In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor). The occurrence of osteosarcoma was dependent on parathyroid hormone dose and treatment duration. This effect was observed at parathyroid hormone exposure levels ranging from 3 to 71 times the exposure levels in humans receiving a 100 mcg dose of Natpara. These data could not exclude a risk to humans.
Because of a potential risk of osteosarcoma, use Natpara only in patients who cannot be well-controlled on calcium and active forms of vitamin D alone and for whom the potential benefits are considered to outweigh this potential risk.
Avoid use of Natpara in patients who are at increased baseline risk for osteosarcoma such as patients with Paget disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma or patients with a prior history of external beam or implant radiation therapy involving the skeleton.
Because of the risk of osteosarcoma, Natpara is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Natpara REMS Program.
Hypoparathyroidism: SubQ: Note: Prior to initiation of therapy, confirm that the serum calcium concentration is >7.5 mg/dL and the 25-hydroxyvitamin D stores are sufficient (correct if insufficient). When initiating parathyroid hormone therapy, the dose of active vitamin D should be decreased by 50%; supplemental calcium may be continued at the current dose.
Initial: 50 mcg once daily.
Dosage adjustment: Note: Active forms of vitamin D and calcium supplementation may require adjustment during parathyroid hormone therapy based on albumin-corrected serum calcium concentrations; consult parathyroid hormone product labeling for more information.
Serum calcium (albumin-corrected) cannot be maintained >8 mg/dL without an active form of vitamin D and/or calcium supplementation: Increase the parathyroid hormone dose in increments of 25 mcg/day every 4 weeks; maximum daily dose: 100 mcg/day.
Serum calcium (albumin-corrected) repeatedly >9 mg/dL after discontinuation of active forms of vitamin D and calcium supplementation decreased to a dose sufficient to meet daily needs: May decrease the parathyroid hormone dose to a minimum of 25 mcg/day.
Maintenance: Use the lowest dose required to prevent both hypocalcemia and hypercalciuria while maintaining albumin-corrected serum calcium concentrations at the lower half of the normal range (ie, between 8 and 9 mg/dL) without the need for active forms of vitamin D and with calcium supplementation sufficient to meet the patient’s daily requirements.
Discontinuation or interruption of therapy: An abrupt interruption or discontinuation may result in severe hypocalcemia; resume treatment with or increase the dose of an active form of vitamin D and calcium supplementation (if indicated).
Missed dose: Administer parathyroid hormone as soon as reasonably feasible; additional calcium should be administered in the event of hypocalcemia.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment (CrCl ≥30 mL/minute): No dosage adjustment necessary.
Severe impairment (CrCl <30 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cartridge, Subcutaneous:
Natpara: 25 mcg (1 ea); 50 mcg (1 ea); 75 mcg (1 ea); 100 mcg (1 ea) [contains metacresol]
No
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Natpara: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125511s016lbl.pdf#page=18
SubQ: Administer subcutaneously into the thigh (alternate thighs each day) using the provided Q-Cliq pen. Follow instructions provided with the medication cartridges and the Q-Cliq pen to prepare the injection device for use. One Q-Cliq pen may be used for up to 2 years, with changing the reconstituted cartridge every 2 weeks. Patients and caregivers who will administer parathyroid hormone should receive appropriate training and instruction by a trained health care professional prior to first use.
Hypoparathyroidism: Adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism
Limitations of use: Because of the potential risk of osteosarcoma, recommended only for patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone; has not been studied in patients with hypoparathyroidism caused by calcium-sensing receptor mutations or in patients with acute postsurgical hypoparathyroidism
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Paresthesia (31%), headache (25%), hypoesthesia (14%)
Endocrine & metabolic: Hypocalcemia (27%), hypercalcemia (19%)
Gastrointestinal: Diarrhea (12%), vomiting (12%)
Genitourinary: Hypercalciuria (11%)
Immunologic: Antibody development (9% to 16%)
Neuromuscular & skeletal: Arthralgia (11%)
1% to 10%:
Cardiovascular: Hypertension (6%)
Central nervous system: Peripheral pain (10%), facial hypoesthesia (6%)
Endocrine & metabolic: Inhibited conversion of vitamin D3 to 25-hydroxy-D3 (6%)
Gastrointestinal: Upper abdominal pain (7%)
Neuromuscular & skeletal: Neck pain (6%)
Respiratory: Upper respiratory tract infection (8%), sinusitis (7%)
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, hypersensitivity reaction, seizure
Hypersensitivity to parathyroid hormone or any component of the formulation.
