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.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.