Drug Interaction Report

MONITOR: Concomitant use with calcimimetic agents may affect serum calcium levels, which may alter the therapeutic effects of palopegteriparatide. Calcimimetic therapy alone may increase the risk of severe hypocalcemia via binding and activation of the calcium-sensing receptor on the parathyroid gland. On the other hand, serious events of both hypercalcemia and hypocalcemia have been reported with palopegteriparatide. The risk for hypocalcemia is reported to be highest when palopegteriparatide is abruptly discontinued, while the risk for hypercalcemia is highest when initiating or increasing the dose of palopegteriparatide. However, both hypocalcemia and hypercalcemia may occur at any time.

MANAGEMENT: Close monitoring of serum calcium levels is recommended if palopegteriparatide is to be administered concomitantly with calcimimetic agents, particularly upon their initiation, cessation, or after dosage adjustment. Patients should be advised to contact their doctor promptly if they develop symptoms of hypercalcemia such as nausea, vomiting, constipation, lethargy, and muscle weakness; or symptoms of hypocalcemia such as muscle spasms, carpopedal spasm, laryngeal spasm, tetany, convulsions, mental changes (irritability, depression, psychosis), increased intracranial pressure, papilledema, QT interval prolongation, and cardiac arrhythmias.

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.