Drug Interactions between palopegteriparatide and pamidronate

MONITOR: According to the manufacturer of palopegteriparatide, concomitant use with drugs that affect serum calcium levels may alter its therapeutic effects. Bone resorption inhibitors such as bisphosphonates, denosumab, romosozumab, or strontium ranelate may lower serum calcium levels. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium. Strontium ranelate may also cause slight decreases in calcium and parathyroid hormone (PTH) serum concentrations. Hypocalcemia has also occurred in patients treated with romosozumab, while denosumab can cause severe symptomatic hypocalcemia. 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 during treatment.

MANAGEMENT: Close monitoring of serum calcium levels is recommended if palopegteriparatide is to be administered concomitantly with bisphosphonates, denosumab, romosozumab or strontium ranelate, 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.