INTERACTIONS Drugs Known to Affect Calcium : When used concomitantly with YORVIPATH, measure serum calcium levels more frequently. ( 7.2 )
7.1 Drugs Affected by Serum Calcium Digoxin YORVIPATH increases serum calcium, therefore, concomitant use with digoxin (which has a narrow therapeutic index) may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy may be reduced if hypocalcemia is present. When YORVIPATH is used concomitantly with digoxin, measure serum calcium and digoxin levels, and monitor for signs and symptoms of digoxin toxicity. Adjustment of the digoxin and/or YORVIPATH dose may be needed.
7.2 Drugs Known to Affect Serum Calcium Drugs that affect serum calcium may alter the therapeutic response to YORVIPATH. Measure serum calcium more frequently when YORVIPATH is used concomitantly with these drugs, particularly after these drugs are initiated, discontinued, or dose-adjusted.
YORVIPATH is contraindicated in patients with severe hypersensitivity to palopegteriparatide or to any of its excipients. Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been observed with parathyroid hormone (PTH) analogs. Severe hypersensitivity to palopegteriparatide or any components of YORVIPATH. ( 4 )
AND PRECAUTIONS Unintended Changes in Serum Calcium Levels Related to Number of Daily Injections : Use only one daily YORVIPATH injection. Using two YORVIPATH injections to achieve the recommended once daily dosage increases the variability of the total delivered dose. ( 5.1 )
Serious
Hypercalcemia and Hypocalcemia : Have occurred with YORVIPATH. Periodically measure serum calcium and monitor for signs and symptoms of hypercalcemia and hypocalcemia. ( 5.2 , 5.3 )
Potential
Risk of Osteosarcoma : YORVIPATH is not recommended in patients at increased risk of osteosarcoma. ( 5.4 )
Orthostatic
Hypotension : Has been reported with YORVIPATH. Monitor for signs and symptoms of orthostatic hypotension. ( 5.5 )
Digoxin
Toxicity : Concomitant use with digoxin may predispose to digitalis toxicity if hypercalcemia develops. With concomitant use, frequently measure serum calcium and digoxin levels, and monitor for signs and symptoms of digoxin toxicity. ( 5.6 , 7.1 )
5.1 Risk of Unintended Changes in Serum Calcium Levels Related to Number of Daily Injections Use only one YORVIPATH injection to achieve the recommended once daily dosage. Using two YORVIPATH injections to achieve the recommended once daily dosage increases the variability of the total delivered dose, which can cause unintended changes in serum calcium levels, including hypercalcemia and hypocalcemia <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) and Warning and Precautions (5.2 , 5.3) ]</span> .
5.2 Serious Hypercalcemia Serious events of hypercalcemia requiring hospitalization have been reported with YORVIPATH. The risk is highest when starting or increasing the dose of YORVIPATH but may occur at any time. Measure serum calcium 7 to 10 days after any dose change or if there are signs or symptoms of hypercalcemia, and at a minimum of every 4 to 6 weeks once the maintenance dose is achieved. Treat hypercalcemia if needed. If albumin-corrected serum calcium is greater than 12 mg/dL, withhold YORVIPATH for at least 2-3 days <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span>. For less serious hypercalcemia, adjust the dose of YORVIPATH, active vitamin D, and/or calcium supplements <span class="opacity-50 text-xs">[see Dosage and Administration (2) , Adverse Reactions (6.1) ]</span> .
5.3 Serious Hypocalcemia Serious events of hypocalcemia have been observed with PTH products, including YORVIPATH. The risk is highest when YORVIPATH is abruptly discontinued, but may occur at any time, even in patients who have been on stable doses of YORVIPATH. Measure serum calcium 7 to 10 days after any dose change or if there are signs or symptoms of hypocalcemia, and at a minimum of every 4 to 6 weeks once the maintenance dosage is achieved. Treat hypocalcemia if needed, and adjust the dose of YORVIPATH, active vitamin D, and/or calcium supplements if hypocalcemia occurs <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .
5.4 Potential Risk of Osteosarcoma YORVIPATH is a PTH analog. An increased incidence of osteosarcoma (a malignant bone tumor) has been reported in male and female rats treated with PTH analogs, including teriparatide. Osteosarcoma occurrence in rats is dependent on teriparatide or PTH dose and treatment duration. Osteosarcoma has been reported in patients treated with teriparatide in the postmarketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use. YORVIPATH is not recommended in patients who are at increased risk of osteosarcoma, such as patients with: Open epiphyses. YORVIPATH is not approved in pediatric patients <span class="opacity-50 text-xs">[see Use in Specific Populations (8.4) ]</span> . Metabolic bone diseases other than hypoparathyroidism, including Paget's disease of bone. Unexplained elevations of alkaline phosphatase. Bone metastases or a history of skeletal malignancies. History of external beam or implant radiation therapy involving the skeleton. Hereditary disorders predisposing to osteosarcoma. Instruct patients to promptly report clinical symptoms (e.g., persistent localized pain) and signs (e.g., soft tissue mass tender to palpation) that could be consistent with osteosarcoma.
5.5 Orthostatic Hypotension Orthostatic hypotension has been reported with YORVIPATH. Associated signs and symptoms may include decreased blood pressure, dizziness (including postural dizziness), palpitations, tachycardia, presyncope, or syncope. Such symptoms can be managed by dosing at bedtime, while reclining. YORVIPATH should be administered initially when the patient can sit or lie down due to the potential of orthostatic hypotension.
5.6 Risk of Digoxin Toxicity with Concomitant Use of Digitalis Compounds YORVIPATH increases serum calcium, and therefore, concomitant use with digoxin (which has a narrow therapeutic index) may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy may be reduced if hypocalcemia is present. When YORVIPATH is used concomitantly with digoxin, measure serum calcium and digoxin levels routinely, and monitor for signs and symptoms of digoxin toxicity. Refer to the digoxin prescribing information for dose adjustments, if needed <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span> .