Jevtana Information
Jevtana (Cabazitaxel) . Indications And Usage
Jevtana (Cabazitaxel) is a microtubule inhibitor indicated in combination with prednisone for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.
Jevtana (Cabazitaxel) . Dosage And Administration
The Jevtana (Cabazitaxel) dose should be reduced to 20 mg/m if patients experience the following adverse reactions.
Discontinue Jevtana (Cabazitaxel) treatment if a patient continues to experience any of these reactions at 20 mg/m.
Premedicate at least 30 minutes prior to each dose of Jevtana (Cabazitaxel) with the following intravenous medications to reduce the risk and/or severity of hypersensitivity:
Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed.
Jevtana (Cabazitaxel) is a cytotoxic anticancer drug and caution should be exercised when handling and preparing Jevtana (Cabazitaxel) solutions, taking into account the use of containment devices, personal protective equipment (e.g., gloves), and preparation procedures. Please refer to .
If Jevtana (Cabazitaxel) Injection, first diluted solution, or second (final) dilution for intravenous infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If Jevtana (Cabazitaxel) Injection, first diluted solution, or second (final) dilution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with water.
Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration of Jevtana (Cabazitaxel) infusion solution.
Read this entire section carefully before mixing and diluting. Jevtana (Cabazitaxel) requires dilutions prior to administration. Please follow the preparation instructions provided below. Both the Jevtana (Cabazitaxel) Injection and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL Jevtana (Cabazitaxel) .
The following two-step dilution process must be carried out under aseptic conditions to prepare the second (final) infusion solution.
Set aside the Jevtana (Cabazitaxel) Injection and supplied diluent vials. The Jevtana (Cabazitaxel) Injection is a clear yellow to brownish-yellow viscous solution, if appropriately stored.
Step 1 – First Dilution
Each vial of Jevtana (Cabazitaxel) 60 mg/1.5 mL must first be mixed with the of supplied diluent. Once reconstituted, the resultant solution contains 10 mg/mL of Jevtana (Cabazitaxel) .
When transferring the diluent, direct the needle onto the inside wall of Jevtana (Cabazitaxel) vial and inject slowly to limit foaming. Remove the syringe and needle and gently mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixing of the drug and diluent. Do not shake.
Let the solution stand for a few minutes to allow any foam to dissipate, and check that the solution is homogeneous and contains no visible particulate matter. It is not required that all foam dissipate prior to continuing the preparation process.
The resulting initial diluted Jevtana (Cabazitaxel) solution (cabazitaxel 10 mg/mL) requires further dilution before administration. The second dilution should be done immediately (within 30 minutes) to obtain the final infusion as detailed in Step 2.
Step 2 – Second (Final) Dilution
Withdraw the recommended dose from the Jevtana (Cabazitaxel) solution containing 10 mg/mL as prepared in Step 1 using a calibrated syringe and further dilute into a sterile 250 mL PVC-free container of either 0.9% sodium chloride solution or 5% dextrose solution for infusion. If a dose greater than 65 mg of Jevtana (Cabazitaxel) is required, use a larger volume of the infusion vehicle so that a concentration of 0.26 mg/mL Jevtana (Cabazitaxel) is not exceeded. The concentration of the Jevtana (Cabazitaxel) final infusion solution should be between 0.10 mg/mL and 0.26 mg/mL.
Jevtana (Cabazitaxel) should not be mixed with any other drugs.
Remove the syringe and thoroughly mix the final infusion solution by gently inverting the bag or bottle.
Jevtana (Cabazitaxel) final infusion solution (in either 0.9% sodium chloride solution or 5% dextrose solution) should be used within 8 hours at ambient temperature (including the one-hour infusion) or within a total of 24 hours if refrigerated (including the one-hour infusion).
As the final infusion solution is supersaturated, it may crystallize over time. Do not use if this occurs and discard.
Inspect visually for particulate matter, any crystals and discoloration prior to administration. If the Jevtana (Cabazitaxel) first diluted solution or second (final) infusion solution is not clear or appears to have precipitation, it should be discarded.
Discard any unused portion.
The final Jevtana (Cabazitaxel) infusion solution should be administered intravenously as a one-hour infusion at room temperature.
