Cabazitaxel Injection (Jevtana)
برای این دارو، اطلاعات عمومی (فارسی) یافت نشد . برای افزودن اطلاعات فارسی به این دارو کلیک نمایید.
Cabazitaxel Injection (Jevtana)

JEVTANA
(cabazitaxel)

WARNING

NEUTROPENIA AND HYPERSENSITIVITY

Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia, frequent blood cell counts should be performed on all patients receiving JEVTANA. JEVTANA should not be given to patients with neutrophil counts of ≤ 1,500 cells/mm³.

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 administration of appropriate therapy [see WARNINGS AND PRECAUTIONS]. Patients should receive premedication [see DOSAGE AND ADMINISTRATIONS]. JEVTANA must not be given to patients who have a history of severe hypersensitivity reactions to JEVTANA or to other drugs formulated with polysorbate 80 [see CONTRAINDICATIONS].

DRUG 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-9oxo-5,20-epoxytax-11-en-2-yl benzoate – propan-2-one(1:1).

Cabazitaxel has the following structural formula:

JEVTANA (cabazitaxel) Structural Formula Illustration

Cabazitaxel is a white to almost-white powder with a molecular formula of C45H57NO14C3H6O 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 is a clear, colorless, sterile, and non-pyrogenic solution containing 13% (w/w) ethanol in water for injection, approximately 5.7 mL.

JEVTANA requires two dilutions prior to intravenous infusion. JEVTANA injection should be diluted only with the supplied DILUENT for JEVTANA, followed by dilution in either 0.9% sodium chloride solution or 5% dextrose solution.

What are the possible side effects of cabazitaxel (Jevtana)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives, red skin rash; difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fever, cough, chills, muscle aches, flu symptoms, sores in your mouth and throat, rapid and shallow breathing, fainting;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • severe or ongoing diarrhea;
  • trouble breathing;
  • feeling very...

Read All Potential Side Effects and See Pictures of Jevtana »

What are the precautions when taking cabazitaxel injection (Jevtana)?

Before receiving cabazitaxel, tell your doctor or pharmacist if you are allergic to it; or to polysorbate 80; or if you have any other allergies. This product may contain other inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, blood/bone marrow disorders (such as bone marrow suppression, neutropenia, thrombocytopenia, anemia), recent/current infections.

Cabazitaxel can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as...

Read All Potential Precautions of Jevtana »

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

JEVTANA® 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.

DOSAGE AND ADMINISTRATION

General Dosing Information

  • The individual dosage of JEVTANA is based on calculation of the Body Surface Area (BSA) and is 25 mg/m² administered as a one-hour 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 infusions 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.

Dose Modifications

The JEVTANA dose should be reduced to 20 mg/m² if patients experience the following adverse reactions.

Table 1: Recommended Dosage Modifications for Adverse Reactions in Patients Treated with JEVTANA

Toxicity Dosage Modification
Prolonged grade ≥ 3 neutropenia (greater than 1 week) despite appropriate medication including G-CSF Delay treatment until neutrophil count is > 1,500 cells/mm³, then reduce dosage of JEVTANA to 20 mg/m². Use G-CSF for secondary prophylaxis.
Febrile neutropenia Delay treatment until improvement or resolution, and until neutrophil count is > 1,500 cells/mm³, then reduce dosage of JEVTANA to 20 mg/m². Use G-CSF for secondary prophylaxis.
Grade ≥ 3 diarrhea or persisting diarrhea despite appropriate medication, fluid and electrolytes replacement Delay treatment until improvement or resolution, then reduce dosage of JEVTANA to 20 mg/m².

Discontinue JEVTANA treatment if a patient continues to experience any of these reactions at 20 mg/m².

Premedication

Premedicate at least 30 minutes prior to each dose of JEVTANA with the following intravenous medications to reduce the risk and/or severity of hypersensitivity:

  • antihistamine (dexchlorpheniramine 5 mg, or diphenhydramine 25 mg or equivalent antihistamine),
  • corticosteroid (dexamethasone 8 mg or equivalent steroid),
  • H2 antagonist (ranitidine 50 mg or equivalent H2 antagonist).

Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed.

Administration Precautions

JEVTANA is a cytotoxic anticancer drug and caution should be exercised when handling and preparing JEVTANA solutions, taking into account the use of containment devices, personal protective equipment (e.g., gloves), and preparation procedures. Please refer to Handling and Disposal (16.3).

If JEVTANA 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 Injection, first diluted solution, or second (final) dilution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with water.

Instructions for Preparation

Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration of JEVTANA infusion solution.

Read this entire section carefully before mixing and diluting. JEVTANA requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the JEVTANA Injection and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL JEVTANA.

The following two-step dilution process must be carried out under aseptic conditions to prepare the second (final) infusion solution.

Set aside the JEVTANA Injection and supplied diluent vials. The JEVTANA 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 entire contents of supplied diluent. Once reconstituted, the resultant solution contains 10 mg/mL of JEVTANA.

When transferring the diluent, direct the needle onto the inside wall of JEVTANA 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 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 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 is required, use a larger volume of the infusion vehicle so that a concentration of 0.26 mg/mL JEVTANA is not exceeded. The concentration of the JEVTANA final infusion solution should be between 0.10 mg/mL and 0.26 mg/mL.

JEVTANA 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 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 first diluted solution or second (final) infusion solution is not clear or appears to have precipitation, it should be discarded.

Discard any unused portion.

Administration

The final JEVTANA 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 (also referred to as 0.2 micrometer) during administration.

The final JEVTANA 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).

