Jevtana, 40 mg/ml 1.5 ml

Pharmacodynamics

Antitumor drug, alkaloid. Mechanism of action is related to disruption of cellular network of microtubules. Cabazitaxel binds to tubulin and promotes the assembly of tubulin into microtubules and simultaneously inhibits their disassembly. This leads to the stabilization of microtubules, which ultimately inhibits mitotic and interphase activity of the cell.

The broad spectrum antitumor activity of cabazitaxel has been shown against late-stage human tumors xenotransplanted to mice. Cabazitaxel is active against docetaxel-sensitive tumors. In addition, cabazitaxel has been shown to be active against tumor models insensitive to chemotherapy, including docetaxel.

The efficacy and safety of Jevtan® in combination with prednisone or prednisolone was evaluated in patients with hormone-resistant metastatic prostate cancer who had previously received chemotherapy including docetaxel (a total of 755 patients).

The patients received cabazitaxel at a dose of 25 mg/m² body surface every 3 weeks for up to 10 cycles, combined with daily oral administration of prednisone or prednisolone at a dose of 10 mg/day. In the comparison group, patients received mitoxantrone at a dose of 12 mg/m² in an IV every 3 weeks in combination with daily oral prednisone or prednisolone at a dose of 10 mg/day. Overall survival was longer in the cabazitaxel group with a 30% reduction in risk of death compared with the mitoxantrone group (median survival 15.1 (14.1-16.3) and 12.7 (11.6-13.7) months, respectively). There was an increase in time to disease progression of 2.8 (2.4-3.0) months in the Jevtan® group compared to the mitoxantrone group versus 1.4 (1.4-1.7) months, respectively.

There was a significantly higher rate of disease remission, at 14.4% in patients treated with Jevtana® compared to 4.4% in patients in the mitoxantrone group.

There were no statistically significant differences in the two groups with respect to pain progression or pain remission.

Pharmacokinetics

Population pharmacokinetic analysis was performed in 170 patients, including patients with locally advanced solid tumors, metastatic breast cancer and metastatic prostate cancer. These patients received cabazitaxel at a dose range of 10-30 mg/m² weekly or every 3 weeks.

Absorption

After an intravenous infusion of cabazitaxel for 1 h at a dose of 25 mg/m² in patients with metastatic prostate cancer C_max of cabazitaxel in plasma was reached by the end of the infusion, with a mean C_max value of 226 ng/mL. The mean AUC was 991 ng×h/mL. In patients with locally disseminated solid tumors, there were no large deviations in the dose-proportionality of plasma concentrations of cabazitaxel in the dose range of 10-30 mg/m².

The distribution

The V_ss was 4870 L (2640 L/m² for patients with a median body surface area leaving 1.84 m²).

In vitro binding of cabazitaxel to human serum proteins is 89-92% and is unsaturated to a concentration of 50,000 ng/mL, which exceeds the C_max observed with clinical use of the drug. Cabazitaxel primarily binds to serum albumin (82%) and lipoproteins (87.9% for HDL, 69.8% for LDL, and 55.8% for LDLNP). In vitro in human blood, the ratios of blood to plasma concentrations are in the range of 0.9-0.99, indicating a similar distribution of cabazitaxel in blood and plasma.

Animal studies have shown that cabazitaxel and its metabolites are excreted into breast milk and that cabazitaxel penetrates the placental barrier.

Metabolism

Cabazitaxel is extensively metabolized in the liver (≥95%), mainly with the participation of CYP3A4 isoenzyme (80-90%). Cabazitaxel is the main compound circulating in blood plasma. In addition to it 7 metabolites were identified in blood plasma (including 3 active metabolites formed as a result of O-demethylation). The plasma concentration of the main one is 5% of the plasma concentration of unchanged cabazitaxel. About 20 metabolites of cabazitaxel are excreted by the kidneys (with urine) and intestines (with feces).

Potential risk of inhibition of hepatic metabolism by cabazitaxel in clinically relevant concentrations is possible for drugs that are mainly substrates of CYP3A isoenzyme. However, there is no potential risk of inhibition of metabolism of drugs that are substrates of other CYP isoenzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2E1 and 2D6), and there is no potential risk of induction of metabolism of drugs that are substrates of CYP1A, CYP2C9, and CYP3A isoenzymes by cabazitaxel.

Powerful inducers or inhibitors of CYP3A isoenzyme may change the plasma concentration of cabazitaxel because cabazitaxel is mainly metabolized with the participation of CYP3A isoenzyme.

Prednisolone or prednisone at a dose of 10 mg/day do not change the pharmacokinetics of cabazitaxel.

In vitro, cabazitaxel does not inhibit multiple chemotherapeutic drug resistance proteins (MRP1 and MRP2). Cabazitaxel inhibits the transport of P-glycoprotein (P-gP) (digoxin, vinblastine) and breast cancer chemotherapeutic drug resistance proteins (BCRP) (methotrexate) at concentrations 38 times higher than those observed in the clinical setting. Therefore, the risk of interaction of cabazitaxel at a dose of 25 mg/m² body surface with MRP, P-gP and BCRP substrates in vivo is unlikely.

Evacuation

After an intravenous infusion of [¹⁴C]-cabazitaxel (radioisotope-labeled cabazitaxel) at a dose of 25 mg/m² for 1 h in cancer patients, approximately 80% of the administered dose is excreted within 2 weeks. Cabazitaxel is primarily excreted via the intestine (with feces) as numerous metabolites (76% of the dose); whereas renal excretion of cabazitaxel and its metabolites is less than 4% of the administered dose (2.3% of the administered dose is excreted unchanged in the urine). Cabazitaxel has a high plasma clearance of 48.5 L/h (26.44 L/h/m² in patients with a median body surface area of 1.84 m²) and a long T_1/2 of 95 h.

Pharmacokinetics in Special Clinical Cases

In a population-based analysis of pharmacokinetic data from patients 65 years of age and older, no effect of age on the pharmacokinetics of cabazitaxel was observed.

There have been no formal pharmacokinetic studies in patients with hepatic impairment. However, due to the fact that cabazitaxel is eliminated from the body mainly by metabolism, increased systemic exposure of cabazitaxel may be expected in patients with hepatic insufficiency.

Cabazitaxel is slightly excreted by the kidneys (2.3% of the dose). No formal pharmacokinetic studies of cabazitaxel in patients with renal impairment have been performed. However, a population pharmacokinetic analysis performed in 170 patients, which included 14 patients with moderate renal impairment (CK 30-50 ml/min) and 59 patients with mild renal impairment (CK 50-80 ml/min), showed that mild to moderate renal impairment had no significant effect on cabazitaxel pharmacokinetics.

Indications

Hormone-resistant metastatic prostate cancer in patients previously treated with chemotherapy including docetaxel (in combination with prednisolone or prednisone).

Active ingredient

Composition

1 ml (1 vial) contains:

Active ingredients: cabazitaxel (in the form of acetone solvate) 40 mg (60 mg).

Excipients: polysorbate 80 (pH 3.5) – 1.56 g.

Solvent: ethanol 96% – 573.3 mg, d/i water – up to 4.5 ml.

How to take, the dosage

Jevtana® should only be used in specialized oncology departments under the supervision of a physician with special training in anti-tumor chemotherapy. The department should have the necessary conditions and medications to assist in the event of hypersensitivity reactions, such as decreased BP and bronchospasm.

Premedication

The following IV medications are premedicated prior to administration of Jevtana® to reduce the risk of developing and severity of hypersensitivity reactions:

If the patient continues to have any of the above reactions at the 20 mg/m2 dose, treatment with Jevtana® should be discontinued.

Patients of advanced age do not require special dosing adjustments with Jevtana®.

Cabazitaxel is extensively metabolized in the liver. As a precautionary measure, the drug Cevtana® should not be used in patients with hepatic insufficiency (serum bilirubin concentration ≥1×VGN, serum ACT and/or ALT activity ≥1.5×VGN).

