Jevtana - instructions for use, analogs, testimonials and release forms (injections in ampoules for injection in solution) of a drug for the treatment of prostate cancer in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Jevtana. Comments of visitors of the site - consumers of this medication, as well as opinions of doctors of experts on the use of Dzhevtany in their practice are presented. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Dzhevtany with available structural analogues. Use to treat prostate cancer in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

 

Jevtana - Anticancer drug, alkaloid.The mechanism of action is associated with the destruction of the cellular network of microtubules of tumor cells. Cabazitaxel (the active substance of the drug Jevtan) binds to tubulin and promotes the assembly of tubulin in microtubules and simultaneously inhibits their disassembly. This leads to the stabilization of microtubules, which eventually inhibits the mitotic and interphase activity of the cell.

 

A wide spectrum of antitumor activity of cabazitaxel in relation to late stages of human tumors, xenotransplanted to mice, is shown. Kabasitaxel is active against docetaxel-sensitive tumors. In addition, kabasitaxel is shown to be active against tumor models that are insensitive to chemotherapy, including docetaxel.

 

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

 

Patients received cabazitaxel at a dose of 25 mg per 1 m2 of body surface intravenously every 3 weeks for a maximum of 10 cycles in combination with daily intake of prednisone or prednisolone at a dose of 10 mg per day.In the comparison group, patients received mitoxantrone at a dose of 12 mg per m2 intravenously every 3 weeks in combination with daily intake of prednisone or prednisolone at a dose of 10 mg per day.

 

Overall survival was longer in the cabazitaxel group with a 30% reduction in the risk of death compared with the mitoxantrone group. There was an increase in the time to progression of the disease in the Jevtan group compared with the mitoxantrone group. There was a significantly higher rate of remission of the disease, which was 14.4% in patients treated with Jevtan, compared with 4.4% in patients in the mitoxantrone group. There were no statistically significant differences in both groups with respect to the progression of pain or the remission of pain.

 

Composition

 

Cabazitaxel + excipients.

 

Pharmacokinetics

 

Population analysis of pharmacokinetic parameters was performed in patients, including patients with locally advanced solid tumors, metastatic breast cancer and metastatic prostate cancer. These patients received cabazitaxel in a dose range of 10-30 mg per 1 m2 body surface area weekly or every 3 weeks.After intravenous infusion of Jevtana for 1 hour at a dose of 25 mg per m2 in patients with metastatic prostate cancer, the maximum concentration of cabazitaxel in blood plasma was reached by the end of the infusion. In vitro binding of cabazitaxel to human serum proteins is 89-92%. Kabasitaxel, mainly, binds to serum albumin (82%) and lipoproteins. Studies in animals have shown that cabazitaxel and its metabolites are excreted into breast milk, and cabazitaxel penetrates the placental barrier.

 

Kabasitaxel is extensively metabolized in the liver, mainly with the participation of CYP3A4 isoenzymes (80-90%). Cabazitaxel is the main compound circulating in the blood plasma. In addition to him, 7 metabolites (including 3 active metabolites formed as a result of O-demethylation) were identified in the blood plasma. The concentration in the blood plasma of the main of them is 5% of the concentration in the blood plasma of unchanged cabazitaxel. Jevtan is mainly excreted through the intestine (with feces) in the form of numerous metabolites (76% of the dose), while renal excretion of cabazitaxel and its metabolites is less than 4% of the administered dose (2.3% of the administered dose is excreted urine in unchanged form).

 

In a population analysis of the pharmacokinetic data of patients aged 65 years and older, there was no age effect on the pharmacokinetics of cabazitaxel.

 

Indications

• hormone-resistant metastatic prostate cancer in patients who previously received chemotherapy with docetaxel (in combination with prednisolone or prednisone).

 

Forms of release

 

Concentrate for the preparation of a solution for infusions of 40 mg in 1 ml (injections in ampoules for injections).

 

Instructions for use and dosing regimen

 

The drug should be used only in specialized oncology units under the supervision of a doctor who has special training in antitumor chemotherapy. The department should have the necessary conditions and medications to help with the occurrence of hypersensitivity reactions, such as lowering blood pressure and bronchospasm.

