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  • Jevtana
    / Sanofi


    Active Ingredient
    Cabazitaxel 60 mg / 1.5 ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 X 60 mg / 1.5 ml

    partial basket chart 24230 10052

    Dosage

    – The individual dosage of JEVTANA is based on calculation of the Body Surface Area (BSA) and is 25 mg/m² administered as a onehour intravenous infusion every three weeks in combination with oral prednisone 10 mg administered daily throughout JEVTANA treatment. • Premedication is recommended prior to treatment.
    – JEVTANA should be administered under the supervision of a qualified physician experienced in the use of antineoplastic medicinal products. Appropriate management of complications is possible only when the adequate diagnostic and treatment facilities are readily available. • JEVTANA Injection single-use vial requires two dilutions prior to administration.
    – Do not use PVC infusion containers and polyurethane infusion sets for preparation and administration of JEVTANA infusion solution.
    – Both the JEVTANA Injection and the DILUENT vials contain an overfill to compensate for liquid loss during preparation.
    For full details see prescribing information.


    Indications

    In combination with prednisone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-based treatment regimen.


    Contra-Indications

    – JEVTANA should not be used in patients with neutrophil counts of ≤ 1,500/mm³.
    – JEVTANA is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.
    – Severe hepatic impairment (total bilirubin > 3 x ULN).


    Special Precautions

    Neutropenia: 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 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 should not be administered to patients with neutrophils ≤ 1,500/mm³. If a patient experiences febrile neutropenia or prolonged neutropenia (greater than one week) despite appropriate medication (e.g., G-CSF), the dose of JEVTANA should be reduced. Patients can restart treatment with JEVTANA only when neutrophil counts recover to a level > 1,500/mm³.
    Hypersensitivity Reactions: All patients should be premedicated prior to the initiation of the infusion of JEVTANA. Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of JEVTANA, thus facilities and equipment for the treatment of hypotension and bronchospasm should be available. Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of the JEVTANA infusion and appropriate therapy. Patients with a history of severe hypersensitivity reactions should not be re-challenged with JEVTANA.
    Gastrointestinal Symptoms: Nausea, vomiting and severe diarrhea, at times, may occur. Death related to diarrhea and electrolyte imbalance occurred in the randomized clinical trial. Intensive measures may be required for severe diarrhea and electrolyte imbalance. Patients should be treated with rehydration, anti-diarrheal or anti-emetic medications as needed. Treatment delay or dosage reduction may be necessary if patients experience Grade ≥ 3 diarrhea. Gastrointestinal (GI) hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome, have been reported in patients treated with JEVTANA. Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, anti-platelet therapy or anti-coagulants, and in patients with a prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding. Abdominal pain and tenderness, fever, persistent constipation, diarrhea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly. JEVTANA treatment delay or discontinuation may be necessary.
    Renal Failure: Renal failure, including four cases with fatal outcome, was reported in the randomized clinical trial. Most cases occurred in association with sepsis, dehydration, or obstructive uropathy . Some deaths due to renal failure did not have a clear etiology. Appropriate measures should be taken to identify causes of renal failure and treat aggressively.
    Elderly Patients: In the randomized clinical trial, 3 of 131 (2%) patients < 65 years of age and 15 of 240 (6%) ≥ 65 years of age died of causes other than disease progression within 30 days of the last cabazitaxel dose. Patients ≥ 65 years of age are more likely to experience certain adverse reactions, including neutropenia and febrile neutropenia.
    Hepatic Impairment: No dedicated hepatic impairment trial for JEVTANA 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 lifethreatening complications in patients receiving other drugs belonging to the same class as JEVTANA. JEVTANA should not be given to patients with hepatic impairment (total bilirubin ≥ ULN, or AST and/or ALT ≥ 1.5 × ULN).
    For full details see prescribing information.