HOW SUPPLIED

Dosage Forms And Strengths

JEVTANA (cabazitaxel) Injection 60 mg/1.5 mL is supplied as a kit consisting of the following:

  • JEVTANA Injection 60 mg/1.5 mL: contains 60 mg cabazitaxel in 1.5 mL polysorbate 80,
  • Diluent for JEVTANA Injection 60 mg/1.5 mL: contains approximately 5.7 mL of 13% (w/w) ethanol in water for injection.

Storage And Handling

JEVTANA 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 (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

Storage
JEVTANA Injection and Diluent for JEVTANA:

Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F). Do not refrigerate.

Stability of the First Diluted Solution in the Vial:

First diluted solution of JEVTANA should be used immediately (within 30 minutes). Discard any unused portion [see DOSAGE AND ADMINISTRATION].

Stability of the Second (Final) Dilution Solution in the Infusion Bag:

Fully prepared JEVTANA 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 for a total of 24 hours (including the one-hour infusion) under the refrigerated conditions.

In addition, chemical and physical stability of the infusion solution has been demonstrated for 24 hours under refrigerated conditions. As both the first diluted solution and the second (final) infusion solution are supersaturated, the solutions may crystallize over time. If crystals and/or particulates appear, the solutions must not be used and should be discarded [see DOSAGE AND ADMINISTRATION].

Handling and Disposal

Procedures for proper handling and disposal of antineoplastic drugs should be followed. Several guidelines on this subject have been published [see REFERENCES]. Any unused product or waste material should be disposed of in accordance with local requirements.

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm 2006; 63:1172-1193.

4. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

sanofi-aventis U.S. LLC Bridgewater, NJ 08807.

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in another section of the label:

Clinical Trial Experience

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%) JEVTANA-treated 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, dysguesia, 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.

Table 2 : Incidence of Reported Adverse Reactions1 and Hematologic Abnormalities in ≥ 5% of Patients Receiving JEVTANA in Combination with Prednisone or Mitoxantrone in Combination with Prednisone

Any Adverse Reaction JEVTANA 25 mg/m² every 3 weeks with prednisone 10 mg daily Mitoxantrone 12 mg/m² every 3 weeks with prednisone 10 mg daily
Grade 1-4
n (%)
Grade 3-4
n (%)
Grade 1-4
n (%)
Grade 3-4
n (%)
Blood and Lymphatic System Disorders
  Neutropenia2 347 (94%) 303 (82%) 325 (87%) 215 (58%)
  Febrile Neutropenia 27 (7%) 27 (7%) 5 (1%) 5 (1%)
  Anemia2 361 (98%) 39 (11%) 302 (82%) 18 (5%)
  Leukopenia2 355 (96%) 253 (69%) 343 (93%) 157 (42%)
  Thrombocytopenia2 176 (48%) 15 (4%) 160 (43%) 6 (2%)
Cardiac Disorders
  Arrhythmia3 18 (5%) 4 (1%) 6 (2%) 1 ( < 1%)
Gastrointestinal Disorders 
  Diarrhea 173 (47%) 23 (6%) 39 (11%) 1 ( < 1%)
  Nausea 127 (34%) 7 (2%) 85 (23%) 1 ( < 1%)
  Vomiting 83 (22%) 6 (2%) 38 (10%) 0
  Constipation 76 (20%) 4 (1%) 57 (15%) 2 ( < 1%)
  Abdominal Pain4 64 (17%) 7 (2%) 23 (6%) 0
  Dyspepsia5 36 (10%) 0 9 (2%) 0
General Disorders and Administration Site Conditions
  Fatigue 136 (37%) 18 (5%) 102 (27%) 11 (3%)
  Asthenia 76 (20%) 17 (5%) 46 (12%) 9 (2%)
  Pyrexia 45 (12%) 4 (1%) 23 (6%) 1 ( < 1%)
  Peripheral Edema 34 (9%) 2 ( < 1%) 34 (9%) 2 ( < 1%)
  Mucosal Inflammation 22 (6%) 1 ( < 1%) 10 (3%) 1 ( < 1%)
  Pain 20 (5%) 4 (1%) 18 (5%) 7 (2%)
Infections and Infestations
  Urinary Tract Infection6 29 (8%) 6 (2%) 12 (3%) 4 (1%)
Investigations
  Weight Decreased 32 (9%) 0 28 (8%) 1 ( < 1%)
Metabolism and Nutrition Disorders
  Anorexia 59 (16%) 3 ( < 1%) 39 (11%) 3 ( < 1%)
  Dehydration 18 (5%) 8 (2%) 10 (3%) 3 ( < 1%)
Musculoskeletal and Connective Tissue Disorders
  Back Pain 60 (16%) 14 (4%) 45 (12%) 11 (3%)
  Arthralgia 39 (11%) 4 (1%) 31 (8%) 4 (1%)
  Muscle Spasms 27 (7%) 0 10 (3%) 0
Nervous System Disorders
  Peripheral Neuropathy7 50 (13%) 3 ( < 1%) 12 (3.2%) 3 ( < 1%)
  Dysgeusia 41 (11%) 0 15 (4%) 0
  Dizziness 30 (8%) 0 21 (6%) 2 ( < 1%)
  Headache 28 (8%) 0 19 (5%) 0
Renal and Urinary Tract Disorders
  Hematuria 62 (17%) 7 (2%) 13 (4%) 1 ( < 1%)
  Dysuria 25 (7%) 0 5 (1%) 0
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea 43 (12%) 4 (1%) 16 (4%) 2 ( < 1%)
  Cough 40 (11%) 0 22 (6%) 0
Skin and Subcutaneous Tissue Disorders
  Alopecia 37 (10%) 0 18 (5%) 0
Vascular Disorders
  Hypotension 20 (5%) 2 ( < 1 %) 9 (2%) 1 ( < 1%)
  Median Duration of Treatment 6 cycles 4 cycles
1Graded using NCI CTCAE version 3
2Based on laboratory values, cabazitaxel: n =369, mitoxantrone: n = 370.
3Includes atrial fibrillation, atrial flutter, atrial tachycardia, atrioventricular block complete, bradycardia, palpitations, supraventricular tachycardia, tachyarrhythmia, and tachycardia.
4Includes abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness, and GI pain.
5Includes gastroesophageal reflux disease and reflux gastritis.
6Includes urinary tract infection enterococcal and urinary tract infection fungal.
7Includes peripheral motor neuropathy and peripheral sensory neuropathy.

