Version July 2025
Dosage guidance:
Safety: Within 2 weeks prior to initiation, ensure 25-hydroxyvitamin D level is within normal limits and albumin-corrected serum calcium is ≥7.8 mg/dL. Administer each daily dose as a single injection to avoid unintended changes in serum calcium levels.
Dosage form information: Prefilled pens are available in 3 different presentations; ensure careful product selection based on required dose and anticipated titration.
Hypoparathyroidism:
Initial dosage: SUBQ: 18 mcg once daily. Upon initiation, adjust daily active vitamin D (eg, calcitriol) or calcium dose as follows:
|
Albumin-corrected serum calcium |
Current calcitriol dose |
Calcitriol or calcium supplement dose adjustments |
|---|---|---|
|
a If calcium supplements are needed to achieve dietary requirements, may continue calcium supplements at doses ≤600 mg/day instead of discontinuing. | ||
|
≥8.3 mg/dL (≥2.08 mmol/L) |
>1 mcg/day |
Reduce calcitriol dose by ≥50% and continue current calcium dose. |
|
≥8.3 mg/dL (≥2.08 mmol/L) |
≤1 mcg/day |
Discontinue calcitriol and continue current calcium dose. |
|
≥7.8 to <8.3 mg/dL (≥1.95 to <2.08 mmol/L) |
Any amount |
Reduce calcitriol dose by ≥50% and continue current calcium dose. |
|
≥7.8 mg/dL (≥1.95 mmol/L) |
Not currently on calcitriol |
Decrease calcium dose by ≥1,500 mg/day or discontinue calcium if current dose <1,500 mg/day.a |
Dosage titration: Increase or decrease daily palopegteriparatide dose in 3 mcg/day increments (maximum: 30 mcg once daily), along with daily active vitamin D (eg, calcitriol) and calcium dose, as follows. Goal of therapy is to maintain serum calcium levels within the normal range without the need for active vitamin D or calcium doses >600 mg/day.
If <7 days since palopegteriparatide initiated/adjusted:
Albumin-corrected serum calcium <8.3 mg/dL (<2.08 mmol/L): Continue same palopegteriparatide dose; increase calcitriol and/or calcium supplement dose towards prior doses based on clinical judgment.
Albumin-corrected serum calcium 8.3 to 10.6 mg/dL (2.08 to 2.65 mmol/L): Continue same palopegteriparatide, calcitriol, and calcium supplement doses.
Albumin-corrected serum calcium >10.6 mg/dL (>2.65 mmol/L): Follow guidance in “Titration of Palopegteriparatide, Active Vitamin D, and Calcium Supplements Based on Albumin-Corrected Serum Calcium” table.
If ≥7 days since palopegteriparatide initiated/adjusted: Adjust dose based on albumin-corrected serum calcium as follows:
|
Albumin-corrected serum calcium |
Palopegteriparatide dose adjustmenta |
Calcitriol and calcium supplement dose adjustment |
|---|---|---|
|
a Dosage should not be increased more often than every 7 days or decreased more often than every 3 days. | ||
|
b If calcium supplements are needed to achieve dietary requirements, may continue calcium supplements at doses ≤600 mg/day instead of discontinuing. | ||
|
<8.3 mg/dL (<2.08 mmol/L) |
Increase by 3 mcg/day (maximum: 30 mcg once daily) |
Continue same supplement doses. |
|
8.3 to 10.6 mg/dL (2.08 to 2.65 mmol/L) while on active vitamin D or calcium supplements |
Increase by 3 mcg/day (maximum: 30 mcg once daily) |
If on calcitriol >1 mcg/day: Reduce calcitriol dose by ≥50%. If on calcitriol ≤1 mcg/day: Discontinue calcitriol. If not on calcitriol: Decrease calcium supplement by ≥1,500 mg/day or discontinue calcium if current dose <1,500 mg/day.b |
|
8.3 to 10.6 mg/dL (2.08 to 2.65 mmol/L) and not on active vitamin D or calcium supplements |
No change |
No supplements.b |
|
10.7 to 11.9 mg/dL (2.68 to 2.98 mmol/L) while on active vitamin D or calcium supplements |
No change |
If on calcitriol >1 mcg/day: Reduce calcitriol dose by ≥50%. If on calcitriol ≤1 mcg/day: Discontinue calcitriol. If not on calcitriol: Decrease calcium supplement by ≥1,500 mg/day or discontinue calcium if current dose <1,500 mg/day.b |
|
10.7 to 11.9 mg/dL (2.68 to 2.98 mmol/L) and not on active vitamin D or calcium supplements |
Decrease by 3 mg/day |
No supplements.b |
|
≥12 mg/dL (≥3 mmol/L) |
Discontinue until albumin-correct serum calcium <12 mg/dL (<3 mmol/L); evaluate serum calcium every 2 to 3 days, then resume based on albumin-corrected serum calcium level. |
Discontinue until serum calcium <12 mg/dL (<3 mmol/L), then resume based on albumin-corrected serum calcium level. |
Missed doses:
If <12 hours from scheduled time: Administer missed dose as soon as possible.