Concerns related to adverse effects:
• Hypercalcemia: Severe hypercalcemia has been reported; the risk is highest during initiation of therapy and dose escalation. Monitor serum calcium concentrations and patients for signs and symptoms of hypercalcemia. Treat hypercalcemia as needed and consider temporary discontinuation or a reduction in dose if severe hypercalcemia occurs.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, dyspnea, angioedema, urticaria, and rash, have been reported with parathyroid hormone therapy. Discontinue therapy if signs of severe hypersensitivity occur.
• Hypocalcemia: Severe hypocalcemia has been reported, including cases that have resulted in seizures, and can occur at any time during therapy; the risk is highest when a dose is missed or when parathyroid hormone therapy is withheld or abruptly discontinued. Monitor serum calcium concentrations and patients for signs and symptoms of hypocalcemia. In patients who must have therapy interrupted or discontinued, resume treatment with or increase the dose of an active form of vitamin D and/or calcium supplements to prevent severe hypocalcemia.
• Osteosarcoma: [US Boxed Warning]: In animal studies, parathyroid hormone has been associated with an increase in osteosarcoma; risk was dependent on both dose and duration. Avoid use in patients with an increased risk of osteosarcoma (including Paget disease, prior external beam or implant radiation therapy involving the skeleton, unexplained elevation of alkaline phosphatase, patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma). Treatment should only be used in patients who cannot be well controlled on calcium supplements and active forms of vitamin D alone. Parathyroid hormone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the NATPARA REMS Program.
None known.
Alendronate: May diminish the therapeutic effect of Parathyroid Hormone. More specifically, Alendronate may interfere with normalization of blood calcium concentrations. Risk X: Avoid combination
Cardiac Glycosides: Parathyroid Hormone may enhance the adverse/toxic effect of Cardiac Glycosides. More specifically, Parathyroid Hormone-related hypercalcemia may predispose to digitalis toxicity. Risk C: Monitor therapy
Severe hypocalcemia has been associated with use of recombinant human parathyroid hormone (1-84) [rhPTH (1-84)]. Hypocalcemia in pregnant women may be associated with spontaneous abortion, premature labor, dysfunctional labor, and preeclampsia; fetal/neonatal hyperparathyroidism, leading to skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica, and neonatal seizures. Newborns exposed in utero to rhPTH (1-84) should be monitored for symptoms of hyper- and hypocalcemia, including apnea, cardiac rhythm disorders, cyanosis, and neuromuscular irritability (eg, myotonic jerks, seizures).
When treatment of hypoparathyroidism in pregnancy is needed, rhPTH (1-84) is not recommended (Khan 2019).
It is not known if recombinant human parathyroid hormone (1-84) (rhPTH [1-84]) 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. Infants exposed to rhPTH (1-84) via breast milk should be monitored for symptoms of hyper- and hypocalcemia; also consider monitoring infant serum calcium concentrations.
Total serum calcium (albumin-corrected) prior to therapy initiation, within 3 to 7 days following initiation or dosage adjustments until maintenance dose has been achieved, and periodically thereafter; urinary calcium excretion (after maintenance dose is achieved); signs and symptoms of hypo- and hypercalcemia
Exogenous parathyroid hormone; parathyroid hormone raises serum calcium concentrations by increasing renal tubular calcium reabsorption, increasing intestinal calcium absorption, and by increasing bone turnover, which releases calcium into the circulation.
Onset of action: Peak effect: 10 to 12 hours
Duration: >24 hours
Distribution: Vdss: 5.35 L
Metabolism: Primarily hepatic; cleavage by cathepsins
Bioavailability: SubQ: 53%
Half-life elimination: ~3 hours
Time to peak: 5 to 30 minutes
Excretion: Renal (primarily by glomerular filtration)
Renal function impairment: Mean Cmax in subjects with mild (CrCl 60 to 90 mL/minute) and moderate (CrCl 30 to 60 mL/minute) renal impairment was ~22% higher than that observed in subjects with normal renal function. AUC0-last and baseline-corrected AUC0-last was ~3.9% and ~2.5%, respectively, higher than that observed for subjects with normal renal function. No studies were conducted in patients with severe renal impairment or in patients on dialysis.
Hepatic function impairment: Mean Cmax and baseline-corrected Cmax values were 18% to 20% greater in the moderately impaired subjects than in those with normal function.
Cartridge (Natpara Subcutaneous)
25 mcg (per each): $5,950.29
50 mcg (per each): $5,950.29
75 mcg (per each): $5,950.29
100 mcg (per each): $5,950.29
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.