Neutropenia and Associated Clinical Events

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. Twenty-two (6%) patients discontinued JEVTANA treatment due to neutropenia, febrile neutropenia, infection, or sepsis. The most common adverse reaction leading to treatment discontinuation in the JEVTANA group was neutropenia (2%).

Hematuria

Adverse events of hematuria, including those requiring medical intervention, were more common in JEVTANA-treated patients. The incidence of grade ≥ 2 hematuria was 6% in JEVTANA-treated patients and 2% in mitoxantrone-treated patients. Other factors associated with hematuria were well-balanced between arms and do not account for the increased rate of hematuria on the JEVTANA arm.

Hepatic Laboratory Abnormalities

The incidences of grade 3-4 increased AST, increased ALT, and increased bilirubin were each ≤ 1%.

Elderly Population

The following grade 1-4 adverse reactions were reported at rates ≥ 5% higher in patients 65 years of age or greater compared to younger patients: fatigue (40% vs. 30%), neutropenia (97% vs. 89%), asthenia (24% vs. 15%), pyrexia (15% vs. 8%), dizziness (10% vs. 5%), urinary tract infection (10% vs. 3%) and dehydration (7% vs. 2%), respectively.

The incidence of the following grade 3-4 adverse reactions were higher in patients ≥ 65 years of age compared to younger patients; neutropenia (87% vs. 74%), and febrile neutropenia (8% vs. 6%) [see Use in Specific Populations].

Read the Jevtana (cabazitaxel injection) Side Effects Center for a complete guide to possible side effects »

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 [see CLINICAL PHARMACOLOGY]. 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) is expected to increase concentrations of cabazitaxel. Therefore, co-administration with strong CYP3A inhibitors should be avoided. 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, phenobarbital) is expected to decrease cabazitaxel concentrations. Therefore, co-administration with strong CYP3A inducers should be avoided. In addition, patients should also refrain from taking St. John's Wort.

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

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 [see DOSAGE AND ADMINISTRATION)].

JEVTANA should not be administered to patients with neutrophils ≤ 1,500/mm³ [see CONTRAINDICATIONS].

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 [see DOSAGE AND ADMINISTRATION]. Patients can restart treatment with JEVTANA only when neutrophil counts recover to a level > 1,500/mm³ [see CONTRAINDICATIONS].

Hypersensitivity Reactions

All patients should be premedicated prior to the initiation of the infusion of JEVTANA [see DOSAGE AND ADMINISTRATION]. 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 [see CONTRAINDICATIONS].

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 [see DOSAGE AND ADMINISTRATION].

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 [see ADVERSE REACTIONS]. 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 [see ADVERSE REACTIONS and Use In Specific Populations].

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 life-threatening 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).

Pregnancy

Pregnancy category D

JEVTANA can cause fetal harm when administered to a pregnant woman. In non-clinical studies in rats and rabbits, cabazitaxel was embryotoxic, fetotoxic, and abortifacient at exposures significantly lower than those expected at the recommended human dose level.

There are no adequate and well-controlled studies in pregnant women using JEVTANA. 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 during treatment with JEVTANA [see Use in Specific Populations].

Patient Counseling Information

See FDA-Approved Patient Labeling

  • Educate patients about the risk of potential hypersensitivity associated with JEVTANA. Confirm patients do not have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80. Instruct patients to immediately report signs of a hypersensitivity reaction.
  • Explain the importance of routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever to the treating oncologist.
  • Explain that it is important to take the oral prednisone as prescribed. Instruct patients to report if they were not compliant with oral corticosteroid regimen.
  • Explain to patients that severe and fatal infections, dehydration, and renal failure have been associated with cabazitaxel exposure. Patients should immediately report fever, significant vomiting or diarrhea, decreased urinary output, and hematuria to the treating oncologist.
  • Inform patients about the risk of drug interactions and the importance of providing a list of prescription and non-prescription drugs to the treating oncologist [see DRUG INTERACTIONS].
  • Inform elderly patients that certain side effects may be more frequent or severe.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of cabazitaxel.

Cabazitaxel was positive for clastogenesis in the in vivo micronucleus test, inducing an increase of micronuclei in rats at doses ≥ 0.5 mg/kg. Cabazitaxel increased numerical aberrations with or without metabolic activation in an in vitro test in human lymphocytes though no induction of structural aberrations was observed. Cabazitaxel did not induce mutations in the bacterial reverse mutation (Ames) test. The positive in vivo genotoxicity findings are consistent with the pharmacological activity of the compound (inhibition of tubulin depolymerization).