If ≥12 hours from scheduled time: Skip missed dose and resume with next scheduled dose.
Delay/interruption of therapy: If treatment is delayed or interrupted for ≥3 days, evaluate for signs and symptoms of hypocalcemia; may require adjustments to calcium and active vitamin D supplementation. Resume palopegteriparatide as soon as possible after interruption.
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Vasodilation (vasodilatory signs and symptoms including dizziness, orthostatic hypotension, palpitations, postural orthostatic tachycardia, presyncope, syncope, vertigo)
Local: Injection-site reaction (including bruising at injection site, erythema at injection site, rash at injection site)
Nervous system: Headache
1% to 10%:
Endocrine & metabolic: Hypercalcemia
Gastrointestinal: Diarrhea
Immunologic: Antibody development
Neuromuscular & skeletal: Back pain
Respiratory: Oropharyngeal pain
Frequency not defined: Endocrine & metabolic: Hypocalcemia
Hypersensitivity to palopegteriparatide or any component of the formulation.
Concerns related to adverse effects:
• Antibodies: Development of antipalopegteriparatide antibodies has been observed; efficacy was maintained with dosage adjustment during clinical trials.
• Hypercalcemia: Hypercalcemia (sometimes requiring hospitalization) has been reported with palopegteriparatide; risk is highest when starting or increasing the dose but may occur at any time during therapy.
• Hypocalcemia: Serious hypocalcemia has been observed with palopegteriparatide; risk is highest if palopegteriparatide is abruptly discontinued but may occur at any time during therapy.
• Orthostatic hypotension: Orthostatic hypotension (including decreased BP, dizziness, palpitations, tachycardia, presyncope or syncope) has been reported with palopegteriparatide.
• Osteosarcoma: An increased incidence of osteosarcoma has been reported with parathyroid hormone analog (eg, teriparatide) use in animal models and in some post marketing human data. Palopegteriparatide use is not recommended in patients with risk factors for osteosarcoma, such as open epiphyses, metabolic bone disease (eg, Paget disease of bone), unexplained elevations in alkaline phosphatase, bone metastases or history of skeletal malignancies, history of external beam or implant radiation involving the skeleton, or hereditary disorders that predispose users to osteosarcoma.
Concurrent drug therapy issues:
• Digoxin: When used concurrently with digoxin, palopegteriparatide may predispose patients to digitalis toxicity if hypercalcemia develops. Additionally, the efficacy of digoxin may be reduced if hypocalcemia occurs.
