cabazitaxel (Rx)

>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

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

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.

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)

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