    Side Effects

    Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. The safety of JEVTANA in combination with prednisone was evaluated in 371 patients with hormone-refractory metastatic prostate cancer treated in a single randomized trial, compared to mitoxantrone plus prednisone. Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) JEVTANAtreated patients and 3 (< 1%) mitoxantrone-treated patients. The most common fatal adverse reactions in JEVTANA-treated patients were infections (n=5) and renal failure (n=4). The majority (4 of 5 patients) of fatal infection-related adverse reactions occurred after a single dose of JEVTANA. Other fatal adverse reactions in JEVTANA-treated patients included ventricular fibrillation, cerebral hemorrhage, and dyspnea. The most common (≥ 10%) grade 1-4 adverse reactions were anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, and alopecia. The most common (≥ 5%) grade 3-4 adverse reactions in patients who received JEVTANA were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia. Treatment discontinuations due to adverse drug reactions occurred in 18% of patients who received JEVTANA and 8% of patients who received mitoxantrone. The most common adverse reactions leading to treatment discontinuation in the JEVTANA group were neutropenia and renal failure. Dose reductions were reported in 12% of JEVTANA-treated patients and 4% of mitoxantrone-treated patients. Dose delays were reported in 28% of JEVTANA-treated patients and 15% of mitoxantrone-treated patients.
    For full details see prescribing information.


    Drug interactions

    No formal clinical drug-drug interaction trials have been conducted with JEVTANA. Prednisone or prednisolone administered at 10 mg daily did not affect the pharmacokinetics of cabazitaxel.
    Drugs That May Increase Cabazitaxel Plasma Concentrations: CYP3A4 Inhibitors: Cabazitaxel is primarily metabolized through CYP3A. Though no formal drug interaction trials have been conducted for JEVTANA, concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) increases concentrations of cabazitaxel. Therefore, co-administration with strong CYP3A inhibitors should be avoided. If co-administration with a strong CYP3A inhibitor cannot be avoided, close monitoring for toxicity and a cabazitaxel dose reduction should be considered. Caution should be exercised with concomitant use of moderate CYP3A inhibitors.
    Drugs That May Decrease Cabazitaxel Plasma Concentrations: CYP3A4 Inducers: Though no formal drug interaction trials have been conducted for JEVTANA, the concomitant administration of strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentin) decreases cabazitaxel concentrations. Therefore, co-administration with strong CYP3A inducers should be avoided as they may decrease cabazitaxel exposure. In addition, patients should also refrain from taking St. John’s Wort.
    For full details see prescribing information.


    Pregnancy and Lactation

    Pregnancy: JEVTANA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of JEVTANA in pregnant women. Non-clinical studies in rats and rabbits have shown that cabazitaxel is embryotoxic, fetotoxic, and abortifacient. Cabazitaxel was shown to cross the placenta barrier within 24 hours of a single intravenous administration of a 0.08 mg/kg dose (approximately 0.02 times the maximum recommended human dose-MRHD) to pregnant rats at gestational day 17. Cabazitaxel administered once daily to female rats during organogenesis at a dose of 0.16 mg/kg/day (approximately 0.020.06 times the Cmax in patients with cancer at the recommended human dose) caused maternal and embryofetal toxicity consisting of increased post-implantation loss, embryolethality, and fetal deaths. Decreased mean fetal birth weight associated with delays in skeletal ossification were observed at doses ≥ 0.08 mg/kg (approximately 0.02 times the Cmax at the MRHD). In utero exposure to cabazitaxel did not result in fetal abnormalities in rats or rabbits at exposure levels significantly lower than the expected human exposures. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking JEVTANA.
    Nursing Mothers: Cabazitaxel or cabazitaxel metabolites are excreted in maternal milk of lactating rats. It is not known whether this drug is excreted in human milk. Within 2 hours of a single intravenous administration of cabazitaxel to lactating rats at a dose of 0.08 mg/kg (approximately 0.02 times the maximum recommended human dose), radioactivity related to cabazitaxel was detected in the stomachs of nursing pups. This was detectable for up to 24 hours post-dose. Approximately 1.5% of the dose delivered to the mother was calculated to be delivered in the maternal milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from JEVTANA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

     


    Overdose

    There is no known antidote for JEVTANA overdose. Overdose has resulted from improper preparation. Please read the entire section Dosage and Administration carefully before mixing or diluting. Complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders. Overdose has led to fatal outcome. 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.


    Manufacturer
    Sanofi-Aventis Deutschland GmbH, Germany
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