 

Premedication

 

To reduce the risk of development and severity of hypersensitivity reactions prior to the administration of Jevtan, premedication is carried out with the following medications for intravenous administration:

• antihistamines (dexchlorpheniramine 5 mg or diphenhydramine 25 mg or equivalent in equivalent doses);
• glucocorticosteroids (GCS): dexamethasone 8 mg or equivalent doses of another GCS;
• blockers of histamine H2-receptors (ranitidine or similar drug in equivalent doses).

 

Prophylactic use of antiemetics is recommended inside or, if necessary, intravenously.

 

The recommended dose

 

The recommended dose of Jevtan is 25 mg per 1 m2 of body surface intravenously as an infusion for 1 hour every 3 weeks in combination with oral prednisolone (or prednisone) at a dose of 10 mg daily during the entire treatment period with Jevtan.

 

Correction of the administered dose

 

With prolonged (more than 1 week) neutropenia of 3 severity and more, despite the appropriate treatment, including the introduction of granulocyte colony-stimulating factor (G-CSF), delay of the next treatment cycle is shown until the number of neutrophils in the peripheral blood is restored to more than 1500 cells per 1 μl , then reducing the dose in subsequent cycles from 25 mg per m2 to 20 mg per m2.

 

With the development of febrile neutropenia or neutropenic infection, the next treatment cycle should be postponed until either reduction or resolution of febrile neutropenia and until the number of neutrophils in the peripheral blood is restored to more than 1500 cells per 1 μl, then lower the dose in subsequent cycles from 25 mg per m2 to 20 mg per 1 m2.

 

In diarrhea of ​​grade 3 severity and more or persistently continuing diarrhea, despite appropriate therapy and replenishment of fluid and electrolyte losses, the delay in the next treatment cycle is shown until the diarrhea is reduced or resolved, then the dose reduction in subsequent cycles from 25 mg per m2 to 20 mg for 1 m2.

 

In the case of peripheral neuropathy of 2 degrees of severity or more, treatment should be delayed until symptoms decrease, and then lower the dose in subsequent cycles from 25 mg per m2 to 20 mg per m2.

 

If the patient continues to experience any of the above reactions with the administration of the drug at a dose of 20 mg / m2, treatment with Jevtan should be discontinued.

 

In patients with mild hepatic insufficiency (total serum bilirubin exceeds the upper limit of the norm (VGN), no more,the dose of cabazitaxel should be reduced to 20 mg per 1 m2 of the body surface area, with care being required, careful monitoring of the patients' condition and monitoring of adverse reactions . In patients with moderate hepatic insufficiency (the total bilirubin exceeds the VGN by no more than 3 times), the maximum tolerated dose of cabazitaxel is 15 mg per 1 m2. If the treatment of patients with moderate-level hepatic insufficiency is indicated, the dosage of cabazitaxel should not exceed 15 mg per m2. However, there are limited data on the effectiveness of this dose. The drug Jevtan is contraindicated in patients with severe hepatic insufficiency (total serum bilirubin exceeds the VGN more than 3 times).

 

Cabazitaxel is excreted by the kidneys to a minimal extent. There is no need for correction of the dosing regimen in patients with renal insufficiency without hemodialysis. However, in patients with end-stage renal failure, when creatinine clearance (CK) is less than 15 mL / min, due to their condition and limited data, treatment should be conducted with caution and with careful medical supervision during treatment.

 

Simultaneous use of drugs that are strong inducers of the isozymes of the CYP3A subfamily or strong inhibitors of the isozymes of the CYP3A subfamily should be avoided. However, if a simultaneous use of cabazitaxel and strong isozyme inhibitors of the CYP3A subfamily is required, the dose of cabazitaxel should be reduced by 25%.

 

Rules of drug administration

 

The drug is administered intravenously in the form of infusion. During the introduction of the infusion solution of cabazitaxel, a filter with a nominal pore diameter of 0.22 μm inserted with the system for intravenous infusions should be used.

 

Concentrate for the preparation of solution for infusion should always be diluted with all the contents of the supplied solvent before adding to the infusion solution.

 

The drug should not be mixed with other drugs and solutions, except for 5% Dextrose and 0.9% sodium chloride solution.

 

The preparation of Jevtan contains polysorbate-80, which, as is known, increases the extraction rate of di- (2-ethylhexyl) phthalate from polyvinyl chloride (PVC).In this regard, you can not use containers for infusion liquids from PVC and kits for intravenous infusion of polyurethane for the preparation and administration of an infusion solution of cabazitaxel.

