Drug Interaction Report

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 30 minutes after the bisphosphonate dose.

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.

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

ADJUST DOSING INTERVAL: Food significantly decreases the bioavailability of risedronate, possibly to negligible levels.

MANAGEMENT: Risedronate should be administered with 180 to 240 mL (6 to 8 ounces) of plain water, at least 30 minutes before the first food, beverage, or medication of the day. Patients should remain upright for at least 30 minutes following administration of risedronate.