cabazitaxel (Rx)

Brand and Other Names:Jevtana
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 60mg/1.5mL

Prostate Cancer

Indicated in combination with prednisone for hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen

25 mg/m² IV q3Weeks; infuse IV over 1 hr  

Give with prednisone 10 mg PO qDay (ie, administer prednisone every day throughout course of treatment with cabazitaxel)

Dose modification

  • Reduce dose to 20 mg/m² with following reactions
  • Febrile neutropenia or prolonged (>1 week) neutropenia grade 3 or greater: Delay until neutrophil count is >1500/mm³, and then reinitiate at reduced dose; consider G-CSF for secondary prophylaxis
  • Persistent diarrhea or diarrhea grade 3 or greater: Delay until improvement, and then reinitiate at reduced dose of 20 mg/m²
  • Grade 2 peripheral neuropathy: Delay treatment until improvement or resolution; then reduce dose to 20 mg/m²
  • Grade 3 peripheral neuropathy: Discontinue therapy
  • Discontinue if reactions persist despite reduced dose

Hepatic Impairment

Mild hepatic impairment (total bilirubin > 1 to ≤ 1.5 x upper limit of normal (ULN) or AST >1.5 x ULN): Reduce dose to 20 mg/m²

Moderate hepatic impairment (total bilirubin > 1.5 to ≤ 3 x ULN and AST = any): 15 mg/m²

Severe hepatic impairment (total bilirubine >3 x ULN): Contraindicated

Administration

Vial contents require 2 dilutions prior to administration

Use entire contents of accompanying diluent to achieve a concentration of 10 mg/mL

Antiemetic prophylaxis recommended as needed

Premedication regimen

  • Initiate premedication 30 minutes before each dose Antihistamine (eg, diphenhydramine 25 mg IV) Corticosteroid (dexamethasone 8 mg IV or equivalent) H2-antagonist (eg, ranitidine 50 mg IV)

Other Information

Use cytotoxic precautions for handling, administration, and disposal

Safety and efficacy not established

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Interactions

Interaction Checker

and cabazitaxel

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      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Anemia (11-98%)

            Leukopenia (69-96%)

            Neutropenia (82-94%)

            Thrombocytopenia (4-48%)

            Diarrhea (6-47%)

            Fatigue (5-37%)

            Nausea (2-34%)

            Vomiting (2-22%)

            Asthenia (5-20%)

            Constipation (1-20%)

            Abdominal pain (2-17%)

            Hematuria (2-17%)

            Anorexia (1-16%)

            Back pain/arthralgia (11-16%)

            Peripheral neuropathy (1-13%)

            Pyrexia (1-12%)

            Dyspnea (1-12%)

            Cough (11%)

            Dysgeusia (11%)

            1-10%

            Dyspepsia (10%)

            Alopecia (10%)

            Peripheral edema (1-9%)

            Weight loss (9%)

            Dizziness (8%)

            Headache (8%)

            UTI (2-8%)

            Dysuria (7%)

            Febrile neutropenia (1-7%)

            Mucosal inflammation (1-6%)

            Hypotension (5%)

            Arrhythmia (1-5%)

            Postmarketing Reports

            Gastrointestinal: Gastritis, intestinal obstruction

            Interstitial pneumonia/pneumonitis

            Interstitial lung disease

            Acute respiratory distress syndrome

            Bone marrow suppression

            Renal failure

            Renal and urinary disorders: Radiation recall hemorrhagic cystitis

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            Warnings

            Black Box Warnings

            Neutropenic deaths have been reported; monitor for neutropenia with frequent blood cell counts; primary prophylaxis with G-CSF recommended in patients with high-risk clinical features

            Do not give if neutrophils 1,500 cells/mm³ or less

            Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension, and bronchospasm; patients should receive premedication; therapy is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80; immediately discontinue therapy if it occurs and initiate treatment as indicated

            Contraindications

            Neutrophil count 1500/mm³ or less

            Hypersensitivity to cabazitaxel or drugs formulated with polysorbate 80

            Severe hepatic impairment (total bilirubin > 3 x ULN)

            Pregnancy

            Cautions

            Extensively metabolized in liver, hepatic impairment likely to increase serum concentrations

            Bone marrow suppression manifested as neutropenia, anemia, thrombocytopenia and/or pancytopenia may occur; neutropenia and febrile neutropenia, including neutropenic deaths, have been reported; monitor blood counts frequently to determine if initiation of G-CSF and/or dosage modification is needed; G-CSF may be administered to reduce the risks of neutropenia complications in patients with high risk clinical features; therapeutic use of G-CSF and secondary prophylaxis should be considered in all patients considered to be at increased risk for neutropenia complications

            Gastrointestinal symptoms (nausea, vomiting, diarrhea), including mortality related to diarrhea, has been reported; rehydrate and treat with antiemetics and antidiarrheals as needed