Cabazitaxel is minimally excreted by the kidneys. In patients with mild renal insufficiency (CKR 50-60 ml/min) dosage regimen adjustment is not required. There are limited data about the preparation usage in patients with renal insufficiency of intermediate degree (CKD 30-50 ml/min), and there are no data on its usage in patients with severe renal insufficiency (CKD less than 30 ml/min) and terminal renal failure. Therefore, treatment of such patients should be carried out with caution and under close medical supervision.

The rules of administration of the drug

The drug is administered by IV (intravenous) infusion.

A filter with a nominal pore diameter of 0.22 µm must be used during infusion of cabazitaxel infusion solution.

The infusion solution concentrate should always be diluted with the provided solvent before adding it to the infusion solution.

Jevtana® should not be mixed with other drugs and solutions except 5% dextrose solution and 0.9% sodium chloride solution.

Jevtana® contains polysorbate-80 which is known to increase the extraction rate of di-(2-ethylhexyl) phthalate from polyvinyl chloride (PVC). Therefore, PVC infusion fluid containers and polyurethane infusion sets should not be used to prepare and administer cabazitaxel infusion solution.

Preparing infusion solution and handling

As with other anticancer drugs, caution and gloves should be used when working with Cevtana® and when preparing its infusion solution. If Cevtana® solution comes into contact with the skin at any stage of handling, it should be immediately and thoroughly washed with soap and water, and if on mucous membranes, with the same water. Only personnel familiar with the handling of cytotoxic drugs should handle Cevtana®. Pregnant women should not handle this drug. The infusion solution is prepared under aseptic conditions in 2 steps.

Step 1: Initial dilution of Cevtana®, concentrate for preparation of solution for infusion, with the included solvent.

Take out the vial of Cevtana® Concentrate and the accompanying solvent. If stored properly, the drug should be clear.

Eject the entire contents of the included solvent using a syringe, partially tilting the vial, and inject into the vial of Javtan® Concentrate. To minimize foaming as much as possible when injecting through the needle into the vial with the solvent concentrate, point the needle toward the inside wall of the vial and slowly inject the solvent.

Please remove the syringe and needle and stir the bottle for approximately 45 seconds, gently turning the bottle several times until a clear and homogeneous solution is obtained.

Still the resulting solution for a few minutes (approximately 5 minutes) and then check the solution for homogeneity and clarity. A small amount of foam is normal during this time.

The resulting mixture has a cabazitaxel concentration of 10 mg/ml (extractable volume is 6 ml). It must be immediately diluted further to produce an infusion solution.

Step 2. Preparation of the infusion solution

. Extract the desired amount of initially diluted Cevtan® (10 mg/ml cabazitaxel) using a graduated syringe (due to the possibility of foam in the vial, insert the syringe needle during solution extraction in the middle of the vial plug) and inject it into a sterile container with infusion solution (except PVC container) (5% dextrose solution or 0.9% sodium chloride solution). The concentration of cabazitaxel infusion solution should be from 0.1 mg/ml to 0.26 mg/ml.

More than one vial of the initially diluted solution may be required to administer the prescribed dose.

The syringe should be removed and the contents of the infusion container or vial should be stirred by hand with a rocking motion.

As with all other parenteral solutions, the resulting solution should be visually inspected prior to use. The solution that contains precipitates must not be administered to the patient and must be disposed of in accordance with national requirements for disposal of such substances.

Jevtan® infusion solution should be administered immediately. However, under special conditions its storage time may be longer.

Unused product or consumables should be disposed of in accordance with national requirements for the disposal of such substances.

Storage conditions for the diluted solution

Stability of the initially diluted concentrate with the included solvent

After initial dilution of Jevtana® with the attached solvent, the resulting concentrate-solvent mixture remains chemically and physically stable for 1 hour when stored at normal temperature (15°-30°C). From a microbiological point of view the concentrate-solvent mixture should be used immediately after preparation. If it is not used immediately after preparation, the time and conditions of storage are the responsibility of the user. Generally, it should not be stored for more than 24 h at 2° to 8°C, provided that the dilution has been performed under controlled and validated aseptic conditions.

