Drug Interaction Report

MONITOR: Coadministration of denosumab with calcimimetic drugs such as cinacalcet and etelcalcetide, may increase the risk of hypocalcemia. This risk may be significantly higher in patients with severe renal dysfunction (creatinine clearance less than 30 mL/min) and in those receiving dialysis. The mechanism of this interaction is thought to be due to additive hypocalcemic effects.

MANAGEMENT: Caution and close monitoring of serum calcium concentrations are recommended when denosumab is used concomitantly with calcimimetic drugs such as cinacalcet and etelcalcetide. Patients and clinicians should be alert for signs and symptoms of hypocalcemia, such as numbness or tingling in the fingers, toes, or around the mouth, muscle spasms, twitches or cramps, seizures, mental status changes (confusion, irritability, depression), and irregular heartbeats.

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.