Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentration and pharmacologic effects of cabazitaxel, which is primarily metabolized via the isoenzyme. A drug interaction study in patients with advanced cancers (n=21), revealed that repeated administration of rifampin (600 mg once daily), a potent CYP450 3A4 inducer, increased the clearance and decreased the systemic exposure (AUC) of cabazitaxel (15 mg/m2 intravenous) by 21% and 17%, respectively. In another study, adult patients with metastatic castration-resistant prostate cancer (n=14), received cabazitaxel (25 mg/m2 intravenous) at baseline (day 0) and then every 3 weeks for 3 doses. The potent CYP450 3A4 inducer enzalutamide (160 mg oral daily) was started at day 8 (+/- 1) and continued until 1 week after the 3rd dose of cabazitaxel (6 weeks of concurrent treatment). A 22% reduction in the AUC of cabazitaxel was observed when compared to baseline, which investigators noted was potentially clinically relevant, and could result in subtherapeutic concentrations when lower doses of cabazitaxel (e.g., 20 mg/m2) are utilized. Clinical data with less potent CYP450 3A4 inducers are not available.

MANAGEMENT: Concomitant use of cabazitaxel, a narrow therapeutic index drug, with CYP450 3A4 inducers should be done with caution. The possibility of diminished therapeutic effects should be considered, particularly when lower dosing of cabazitaxel is utilized. Alternative agents that do not induce CYP450 3A4 may be required if an interaction is suspected.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.