Cabazitaxel may impair fertility in humans. In a fertility study performed in female rats at cabazitaxel doses of 0.05, 0.1, or 0.2 mg/kg/day there was no effect of administration of the drug on mating behavior or the ability to become pregnant. There was an increase in pre-implantation loss at the 0.2 mg/kg/day dose and an increase in early resorptions at doses ≥ 0.1 mg/kg/day (approximately 0.02-0.06 times the human clinical exposure based on Cmax). In multi-cycle studies following the clinically recommended dosing schedule, atrophy of the uterus was observed at the 5 mg/kg dose level (approximately the AUC in patients with cancer at the recommended human dose) along with necrosis of the corpora lutea at doses ≥ 1 mg/kg (approximately 0.2 times the AUC at the clinically recommended human dose).

Cabazitaxel did not affect mating performances or fertility of treated male rats at doses of 0.05, 0.1, or 0.2 mg/kg/day. In multiple-cycle studies following the clinically recommended dosing schedule, however, degeneration of seminal vesicle and seminiferous tubule atrophy in the testis were observed in rats treated intravenously with cabazitaxel at a dose of 1 mg/kg (approximately 0.2-0.35 times the AUC in patients with cancer at the recommended human dose), and minimal testicular degeneration (minimal epithelial single cell necrosis in epididymis) was observed in dogs treated with a dose of 0.5 mg/kg (approximately one-tenth of the AUC in patients with cancer at the recommended human dose).

Use In Specific Populations

Pregnancy

Pregnancy category D

See WARNINGS AND PRECAUTIONS section.

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 0.02-0.06 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.

Pediatric Use

The safety and effectiveness of JEVTANA in pediatric patients have not been established.

Geriatric Use

Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of cabazitaxel between patients < 65 years (n=100) and older (n=70).

Of the 371 patients with prostate cancer treated with JEVTANA 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 [see ADVERSE REACTIONS].

Renal Impairment

No dedicated renal impairment trial for JEVTANA has been conducted. Based on the population pharmacokinetic analysis, no significant difference in clearance was observed in patients with mild (50 mL/min ≤ creatinine clearance (CLcr) < 80 mL/min) and moderate renal impairment (30 mL/min ≤ CLcr < 50 mL/min). No data are available for patients with severe renal impairment or end-stage renal disease [see CLINICAL PHARMACOLOGY]. Caution should be used in patients with severe renal impairment (CLcr < 30 mL/min) and patients with end-stage renal diseases.

Hepatic Impairment

No dedicated hepatic impairment trial for JEVTANA has been conducted. The safety of JEVTANA has not been evaluated in patients with hepatic impairment [see WARNINGS AND PRECAUTIONS].

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.

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There is no known antidote for JEVTANA 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.

CONTRAINDICATIONS

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.

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions.

Pharmacodynamics

Cabazitaxel demonstrated antitumor activity against advanced human tumors xenografted in mice. Cabazitaxel is active in docetaxel-sensitive tumors. In addition, cabazitaxel demonstrated activity in tumor models insensitive to chemotherapy including docetaxel.

Pharmacokinetics

A population pharmacokinetic analysis was conducted in 170 patients with solid tumors at doses ranging from 10 to 30 mg/m² weekly or every three weeks.

Absorption

Based on the population pharmacokinetic analysis, after an intravenous dose of cabazitaxel 25 mg/m2 every three weeks, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng•h/mL (CV 34%).

No major deviation from the dose proportionality was observed from 10 to 30 mg/m² in patients with advanced solid tumors.

Distribution

The volume of distribution (Vss) was 4,864 L (2,643 L/m² for a patient with a median BSA of 1.84 m²) at steady state.

In vitro, the binding of cabazitaxel to human serum proteins was 89 to 92% and was not saturable up to 50,000 ng/mL, which covers the maximum concentration observed in clinical trials. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). The in vitro blood-to-plasma concentration ratio in human blood ranged from 0.90 to 0.99, indicating that cabazitaxel was equally distributed between blood and plasma.

Metabolism

Cabazitaxel is extensively metabolized in the liver ( > 95%), mainly by the CYP3A4/5 isoenzyme (80% to 90%), and to a lesser extent by CYP2C8. Cabazitaxel is the main circulating moiety in human plasma. Seven metabolites were detected in plasma (including the 3 active metabolites issued from O-demethylation), with the main one accounting for 5% of cabazitaxel exposure. Around 20 metabolites of cabazitaxel are excreted into human urine and feces.

Based on in vitro studies, the potential for cabazitaxel to inhibit drugs that are substrates of other CYP isoenzymes (1A2,-2B6,-2C9, -2C8, -2C19, -2E1, -2D6, and CYP3A4/5) is low. In addition, cabazitaxel did not induce CYP isozymes (-1A, -2C and -3A) in vitro.

Elimination

After a one-hour intravenous infusion [14C]-cabazitaxel 25 mg/m², approximately 80% of the administered dose was eliminated within 2 weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose); while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine).

Based on the population pharmacokinetic analysis, cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m² for a patient with a median BSA of 1.84 m²) in patients with metastatic prostate cancer. Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ-half-lives of 4 minutes, 2 hours, and 95 hours, respectively.

Renal Impairment

Cabazitaxel is minimally excreted via the kidney. No formal pharmacokinetic trials have been conducted with cabazitaxel in patients with renal impairment. The population pharmacokinetic analysis carried out in 170 patients including 14 patients with moderate renal impairment (30 mL/min ≤ CLcr < 50 mL/min) and 59 patients with mild renal impairment (50 mL/min ≤ CLcr < 80 mL/min) showed that mild to moderate renal impairment did not have meaningful effects on the pharmacokinetics of cabazitaxel. No data are available for patients with severe renal impairment or end-stage renal disease [see Use in Special Populations].

Hepatic Impairment

No formal trials in patients with hepatic impairment have been conducted. As cabazitaxel is extensively metabolized in the liver, hepatic impairment is likely to increase the cabazitaxel concentrations [see WARNINGS AND PRECAUTIONS, and Use in Special Populations].

