Drug Interaction Report

MONITOR: Coadministration with cinacalcet may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by cinacalcet, which is expected to occur in patients who are CYP450 2D6 extensive metabolizers (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). Concurrent administration of cinacalcet (25 or 100 mg) increased the systemic exposure of amitriptyline (50 mg) and its active metabolite, nortriptyline, by approximately 20% in CYP450 2D6 extensive metabolizers. However, because amitriptyline is metabolized by multiple CYP450 isoenzymes in addition to 2D6, the degree of interaction with cinacalcet may be less than that expected for other drugs that are primarily metabolized by 2D6.

MANAGEMENT: Caution is advised if cinacalcet must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range (e.g., class IC antiarrhythmic agents, phenothiazines, certain beta blockers, and most tricyclic antidepressants). Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cinacalcet is added to or withdrawn from therapy.

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.