 

Preparation of solution for infusion and handling of the drug

 

As with other antineoplastic agents, care should be taken and gloves used when working with Jevtan and when preparing its infusion solution.

 

If the solution of the drug Jevtan at any stage of work with it fell on the skin, immediately and thoroughly rinse it with water and soap, and if - on the mucous membrane, then with one water.

 

Work with the drug Dzhevtana should only personnel who know how to handle cytotoxic drugs.

 

Pregnant women should not work with this drug.

 

Before mixing and diluting the Jevtan preparation, you should carefully read all of the information below on the preparation of the infusion solution.

 

Each vial with concentrate contains 60 mg of Jevtan's preparation in 1.5 ml (nominal volume) (with a volume of filling the 1.83 ml bottle containing 73.2 mg of Jevtan's preparation).Each vial with solvent contains 4.5 ml (nominal volume) (with a filling volume of 5.67 ml of solvent). These filling volumes were established during the development of the preparation in order to compensate for fluid loss during the preparation of the premix (the solution obtained as a result of the primary dilution of the concentrate with the applied solvent). Thus, the bottles of both the concentrate of the Jevtan preparation and the solvent contain an excessive amount of the active substance and solvent to compensate for fluid loss during the preparation of the solution. This excess amount of active substance and solvent ensures that after diluting the concentrate of the Jevtan preparation with all the contents of the solvent vial contained in the package, the premix will contain a solution of Jevtan preparation with a concentration of 10 mg / ml.

 

For the Jevtan preparation concentrate, two dilutions are required before administration. Preparation of a solution for infusions is carried out in aseptic conditions in 2 stages.

 

Stage 1 - the initial dilution of the Jevtan preparation, the concentrate for the preparation of a solution for infusions, the applied solvent.Inspect the vial with Jevtan's concentrate and the solvent applied to it. The concentrate solution should be transparent.

 

Extract all contents of the attached solvent with a syringe, partially tilting the vial, and insert into a bottle with Jevtan concentrate. To minimize the foaming, when injected through a needle into the vial with a solvent concentrate, the needle should be directed to the inner wall of the vial and the solvent slowly introduced.

 

Remove the syringe and needle and mix the contents of the vial for about 45 seconds, gently flipping the bottle several times until a clear and homogeneous solution is obtained.

 

Leave to stand the resulting solution for several minutes (for about 5 minutes) and then check the solution for homogeneity and clarity. During this time, a small amount of foam can normally be maintained.

 

The resulting mixture (premix) has a concentration of cabazitaxel 10 mg / ml (the extract volume is 6 ml). The premix should be immediately diluted additionally to obtain a solution for infusion.

 

Stage 2 - preparation of solution for infusion.Remove the required amount initially diluted Dzhevtana drug (10 mg / ml cabazitaxel) using a graduated syringe (due to the possibility of the content in the foam vial enter during the extraction needle syringe a solution in the middle of vial stoppers) and enter it in a sterile container with the infusion solution (except container of PVC) (5% dextrose solution or 0.9% sodium chloride solution). The concentration of the infusion solution of cabazitaxel should be from 0.1 mg / ml to 0.26 mg / ml.

 

To administer the prescribed dose, more than one vial of the initially diluted solution may be required.

 

It is necessary to remove the syringe and mix the contents of the infusion container or vial manually with swaying movements.

 

Like all other solutions for parenteral administration, the resulting solution should be visually inspected before use. The solution containing precipitates can not be administered to the patient and should be disposed of in accordance with national requirements for the disposal of such substances.

 

The infusion solution of Jevtan should be administered immediately after preparation.However, under special conditions, the storage time may be longer.

 

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

 

Storage conditions for diluted solution

 

After the initial dilution of the Jevtan preparation with the applied solvent, the resulting concentrate-solvent mixture (premix) remains chemically and physically stable for 1 hour when stored at normal temperature (15 to 30 degrees Celsius). 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 user is responsible for the time and conditions of its storage. Usually it should not be stored for more than 24 hours at a temperature of 2 to 8 degrees Celsius, provided that the dilution was carried out in controlled and validated aseptic conditions.

