cabazitaxel (Rx)

Brand and Other Names:Jevtana
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

kit

  • Each kit contains
    • 60mg/1.5mL cabazitaxel injection
    • 5.7mL diluent

Prostate Cancer

Indicated in combination with prednisone for metastatic castration-resistant prostate cancer in patients previously treated with a docetaxel-containing treatment regimen

20 mg/m2 IV q3Weeks, PLUS  

Prednisone 10 mg PO qDay throughout cabazitaxel treatment

Select patients may use 25 mg/m2 IV at prescriber’s discretion

Dosage Modifications

Dosage reductions

  • If at 20 mg/m2: Reduce to 15 mg/m2
  • If at 25 mg/m2: Reduce to 20 mg/m2; once additional dose reduction to 15 mg/m2 may be considered

Neutropenia

  • Prolonged grade ≥3 neutropenia (>1 week) despite appropriate medication including G-CSF: Delay treatment until neutrophil count >1,500 cells/mm3, then reduce dose by 1 level; use G-CSF for secondary prophylaxis
  • Febrile neutropenia or neutropenic infection: Delay treatment until improvement or resolution, and until neutrophil count >1,500 cells/mm3, then reduce dose by 1 level; use G-CSF for secondary prophylaxis

Diarrhea

  • Grade ≥3 or persisting despite appropriate medication, fluid, and electrolyte replacement: Delay treatment until improvement or resolution, then reduce dose by 1 level

Peripheral neuropathy

  • Grade 2: Delay treatment until improvement or resolution, then reduce dose by 1 level
  • Grade >3: Discontinue

Strong CYP3A4 inhibitors

  • Avoid coadministration
  • If unavoidable, consider reducing dose by 25%

Renal impairment

  • All severities (not requiring hemodialysis): No dosage adjustment necessary
  • End-stage renal disease (CrCl <15 mL/min): Carefully monitor

Hepatic impairment

  • Mild (total bilirubin [TB] >1 to <1.5x ULN or AST >1.5x ULN): Administer at a dose of 20 mg/m2
  • Moderate (TB >1.5 to ≤3x ULN and any AST): Reduce dose to 15 mg/m2; based on tolerability; efficacy of this dose is unknown
  • Severe (TB >3x ULN): Contraindicated

Safety and efficacy not established

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Interactions

Interaction Checker

and cabazitaxel

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    No Interactions Found
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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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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

            Neutropenia

            • Neutropenic deaths reported
            • Monitor for neutropenia with frequent blood cell counts
            • Contraindicated with neutrophil counts ≤1,500 cell/mm3
            • Primary prophylaxis with G-CSF recommended in high- risk patients
            • Consider G-CSF prophylaxis with dose of 25 mg/m2

            Severe hypersensitivity

            • Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension, and bronchospasm
            • Premedicate with IV antihistamine, corticosteroid, and H2 antagonist
            • Contraindicated with history of severe hypersensitivity reactions to cabazitaxel or other drugs formulated with polysorbate 80
            • Immediately discontinue therapy if hypersensitivity occurs and initiate supportive treatment as indicated

            Contraindications

            Neutrophil count ≤1,500/mm3

            Hypersensitivity to cabazitaxel or to other drugs formulated with polysorbate 80

            Severe hepatic impairment (total bilirubin >3x ULN)

            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; neutropenic deaths reported

            Patients ≥65 years were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia

            Severe hypersensitivity reactions can occur; premedicate with IV antihistamine, corticosteroid, and H2 antagonist; discontinue infusion immediately if hypersensitivity observed and treat as indicated

            Gastrointestinal symptoms (nausea, vomiting, diarrhea), including mortality related to diarrhea, has been reported; rehydrate and treat with antiemetics and antidiarrheals as needed; incidence of gastrointestinal adverse reactions is greater in patients who have received prior radiation

            Renal failure, including cases with fatal outcomes, reported

            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

            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

            Extensively metabolized in liver; contraindicated in patients with severe hepatic impairment and reduce dose in patients with mild and moderate hepatic impairment

            May cause fetal harm when administered to pregnant females

            Respiratory disorders

            • 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, carefully evaluate the risks versus benefits before resumption

            Drug interaction overview

            • CYP3A substrate
            • Strong CYP3A4 inhibitors

              • Avoid coadministration
              • Strong CYP3A4 inhibitors that may alter drug serum levels
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            Pregnancy & Lactation

            Pregnancy

            Safety and efficacy not established in females

            No human data available on use in pregnant females

            Contraception

            • Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months after final dose

            Infertility

            • Fertility in males of reproductive potential may be impaired

            Animal data

            • IV administration in pregnant rats during organogenesis cause embryonic and fetal death at doses lower than maximum recommended human dose

            Lactation

            Not indicated for use in females

            No data available on presence in human milk, effects on breastfed infants, 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 Incompatibilities

            Do not mix with any other drugs

            IV Compatibilities

            D5W

            0.9% NaCl

            IV Preparation

            Cytotoxic anticancer drug; follow applicable special handling and disposal procedure

            If diluted solutions come into contact with skin or mucous, immediately and thorough wash with soap and water

            Drug requires TWO dilutions before administration

            Visually inspect injection and supplied diluent vials; injection is a clear yellow to brownish-yellow viscous solution

            First dilution

            • Mix each vial with entire contents of supplied diluent
            • Slowly inject diluent by directing needle onto inside wall of vial to limit foaming
            • Gently mix first dilution by repeated inversion for at least 45 seconds to ensure complete mixing of drug and diluent; do not shake
            • Allow solution to stand for a few minutes to allow any foam to dissipate; not all foam needs to dissipate before continuing to second dilution
            • Check solution is not homogeneous and contains no visible particle matter; resulting concentration of first dilution is 10 mg/mL
            • Prepare second dilution immediately (within 30 min) to obtain final infusion

            Second dilution

            • Withdraw dose from first dilution and further dilute into a sterile 250 mL PVC-free container of either 0.9% NaCl or D5W for infusion; concentration of final infusion solution should be 0.1-0.26 mg/mL
            • For doses >65 mg, use a larger infusion bag (>250 mL PVC-free container) to assure 0.26 mg/mL concentration not exceeded
            • Gently invert bag to thoroughly mix final infusion
            • Final infusion solution is supersaturated and may crystallize over time; do not use if this occurs and discard

            IV Administration

            Visually inspect for particulate matter, any crystals, and discoloration before administering; discard second (final) dilution if not clear or appears to have precipitated

            Use a 0.22- or 0.2-micron inline filter during infusion

            Administer premedication regimen of IV antihistamine, corticosteroid, and H2-antagonist 30 minute before each cabazitaxel dose

            Infuse over 1 hr at room temperature

            Premedication IV regimen

            • Antihistamine (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent antihistamine)
            • Corticosteroid (dexamethasone 8 mg or equivalent steroid)
            • H2-antagonist (ranitidine 50-mg or equivalent H2-antagonist)

            Primary prophylaxis with G-CSF

            • Recommended in patients with high-risk clinical features
            • Consider in all patients receiving 25 mg/m2

            Storage

            Unopened injection and diluent

            • Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
            • Do not refrigerate

            Diluted infusion bags (second dilution)

            • Ambient room temperature: Use within 8 hr (including 1-hour infusion)
            • Refrigerated: Up to 24 hr (including 1-hour infusion)
            • Discard any unused portion
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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.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
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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.