The stability of the final diluted solution in the infusion container

After final dilution in the infusion container/flask, the chemical and physical stability of the solution has been demonstrated for 8 h at room temperature (including 1-hour infusion) and for 48 h when stored in the refrigerator.

Microbiologically, the infusion solution should be administered immediately after preparation. If it is not administered immediately after preparation, the time and conditions of storage are the responsibility of the user. Normally, it should not be stored for more than 24 h at 2° to 8°C, provided that the dilution has been performed under controlled and validated aseptic conditions.

Because the infusion solution is super-saturated, it may crystallize over time. In this case, the solution should not be administered, it should be disposed in accordance with national requirements for the disposal of such substances.

Interaction

Special studies on the interaction of the drug Cevtana® with other medicinal products have not been conducted.

In in vitro studies it has been shown that cabazitaxel is predominantly metabolized with the participation of CYP3A isoenzyme (80-90%) and inhibits CYP3A isoenzyme.

CYP3A isoenzyme inhibitors. Although no special studies on drug interaction have been conducted, concomitant use of cabazitaxel with potent CYP3A isoenzyme inhibitors (such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) is expected to increase the concentration of cabazitaxel in blood plasma. Therefore, concomitant use of cabazitaxel and potent CYP3A isoenzyme inhibitors should be avoided. Caution should be exercised when concomitant use of cabazitaxel and moderate CYP3A isoenzyme inhibitors.

CYP3A isoenzyme inducers. Although no special studies on drug interaction have been conducted, concomitant use of cabazitaxel with potent inducers of CYP3A isoenzyme (such as phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital) is expected to reduce the concentration of cabazitaxel in blood plasma. Therefore, concomitant use of cabazitaxel and potent inducers of CYP3A isoenzyme should be avoided. In addition, patients receiving cabazitaxel should refrain from taking preparations of the herb St. John’s wort.

Prednisolone/prednisone at a dose of 10 mg daily have no effect on the pharmacokinetics of cabazitaxel.

Warfarin. Cabazitaxel does not inhibit in vitro the major biotransformation pathway of warfarin to 7-hydroxywarfarin, which involves the CYP2C9 isoenzyme. Therefore, no pharmacokinetic interaction between cabazitaxel and warfarin is expected in vivo.

Vaccination. The use of live vaccines or attenuated live vaccines in patients with reduced immunity as a result of chemotherapeutic drug treatment may result in serious or fatal infections. Vaccination with live attenuated vaccines in patients treated with cabazitaxel should be avoided. Killed or inactivated vaccines can be used; however, the body’s response to such vaccines may be less pronounced.

Special Instructions

Hypersensitivity reactions

All patients should receive premedication prior to administration of Jevtana®.

Patients should be monitored closely to detect the development of hypersensitivity reactions, especially during the first few minutes after the start of the cabazitaxel infusion. Appropriate equipment and medications should be available during the infusion to provide emergency treatment in case of a decrease in BP or development of bronchospasm. Severe reactions such as generalized rash/erythema, BP decrease and bronchospasm may occur. If severe hypersensitivity reactions develop, immediate discontinuation of cabazitaxel infusion and appropriate treatment is required. Patients with a history of severe hypersensitivity reactions should not be given a second infusion of Cevtan®.

The risk of neutropenia

In accordance with the American Society of Clinical Oncology guidelines and/or current approved guidelines, G-CSF may be administered prophylactically to patients receiving Jevtana® to reduce the risk of developing or managing neutropenic complications (febrile neutropenia, prolonged neutropenia or neutropenic infection).

The primary prophylaxis of neutropenia with G-CSF should be considered in patients with high-risk factors (age over 65 years, poor general health, prior episodes of febrile neutropenia, intense prior radiation therapy, reduced nutrition, or other serious comorbidities) that predispose to increased complications of prolonged neutropenia. G-CSF use has been shown to reduce the incidence and severity of neutropenia.

