Palopegteriparatide

Palopegteriparatide is a prescription medication used for the treatment of hypoparathyroidism in adults.

• Palopegteriparatide is available under the following different brand names: Yorvipath.

Common side effects of Palopegteriparatide include:

• injection site reactions
• vasodilatory signs or symptoms such as a drop in blood pressure or lightheadedness when standing up
• headache 
• diarrhea
• back pain
• high calcium levels
• sore throat

Serious side effects of Palopegteriparatide include:

• high levels of calcium in the blood (hypercalcemia)
• low levels of calcium in the blood (hypocalcemia)
• possible bone cancer (osteosarcoma)
• allergic (hypersensitivity) reaction, including anaphylaxis symptoms, include swelling of your face, lips, mouth, or tongue, fast heartbeat, breathing problems, itching, fainting, dizziness, feeling lightheaded (low blood pressure), rash, hives
• orthostatic hypotension
• risk of digoxin toxicity - if you are using Digoxin and Palopegteriparatide simultaneously. Tell your healthcare provider if you experience irregular heart rhythm, heart palpitations, confusion, loss of appetite, nausea, vomiting, diarrhea, or vision problems.

Rare side effects of Palopegteriparatide include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult dosage

Injection, SC solution (prefilled pen)

• 168 mcg/0.56 mL, doses of 6, 9, or 12 mcg
• 294 mcg/0.98 mL, doses of 15, 18, or 21 mcg
• 420 mcg/1.4 mL, doses of 24, 27, or 30 mcg

Hypoparathyroidism

Adult dosage

• Initial dose
  • 18 mcg SC once a day initially
    • Adjust the dose in 3-mcg increments or decrements
    • Do not increase the dose more often than every 7 days
    • Do not decrease the dose more often than every 3 days
    • Measure serum calcium within 7-10 days after the first dose and any dose change in Palopegteriparatide, active vitamin D (calcitriol), or calcium supplements, and monitor for clinical symptoms of hypocalcemia or hypercalcemia 
• Maintenance dose
  • Recommended dose range: 6-30 mcg once daily
  • Individualize maintenance dose to achieve serum calcium within normal range, without the need for calcitriol or therapeutic doses of calcium
  • Calcium supplementation sufficient to meet daily dietary requirements may be continued
  • Once maintenance dosage is achieved, monitor for clinical signs and symptoms of hypocalcemia or hypercalcemia; measure serum calcium levels as indicated and at a minimum every 4-6 weeks
  • Some patients may require further dose titration
  • If calcium levels remain low despite the maximum recommended dosage (ie, 30 mcg once a day), consider adding or restarting calcium and/or calcitriol therapy and seek other treatment

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Palopegteriparatide has severe interactions with no other drugs
• Palopegteriparatide has serious interactions with no other drugs
• Palopegteriparatide has moderate interactions with the following drugs:
  • alendronate
  • calcium acetate
  • calcium carbonate
  • calcium chloride
  • calcium citrate
  • calcium gluconate
  • calcium/vitamin D
  • chlorothiazide
  • chlorthalidone
  • digoxin
  • etidronate
  • hydrochlorothiazide
  • ibandronate
  • lithium
  • methyclothiazide
  • risedronate
  • tiludronate
  • zoledronic acid
• Palopegteriparatide has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Severe hypersensitivity, including anaphylaxis, angioedema, and urticaria

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Palopegteriparatide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Palopegteriparatide?”

Cautions

• Risk of unintended serum calcium changes
• Use only 1 injection to achieve the recommended once-daily dosage
• Using 2 injections increases the variability of the total delivered dose, which can cause unintended changes in serum calcium levels, including hypercalcemia and hypocalcemia
• Serious hypercalcemia
  • Serious events of hypercalcemia requiring hospitalization reported
  • Risk is highest when starting or increasing dose, but may occur at any time
  • Measure serum calcium 7-10 days after any dose change or if there are signs or symptoms of hypercalcemia, and at a minimum of every 4-6 weeks once maintenance dose achieved
  • Treat hypercalcemia if needed
  • If albumin-corrected serum calcium is more than 12 mg/dL, withhold palopegteriparatide for at least 2-3 days; for less serious hypercalcemia, adjust the dose, active vitamin D, and/or calcium supplements
• Serious hypocalcemia
  • Serious events of hypocalcemia observed with PTH products
  • Risk is highest when palopegteriparatide is abruptly discontinued but may occur at any time, even in patients who have been on stable doses
  • Measure serum calcium 7-10 days after any dose change or if there are signs or symptoms of hypocalcemia, and at a minimum of every 4-6 weeks once maintenance dose achieved
  • Treat hypocalcemia if needed, and adjust the dose of palopegteriparatide, active vitamin D, and/or calcium supplements if hypocalcemia occurs
• Risk of osteosarcoma
  • Increased incidence of osteosarcoma reported in male and female rats treated with PTH analogs
  • Osteosarcoma occurrence in rats is dependent on teriparatide or PTH dose and treatment duration
  • Osteosarcoma was 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
  • Data are limited that assess the risk of osteosarcoma beyond 2 years of teriparatide use
  • Instruct patients to promptly report clinical symptoms (eg, persistent localized pain) and signs (eg, soft tissue mass tender to palpation) that could be consistent with osteosarcoma
  • Not recommended for patients at increased risk of osteosarcoma
  • Patients at increased risk of osteosarcoma
  • Open epiphyses; not approved in pediatric patients
  • Metabolic bone diseases other than hypoparathyroidism, including Paget disease of bone
  • Unexplained alkaline phosphatase elevations
  • Bone metastases or history of skeletal malignancies
  • History of external beam or implant radiation therapy involving the skeleton
  • Hereditary disorders predisposing to osteosarcoma
• Orthostatic hypotension
  • Orthostatic hypotension reported
  • 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 or while reclining
• Drug interaction overview
  • Digoxin
  • Modify dose/monitor
  • Coadministration with digoxin may predispose patients to digitalis toxicity if hypercalcemia develops
  • Digoxin efficacy may be reduced if hypocalcemia is present
  • Measure serum calcium and digoxin levels; monitor for signs and symptoms of digoxin toxicity; adjust digoxin and/or palopegteriparatide dose as needed
  • Drugs affecting serum calcium
  • Drugs that affect serum calcium may alter the therapeutic response to Palopegteriparatide
  • Measure serum calcium more frequently if coadministered, particularly after these drugs are initiated, discontinued, or dose-adjusted

Pregnancy and Lactation

• Available data from reports of pregnancies in clinical trials from drug development are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Clinical considerations
  • Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia
  • Infants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which may cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica, and neonatal seizures
  • Monitor infants born to mothers with hypocalcemia for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability (eg, myotonic jerks, seizures), apnea, cyanosis, and cardiac arrhythmias
• Lactation
  • Data are unavailable regarding the presence of palopegteriparatide or its metabolite in either human or animal milk, its effects on breastfed infants, or milk production
  • Monitor infants breastfed by women treated with palopegteriparatide for signs and symptoms of hypercalcemia or hypocalcemia
  • Consider monitoring serum calcium in infant