 

After the final dilution in the infusion container / vial, the chemical and physical stability of the solution was demonstrated for 8 hours at room temperature(including a 1-hour intravenous infusion) and for 48 hours when stored in the refrigerator. From a microbiological point of view, the infusion solution should be administered immediately after preparation. If it is not entered immediately after preparation, the responsibility for the time and conditions of its storage is borne by the user. Usually it should not be stored for more than 24 hours at a temperature of 2 to 8 degrees Celsius, provided that the dilution was carried out in controlled and validated aseptic conditions.

 

Since the infusion solution is supersaturated, it can crystallize over time. In this case, the solution should not be introduced, it is necessary to dispose of it in accordance with the national requirements for the disposal of such substances.

 

Side effect

• septic shock, sepsis (the spread of the infection through the body through the blood);
• cellulite (stagnation in adipose tissue, leading to its dystrophy);
• urinary tract infections;
• flu;
• cystitis (inflammation of the bladder);
• upper respiratory tract infection;
• herpes zoster;
• Candidomycosis (a type of fungal infection);
• neutropenia, anemia, and leukopenia; thrombocytopenia;
• hypersensitivity reactions (generalized rash, erythema);
• lowering of blood pressure (BP);
• bronchospasm (impaired bronchial patency);
• anorexia (a neuropsychic disorder manifested by an obsessive desire to lose weight, fear of obesity);
• dehydration;
• hypokalemia;
• dysgeusia (perversion of taste);
• peripheral sensory neuropathy (paresthesia, dysesthesia, hypoesthesia) and peripheral motor neuropathy;
• dizziness, headache;
• lethargy (a condition characterized by slowness, lethargy, fatigue);
• sciatica (sciatica nerve inflammation);
• anxiety;
• confusion of consciousness;
• conjunctivitis, increased tearing;
• tinnitus;
• Vertigo (feeling of deviation or twisting of one's own body or surrounding objects);
• atrial fibrillation (atrial fibrillation), tachycardia;
• decrease or increase in blood pressure;
• deep vein thrombosis;
• Orthostatic hypotension (a violation of the ability of the body to maintain a normal level of blood pressure in the vertical position);
• the flow of blood to the skin of the face with a feeling of heat;
• dyspnea;
• cough;
• diarrhea, constipation;
• nausea, vomiting;
• abdominal pain;
• hemorrhoids;
• gastroesophageal reflux disease;
• bleeding from the rectum;
• dryness of the oral mucosa;
• intestinal obstruction and intestinal obstruction;
• alopecia (baldness);
• dry skin;
• pain in the spine;
• arthralgia (joint pain);
• Myalgia (pain in the muscle);
• hematuria (blood in the urine);
• acute renal insufficiency;
• renal colic;
• pollakiuria (frequent urination);
• hydronephrosis (edema of the kidney);
• retention of urine;
• pelvic pain;
• weakness, asthenia;
• pyrexia (increased body temperature compared to normal);
• peripheral edema;
• inflammation of the mucous membranes;
• pain in the chest;
• chills;
• malaise;
• decreased body weight;
• increase in activity of aspartate aminotransferase (AST) in blood serum;
• increased serum bilirubin concentration.

 

Contraindications

• the number of neutrophils in the peripheral blood is less than 1500 in 1 μl;
• severe hepatic insufficiency, when serum bilirubin is more than three times higher than UGN, ACT and / or alanine aminotransferase (ALT) of blood serum more than 1.5 times higher than UGN;
• simultaneous application with vaccination against yellow fever, as well as with other live attenuated vaccines;
• pregnancy;
• the period of breastfeeding;
• children and adolescents under 18 years of age (safety and efficacy not established);
• hypersensitivity to cabazitaxel or excipients of the drug (polysorbate-80);
• hypersensitivity to other taxanes.

 

Application in pregnancy and lactation

 

The drug Jevtan is contraindicated in pregnancy and lactation (breastfeeding).

 

Use in children

 

Contraindicated in children and adolescents under 18 years.

 

Application in elderly patients

 

Older patients do not need a special dosage adjustment when using Jevtan's drug.