Neutropenia is the most common adverse reaction with Jevtan®. During the first cycle (cycle 1) of treatment and before each new cycle of treatment, weekly monitoring of blood cell counts (general blood count) is required in order to reduce the dose in the next cycle, if necessary.

If febrile neutropenia or prolonged neutropenia develops despite appropriate treatment, treatment with cabazitaxel may be continued only after peripheral blood neutrophil counts increase to ≥1500/μL.

Risk of nausea, vomiting, diarrhea and dehydration

If patients develop diarrhea after administration of Cevtan® , treatment with the usual anti-diarrheal drugs should be given. Appropriate measures should be taken to restore fluid loss, monitor and correct electrolyte composition of blood, especially the concentration of potassium ions. Diarrhea may be more common in patients who have previously received abdominal-pelvic radiation therapy. Dehydration is more common in patients 65 years of age or older. If diarrhea of grade 3 severity develops, the next cycle of treatment may need to be delayed or the dose reduced. In case of nausea and vomiting, antiemetics may be used.

Peripheral neuropathy

Patients receiving cabazitaxel have had cases of peripheral neuropathy, peripheral sensory neuropathy (paresthesia, dysesthesia) and peripheral motor neuropathy. Patients receiving cabazitaxel should be advised to inform their physician of their developing symptoms of neuropathy such as pain, burning, tingling, numbness before continuing treatment. The physician should assess the presence or worsening of neuropathy symptoms before each treatment cycle. The administration of cabazitaxel should be delayed until symptoms decrease. For persistent peripheral neuropathy ≥2 severity, the cabazitaxel dose should be reduced from 25 mg/m2 body surface to 20 mg/m2 body surface.

Risk of renal failure

Recreased renal function has been reported in conjunction with sepsis, severe dehydration due to diarrhea and vomiting, and obstructive uropathy. The development of renal failure has been observed, including cases with fatal outcome. Appropriate measures should be taken to identify the cause and provide intensive therapy if renal failure develops. Renal function should be monitored.

In treatment with Cabazitaxel adequate hydration of the body should be performed.

The patient should be advised to immediately report any changes in daily urine output. Creatinine should be determined prior to treatment, at each study of the general blood test, and if the patient reports a change in urine excretion. Treatment with cabazitaxel should be discontinued in case of renal failure ≥ grade 3 severity.

Risk of developing cardiac rhythm disturbances

The development of cardiac rhythm disturbances has been reported, with atrial fibrillation and tachycardia being the most frequently observed.

Elderly patients

Patients of advanced age (≥65 years) may be more prone to some adverse reactions, including neutropenia and febrile neutropenia.

Patients with hepatic insufficiency

The treatment with Jevtana® is contraindicated because cabazitaxel is extensively metabolized in the liver, and in hepatic insufficiency there may be an increase in the blood concentration of cabazitaxel.

Patients with anemia

Cabazitaxel should be used with caution in patients with peripheral blood hemoglobin levels of < 10 g/dL. Appropriate therapeutic measures aimed at increasing the hemoglobin concentration in peripheral blood should be undertaken.

Reproductive function

Due to possible adverse effects on male gametes and possible seminal leakage, patients receiving cabazitaxel and their sexual partners should use effective contraception during treatment and for 6 months after the last dose of cabazitaxel. Because of the possible passage of cabazitaxel into the seminal fluid, men receiving cabazitaxel should prevent ejaculate contact with the tissues of another man during treatment. Patients scheduled to receive cabazitaxel treatment are advised to have their sperm cryopreserved prior to treatment.

Ancillary substances

The included solvent contains ethanol, which should be considered when using the drug in patients with alcoholism and if patients have high-risk factors (liver disease, epilepsy).

Pediatric use

The drug is contraindicated in children and adolescents under 18 years of age, since the safety and effectiveness of the drug in this patient group has not been established.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

Patients should refrain from driving and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions during treatment.

