Keptrix IV Injection

In combination with prednisone or prednisolone, for patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. Due to high incidence of neutropenia, granulocyte-colony stimulating factor (G-CSF) should be administered within 24-72 hr since 1st cycle of Cabazitaxel administration.

Cabazitaxel is a microtubule inhibitor. Cabazitaxel 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.

25 mg/m2 administered as a 1 hr IV infusion every 3 wk in combination with oral prednisone or prednisolone 10 mg administered daily throughout treatment.

May increase plasma conc with strong CYP3A4 inhibitors. May lead to decreased plasma conc with strong CYP3A4 inducers. Vaccination with a live attenuated vaccine should be avoided.

Neutrophil counts <1,500/mm3; platelets >100,000/mm3, haemoglobin >10 g/dL, creatinine <1.5 x ULN, hepatic impairment (bilirubin ≥1 x ULN, or AST &/or ALT ≥1.5 × ULN); concomitant vaccination with yellow fever vaccine.

Most commonly in all grades, anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea. Most commonly in ≥3 grade, neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea.

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Hypersensitivity reaction; risk of neutropenia; risk of nausea, vomiting, diarrhea, dehydration, peripheral neuropathy; renal failure, cardiac arrhythmias; liver impairment; anemia. Pregnancy & lactation. Elderly.

Cytotoxic Chemotherapy

Children: The safety and the efficacy of Cabazitaxel in children have not been established.

Elderly: No specific dose adjustment for the use of Cabazitaxel in elderly patients is recommended (see Pharmacology: Pharmacokinetics under Actions, Precautions and Adverse Reactions).

Hepatic Impairment: Cabazitaxel is extensively metabolized by the liver. Patients with mild hepatic impairment [total bilirubin >1 to ≤1.5 x Upper Limit of Normal (ULN) or AST >1.5 x ULN], should have cabazitaxel dose reduced to 20 mg/m2. Administration of cabazitaxel to patients with mild hepatic impairment should be undertaken with caution and close monitoring of safety. Limited efficacy data for cabazitaxel at 15 mg/m2, the maximum tolerated dose in patients with moderate hepatic impairment (total bilirubin >1.5 to ≤3.0 x ULN), are available to recommend this dose in this population. Cabazitaxel should not be given to patients with severe hepatic impairment (total bilirubin >3 x ULN).

Renal Impairment: Cabazitaxel is minimally excreted through the kidney. No dose adjustment is necessary in patients with renal impairment not requiring hemodialysis. Patients presenting end-stage renal disease (CLCR <15 mL/min/1.73 m2), by their condition and the limited amount of available data, therefore these patients should be treated with caution and monitored carefully during treatment.

Concomitant Drug Use: Concomitant drugs that are strong CYP3A inducers or strong CYP3A inhibitors should be avoided (see Pharmacology: Pharmacokinetics under Actions and Interactions). However, if patients require co-administration of a strong CYP3A inhibitor, a 25% cabazitaxel dose reduction should be considered (see Pharmacology: Pharmacokinetics under Actions and Interactions).

Store between 15-30° C. Do not refrigerate.