cabazitaxel

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to tissues.

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 ≤1500/mm³
;
Hepatic impairment (total bilirubin ≥3 times upper limit of normal [ULN]).

Use Cautiously in:

Neutropenia or a history of pelvic radiation, adhesions, ulceration, or GI bleeding (↑ risk of GI and urinary adverse reactions);
Concurrent use of steroids, NSAIDs, or antithrombotics (↑ risk of GI adverse reactions);
Severe renal impairment or end-stage renal disease;
Hemoglobin <10 g/dL;
Lung disease (↑ risk of pulmonary toxicity);
Mild or moderate hepatic impairment (↓ dose);
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, may ↑ 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; concurrent 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–≤1.5 times ULN or AST >1.5 times ULN): 20 mg/m² every 3 wk (with prednisone 10 mg PO daily); Moderate hepatic impairment (total bilirubin >1.5–≤3 times ULN): 15 mg/m² every 3 wk (with prednisone 10 mg PO daily); Severe hepatic impairment (total bilirubin >3 times 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 minutes following initiation of infusion. If severe reaction occurs, 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); resulting electrolyte imbalances may result in death. Premedication is recommended. Treat with rehydration, antidiarrheal, or antiemetic therapy as needed. If Grade ≥3 or persisting diarrhea occurs despite appropriate medication and fluid and electrolyte replacement, hold cabazitaxel until improvement or resolution; then ↓ by one dose level.
Assess for signs and symptoms of peripheral neuropathy (pain, burning, or numbness in hands, feet, or legs) during therapy. If Grade 2 peripheral neuropathy occurs, withhold until improvement or resolution; then ↓ by one dose level. If Grade ≥3 peripheral neuropathy occurs, permanently discontinue cabazitaxel.
Monitor for signs and symptoms of respiratory compromise (trouble breathing, dyspnea, chest pain, cough, fever) during therapy; hold for new or worsening symptoms and consider discontinuation.

Lab Test Considerations:

Monitor CBC with differential weekly during Cycle 1 and before each cycle thereafter. If prolonged grade 3 neutropenia (>1 wk) despite appropriate treatment, including filgrastim, occurs, hold cabazitaxel until neutrophils >1500/mm³; then ↓ by one dose level. If febrile neutropenia occurs, hold cabazitaxel until improvement or resolution and neutrophils >1500/mm³; then ↓ by one dose level. Use filgrastim for secondary prophylaxis.
- May cause hematuria.
- May ↑ AST, ALT, and bilirubin.

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 ≥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.
Primary prophylaxis with G-CSF (filgrastim) recommended in older adults, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, and 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 minutes 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 particulates.
Rate: Infuse over 1 hr at room temperature through a 0.22 micrometer nominal pore size filter.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

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.
Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
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 mouth or lips; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; unusual swelling; shortness of breath; trouble breathing; chest pain; or cough 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 men with female partners of reproductive potential to use effective contraception during therapy and for ≥4 mo after last dose of cabazitaxel. May impair male fertility.
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.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0024- Sanofi-Aventis U.S. LLC
- 0024-5824- Jevtana
  - 0024-5824-11- 1 KIT in 1 CARTON (0024-5824-11) * 5.7 mL in 1 VIAL, GLASS (0024-5822-01) * 5.7 mL in 1 VIAL, GLASS (0024-5823-15)

17359- Indena SpA
- 17359-1700-
  - 17359-1700-1- 150 g in 1 BOTTLE (17359-1700-1)

47848- Teva Czech Industries s.r.o
- 47848-044-
  - 47848-044-00- 1 kg in 1 CARTON (47848-044-00)

54893- MSN Laboratories Private Limited
- 54893-0016-
  - 54893-0016-5- 15 kg in 1 DRUM (54893-0016-5)

55111- Dr.Reddy's Laboratories Limited
- 55111-962-
  55111-962-00- 1 kg in 1 DRUM (55111-962-00)

61200- Sichuan Xieli Pharmaceutical Co., Ltd.
- 61200-101-
  61200-101-15- 15 kg in 1 DRUM (61200-101-15)

63126- Yung Shin Pharm. Ind. Co., Ltd.
- 63126-909-
  63126-909-01- 50 g in 1 BOTTLE, GLASS (63126-909-01)

63126- Yung Shin Pharm. Ind. Co., Ltd.
- 63126-909-
  63126-909-03- 1 g in 1 BOTTLE, GLASS (63126-909-03)

68554- Hetero Labs Limited
- 68554-0080-
  68554-0080-1- .45 kg in 1 DRUM (68554-0080-1)

84644- TAPI Czech Industries s.r.o.
- 84644-044-
  84644-044-00- 1 kg in 1 CARTON (84644-044-00)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