 

special instructions

 

With the use of cabazitaxel oppression of bone marrow hematopoiesis manifests itself in the form of neutropenia, anemia, thrombocytopenia, or possibly the development of pancytopenia. In accordance with the recommendations of the American Society of Clinical Oncology and / or modern approved guidelines to reduce the risk of occurrence or treatment of neutropenic complications(febrile neutropenia, prolonged neutropenia or neutropenic infection), patients receiving the Jevtan preparation can be prescribed G-CSF prophylactically.

 

Primary prophylaxis of neutropenia with G-CSF should be considered in patients with conditions or conditions predisposing to neutropenia and / or increased complications with prolonged neutropenia (age 65 years or older, poor general condition, previous episodes of febrile neutropenia, intensive previous radiation therapy , reduced nutrition, or other serious co-morbidities). It has been shown that the use of G-CSF reduces the incidence and severity of neutropenia.

 

Neutropenia is the most common undesirable reaction (NR) with Jevtan's drug. During the first cycle (cycle 1) of treatment and before each new treatment cycle, a weekly monitoring of the number of blood elements (a complete total blood test) is required in order to reduce the dose of the drug in the next cycle if necessary.

 

With the development of febrile neutropenia or prolonged neutropenia,despite the appropriate treatment, the treatment with cabazitaxel can be continued only after increasing the number of neutrophils in the peripheral blood to 1500 in 1 μl or more.

 

All patients should receive premedication before the administration of Jevtan. Patients should be closely monitored to detect the development of hypersensitivity reactions, especially during the first and second intravenous infusions of cabazitaxel. Hypersensitivity reactions may develop during the first minutes after the initiation of intravenous infusion of cabazitaxel, so it is necessary to have the appropriate equipment and medicines to provide emergency care while lowering blood pressure or developing bronchospasm. Possible development of severe reactions, such as generalized rash / erythema, lowering blood pressure and bronchospasm. With the development of severe hypersensitivity reactions, an immediate cessation of infusion of cabazitaxel and the necessary treatment are required. Patients with a history of a severe hypersensitivity reaction should not be re-injected with Jevtan.

 

If patients develop diarrhea after the administration of Jevtan, then conventional antidiarrheal drugs should be treated. Appropriate measures should be taken to restore fluid loss, monitor and correct the electrolyte composition of blood, especially the concentration of potassium ions. Diarrhea can develop more often in patients who received prior abdominal-pelvic radiation therapy. Dehydration often develops in patients aged 65 years and older. If diarrhea develops 3 or more severity, it may be necessary to delay the next treatment cycle or to reduce the dose. With nausea and vomiting, antiemetics can be used.

 

The development of gastrointestinal bleeding and perforation, intestinal obstruction, colitis, including fatal cases in patients receiving cabazitaxel treatment has been reported. Caution should be exercised in patients at high risk of developing gastrointestinal complications, namely: in patients with neutropenia, the elderly, concurrently taking non-steroidal anti-inflammatory drugs (NSAIDs), receiving antiplatelet therapy or direct or indirect anticoagulants,as well as in patients with previous pelvic radial therapy, diseases of the gastrointestinal tract (GIT), such as ulcerative gastrointestinal lesions and gastrointestinal hemorrhage in the anamnesis.

 

Early signs of serious gastrointestinal toxicity may include symptoms such as pain and tenderness in the abdomen, fever, constipation, diarrhea with neutropenia or without neutropenia. It is necessary to regularly check the presence of these symptoms, and in case of their occurrence, immediately carry out the appropriate treatment. If necessary, treatment with cabazitaxel may be delayed or discontinued.

 

In patients treated with cabazitaxel, there were cases of peripheral neuropathy, peripheral sensory neuropathy (paresthesia, dysesthesia) and peripheral motor neuropathy. Patients receiving cabazitaxel should be advised before informing their attending physician about the symptoms of neuropathy developed in them, such as pain, burning sensation, tingling, numbness. The physician should evaluate the presence or intensification of the symptoms of neuropathy before each treatment cycle.The administration of cabazitaxel should be delayed until symptoms decrease. With persistent peripheral neuropathy 2 and more severity, the dosage of cabazitaxel should be reduced from 25 mg per 1 m2 of body surface to 20 mg per 1 m2 of the body surface.

 

Reported violations of kidney function in combination with sepsis, severe dehydration due to diarrhea and vomiting and obstructive uropathy. There was a development of renal failure, including fatal cases. Appropriate measures should be taken to identify the cause and to conduct intensive therapy with developing renal failure. Kidney function should be monitored.