Use an in-line filter of 0.22 micrometer nominal pore size during administration.
The final Jevtana (Cabazitaxel) infusion solution should be used immediately. However, in-use storage time can be longer under specific conditions, i.e. 8 hours under ambient conditions (including the one-hour infusion) or for a total of 24 hours if refrigerated (including the one-hour infusion) .
Jevtana (Cabazitaxel) . Dosage Forms And Strengths
Jevtana (Cabazitaxel) Injection 60 mg/1.5 mL is supplied as a kit consisting of the following:
Jevtana (Cabazitaxel) . Contraindications
Jevtana (Cabazitaxel) should not be used in patients with neutrophil counts of ≤ 1,500/mm.
Jevtana (Cabazitaxel) is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.
Jevtana (Cabazitaxel) . Warnings And Precautions
Five patients experienced fatal infectious adverse events (sepsis or septic shock). All had grade 4 neutropenia and one had febrile neutropenia. One additional patient's death was attributed to neutropenia without a documented infection.
G-CSF may be administered to reduce the risks of neutropenia complications associated with Jevtana (Cabazitaxel) use. Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features (age > 65 years, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities) that predispose them to increased complications from prolonged neutropenia. Therapeutic use of G-CSF and secondary prophylaxis should be considered in all patients considered to be at increased risk for neutropenia complications.
Monitoring of complete blood counts is essential on a weekly basis during cycle 1 and before each treatment cycle thereafter so that the dose can be adjusted, if needed .
Jevtana (Cabazitaxel) should not be administered to patients with neutrophils ≤ 1,500/mm .
If a patient experiences febrile neutropenia or prolonged neutropenia (greater than one week) despite appropriate medication (e.g., G-CSF), the dose of Jevtana (Cabazitaxel) should be reduced . Patients can restart treatment with Jevtana (Cabazitaxel) only when neutrophil counts recover to a level > 1,500/mm .
No dedicated hepatic impairment trial for Jevtana (Cabazitaxel) has been conducted. Patients with impaired hepatic function (total bilirubin ≥ ULN, or AST and/or ALT ≥ 1.5 × ULN) were excluded from the randomized clinical trial.
Cabazitaxel is extensively metabolized in the liver, and hepatic impairment is likely to increase cabazitaxel concentrations.
Hepatic impairment increases the risk of severe and life-threatening complications in patients receiving other drugs belonging to the same class as Jevtana (Cabazitaxel) . Jevtana (Cabazitaxel) should not be given to patients with hepatic impairment (total bilirubin ≥ ULN, or AST and/or ALT ≥ 1.5 × ULN).
Jevtana (Cabazitaxel) . Adverse Reactions
The following serious adverse reactions are discussed in greater detail in another section of the label:
Jevtana (Cabazitaxel) . Drug Interactions
No formal clinical drug-drug interaction trials have been conducted with Jevtana (Cabazitaxel) .
Prednisone or prednisolone administered at 10 mg daily did not affect the pharmacokinetics of cabazitaxel.
Jevtana (Cabazitaxel) . Use In Specific Populations
Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of cabazitaxel between patients
Of the 371 patients with prostate cancer treated with Jevtana (Cabazitaxel) every three weeks plus prednisone, 240 patients (64.7%) were 65 years of age and over, while 70 patients (18.9%) were 75 years of age and over. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. Elderly patients (≥ 65 years of age) may be more likely to experience certain adverse reactions. The incidence of neutropenia, fatigue, asthenia, pyrexia, dizziness, urinary tract infection and dehydration occurred at rates ≥ 5% higher in patients who were 65 years of age or greater compared to younger patients .
No dedicated hepatic impairment trial for Jevtana (Cabazitaxel) has been conducted. The safety of Jevtana (Cabazitaxel) has not been evaluated in patients with hepatic impairment .
As cabazitaxel is extensively metabolized in the liver, hepatic impairment is likely to increase the cabazitaxel concentrations. Patients with impaired hepatic function (total bilirubin ≥ ULN, or AST and/or ALT ≥ 1.5 × ULN) were excluded from the randomized clinical trial.
Jevtana (Cabazitaxel) Overdosage
There is no known antidote for Jevtana (Cabazitaxel) overdose. Anticipated complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders.
In case of overdose, the patient should be kept in a specialized unit where vital signs, chemistry and particular functions can be closely monitored. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.
Jevtana (Cabazitaxel) Description
Jevtana (Cabazitaxel) is an antineoplastic agent belonging to the taxane class. It is prepared by semi-synthesis with a precursor extracted from yew needles.
The chemical name of cabazitaxel is (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S)-3-[(tertbutoxycarbonyl) amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate – propan-2-one(1:1).
Cabazitaxel has the following structural formula:
Cabazitaxel is a white to off-white powder with a molecular formula of CHNO CHO and a molecular weight of 894.01 (for the acetone solvate) / 835.93 (for the solvent free). It is lipophilic, practically insoluble in water and soluble in alcohol.
Jevtana (Cabazitaxel) Injection 60 mg/1.5 mL is a sterile, non-pyrogenic, clear yellow to brownish-yellow viscous solution and is available in single-use vials containing 60 mg cabazitaxel (anhydrous and solvent free) and 1.56 g polysorbate 80.
Each mL contains 40 mg cabazitaxel (anhydrous) and 1.04 g polysorbate 80.
DILUENT for Jevtana (Cabazitaxel) is a clear, colorless, sterile, and non-pyrogenic solution containing 13% (w/w) ethanol in water for injection, approximately 5.7 mL.
Jevtana (Cabazitaxel) requires two dilutions prior to intravenous infusion. Jevtana (Cabazitaxel) injection should be diluted only with the supplied DILUENT for Jevtana (Cabazitaxel) , followed by dilution in either 0.9% sodium chloride solution or 5% dextrose solution.
Jevtana (Cabazitaxel) . Clinical Studies
The efficacy and safety of Jevtana (Cabazitaxel) in combination with prednisone were evaluated in a randomized, open-label, international, multi-center study in patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.
A total of 755 patients were randomized to receive either Jevtana (Cabazitaxel) 25 mg/m intravenously every 3 weeks for a maximum of 10 cycles with prednisone 10 mg orally daily (n=378), or to receive mitoxantrone 12 mg/m intravenously every 3 weeks for 10 cycles with prednisone 10 mg orally daily (n=377) for a maximum of 10 cycles.
This study included patients over 18 years of age with hormone-refractory metastatic prostate cancer either measurable by RECIST criteria or non-measurable disease with rising PSA levels or appearance of new lesions, and ECOG (Eastern Cooperative Oncology Group) performance status 0–2. Patients had to have neutrophils >1,500 cells/mm, platelets > 100,000 cells/mm, hemoglobin > 10 g/dL, creatinine
Demographics, including age, race, and ECOG performance status (0–2) were balanced between the treatment arms. The median age was 68 years (range 46–92) and the racial distribution for all groups was 83.9% Caucasian, 6.9% Asian, 5.3% Black, and 4% Others in the Jevtana (Cabazitaxel) group.
Efficacy results for the Jevtana (Cabazitaxel) arm versus the control arm are summarized in Table 3 and Figure 1.
Investigator-assessed tumor response of 14.4% (95%CI: 9.6–19.3) was higher for patients in the Jevtana (Cabazitaxel) arm compared to 4.4% (95%CI: 1.6–7.2) for patients in the mitoxantrone arm, p=0.0005.
Jevtana (Cabazitaxel) . How Supplied/storage And Handling
Jevtana (Cabazitaxel) is supplied as a kit containing one single-use vial of Jevtana (Cabazitaxel) Injection (clear glass vial with a grey rubber closure, aluminum cap and light green plastic flip-off cap) and one vial of Diluent for Jevtana (Cabazitaxel) (13% (w/w) ethanol in water for injection) in a clear glass vial with a grey rubber closure, gold-color aluminum cap and colorless plastic flip-off cap. Both items are in a blister pack in one carton.
NDC 0024-5824-11
Jevtana (Cabazitaxel) . Patient Counseling Information
Jevtana (Cabazitaxel)
Jevtana (Cabazitaxel)
Jevtana (Cabazitaxel)
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