            GI hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome; risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, antiplatelets, or anticoagulants, and prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding

            Closely monitor patients with hemoglobin < 10 g/dL

            Renal failure, including cases with fatal outcomes, reported

            Elderly patients (ie, aged 65 years or older) were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia

            Cabazitaxel is a CYP3A substrate; caution with CYP3A inhibitors or inducers that may alter drug serum levels

            May cause fetal harm when administered to a pregnant woman

            Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome, including fatal outcomes reported; patients with underlying lung disease may be at higher risk for respiratory distress; acute respiratory distress syndrome may occur in the setting of infection; delay or discontinue therapy and treat as indicated; if therapy is discontinued, the benefit of resuming treatment must be carefully evaluated; incidence of gastrointestinal adverse reactions is greater in patients who have received prior radiation

            Severe hypersensitivity reactions can occur; premedicate with corticosteroids and H2 antagonists; discontinue infusion immediately if hypersensitivity is observed and treat as indicated

            Reduce dose to 20 mg/m² in patients with mild hepatic impairment and to 15 mg/m² in patients with moderate hepatic impairment

            Cystitis, radiation cystitis, and hematuria, including that requiring hospitalization, reported; monitor patients who previously received pelvic radiation for signs and symptoms of cystitis while on therapy; interrupt or discontinue treatment in patients experiencing severe hemorrhagic cystitis; medical and/or surgical supportive treatment may be required to treat severe hemorrhagic cystitis

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            Pregnancy & Lactation

            Pregnancy Category: D

            Pregnancy

            Contraindicated for use in pregnant women because drug can cause fetal harm and potential loss of pregnancy; not indicated for use in female patients; there are no human data on use of cabazitaxel injection in pregnant women; in animal reproduction studies, intravenous administration of drug in pregnant rats during organogenesis caused embryonic and fetal death at doses lower than maximum recommended human dose

            Contraception

            • Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after administering final dose

            Infertility

            • Based on animal toxicology studies, cabazitaxel injection may impair human fertility in males of reproductive potential

            Lactation

            Not indicated for use in female patients; there is no information available on presence in human milk, effects on breastfed infant, or on milk production; drug or drug metabolites are excreted in maternal milk of lactating rats

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Microtubule inhibitor; binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly; this results in microtubule stabilization, which results in the inhibition of mitotic and interphase cellular functions

            Absorption

            Peak plasma time: 1 hr

            Peak plasma concentration: 226 ng/mL

            AUC: 991 ng•h/mL

            Distribution

            Vd: 4,864 L at steady state

            Protein bound: 89-92%; mainly bound to albumin (82%)

            Metabolism

            CYP3A substrate (main), CYP2C8 (less), P-gp substrate; extensively metabolized in liver by CYP3A4/5; 7 metabolites (3 active) detected in plasma; 20 metabolites detected in feces/urine

            Elimination

            Excretion: Feces (76%), urine (3.7%)

            Half-Life: 95 hr (terminal half-life)

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            Administration

            IV Compatibilities

            Solution: 0.9% NaCl or dextrose 5%

            IV Preparation

            Use aseptic technique

            2-step dilution process

            Do not mix with any other drugs

            Step 1 (1st dilution)

            • Mix cabazitaxel 60 mg/1.5 mL vial with entire contents of supplied diluent
            • Once reconstituted, resultant solution contains 10 mg/mL
            • Vial contains slight overfill (ie, entire vial contains about 65 mg)
            • When transferring the diluent, direct the needle onto the inside wall of vial and inject slowly to limit foaming
            • Remove 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 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

            Step 2 (2nd dilution)

            • Withdraw recommended dose from reconstituted vial containing 10 mg/mL (1st dilution)
            • Further dilute into sterile 250 mL PVC-free container (glass, polyolefin) of either 0.9% NaCl or dextrose 5% solution for infusion
            • Final concentration should range between 0.1-0.26 mg/mL
            • Thoroughly mix final infusion solution by gently inverting the bag/bottle

            IV Administration

            Administer IV infusion via volumetric infusion pump

            Administer over 1 hr

            Use an in-line filter (0.22 micron pore size) during administration

            Storage

            Appearance is clear, yellow to brownish-yellow, viscous solution under proper storage conditions

            Store drug and diluent at room temp 25 degrees C (77 degrees F); brief exposure permitted between 15-30 degrees C (59-86 degrees F)

            Do not refrigerate undiluted vial or diluent

            Stability

            • Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration
            • 1st diluted solution in vial: Use immediately (within 30 min) and discard unused portion
            • 2nd (final) dilution in infusion bag: Use within 8 hr (ambient temperature, including infusion time), or for a total of 24 hr refrigerated
            • Both 1st diluted solution and 2nd (final) infusion solution are supersaturated and may crystallize over time; if crystals and/or particulates appear, solutions must not be used and should be discarded
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.