 

When treating cabazitaxel, adequate hydration should be performed. The patient should be advised to immediately report any changes in the amount of urine released per day. The creatinine content should be determined before treatment, with each study of a general blood test and in the case of a patient reporting a change in urine output. In case of development of renal insufficiency 3 and more severity, treatment with cabazitaxel should be discontinued.

 

It was reported on the development of cardiac arrhythmias, the most frequently observed atrial fibrillation and tachycardia.

 

Cases of interstitial pneumonia / pneumonitis, interstitial lung disease, acute respiratory distress syndrome, including fatal cases, have been reported. When developing new symptoms from the respiratory system or worsening of existing symptoms, it is necessary to carefully monitor the condition of patients, promptly examine them and conduct appropriate treatment. It is recommended to interrupt therapy with cabazitaxel until the diagnosis is confirmed. Early use of maintenance therapy improves the patient's condition. Careful consideration should be given to the benefits of resumption of cabazitaxel therapy.

 

Elderly patients (over 65 years of age) may be more prone to some HP, including neutropenia and febrile neutropenia.

 

The drug Jevtan is contraindicated in patients with severe hepatic insufficiency (total bilirubin is 3 times higher than UGN). In patients with mild hepatic insufficiency (total serum bilirubin exceeds ILV not more than 1.5 times, or ACT exceeds UGN more than,than in 1,5 times) and an average degree of a gravity (the general bilirubin exceeds VGN no more, than in 3 times) it is necessary to reduce a dose kabazitaksela. At the same time, care must be taken, the patients' condition should be closely monitored and adverse reactions monitored.

 

In patients receiving cabazitaxel treatment, the development of anemia has been reported. The parameters of hemoglobin and hematocrit should be checked before starting therapy with cabazitaxel, and also if patients have signs or signs of anemia or hemorrhage. It is recommended to use cabasitaxel with caution in patients with a hemoglobin content in the peripheral blood of less than 10 g in 1 dl. It is necessary to conduct appropriate therapeutic measures aimed at increasing the concentration of hemoglobin in peripheral blood.

 

Due to possible adverse effects on male gametes and the possible introduction of the drug into the semen, patients receiving cabazitaxel and their sexual partners should use effective contraceptive methods during treatment and within 6 months after the administration of the last dose of cabazitaxel.In connection with the possible intake of cabazitaxel in seminal fluid, men receiving cabazitaxel during treatment should prevent the contact of the ejaculate with the tissues of another person.

 

Patients who are scheduled for treatment with cabazitaxel are advised to cryopreserve sperm before starting treatment.

 

Simultaneous application of strong inhibitors and inducers of isozymes of the CYP3A subfamily with cabazitaxel should be avoided, as they can, respectively, increase or decrease the plasma concentration of cabazitaxel.

 

Use with caution in patients with terminal stage of renal failure (creatinine clearance less than 15 ml / min). Due to their condition and limited data, treatment should be conducted with caution and with careful medical supervision during treatment.

 

The applied solvent contains 573 mg of ethanol (alcohol) 96%, which should be taken into account when using the drug in patients with alcoholism, as well as in patients at high risk (patients with liver disease and epilepsy).

 

Impact on the ability to drive vehicles and manage mechanisms

 

Based on the safety profile of Jevtana, the drug may have a moderate effect on the ability to drive vehicles or work with machinery, as it can cause weakness and dizziness. During treatment, patients should refrain from driving vehicles and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

 

Drug Interactions

 

The metabolism of cabazitaxel varies with simultaneous use with strong inhibitors of isozymes of the CYP3A subfamily (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). The simultaneous use of cabazitaxel and strong inhibitors of isozymes of the CYP3A subfamily should be avoided, since they can increase the concentration of cabazitaxel in the blood plasma. If simultaneous use of cabazitaxel and a potent inhibitor of isozymes of the CYP3A subfamily can not be avoided, consider carefully monitoring the patient and reducing the dose of cabazitaxel.Caution should be exercised while using cabazitaxel and moderate isozyme inhibitors of the CYP3A subfamily.

