Introduction
Jevtana IV Infusion 60 mg/1.5 ml is an anti-neoplastic used with the steroid medicine prednisone. Jevtana IV Infusion 60 mg/1.5 ml is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. Jevtana IV Infusion 60 mg/1.5 ml is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III).
Uses
Jevtana IV Infusion 60 mg/1.5 ml is an antineoplastic agent used for the treatment of hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.
For treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.
Associated Conditions
Pharmacodynamics
Cabaitaxel has anti-tumour properties and is effective against docetaxel-sensitive and -insensitive tumours.
Mechanism of Action
Jevtana IV Infusion 60 mg/1.5 ml is a microtubule inhibitor. Jevtana IV Infusion 60 mg/1.5 ml binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the interference of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.
Absorption
After an intravenous dose of cabazitaxel 25 mg/m2 every three weeks to a population of 170 patients with solid tumors, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng.h/mL (CV 34%). Administration with prednisone or prednisolone do not effect the pharmacokinetic profile of cabazitaxel.
Volume of Distribution
The volume of distribution (Vss) was 4,864 L (2,643 L/m2 for a patient with a median BSA of 1.84 m2) at steady state. Compared to other taxanes, penetrates the CNS to a greater extent.
Protein Binding
Jevtana IV Infusion 60 mg/1.5 ml is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL).
Route of Elimination
After a one-hour intravenous infusion [14C]-cabazitaxel 25 mg/m2, approximately 80% of the administered dose was eliminated within 2 weeks. Jevtana IV Infusion 60 mg/1.5 ml is mainly excreted in the feces as numerous metabolites (76% of the dose); while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine).
Half Life
Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of 4 minutes, 2 hours, and 95 hours, respectively.
Clearance
Jevtana IV Infusion 60 mg/1.5 ml has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m2 for a patient with a median BSA of 1.84 m2) in patients with metastatic prostate cancer.
Toxicity
Jevtana IV Infusion 60 mg/1.5 ml may cause serious side effects including neutropenia, hypersensitivity reactions, gastrointestinal symptoms, and renal failure. Anticipated complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders. Jevtana IV Infusion 60 mg/1.5 ml penetrates the blood-brain barrier. LD50, rat = 500 mg/kg
Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of cabazitaxel, which may increase its serum concentration.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of cabazitaxel and may reduce its serum concentration.
