Drug Interactions between Lithonate and palopegteriparatide

MONITOR: Treatment with thiazide diuretics, loop diuretics, and lithium may increase serum calcium levels, which may alter the therapeutic effects of palopegteriparatide. There are no clinical data available evaluating the safety of concomitant use of palopegteriparatide with these medicines, therefore, the clinical significance of the interaction is unclear. However, concomitant administration of teriparatide, of which palopegteriparatide is a pro-drug, with intravenous furosemide 20 mg to 100 mg, did not significantly affect calcium response in normal subjects or patients with mild to severe renal insufficiency. The increases in serum calcium and urinary excretion of calcium of 2% and 37%, respectively, was determined to be clinically insignificant. Similarly, the concomitant administration of hydrochlorothiazide 25 mg and teriparatide did not significantly affect serum calcium response. The reduction in urinary excretion of calcium of 15% was also determined to be clinically insignificant. However, the effect of higher doses of hydrochlorothiazide is unknown. On the other hand, long term use of lithium has been associated with hypercalcemia and hyperparathyroidism.

MANAGEMENT: More frequent monitoring of serum calcium is recommended when palopegteriparatide is administered concomitantly with thiazide diuretics, loop diuretics, or lithium, 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, 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.