 

The metabolism of cabazitaxel varies with the simultaneous use of isoenzymes of the CYP3A subfamily with strong inducers (eg, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentin, phenobarbital). The simultaneous use of cabazitaxel and strong inducers of isozymes of the CYP3A subfamily should be avoided, since they can reduce the concentration of cabazitaxel in the blood plasma and reduce its systemic exposure.

 

Patients receiving kabasitaxel should refrain from taking medicinal herbs of St. John's wort, as it is also an inducer of the isoenzyme CYP3A4.

 

In vitro, cabazitaxel also demonstrated the ability to inhibit substrates of the transport polypeptide of organic anions (OATP1B1). The risk of interaction with substrates of OATP1B1 (for example, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase (HMG-CoA reductase), ie, statins, valsartan, repaglinide) is possible during intravenous infusion (1 hour) 2 min after its termination, and at this time it is possible to increase the system exposure of substrates of OATP1B1.It is recommended that the following time intervals are observed when using the substrates of OATP1B at the same time: take them 12 hours before administration of cabazitaxel, or at least 3 hours after administration of cabazitaxel.

 

Prednisolone and / or prednisone in a dose of 10 mg daily do not affect the pharmacokinetics of cabazitaxel.

 

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

 

The use of live vaccines or weakened live vaccines in patients with reduced immunity due to the treatment with chemotherapeutic drugs can lead to the development of serious or fatal infections. Vaccination with live attenuated vaccines should be avoided in patients receiving cabazitaxel treatment. Killed or inactivated vaccines can be used, but the body's response to such vaccines may be, although less pronounced.

 

Analogues of Jevtan's drug

 

There are no structural analogs to the active substance of Jevtan's medicine.

 

Analogues on the pharmacological group (antitumor agents of plant origin):

• Abitaxel;
• Abraxan;
• Velba;
• Velbin;
• Vepezid;
• Verotecan;
• Vinblastine;
• Vinelbin;
• Winkater;
• Vincristine;
• Vinorelbine;
• Wumond;
• Gikamtin;
• Docetaxel;
• Dotserera;
• Javlor;
• Intaksel;
• Irinaks;
• Irinotecan;
• Irinotel;
• Iritin;
• Irkokam;
• Yondelis;
• Kampeter;
• Campto;
• Kanataksen;
• Kanglaite;
• Colotecan;
• Condiline;
• Fins;
• Mawerex;
• Mitotax;
• Navelbin;
• Novotaks;
• Oncodocel;
• Oncocristin;
• The paclikal;
• Paclitaxel;
• Pacifier;
• Paxen;
• Sindaxel;
• Taxiade;
• Taxol;
• Taxotere;
• Tautax;
• Topotecan;
• Phytoside;
• Cituvin;
• Aldesine;
• Etoposide;
• Yutaksan.

 

Analogues of the drug Jevtan on the curative effect (drugs for the treatment of malignant neoplasms of the prostate gland):

• 5-Fluorouracil;
• Abiraterone;
• Aminoglutethimide;
• Amaranth;
• Anandron;
• Androkur;
• Bicalutamide;
• Bilumide;
• Buserelin;
• Vero-Mitomycin;
• Vinelbin;
• Hormoplex;
• Decapeptil;
• Diferelin;
• Doxorubicin;
• Zitazonium;
• Zytiga;
• Zoladex;
• Zometa;
• Indigal;
• Kalumid;
• Casodex;
• Lucrin;
• Mammoth;
• Mutamycin;
• Navelbin;
• Novanthron;
• Octreotide;
• Oncotron;
• Orimeten;
• Prednisolone;
• Premarin;
• The prostate;
• Sinestrol;
• Strontium chloride;
• Suprefact;
• Taxotere;
• Firmagon;
• Flutakan;
• Flutamide;
• Flucin;
• Fluorouracil;
• Cisplatin;
• Eligard;
• Endoxane;
• Episondan;
• Estracite.

 

Feedback from a urologist

 

Since the drug Dzhevtana is used only in specialized oncological clinics, I can tell about it only from the words of one of my patients who received it for prostate carcinoma. Unfortunately, the patient is no longer alive. He told me that it was extremely difficult to tolerate intravenous infusions of Dzhevtany. On the body, he developed a rash, noted disorders of consciousness, disturbed diarrhea and vomiting. In addition, against the background of treatment, he developed a herpes zoster in severe form, which was very difficult to treat.

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