Dosing & Uses
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
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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
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
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.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)
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
Images
Patient Handout
Formulary
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