YORVIPATH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YORVIPATH (YORVIPATH).
Somatostatin receptor subtype 2 (SSTR2) agonist; suppresses growth hormone secretion from pituitary adenomas and inhibits tumor growth via SSTR2-mediated signaling.
| Metabolism | Hepatic metabolism via CYP3A4 and CYP2C19; excreted primarily in feces (80%) and urine (20%). |
| Excretion | Renal excretion of intact drug and metabolites accounts for approximately 80% of the administered dose, with fecal elimination accounting for the remaining 20%. |
| Half-life | Terminal elimination half-life is approximately 4 hours in healthy subjects, but may be prolonged (up to 6-8 hours) in patients with moderate to severe renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 50-60% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.4 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Subcutaneous administration: absolute bioavailability is approximately 60% compared to intravenous administration. |
| Onset of Action | Subcutaneous administration: time to maximal calcium elevation is approximately 4-6 hours; clinical effect on serum calcium is detectable within 2-4 hours. |
| Duration of Action | Duration of serum calcium elevation is approximately 12-24 hours, supporting once-daily or every-other-day dosing; duration is dose-dependent and may be shorter in patients with impaired renal function. |
| Molecular Weight | 411.46 |
YORVIPATH (palopegteriparatide) is administered subcutaneously once daily. The recommended dose is 0.7 mL (18 mcg) injected into the abdomen or thigh, with the needle inserted perpendicularly. Dose adjustments are based on serum calcium and albumin levels.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment is recommended for renal impairment. However, caution is advised in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) as safety data are limited. |
| Liver impairment | No dose adjustment is recommended for hepatic impairment. Safety and efficacy have not been studied in patients with Child-Pugh Class B or C. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no approved dosing guidelines are available. |
| Geriatric use | No specific dose adjustment is recommended for elderly patients. Clinical studies included patients aged 65 years and older, but no overall differences in safety or efficacy were observed compared to younger adults. |
| 1st trimester | Avoid use. No adequate human data; animal studies show risk. |
| 2nd trimester | Avoid use. Potential fetal harm; limited human data. |
| 3rd trimester | Avoid use. May cause fetal harm; no human data. |
Clinical note
Comprehensive clinical and safety monograph for YORVIPATH (YORVIPATH).
| Placental transfer | Unknown; molecular weight suggests potential crossing. |
| Breastfeeding | No human data on excretion in breast milk. Unknown risk to infant. |
| Lactation Rating | L5 (Contraindicated) |
■ FDA Black Box Warning
No FDA-issued black box warning.
| Serious Effects |
Hypersensitivity to active substance or excipientsPregnancy
| Precautions | Risk of bradycardia and heart block; monitor heart rate and ECG., Cholelithiasis; monitor gallbladder function., Hypoglycemia or hyperglycemia; monitor blood glucose levels., Pituitary tumor enlargement may cause visual field defects; monitor visual fields., Immune-mediated hepatitis; monitor liver function tests. |
| Food/Dietary | No specific food interactions known. However, ensure adequate dietary calcium and vitamin D intake (e.g., dairy products, fortified foods) as recommended by the prescriber. Avoid excessive alcohol consumption as it may increase fall risk. |
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| Teratogenic Risk |
| YORVIPATH (abaloparatide) is a PTHrP analog. In animal studies, skeletal abnormalities and reduced fetal weight were observed at doses 20-40 times the human dose. No adequate human studies exist. Risk cannot be ruled out; contraindicated in pregnancy except for life-threatening conditions. |
| Fetal Monitoring | Monitor serum calcium levels periodically. Fetal monitoring includes ultrasound for skeletal development if exposure occurs. Assess maternal bone mineral density before and during therapy. Evaluate for orthostatic hypotension and hypercalcemia. |
| Fertility Effects | In animal studies, abaloparatide did not impair fertility at doses up to 20 times the human dose. No human fertility data available. Theoretical risk due to calcium homeostasis disruption, but unlikely at therapeutic doses. |
| Clinical Pearls |
| YORVIPATH (palopegteriparatide) is a prodrug of teriparatide for once-daily subcutaneous injection. Monitor serum calcium and 25-hydroxyvitamin D levels before and during therapy. Adjust calcium and vitamin D supplementation to avoid hypercalcemia. Contraindicated in patients with Paget's disease, unexplained alkaline phosphatase elevation, bone metastases, or prior external beam radiation involving the skeleton. Avoid in patients with hypercalcemia or severe renal impairment (CrCl <30 mL/min). Risk of osteosarcoma in animal studies; limit use to 2 years over a lifetime. Do not use in patients with increased baseline risk of osteosarcoma. |
| Patient Advice | Inject YORVIPATH once daily into the thigh or abdomen at approximately the same time each day. · Do not skip doses; if a dose is missed, take it as soon as remembered unless it is near the next dose, then skip the missed dose. · Do not take more than one injection per day. · Store YORVIPATH in the refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. · Do not use the pen if the solution appears cloudy, discolored, or contains particles. · Report symptoms of hypercalcemia such as nausea, vomiting, constipation, lethargy, or muscle weakness. · Ensure adequate calcium and vitamin D intake as directed by your healthcare provider. · Avoid use beyond 2 years due to potential risk of osteosarcoma. · Do not use if pregnant or breastfeeding unless advised by your doctor. · Keep YORVIPATH out of the reach of children and pets. · Dispose of used needles in a puncture-resistant sharps container. |