cabazitaxel

Absorption: IV administration results in complete bioavailability.

Distribution: Equally distributed between blood and plasma.

Metabolism/Excretion: Extensively (>95%) metabolized by the liver, 80–90% by the CYP3A4/5 isoenzymes. Metabolites are excreted in urine and feces. Minimal renal excretion.

Half-Life: 95 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hypersensitivity to cabazitaxel or polysorbate 80;
Neutrophil count ≤1,500/mm³;
Hepatic impairment (total bilirubin ≥3× upper limit of normal [ULN]);
Concurrent use of strong CYP3A4 inhibitors or inducers.

Use Cautiously in:

Patients with neutropenia or a history of pelvic radiation, adhesions, ulceration, or GI bleeding (↑ risk of GI and urinary adverse reactions);
Concomitant use of steroids, NSAIDs, or antithrombotics (↑ risk of GI adverse reactions);
Severe renal impairment (CCr <30 mL/min) or end-stage renal disease;
Hemoglobin <10 g/dL;
Lung disease (↑ risk of pulmonary toxicity);
Mild or moderate hepatic impairment (dose ↓ required);
Poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, or poor nutritional status (↑ risk of complications from prolonged neutropenia);
Rep: Men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: risk of adverse reactions in older adults (especially prolonged neutropenia and febrile neutropenia).

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, hypotension

Derm: alopecia

F and E: electrolyte imbalance

GI: abdominal pain, abnormal taste, anorexia, constipation, diarrhea, gi bleed, gi perforation, nausea, vomiting, dyspepsia, ENTEROCOLITIS, ILEUS

GU: hematuria, cystitis, RENAL FAILURE

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia

MS: arthralgia, back pain, muscle spasms

Neuro: peripheral neuropathy, weakness, fatigue

Resp: dyspnea, ACUTE RESPIRATORY DISTRESS SYNDROME, INTERSTITIAL LUNG DISEASE

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors including ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, and voriconazole↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A inducers including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, and phenobarbital may ↓ levels and effectiveness; concurrent use contraindicated.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; concomitant use contraindicated.

Route/Dosage ⬆ ⬇

IV (Adults ): 20 mg/m² every 3 wk (with prednisone 10 mg PO daily). A dose of 25 mg/m² may be considered in select patients.

Hepatic Impairment

IV (Adults ): Mild hepatic impairment (total bilirubin >1× to ≤1.5× ULN or AST >1.5× ULN): 20 mg/m² every 3 wk (with prednisone 10 mg PO daily); Moderate hepatic impairment (total bilirubin >1.5× to ≤3× ULN): 15 mg/m² every 3 wk (with prednisone 10 mg PO daily); Severe hepatic impairment (total bilirubin >3× ULN): Contraindicated.

Availability ⬆ ⬇

(Generic available)

Viscous solution for injection: 40 mg/mL (contains polysorbate 80); comes with diluent (5.7 mL of 13% [w/w] ethanol in water for injection)
Solution for injection: 10 mg/mL

Assessment ⬆ ⬇

Assess for hypersensitivity reactions (generalized rash/erythema, hypotension, bronchospasm, swelling of face). May occur within min following initiation of infusion. If severe reactions occur, discontinue infusion immediately and provide supportive therapy.
Assess for signs and symptoms of GI toxicity (abdominal pain and tenderness, fever, persistent constipation, nausea, vomiting, severe diarrhea); may result in death due to electrolyte imbalance. Premedication is recommended. Treat with rehydration, antidiarrheal, or antiemetic therapy as needed. If Grade ≥3 diarrhea or persisting diarrhea occurs despite appropriate medication, fluid and electrolyte replacement, delay treatment until improvement or resolution, then reduce dose to 20 mg/mL.
Assess for signs and symptoms of peripheral neuropathy (pain, burning, numbness in hands, feet, or legs) during therapy. If Grade 2 occurs, withhold until improvement or resolution, then reduce dose to 20 mg/mL. If ≥Grade 3 occurs, discontinue therapy.
Monitor for signs and symptoms of respiratory compromise (trouble breathing, dyspnea, chest pain, cough, fever) during therapy. Interrupt therapy if new or worsening symptoms occur. Consider discontinuation.

Lab Test Considerations:

Monitor CBC weekly during cycle 1 and before each treatment cycle thereafter. Do not administer if neutrophils ≤1500/mm³. If prolonged grade 3 neutropenia (>1 wk) despite appropriate medication including filgrastim, delay treatment until neutrophil count is >1500 mm³, then reduce dose to 20 mg/m². Use filgrastim for secondary prophylaxis. Risk is ↑ in elderly patients.
- If febrile neutropenia occurs, delay therapy until improvement or resolution and neutrophil count is >1500/mm³, then reduce dose to 20 mg/m². Use filgrastim for primary or secondary prophylaxis.
- Discontinue cabazitaxel if prolonged Grade 3 neutropenia, febrile neutropenia, or Grade 3 diarrhea occur at the 20 mg/m² dose.
- May cause hematuria.
- May cause Grade 3–4 ↑ AST, ↑ ALT, and ↑ bilirubin.

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order and dose calculations.
Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers. If solution comes in contact with skin or mucosa, wash with soap and water immediately.
Premedicate at least 30 min before each dose with antihistamine (diphenhydramine 25 mg or equivalent), corticosteroid (dexamethasone 8 mg or equivalent), and H₂ antagonist (famotidine 20 mg or equivalent). Antiemetic prophylaxis, PO or IV, is recommended.
Begin prophylaxis with G-CSF (filgrastim) in all patients receiving a dose of 25 mg/m² to minimize complications due to prolonged neutropenia.

IV Administration:

Two dilutions are required. Do not use PVC infusion containers or polyurethane infusion sets for preparation or infusion.
- First Dilution:Reconstitution: Mix vial with entire contents of supplied diluent. Direct needle to inside wall of vial and inject slowly to avoid foaming. Mix gently by repeated inversions for at least 45 sec; do not shake. Let stand for a few min to allow foam to dissipate.Concentration: 10 mg/mL.
- Second Dilution:Diluent: Withdraw recommended dose from cabazitaxel solution and dilute further into a sterile 250 mL PVC-free container of 0.9% NaCl or D5W. If dose >65 mg is required, use a larger volume of infusion vehicle so concentration does not exceed 0.26 mg/mL. Gently invert container to mix.Concentration: 0.10–0.26 mg/mL. Stable for 8 hr (including 1 hr infusion) at room temperature or 24 hr if refrigerated. May crystallize over time. Do not use if crystallized, discolored, or contains particulate matter; discard.
Rate: Infuse over 1 hr at room temperature through a 0.22 micrometer nominal pore size filter.
Y-Site Incompatibility: Do not mix with other medication.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take oral prednisone as prescribed and to notify health care professional if a dose is missed or not taken in time.
Advise patient to notify health care professional immediately if signs or symptoms of hypersensitivity reactions; fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores on the mouth or on the lips; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; unusual swelling, shortness of breath, trouble breathing, chest pain, cough, or fever occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs; may precipitate GI hemorrhage.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: Advise male patients with female partners of reproductive potential to use effective contraception during and for at least 4 mo after last dose of cabazitaxel. May impair fertility in males.
Emphasize need for periodic lab tests to monitor for side effects. Advise patient to monitor temperature frequently.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