YORVIPATH (palopegteriparatide)

There are 0 contraindications.

There are 2 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Hypercalcemia
Hypocalcemia

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hypotension

There are 0 severe adverse reactions.

There are 12 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Injection site erythema Injection site inflammation Injection site sequelae Orthostatic hypotension Palpitations Syncope Vertigo	Back pain Diarrhea Hypercalcemia Pain in oropharynx

Rare/Very Rare
None.

Available data from reports of pregnancies in the 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. There are disease-associated risks to the mother and fetus related to hypocalcemia in pregnancy. In animal reproduction studies, administration of palopegteriparatide to pregnant rats and rabbits during the period of organogenesis resulted in no significant adverse effects up to doses 16- and 13-fold, respectively, the maximum recommended human dose (MRHD), based on PTH(1-34) and active metabolite PTH(1-33) exposure by AUC.

The background risk of birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. If palopegteriparatide is administered during pregnancy, or if a patient becomes pregnant while receiving palopegteriparatide, healthcare providers should report palopegteriparatide exposure by calling 1-844-442-7236. 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. Infants born to mothers with hypocalcemia should be monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability (e.g., myotonic jerks, seizures), apnea, cyanosis, and cardiac arrhythmias.

There are no data available on the presence of palopegteriparatide or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Infants breastfed by females treated with palopegteriparatide should be monitored for signs and symptoms of hypercalcemia or hypocalcemia. Monitoring of serum calcium in the infant should be considered. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for palopegteriparatide and any potential adverse effects on the breastfed child from the drug or from the underlying sub-optimally treated maternal condition.

In Study 1, 8 of 61 (13%) palopegteriparatide-treated subjects were 65 years of age or older compared to 2 of 21 (10%) subjects in the placebo group. Clinical studies of palopegteriparatide did not include a sufficient number of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.