Drug Interaction Report

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.

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

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

MANAGEMENT: Alendronate should be administered with 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 alendronate.