Drug Interaction Report

GENERALLY AVOID: Concomitant use of the calcimimetics etelcalcetide and cinacalcet may lead to severe, life-threatening, hypocalcemia. The proposed mechanism is additive reduction in serum calcium levels through binding and activation of the calcium-sensing receptor on the parathyroid gland. Significant decreases in serum calcium may cause paraesthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmia. Both medications given alone may lead to severe hypocalcemia requiring treatment with therapies to increase serum calcium levels.

MANAGEMENT: Concomitant use of etelcalcetide and cinacalcet is not recommended. At least 7 days should elapse when switching from cinacalcet to etelcalcetide, and the corrected serum calcium level should be at or above the lower limit of the normal range. In addition, the corrected serum calcium level should be measured within one week of initiation or dose adjustment of either etelcalcetide or cinacalcet and monitored approximately every 4 weeks. The manufacturer product labeling should be consulted for management guidelines in the event of a reduction in corrected serum calcium levels below the lower limit of the normal range and/or symptoms hypocalcemia. Patients should also be advised to contact their health care professional if they experience symptoms of hypocalcemia, such as numbness or tingling in the fingers, toes, or around the mouth, muscle spasms, twitches or cramps, seizures, confusion, 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.

The recommended maximum number of medicines in the 'calcimimetics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'calcimimetics' category:

• etelcalcetide
• Sensipar (cinacalcet)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.