Drug interactions

As cabazitaxel is mainly metabolized by CYP3A in vitro, strong CYP3A inducers or inhibitors are expected to affect the pharmacokinetics of cabazitaxel.

Prednisone or prednisolone administered at 10 mg daily did not affect the pharmacokinetics of cabazitaxel.

In vitro, cabazitaxel did not inhibit the multidrug-resistance protein 1 (MRP1), 2 (MRP2) or organic cation transporter (OCT1). In vitro, cabazitaxel inhibited P-gp, BRCP, and organic anion transporting polypeptides (OATP1B1, OATP1B3). However the in vivo risk of cabazitaxel inhibiting MRPs, OCT1, P-gp, BCRP, OATP1B1 or OATP1B3 is low at the dose of 25 mg/m².

In vitro, cabazitaxel is a substrate of P-gp, but not a substrate of MRP1, MRP2, BCRP, OCT1, OATP1B1 or OATP1B3.

Cardiac Electrophysiology

The effect of cabazitaxel following a single dose of 25 mg/m2 administered by intravenous infusion on QTc interval was evaluated in 94 patients with solid tumors. No large changes in the mean QT interval (i.e., > 20 ms) from baseline based on Fridericia correction method were detected. However, a small increase in the mean QTc interval (i.e., < 10 ms) cannot be excluded due to study design limitations.

Clinical Studies

The efficacy and safety of JEVTANA 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 25 mg/m² intravenously every 3 weeks for a maximum of 10 cycles with prednisone 10 mg orally daily (n=378), or to receive mitoxantrone 12 mg/m² 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/mm³, platelets > 100,000 cells/mm³, hemoglobin > 10 g/dL, creatinine < 1.5 x upper limit of normal (ULN), total bilirubin < 1xULN, AST < 1.5 x ULN, and ALT < 1.5 x ULN. Patients with a history of congestive heart failure, or myocardial infarction within the last 6 months, or patients with uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension were not included in the study.

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 group.

Efficacy results for the JEVTANA arm versus the control arm are summarized in Table 3 and Figure 1.

Table 3 : Efficacy of JEVTANA in the Treatment of Patients with Hormone Refractory Metastatic Prostate Cancer (Intent-to-Treat Analysis)

  JEVTANA + Prednisone
n=378
Mitoxantrone + Prednisone
n=377
Overall Survival
Number of deaths (%) 234 (61.9 %) 279 (74%)
Median survival (month) (95% CI) 15.1 (14.1-16.3) 12.7 (11.6-13.7)
Hazard Ratio1 (95% CI) 0.70 (0.59-0.83)
p-value < 0.0001
1Hazard ratio estimated using Cox model; a hazard ratio of less than 1 favors JEVTANA

Kaplan-Meier Overall Survival Curves - Illustration

Investigator-assessed tumor response of 14.4% (95%CI: 9.6-19.3) was higher for patients in the JEVTANA arm compared to 4.4% (95%CI: 1.6-7.2) for patients in the mitoxantrone arm, p=0.0005.

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

JEVTANA®
(JEV-TA-NA)
(cabazitaxel) Injection

Read this Patient Information before you start receiving JEVTANA and each time before you receive your infusion. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about JEVTANA?

JEVTANA may cause serious side effects including:

1. Low white blood cells. Low white blood cells can cause you to get serious infections, and may lead to death. People who are 65 years or older may be more likely to have these problems. Your doctor:

  • will do blood tests regularly to check your white blood cell counts during your treatment with JEVTANA.
  • may lower your dose of JEVTANA, change how often you receive it, or stop JEVTANA until your doctor decides that you have enough white blood cells.
  • may prescribe a medicine for you called G-CSF, to help prevent complications if your white blood cell count is too low.
    Tell your doctor right away if you have any of these symptoms of infection while receiving JEVTANA:
  • fever. Take your temperature often during treatment with JEVTANA.
  • cough
  • burning on urination
  • muscle aches

Also, tell your doctor if you have any diarrhea during the time that your white blood cell count is low. Your doctor may prescribe treatment for you as needed.

2. Severe allergic reactions. Severe allergic reactions can happen within a few minutes after your infusion of JEVTANA starts, especially during the first and second infusions. Your doctor should prescribe medicines before each infusion to help prevent severe allergic reactions.

Tell your doctor or nurse right away if you have any of these symptoms of a severe allergic reaction during or soon after an infusion of JEVTANA:

  • rash or itching
  • skin redness
  • feeling dizzy or faint
  • breathing problems
  • chest or throat tightness
  • swelling of face

3. Gastrointestinal symptoms. Vomiting and diarrhea can happen when you take JEVTANA. Severe vomiting and diarrhea with JEVTANA can lead to loss of too much body fluid (dehydration), or too much of your body salts (electrolytes). Death has happened from having severe diarrhea and losing too much body fluid or body salts with JEVTANA. Tell your doctor if you have vomiting or diarrhea. Your doctor will prescribe medicines to prevent or treat vomiting and diarrhea, as needed with JEVTANA. Tell your doctor if your symptoms get worse or do not get better. You may need to go to the hospital for treatment.

4. Kidney failure. Kidney failure may happen with JEVTANA, because of severe infection, loss of too much body fluid (dehydration), and other reasons, which may lead to death. Your doctor will check you for this problem and treat you if needed. Tell your doctor if you develop:

  • swelling of your face or body
  • decrease in the amount of urine that your body makes each day.

What is JEVTANA?

JEVTANA is a prescription anti-cancer medicine used with the steroid medicine prednisone. JEVTANA is used to treat people with prostate cancer that has worsened (progressed) after treatment with other anti-cancer medicines, including docetaxel.

