cabazitaxel

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
ka-ba-zi-TAX-el

Trade Name(s)

• Jevtana

Pregnancy Category
Category D

Ther. class.
antineoplastics

Pharm. class.
taxoids

Indications

Hormone-refractory metastatic prostate cancer previously treated with a regimen including docetaxel (used in combination with prednisone).

Action

Binds to intracellular tubulin and promotes its assembly into microtubules while inhibiting disassembly. Result is inhibition of mitotis and interphase.

Therapeutic Effect(s):
Death of rapidly replicating cells, particularly malignant ones, with ↓ spread of metastatic prostate cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Equally distributed between blood and plasma.

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

Half-life: Terminal elimination—95 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraindication/Precautions

Contraindicated in:

• Severe hypersensitivity to cabazitaxel or polysorbate 80;

• Neutrophils ≤1,500/mm³;

• Hepatic impairment (total bilirubin ≥upper limits of normal, or AST and/or ALT ≥1.5 × upper limits of normal);

• Concurrent use of strong CYP3A4 inhibitors, inducers and St. John's wort;

• OB: Avoid use during pregnancy (may cause fetal harm);

• Lactation: Breastfeeding should be avoided.

Use Cautiously in:

• Concurrent use of moderate CYP3A4 inhibitors;

• OB: Patients with child-bearing potential (pregnancy should be avoided);

• Patients with severe renal impairment (CCr <30 mL/min) or end-stage renal disease;

• Geri: Patients >65 yr ↑ risk of adverse reactions;

• Pedi: Safe and effective use in children has not been established..

Adverse Reactions/Side Effects

CNS: weakness, fatigue.

Resp: dyspnea.

CV: arrhythmias, hypotension.

GI: DIARRHEA, abdominal pain, abnormal taste, anorexia, constipation, nausea, vomiting, dyspepsia.

GU: RENAL FAILURE, hematuria.

Derm: alopecia.

F and E: electrolyte imbalance.

Hemat: NEUTROPENIA, THROMBOCYTOPENIA, anemia, leukopenia.

MS: arthralgia, back pain, muscle spasms.

Neuro: peripheral neuropathy.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS , fever.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.
*CAPITALS/italic indicates life-threatening and most frequent.

Interactions

Drug-Drug

• Concomitant administration of strong CYP3A inhibitors including ketoconazole , itraconazole , clarithromycin , atazanavir , indinavir , nefazodone , nelfinavir , ritonavir , saquinavir , telithromycin and voriconazole ↑ levels and risk of toxicity and should be avoided.

• Concomitant administration of strong CYP3A inducers including phenytoin , carbamazepine , rifampin , rifabutin , rifapentin , and phenobarbital may ↓ levels and effectiveness and should be avoided.

Drug-Natural Products
St. John's wort may ↓ levels and effectiveness and should be avoided.

Route/Dosage

• PO (Adults): 25 mg/m² every three wks as a one-hour infusion (with prednisone 10 mg PO daily)..

Availability

• Viscous solution for injection (requires two dilutions prior to IV administration): 60 mg/1.5 mL (contains polysorbate 80) comes with diluent (5.7 mL of 13% [w/w] ethanol in water for injection).

Assessment

• Assess for hypersensitivity reactions (generalized rash/erythema, hypotension, bronchospasm, swelling of face). May occur within minutes following initiation of infusion. If severe reactions occur, discontinue infusion immediately and provide supportive therapy.

• Assess for nausea, vomiting, and severe diarrhea; may result in death due to electrolyte imbalance. Premedication is recommended. Treat with rehydration, anti-diarrheal, 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.

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.

» 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 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.

Potential Nursing Diagnoses

• Risk for infection (Adverse Reaction)

Implementation

• High Alert: 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 (ranitidine 50 mg or equivalent). Antiemetic prophylaxis, PO or IV, is recommended.

IV Adminstration:

• pH:
No Data.

• Two dilutions are required. Do not use PVC infusion containers or polyurethane infusion sets for preparation or infusion.
First Dilution:Diluent: Mix vial with entire contents of supplied diluent
Direct needle to inside wall id vial and inject slowly to avoid foaming. Mix gently by repeated inversions for at least 45 seconds; do not shake. Let stand for a few minutes to allow foam to dissipate. Concentration: 10 mg/mL.
Second Dilution:Diluent: Withdraw recommended dose from cabazitaxel solution and dilute further into a setrile 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 hrs (including 1 hr infusion) at room temperature or 24 hrs if refrigerated. May crystalize over time. Do not use if crystalized, 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 occurs. 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.

• 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.

• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.

• Advise female patients of the need for contraception and to avoid breastfeeding during therapy.

• Instruct patient not to receive any vaccinations without advice of health care professional.

• Emphasize need for periodic lab tests to monitor for side effects. Advise patient to monitor temperature frequently.

Evaluation/Desired Outcomes

↓ in size and spread of metastatic prostate cancer.