se. Approximately 1.5% of the dose delivered to the mother was calculated to be delivered in the maternal milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from JEVTANA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and effectiveness of JEVTANA in pediatric patients have not been established.
8.5 Geriatric Use
Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of cabazitaxel between patients < 65 years (n=100) and older (n=70).
Of the 371 patients with prostate cancer treated with JEVTANA every three weeks plus prednisone, 240 patients (64.7%) were 65 years of age and over, while 70 patients (18.9%) were 75 years of age and over. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. Elderly patients (≥ 65 years of age) may be more likely to experience certain adverse reactions. The incidence of neutropenia, fatigue, asthenia, pyrexia, dizziness, urinary tract infection and dehydration occurred at rates ≥ 5% higher in patients who were 65 years of age or greater compared to younger patients [see Adverse Reactions (6.1)].
8.6 Renal Impairment
No dedicated renal impairment trial for JEVTANA has been conducted. Based on the population pharmacokinetic analysis, no significant difference in clearance was observed in patients with mild (50 mL/min ≤ creatinine clearance (CLcr) < 80 mL/min) and moderate renal impairment (30 mL/min ≤ CLcr < 50 mL/min). No data are available for patients with severe renal impairment or end-stage renal disease [see Clinical Pharmacology (12.3)]. Caution should be used in patients with severe renal impairment (CLcr < 30 mL/min) and patients with end-stage renal diseases.
8.7 Hepatic Impairment
No dedicated hepatic impairment trial for JEVTANA has been conducted. The safety of JEVTANA has not been eva luated in patients with hepatic impairment [see Warnings and Precautions (5.6)].
As cabazitaxel is extensively metabolized in the liver, hepatic impairment is likely to increase the cabazitaxel concentrations. Patients with impaired hepatic function (total bilirubin ≥ ULN, or AST and/or ALT ≥ 1.5 × ULN) were excluded from the randomized clinical trial.
10 OVERDOSAGE
There is no known antidote for JEVTANA overdose. Anticipated complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders.
In case of overdose, the patient should be kept in a specialized unit where vital signs, chemistry and particular functions can be closely monitored. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.
11 DESCRIPTION
JEVTANA (cabazitaxel) is an antineoplastic agent belonging to the taxane class. It is prepared by semi-synthesis with a precursor extracted from yew needles.
The chemical name of cabazitaxel is (2α,5β,7β,10β,13α)-4-acetoxy-13-({(2R,3S)-3-[(tertbutoxycarbonyl) amino]-2-hydroxy-3-phenylpropanoyl}oxy)-1-hydroxy-7,10-dimethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate – propan-2-one(1:
