Drug Interactions between cabazitaxel and rifabutin

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inducers may significantly 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). When compared to baseline, a 22% reduction in the AUC of cabazitaxel was observed, which investigators noted as potentially clinically relevant. They cautioned that subtherapeutic concentrations may occur when lower doses of cabazitaxel (e.g., 20 mg/m2) are utilized.

MANAGEMENT: Some authorities recommend avoiding concomitant use of cabazitaxel, a narrow therapeutic index drug, with potent CYP450 3A4 inducers. This may be particularly important in situations where reduced cabazitaxel dosing is utilized. If concomitant use is necessary, increased monitoring of cabazitaxel's efficacy may be advisable.