Contraindications

With caution: In patients with moderate renal impairment (CKR 30-50 ml/min) (limited clinical data on drug administration), in patients with severe renal impairment (CKR less than 30 ml/min) and terminal renal failure (no clinical data on drug administration) (close medical monitoring during treatment required); in patients with peripheral blood hemoglobin < 10 g/dl; in patients with conditions or diseases that predispose to the development of neutropenia and/or increased complications with prolonged neutropenia (age over 65 years, low general condition, low body weight, previous episodes of febrile neutropenia, previous intensive radiation therapy, other serious comorbidities) (requires close medical monitoring during treatment, prophylactic administration of G-CSF is possible).

Side effects

The safety of Jevtan® in combination with prednisolone or prednisone was evaluated in 371 patients with hormone-resistant prostate cancer. The median number of cycles of Jevtana® received by patients was 6 cycles.

The following adverse reactions of all severities were observed very frequently (≥10%): anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, weakness, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, spinal pain, arthralgia, anorexia, pyrexia, shortness of breath, cough and alopecia.

The following adverse reactions of ≥3 severity were observed frequently (≥5%): neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, peripheral neuropathy (including peripheral sensory and motor neuropathy), weakness, and asthenia. Discontinuation of treatment due to adverse reactions was observed in 68 patients (18.3%) treated with Jevtana®. The most common reason was the development of neutropenia.

The adverse reactions are presented below, classified according to the MedDRA system-organ classification terms and WHO gradations of frequency of adverse reactions. Within each adverse reaction frequency group, they are given in decreasing order of severity. The severity of adverse reactions was graded according to the Common Terminology Criteria for Adverse Events (CTSAE 4.0) (severity ≥3 = G ≥3).

Frequency determination of adverse reactions: very common (≥10%), common (≥1% and < 10%), infrequent (≥0.1% and < 1%); rare (≥0.01% and < 0.1%), very rare ( < 0.01%), frequency unknown (no data available to determine the frequency of adverse reactions).

Infectious and parasitic diseases: Frequent – septic shock (all cases ≥3 severity), sepsis (all cases ≥3 severity), cellulitis, urinary tract infections of all severity, influenza, cystitis, upper respiratory tract infections, herpes zoster, candidomycosis; infrequent – cellulitis ≥3 severity, cystitis ≥3 severity.

Hematopoietic system: very common – neutropenia of all degrees of severity, including neutropenia with clinical manifestations of ≥ 3 severity, anemia of all degrees of severity, leukopenia of all degrees of severity, thrombocytopenia; frequently – febrile neutropenia, thrombocytopenia ≥ 3 severity. Neutropenic infections, neutropenic sepsis and septic shock were fatal in some cases. G-CSF use has been shown to reduce the incidence and severity of neutropenia.

Immune system disorders: often – hypersensitivity reactions, including severe reactions such as generalized rash/erythema, BP decrease and bronchospasm.

Metabolism disorders: very frequently – anorexia; frequently – dehydration of all degrees of severity, hyperglycemia, hypokalemia, weight loss; infrequently – anorexia ≥3 degree of severity, hyperglycemia ≥3 degree of severity, hypokalemia ≥3 degree of severity.

Nervous system disorders: very common – dysgeusia (perversion of taste); common – peripheral neuropathy: Peripheral sensory neuropathy (paraesthesia, dysesthesia, hypoesthesia) and peripheral motor neuropathy; dizziness, headache, lethargy, sciatica; infrequent – peripheral neuropathy ≥3 severity, peripheral sensory neuropathy ≥3 severity, lethargy ≥3 severity, sciatica ≥3 severity.

Psychiatric disorders: often – anxiety, confusion.

An organ of vision: often – conjunctivitis, increased lacrimation.

Hearing and balance: often – tinnitus, vertigo (feeling of deviation or spinning of own body or surrounding objects).

Cardiovascular system disorders: frequent – atrial fibrillation, tachycardia, decreased BP, deep vein thrombosis of all degrees of severity, increased BP, orthostatic hypotension, flushes to the skin of the face with a feeling of heat, hyperemia; infrequent – atrial fibrillation ≥3 severity, BP decrease ≥3 severity, BP increase ≥3 severity, orthostatic hypotension ≥3 severity. Cases of heart failure were observed while taking cabazitaxel, in 2 patients (0.5%). One patient in the cabazitaxel group died of heart failure. Fatal ventricular fibrillation in 1 patient (0.3%) and cardiac arrest in 2 patients (0.5%) were observed. However, none of these cases was considered by the investigators to be related to cabazitaxel.

Respiratory system: very common – dyspnea, cough; common – dyspnea ≥3 degree of severity, pain in the oral cavity and pharynx, pneumonia of all degrees of severity.

Digestive system disorders: very common – diarrhea, nausea, vomiting, constipation, abdominal pain; frequent – increased ACT activity, diarrhea ≥ 3 severity, nausea ≥ 3 severity, vomiting ≥ 3 severity, constipation ≥ 3 severity, abdominal pain ≥ 3 severity, dyspepsia, epigastric pain, hemorrhoids, gastroesophageal reflux disease, rectal bleeding, dry mouth, bloating; infrequent – increased serum bilirubin concentration, increased ALT activity, rectal bleeding ≥ 3 severity, dry mouth ≥ 3 severity, bloating ≥ 3 severity.

Skin and subcutaneous tissue: very common – alopecia; common – dry skin, erythema.

Muscular system disorders: very often – spinal pain, arthralgia; often – spinal pain ≥ 3 degrees of severity, arthralgia ≥ 3 degrees of severity, limb pain of all degrees of severity, muscle spasms, myalgia, musculoskeletal pain in the chest, pain on the lateral surfaces of the trunk; infrequent – myalgia ≥ 3 severity, musculoskeletal pain in thorax ≥ 3 severity, pain on lateral surfaces of trunk ≥ 3 severity.

Urinary system disorders: very common – hematuria; common – acute renal failure of all degrees of severity, renal failure of all degrees of severity, dysuria, renal colic, hematuria ≥ 3 degrees of severity, pollakiuria, hydronephrosis, urinary retention, urinary incontinence, ureteral obstruction of all degrees of severity; infrequent – renal colic ≥ 3 degree of severity, pollakiuria ≥ 3 degree of severity, hydronephrosis ≥ 3 degree of severity, urinary retention ≥ 3 degree of severity.

Genital organs: often – pelvic pain; infrequent – pelvic pain ≥ 3 degree of severity.

General disorders: very common – weakness, asthenia, pyrexia; common – weakness ≥ 3 degree severity; asthenia ≥ 3 degree severity, pyrexia ≥ 3 degree severity, peripheral edema, mucous membrane inflammation, all degree pain, chest pain, edema, chills, malaise; infrequent – peripheral edema ≥3 severity, mucous membrane inflammation ≥3 severity, chest pain ≥3 severity, edema ≥3 severity.

Elderly patients

Of the 371 patients who received Jevtana® in the prostate cancer trial, 240 patients were 65 years of age or older, including 70 patients over 75 years of age. The following adverse reactions were observed ≥ 5% more frequently in patients 65 years of age and older compared to younger patients: weakness, neutropenia with clinical manifestations, asthenia, pyrexia, dizziness, urinary tract infections, dehydration.

The incidence of the following adverse reactions of ≥3 severity was higher in patients aged ≥65 years compared to younger patients: neutropenia by laboratory test results, neutropenia with clinical manifestations, and febrile neutropenia.

Overdose

Symptoms: dose-dependent side effects may increase, such as symptoms of suppression of medullary hematopoiesis and gastrointestinal disorders.

Treatment: There is no known antidote for cabazitaxel. In case of overdose, the patient should be admitted to a specialized ward and closely monitored by medical personnel. Once an overdose is known, G-CSF should be administered as soon as possible. Other symptomatic treatment should also be given.

Pregnancy use

The drug Jevtana is contraindicated in pregnant women and during lactation (breastfeeding).

The use in children.

Contraindicated in children and adolescents under 18 years of age (safety and efficacy not established).