It is not known if JEVTANA is safe and works in children.

Who should not receive JEVTANA?

Do not receive JEVTANA if:

  • your white blood cell (neutrophil count) is too low
  • you have had a severe allergic reaction to cabazitaxel or other medicines that contain polysorbate 80. Ask your doctor if you are not sure.

What should I tell my doctor before receiving JEVTANA?

Before receiving JEVTANA, tell your doctor if you:

  • had allergic reactions in the past
  • have kidney or liver problems
  • are over the age of 65
  • have any other medical conditions
  • if you are a female and:
    • are pregnant or plan to become pregnant. JEVTANA can harm your unborn baby. Talk to your doctor about the best way for you to prevent pregnancy while you are receiving JEVTANA.
    • are breastfeeding or plan to breastfeed. It is not known if JEVTANA passes into your breast milk. You and your doctor should decide if you will take JEVTANA or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. JEVTANA can interact with many other medicines. Do not take any new medicines without asking your doctor first. Your doctor will tell you if it is safe to take the new medicine with JEVTANA.

How will I receive JEVTANA?

  • JEVTANA will be given to you by an intravenous (IV) infusion into your vein.
  • Your treatment will take about 1 hour.
  • JEVTANA is usually given every 3 weeks. Your doctor will decide how often you will receive JEVTANA .
  • Your doctor will also prescribe another medicine called prednisone, for you to take by mouth every day during treatment with JEVTANA. Your doctor will tell you how and when to take your prednisone.

It is important that you take prednisone exactly as prescribed by your doctor. If you forget to take your prednisone, or do not take it on schedule, make sure to tell your doctor or nurse. Before each infusion of JEVTANA, you may receive other medicines to prevent or treat side effects.

What are the possible side effects of JEVTANA?

JEVTANA may cause serious side effects including:

  • See “What is the most important information I should know about JEVTANA?”

Common side effects of JEVTANA include:

  • Low red blood cell count (anemia). Your doctor will regularly check your red blood cell count. Symptoms of anemia include shortness of breath and tiredness.
  • Low blood platelet count. Tell your doctor if you have any unusual bruising or bleeding.

  • fever
  • shortness of breath
  • stomach (abdominal) pain
  • change in your sense of taste
  • cough
  • joint pain
  • hair loss
  • numbness, tingling, burning or
  • decreased sensation in your
  • hands or feet

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of JEVTANA. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about JEVTANA

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

This leaflet summarizes the most important information about JEVTANA. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about JEVTANA that is written for health professionals.

For more information, go to www.sanofi-aventis.us or call 1-800-633-1610.

What are the ingredients in JEVTANA?

Active ingredient: cabazitaxel

Inactive ingredient: polysorbate 80

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

JEVTANA®
(JEV-TA-NA)
(cabazitaxel) Injection

Read this Patient Information before you start receiving JEVTANA and each time before you receive your infusion. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about JEVTANA?

JEVTANA may cause serious side effects including:

1. Low white blood cells. Low white blood cells can cause you to get serious infections, and may lead to death. People who are 65 years or older may be more likely to have these problems. Your doctor:

  • will do blood tests regularly to check your white blood cell counts during your treatment with JEVTANA.
  • may lower your dose of JEVTANA, change how often you receive it, or stop JEVTANA until your doctor decides that you have enough white blood cells.
  • may prescribe a medicine for you called G-CSF, to help prevent complications if your white blood cell count is too low.
    Tell your doctor right away if you have any of these symptoms of infection while receiving JEVTANA:
  • fever. Take your temperature often during treatment with JEVTANA.
  • cough
  • burning on urination
  • muscle aches

Also, tell your doctor if you have any diarrhea during the time that your white blood cell count is low. Your doctor may prescribe treatment for you as needed.

2. Severe allergic reactions. Severe allergic reactions can happen within a few minutes after your infusion of JEVTANA starts, especially during the first and second infusions. Your doctor should prescribe medicines before each infusion to help prevent severe allergic reactions.

Tell your doctor or nurse right away if you have any of these symptoms of a severe allergic reaction during or soon after an infusion of JEVTANA:

  • rash or itching
  • skin redness
  • feeling dizzy or faint
  • breathing problems
  • chest or throat tightness
  • swelling of face

3. Gastrointestinal symptoms. Vomiting and diarrhea can happen when you take JEVTANA. Severe vomiting and diarrhea with JEVTANA can lead to loss of too much body fluid (dehydration), or too much of your body salts (electrolytes). Death has happened from having severe diarrhea and losing too much body fluid or body salts with JEVTANA. Tell your doctor if you have vomiting or diarrhea. Your doctor will prescribe medicines to prevent or treat vomiting and diarrhea, as needed with JEVTANA. Tell your doctor if your symptoms get worse or do not get better. You may need to go to the hospital for treatment.

4. Kidney failure. Kidney failure may happen with JEVTANA, because of severe infection, loss of too much body fluid (dehydration), and other reasons, which may lead to death. Your doctor will check you for this problem and treat you if needed. Tell your doctor if you develop:

  • swelling of your face or body
  • decrease in the amount of urine that your body makes each day.

What is JEVTANA?

JEVTANA is a prescription anti-cancer medicine used with the steroid medicine prednisone. JEVTANA is used to treat people with prostate cancer that has worsened (progressed) after treatment with other anti-cancer medicines, including docetaxel.

It is not known if JEVTANA is safe and works in children.

Who should not receive JEVTANA?

Do not receive JEVTANA if:

  • your white blood cell (neutrophil count) is too low
  • you have had a severe allergic reaction to cabazitaxel or other medicines that contain polysorbate 80. Ask your doctor if you are not sure.

