Is yorvipath (generic name) contraindicated in patients with a history of radiation therapy?

Is Yorvipath Contraindicated in Patients with Prior Radiation Therapy?

No, Yorvipath (palopegteriparatide) is not contraindicated in patients with a history of radiation therapy, but it is not recommended in patients who received external beam or implant radiation therapy involving the skeleton due to theoretical osteosarcoma risk. 1

Specific Contraindications and Warnings

The FDA label for Yorvipath lists only one absolute contraindication: severe hypersensitivity to palopegteriparatide or its excipients 1. However, the drug carries important warnings regarding radiation exposure:

Radiation Involving the Skeleton

Yorvipath is not recommended (but not absolutely contraindicated) in patients with history of external beam or implant radiation therapy involving the skeleton due to theoretical increased risk of osteosarcoma 1. This recommendation stems from:

• PTH analogs (the drug class to which Yorvipath belongs) caused dose-dependent osteosarcoma in rat studies 1
• Patients with prior skeletal radiation are considered at increased baseline risk for osteosarcoma 1
• The combination of these two risk factors creates a theoretical additive concern 1

Radiation Not Involving the Skeleton

For patients who received radiation therapy that did not involve the skeleton (e.g., head and neck radiation, thoracic radiation for lung cancer, pelvic radiation for gynecologic malignancies where bone exposure was minimal), there is no specific contraindication or warning against Yorvipath use 1.

Clinical Decision-Making Algorithm

When evaluating a patient with prior radiation for Yorvipath therapy:

1. Determine radiation field and skeletal involvement:

   • Review radiation therapy records to identify total dose delivered to bone 2
   • If skeletal structures received therapeutic radiation doses (typically ≥50 Gy), exercise caution 2
   • If radiation was directed away from skeletal structures, proceed with standard evaluation 1

2. Assess other osteosarcoma risk factors:

   • Open epiphyses (pediatric patients - Yorvipath not approved in this population) 1
   • Metabolic bone diseases other than hypoparathyroidism (e.g., Paget's disease) 1
   • Unexplained elevated alkaline phosphatase 1
   • Bone metastases or history of skeletal malignancies 1
   • Hereditary disorders predisposing to osteosarcoma 1

3. Risk-benefit assessment:

   • If patient has skeletal radiation history but severe hypoparathyroidism uncontrolled on conventional therapy, the benefit may outweigh theoretical osteosarcoma risk 1
   • Document shared decision-making discussion with patient about theoretical risks 1
   • Counsel patients to report bone pain, swelling, or other skeletal symptoms promptly 1

Real-World Evidence

Recent real-world data from 123 patients in the U.S. expanded access program showed no new safety signals with up to 12 months of palopegteriparatide treatment 3. While this study did not specifically report on patients with prior radiation exposure, it demonstrates the drug's safety profile in diverse patient populations outside clinical trials 3.

Important Caveats

• The osteosarcoma concern is based on animal data; observational studies in humans have not demonstrated increased osteosarcoma risk with PTH analogs, though data beyond 2 years of use are limited 1
• The "not recommended" designation differs from an absolute contraindication - clinical judgment and shared decision-making should guide therapy 1
• Patients should be monitored for skeletal symptoms regardless of radiation history 1