract infection and dehydration. Frequency of the following grade 3 adverse reactions. was higher in patients ≥65 years compared to younger patients: neutropenia based on laboratory tests, clinical neutropenia and febrile neutropenia.

The drug should only be used in units specialized in the administration of cytotoxic drugs and should be administered only under the supervision of a doctor who is qualified to use cancer chemotherapy. In order to reduce the risk of hypersensitivity reactions and intensification, the recommended premedication schedule should be performed at least 30 minutes prior to each drug administration by intravenous administration of the following preparations: antihistamines (5 mg dexphenolramine or 25 mg diphenhydramine or equivalent strength), corticosteroid (8 mg Dexamethasone or a drug with an equivalent potency) and an H receptor antagonist₂ (ranitidine or a drug with equivalent potency). It is recommended to use prophylactic antiemetics, which can be given orally or intravenously, depending on the need. During treatment, adequate hydration should be provided. The recommended dose is 25 mg / m² pc. administered in 1 hour intravenous infusion every 3 weeks, in combination with oral prednisone or Prednisolone 10 mg administered daily during treatment. The dose should be modified if the following side effects occur: long-term (> 1 week) grade3 neutropenia, despite appropriate treatment, including G-CSF - treatment should be postponed until the neutrophil count reaches> 1500 cells / mm³and then reduce the dose of cabazitaxel with 25 mg / m² pc. up to 20 mg / m² pc .; neutropenic fever or neutropenic infection - treatment should be postponed until the symptoms improve or resolve and neutrophil count reaches> 1500 cells / mm³, then reduce the dose of cabazitaxel with 25 mg / m² pc. up to 20 mg / m² pc .; Grade diarrhea ≥3. or persistent diarrhea despite appropriate treatment, including fluid and electrolyte depletion - treatment should be postponed until the symptoms improve or disappear, and then reduce the dose of cabazitaxel with 25 mg / m² pc. up to 20 mg / m² pc .; peripheral neuropathy> 2. - the treatment should be deferred until the improvement and then the dose of cabazitaxel decreased to 25 mg / m² pc. up to 20 mg / m² pc. Treatment should be discontinued if the patient still has any of the side effects reported after taking 20 mg / m² pc. The drug should not be used in patients with impaired liver function. No dose adjustment is required in patients with mild renal impairment (creatinine clearance: 50-80 ml / min), and caution should be exercised in patients with moderate or severe renal impairment and end-stage renal disease. There are no special recommendations regarding the dose adjustment of cabazitaxel in elderly patients.