Dosage form specific issues:
• SUBQ administration: Use only one injection for daily dosage; more than one daily injection can increase the variability in the delivered dose and cause unintended changes in serum calcium levels (including hypercalcemia or hypocalcemia).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Yorvipath: 168 mcg/0.56 mL (0.56 mL); 294 mcg/0.98 mL (0.98 mL); 420 mcg/1.4 mL (1.4 mL) [contains metacresol]
No
Solution Pen-injector (Yorvipath Subcutaneous)
168MCG/0.56ML (per 0.56 mL): $13,155.00
294MCG/0.98ML (per 0.98 mL): $13,155.00
420MCG/1.4ML (per mL): $9,396.43
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
SUBQ: Administer by SUBQ injection to the abdomen or front of the thigh; rotate injection sites daily. Administer while sitting or lying down; may administer at bedtime to reduce risk of orthostatic hypotension. Administer entire dose as a single injection from a single prefilled pen; do not divide daily dose into >1 injection. Use only if solution is clear and colorless; do not use if solution contains particulate matter or is colored. When using a pen for the first time, test pen flow prior to administration.
Hypoparathyroidism: Treatment of hypoparathyroidism in adults.
Limitations of use: Not studied for acute postsurgical hypoparathyroidism; titration scheme was only evaluated in adults who first achieved an albumin-corrected serum calcium of ≥7.8 mg/dL (≥1.95 mmol/L) using calcium and active vitamin D treatment.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Bisphosphonate Derivatives: May decrease therapeutic effects of Palopegteriparatide. Bisphosphonate Derivatives may increase therapeutic effects of Palopegteriparatide. Risk C: Monitor
Calcimimetic Agents: May increase therapeutic effects of Palopegteriparatide. Calcimimetic Agents may decrease therapeutic effects of Palopegteriparatide. Risk C: Monitor
Cardiac Glycosides: Parathyroid Hormone Products may increase arrhythmogenic effects of Cardiac Glycosides. Risk C: Monitor
Denosumab: May increase therapeutic effects of Palopegteriparatide. Denosumab may decrease therapeutic effects of Palopegteriparatide. Risk C: Monitor
Loop Diuretics: May decrease therapeutic effects of Palopegteriparatide. Loop Diuretics may increase therapeutic effects of Palopegteriparatide. Risk C: Monitor
Pegloticase: May decrease therapeutic effects of PEGylated Drug Products. Risk C: Monitor
Pegvaliase: PEGylated Drug Products may increase adverse/toxic effects of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May increase therapeutic effects of Palopegteriparatide. Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Palopegteriparatide. Risk C: Monitor
Adverse events were not observed in animal reproduction studies.
Hypocalcemia is associated with adverse maternal and fetal outcomes. Monitor infants of mothers with hypocalcemia for apnea, cyanosis, cardiac arrhythmias, neuromuscular irritability (eg, myotonic jerks, seizures), or other signs of hyper- or hypocalcemia.
Data collection to monitor pregnancy and infant outcomes following exposure to palopegteriparatide is ongoing. Health care providers should report palopegteriparatide pregnancy exposures (1-844-442-7236).
It is not known if palopegteriparatide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Breastfed infants of mothers taking palopegteriparatide should be monitored for signs and symptoms of hyper- or hypocalcemia. Consider monitoring infant serum calcium.
Prior to initiation: Within 2 weeks before the first dose of palopegteriparatide, obtain 25-hydroxyvitamin D level, serum calcium, and albumin level.
During therapy: Monitor daily for signs and symptoms of hypercalcemia or hypocalcemia. Obtain serum calcium and albumin levels 7 to 10 days after the first dose or any dosage changes, then every 4 to 6 weeks or as clinically indicated based on presence of hypercalcemia- or hypocalcemia-related symptoms. Promptly evaluate signs or symptoms of osteosarcoma (eg, persistent localized pain, tender soft tissue mass).
Palopegteriparatide is a parathyroid hormone analog prodrug containing an inert carrier of teriparatide, which provides parathyroid hormone (1-34) continuously. Palopegteriparatide mimics endogenous parathyroid hormone to exert effects on parathyroid hormone 1 receptor to maintain calcium and phosphate homeostasis.
Distribution: Vd: 4.8 L.
Half-life elimination: ~60 hours.
Time to peak: Median: 4 hours (range: 4 to 8 hours).
Excretion: Clearance: 0.58 L/day.
