Drug Interaction Report

MONITOR: Coadministration with ketoconazole or other potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cinacalcet, which is partially metabolized by the isoenzyme. According to the product labeling, ketoconazole (200 mg twice a day for 7 days) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cinacalcet (90 mg single dose on day 5) by over 2-fold compared to administration of cinacalcet alone.

MANAGEMENT: Pharmacologic response to cinacalcet (i.e., parathyroid hormone and serum calcium levels) should be monitored more closely whenever potent inhibitors of CYP450 3A4 are added to or withdrawn from therapy, and the cinacalcet dosage adjusted accordingly.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of cinacalcet. According to the product labeling for cinacalcet, administration with a high-fat meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cinacalcet by 82% and 68%, respectively, compared to administration in the fasting state. The Cmax and AUC were increased 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal compared to fasting.

MANAGEMENT: To ensure maximal oral absorption, cinacalcet should be administered with or immediately after a meal. The tablets should be taken whole and not divided or crushed.