Boxed Warning
Potential risk of osteosarcoma:
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.
Dosage Forms
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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: 5.35 L
Metabolism
Primarily hepatic; cleavage by cathepsins
Excretion
Renal (primarily by glomerular filtration)
Onset of Action
Peak effect: 10 to 12 hours
Time to Peak
5 to 30 minutes
Duration of Action
>24 hours
Half-Life Elimination
~3 hours
Use in Specific Populations
Special Populations: 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.
Special Populations: 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.
Use: Labeled Indications
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
Contraindications
Hypersensitivity to parathyroid hormone or any component of the formulation.
Dosage and Administration
Dosing: Adult
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)
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.
Dosing: Geriatric
Refer to adult dosing; use with caution.
Reconstitution
Reconstitute medication cartridge with provided mixing device. The mixing device can be used to reconstitute up to six medication cartridges.
Administration
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.
Storage
Prior to reconstitution, the dual-chamber medication cartridge should be stored in the package provided at 2°C to 8°C (36°F to 46°F). After reconstitution, the medication cartridge should be stored in the Q-Cliq pen at 2°C to 8°C (36°F to 46°F) for up to 14 days. Store away from heat and light. Discard reconstituted medication cartridges after 14 days. Do not freeze or shake or use if it has been frozen or shaken. The mixing device and empty Q-Cliq pen can be stored at room temperature.
Drug Interactions
Alendronate: May diminish the therapeutic effect of Parathyroid Hormone. More specifically, Alendronate may interfere with normalization of blood calcium concentrations. 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. Monitor therapy
Adverse Reactions
>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
Warnings/Precautions
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitoring Parameters
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
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal reproduction studies.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea; joint pain; painful extremities; nausea; vomiting; common cold symptoms; neck pain; abdominal pain; or tingling, tickling, or burning of skin. Have patient report immediately to prescriber signs of high calcium (weakness, confusion, feeling tired, headache, nausea and vomiting, constipation, or bone pain), skin growths, persistent pain, severe dizziness, severe headache, passing out, vision changes, fast heartbeat, or signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