What should I tell my doctor before receiving JEVTANA?

Before receiving JEVTANA, tell your doctor if you:

  • had allergic reactions in the past
  • have kidney or liver problems
  • are over the age of 65
  • have any other medical conditions
  • if you are a female and:
    • are pregnant or plan to become pregnant. JEVTANA can harm your unborn baby. Talk to your doctor about the best way for you to prevent pregnancy while you are receiving JEVTANA.
    • are breastfeeding or plan to breastfeed. It is not known if JEVTANA passes into your breast milk. You and your doctor should decide if you will take JEVTANA or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. JEVTANA can interact with many other medicines. Do not take any new medicines without asking your doctor first. Your doctor will tell you if it is safe to take the new medicine with JEVTANA.

How will I receive JEVTANA?

  • JEVTANA will be given to you by an intravenous (IV) infusion into your vein.
  • Your treatment will take about 1 hour.
  • JEVTANA is usually given every 3 weeks. Your doctor will decide how often you will receive JEVTANA .
  • Your doctor will also prescribe another medicine called prednisone, for you to take by mouth every day during treatment with JEVTANA. Your doctor will tell you how and when to take your prednisone.

It is important that you take prednisone exactly as prescribed by your doctor. If you forget to take your prednisone, or do not take it on schedule, make sure to tell your doctor or nurse. Before each infusion of JEVTANA, you may receive other medicines to prevent or treat side effects.

What are the possible side effects of JEVTANA?

JEVTANA may cause serious side effects including:

  • See “What is the most important information I should know about JEVTANA?”

Common side effects of JEVTANA include:

  • Low red blood cell count (anemia). Your doctor will regularly check your red blood cell count. Symptoms of anemia include shortness of breath and tiredness.
  • Low blood platelet count. Tell your doctor if you have any unusual bruising or bleeding.

  • fever
  • shortness of breath
  • stomach (abdominal) pain
  • change in your sense of taste
  • cough
  • joint pain
  • hair loss
  • numbness, tingling, burning or
  • decreased sensation in your
  • hands or feet

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of JEVTANA. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about JEVTANA

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

This leaflet summarizes the most important information about JEVTANA. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about JEVTANA that is written for health professionals.

For more information, go to www.sanofi-aventis.us or call 1-800-633-1610.

What are the ingredients in JEVTANA?

Active ingredient: cabazitaxel

Inactive ingredient: polysorbate 80

Last reviewed on RxList: 10/16/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Jevtana Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

CABAZITAXEL - INJECTION

COMMON BRAND NAME(S): Jevtana

WARNING: Cabazitaxel may cause a serious blood disorder (a low number of white blood cells). This effect can lower your body's ability to fight an infection and thus lead to serious (rarely fatal) infections. Your doctor will monitor you closely and check your blood often during treatment. You may also receive another medication to reduce the risk of this side effect. If your white blood cell count is too low, you should not receive cabazitaxel. Tell your doctor immediately if you develop any signs of infection such as fever, chills, cough, persistent sore throat, painful/difficult urination.

Cabazitaxel may infrequently cause serious allergic reactions. This drug must not be used in patients who have previously had an allergic reaction to it or to other medications containing polysorbate 80. Your doctor should prescribe other medications (such as antihistamines, corticosteroids) to help prevent an allergic reaction. Get medical help right away if you develop any signs of an allergic reaction such as rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

USES: Cabazitaxel is used with another medication (prednisone) to treat prostate cancer. It works by slowing or stopping the growth of cancer cells.

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using cabazitaxel and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

This medication is given by injection into a vein over 1 hour by a health care professional. It is usually given every 3 weeks. While you receive treatment with cabazitaxel, take the prednisone medication as directed by your doctor, usually once daily.

Your doctor may prescribe premedications (such as antihistamines, corticosteroids) to reduce the risk of allergic reactions or prevent side effects such as nausea/vomiting. These medications are usually given at least 30 minutes before your dose of cabazitaxel.

The dosage is based on your size, medical condition, laboratory test results, and response to treatment.

Disclaimer

Jevtana Consumer (continued)

SIDE EFFECTS: See also Warning section.

Loss of appetite, stomach/abdominal pain, or change in sense of taste may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Nausea, vomiting, and diarrhea can also occur and may be severe. Tell your doctor immediately if these effects occur. In some cases, your doctor may prescribe medication to prevent or relieve nausea, vomiting, or diarrhea. Eating several small meals, not eating before treatment, or limiting activity may help to lessen the nausea and vomiting.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Many people using this medication develop serious side effects. However, your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

Tell your doctor immediately if any of these unlikely but serious side effects occur: change in the amount of urine, bloody urine, muscle cramps, weakness, dizziness, extreme thirst, unusual tiredness, fast/irregular heartbeat, easy bruising/bleeding, numbness/tingling of arms/legs.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Jevtana (cabazitaxel injection) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before receiving cabazitaxel, tell your doctor or pharmacist if you are allergic to it; or to polysorbate 80; or if you have any other allergies. This product may contain other inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, blood/bone marrow disorders (such as bone marrow suppression, neutropenia, thrombocytopenia, anemia), recent/current infections.

Cabazitaxel can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be at greater risk for side effects (such as low number of white blood cells, fever, dizziness, bladder infections, dehydration/loss of too much body water) while using this drug.

