Usage
Cabazitaxel is prescribed in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen.
Pharmacological Classification: Antineoplastic agent, taxane, antimicrotubule agent.
Mechanism of Action: Cabazitaxel inhibits cell division by binding to tubulin and promoting the assembly of microtubules while simultaneously inhibiting their disassembly. This disruption of the microtubule dynamics interferes with the cell cycle, ultimately leading to cell death.
Alternate Names
INN: cabazitaxel. Brand Name: Jevtana.
How It Works
Pharmacodynamics: Cabazitaxel exerts its cytotoxic effect by disrupting the normal dynamic reorganization of the microtubule network essential for vital cellular functions, including mitosis. Its binding to tubulin leads to an imbalance in microtubule polymerization and depolymerization, causing cell cycle arrest and subsequent apoptosis.
Pharmacokinetics:
- Absorption: Administered intravenously.
- Distribution: Widely distributed in the body.
- Metabolism: Primarily hepatic, extensively metabolized by CYP3A4 enzymes.
- Elimination: Primarily through feces, with minimal renal excretion.
Mode of Action: Binds to tubulin, promoting microtubule assembly and inhibiting disassembly.
Receptor Binding/Enzyme Inhibition: Binds to tubulin in microtubules. Metabolized by CYP3A4.
Elimination Pathways: Primarily fecal (70-80%), with a small fraction through urine.
Dosage
Standard Dosage
Adults:
The recommended dose of Cabazitaxel is 20 mg/m² administered as a one-hour intravenous infusion every three weeks, in combination with oral prednisone 10 mg daily. In select patients, 25 mg/m² can be considered at the prescriber’s discretion.
Children:
The safety and efficacy of Cabazitaxel in children have not been established.
Special Cases:
- Elderly Patients: No specific dose adjustment is recommended, but closer monitoring is advised due to increased risk of certain adverse reactions.
- Patients with Renal Impairment: No dose adjustment is necessary in patients with renal impairment not requiring hemodialysis.
- Patients with Hepatic Dysfunction:
- Mild impairment: 20 mg/m².
- Moderate impairment: 15 mg/m².
- Severe impairment: Contraindicated.
- Patients with Comorbid Conditions: Dose adjustments may be required depending on the specific comorbidity and its impact on drug metabolism or clearance.
Clinical Use Cases
Cabazitaxel is specifically indicated for metastatic castration-resistant prostate cancer that has progressed following docetaxel treatment. It is not indicated for use in the contexts of intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations.
Dosage Adjustments
Dose reductions are based on the severity and persistence of adverse reactions, particularly hematological toxicity and gastrointestinal issues. See source material for dosage adjustments for neutropenia, febrile neutropenia, diarrhea, and peripheral neuropathy. For patients receiving strong CYP3A4 inhibitors concomitantly, a 25% dose reduction of cabazitaxel should be considered.
Side Effects
Common Side Effects:
Neutropenia, anemia, thrombocytopenia, leukopenia, diarrhea, nausea, vomiting, fatigue, asthenia, constipation, anorexia, abdominal pain, dysgeusia, alopecia, neuropathy, musculoskeletal pain.
Rare but Serious Side Effects:
Febrile neutropenia, severe hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, acute renal failure, intestinal perforation.
Long-Term Effects:
Peripheral neuropathy, secondary malignancies.
Adverse Drug Reactions (ADR):
Severe neutropenia, febrile neutropenia, severe hypersensitivity, severe diarrhea.
Contraindications
- Neutrophil count ≤1,500/mm³.
- History of severe hypersensitivity reactions to cabazitaxel or polysorbate 80.
- Severe hepatic impairment (total bilirubin >3 x ULN).
Drug Interactions
- CYP3A4 inducers and inhibitors: Strong inhibitors should be avoided if possible, or a dose reduction of cabazitaxel should be considered. Strong inducers should be avoided.
- Other drugs that may increase bleeding risk: Concomitant use with anticoagulants and antiplatelet agents may increase the risk of bleeding.
- Live attenuated vaccines: Contraindicated during treatment with cabazitaxel.
Pregnancy and Breastfeeding
Pregnancy Category D. Cabazitaxel can cause fetal harm and is contraindicated during pregnancy. It is excreted in breast milk and should not be used during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits microtubule depolymerization, disrupting cell division.
- Side Effects: Neutropenia, anemia, diarrhea, nausea, vomiting, fatigue.
- Contraindications: Neutropenia, hypersensitivity, severe hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors and inducers.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 20 mg/m² IV every three weeks, with prednisone.
- Monitoring Parameters: Complete blood counts (CBCs) including neutrophil count, liver function tests, and renal function tests.
Popular Combinations
Cabazitaxel is typically administered in combination with prednisone (or prednisolone).
Precautions
Premedication with an antihistamine, corticosteroid, and H2 antagonist is recommended before each cabazitaxel infusion to reduce the risk of hypersensitivity reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cabazitaxel?
A: The recommended dose is 20 mg/m² IV every 3 weeks in combination with 10mg daily oral prednisone. 25 mg/m² can be considered for select patients.
Q2: What are the most common side effects?
A: Neutropenia, anemia, diarrhea, fatigue, nausea, and vomiting.
Q3: What are the contraindications for Cabazitaxel?
A: Severe neutropenia, hypersensitivity to cabazitaxel or polysorbate 80, and severe hepatic impairment.
Q4: What are the key drug interactions?
A: Strong CYP3A4 inhibitors and inducers. Concomitant use with drugs that may increase bleeding risk.
Q5: Can Cabazitaxel be given to pregnant or breastfeeding women?
A: No, it’s contraindicated.
Q6: How should hepatic impairment be managed when prescribing Cabazitaxel?
A: For mild impairment, the dose is 20 mg/m². For moderate, it’s 15 mg/m². It’s contraindicated in severe hepatic impairment.
Q7: What premedication is recommended before Cabazitaxel administration?
A: An antihistamine, a corticosteroid, and an H2 antagonist.
Q8: What is the primary mechanism of action of Cabazitaxel?
A: It inhibits microtubule depolymerization, leading to cell cycle arrest and apoptosis.
Q9: What monitoring is required during Cabazitaxel treatment?
A: Frequent monitoring of complete blood counts (CBCs) including neutrophil count, liver function tests (LFTs), and renal function tests should be conducted.