Cabazitaxel is not recommended for use during pregnancy. It may harm an unborn baby. Discuss the use of reliable forms of birth control with your doctor. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Disclaimer

Jevtana Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Other medications can affect the removal of cabazitaxel from your body, which may affect how cabazitaxel works. Examples include azole antifungals (such as itraconazole), macrolide antibiotics (such as clarithromycin), HIV protease inhibitors (such as ritonavir), nefazodone, rifamycins (such as rifabutin), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin, phenobarbital), among others.

This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Laboratory and/or medical tests (such as complete blood count, kidney function) must be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor to establish a new dosing schedule.

STORAGE: Not applicable. This medication is given in a hospital and will not be stored at home.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (US) or 1-800-668-1507 (Canada).

Information last revised August 2010. Copyright(c) 2010 First Databank, Inc.

Jevtana Patient Information Including Side Effects

Brand Names: Jevtana

Generic Name: cabazitaxel (Pronunciation: ka BAZ i TAX el)

What is cabazitaxel (Jevtana)?

Cabazitaxel is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Cabazitaxel is used together with prednisone to treat prostate cancer that has spread to other parts of the body (metastatic).

Cabazitaxel is usually given after other cancer medicines have been tried without successful treatment.

Cabazitaxel may also be used for purposes not listed in this medication guide.

What are the possible side effects of cabazitaxel (Jevtana)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives, red skin rash; difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • fever, cough, chills, muscle aches, flu symptoms, sores in your mouth and throat, rapid and shallow breathing, fainting;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • severe or ongoing diarrhea;
  • trouble breathing;
  • feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;
  • swelling or rapid weight gain; or
  • blood in your urine, pain or burning when you urinate.

Less serious side effects may include:

  • nausea, vomiting, stomach pain;
  • constipation, mild diarrhea;
  • weakness, tired feeling;
  • joint pain, back pain;
  • numbness, burning pain, or tingly feeling en your hands or feet;
  • changes in your sense of taste; or
  • hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Jevtana (cabazitaxel injection) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about cabazitaxel (Jevtana)?

You should not use this medication if you are allergic to cabazitaxel, or if you have liver disease, low white blood cell counts, or an allergy to any medicine that contains polysorbate 80.

You should not breast-feed while you are receiving cabazitaxel.

Before you receive cabazitaxel, tell your doctor if you have ever had a severe allergic reaction to any medication.

Cabazitaxel is used together with prednisone, and you may also be given other medications to help prevent certain side effects. Use all medications as directed by your doctor.

To make sure cabazitaxel is helping your condition and not causing harmful effects, your blood will need to be tested often.

Side Effects Centers

Jevtana Patient Information including How Should I Take

What should I discuss with my health care provider before receiving cabazitaxel (Jevtana)?

You should not use this medication if you are allergic to cabazitaxel, or if you have:

  • liver disease;
  • low white blood cell counts; or
  • an allergy to any medicine that contains polysorbate 80.

To make sure you can safely receive cabazitaxel, tell your doctor if you have ever had a severe allergic reaction to any medication.

FDA pregnancy category D. Do not use cabazitaxel if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether cabazitaxel passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are receiving cabazitaxel.

Serious side effects may be more likely in older adults receiving cabazitaxel.

How is cabazitaxel given (Jevtana)?

Cabazitaxel is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Cabazitaxel must be given slowly, and the IV infusion can take about 1 hour to complete.

Cabazitaxel is usually given once every 3 weeks. You will most likely take prednisone by mouth every day throughout your cabazitaxel treatment. Follow your doctor's dosing instructions very carefully.

Do not stop taking prednisone without your doctor's advice, or you could have unpleasant side effects caused by cabazitaxel. Tell your doctor if you have missed any doses or have stopped taking prednisone for any reason.

About 30 minutes before you receive cabazitaxel, you may be given other medications to help prevent certain side effects.

Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow-up visits to your doctor.

Your doctor may tell you to check your temperature at home throughout your treatment with cabazitaxel.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while receiving cabazitaxel, which can lead to a serious electrolyte imbalance.

Side Effects Centers

Jevtana Patient Information including If I Miss a Dose

What happens if I miss a dose (Jevtana)?

Call your doctor for instructions if you miss an appointment for your cabazitaxel injection.

What happens if I overdose (Jevtana)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

What should I avoid while receiving cabazitaxel (Jevtana)?

Avoid taking an herbal supplement containing St. John's wort while you are being treated with cabazitaxel.

What other drugs will affect cabazitaxel (Jevtana)?

Many drugs can interact with cabazitaxel. Below is just a partial list. Tell your doctor if you are using:

  • conivaptan (Vaprisol);
  • imatinib (Gleevec);
  • isoniazid (for treating tuberculosis);
  • aprepitant (Emend);
  • cimetidine (Tagamet);
  • cyclosporine (Gengraf, Neoral, Sandimmune);
  • haloperidol (Haldol);
  • lidocaine (Xylocaine);
  • an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), doxycycline (Adoxa, Alodox, Avidoxy, Oraxyl, Doryx, Oracea, Vibramycin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), metronidazole (Flagyl), norfloxacin (Noroxin), telithromycin (Ketek), or tetracycline (Ala-Tet, Brodspec, Panmycin, Sumycin, Tetracap);
  • antifungal medication such as clotrimazole (Mycelex Troche), fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend);
  • an antidepressant such as nefazodone, desipramine (Norpramin), or sertraline (Zoloft);
  • heart or blood pressure medication such as amiodarone (Cordarone, Pacerone), diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others; or
  • HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir).

Where can I get more information?

Your doctor or pharmacist can provide more information about cabazitaxel.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

توزیع کنندگان این دارو
شرکت های تولید کننده یا وارد کننده دارو

دارونـــما
نوآوری برای سلامت

طراحی و اجرا M.Ramezani
ارتباط با ما Info@darunama.com