NATPARA (PARATHYROID HORMONE)- parathyroid hormone injection, powder, lyophilized, for solution
Shire-NPS Pharmaceuticals, Inc.
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 [see Warnings and Precautions (5.1), Nonclinical Toxicology (13.1)].
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 [see Indications and Usage (1) and Warnings and Precautions (5.1)].
Avoid use of NATPARA in patients who are at increased baseline risk for osteosarcoma, such as patients with Paget's 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 [see Warnings and Precautions (5.1)].
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 [see Warnings and Precautions (5.2)].
1 INDICATIONS AND USAGE
NATPARA is a parathyroid hormone indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism.
Limitations of Use:
Because of the potential risk of osteosarcoma, NATPARA is recommended only for patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone [see Warnings and Precautions (5.1)].
NATPARA was not studied in patients with hypoparathyroidism caused by calcium-sensing receptor mutations.
NATPARA was not studied in patients with acute post-surgical hypoparathyroidism.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Guidelines
The dose of NATPARA should be individualized based on total serum calcium (albumin-corrected) and 24-hour urinary calcium excretion. The recommended NATPARA dose is the minimum dose required to prevent both hypocalcemia and hypercalciuria. This dose will generally be the dose that maintains total serum calcium (albumin-corrected) within the lower half of the normal range (i.e., between 8 and 9 mg/dL) without the need for active forms of vitamin D and with calcium supplementation sufficient and individualized to meet the patient's daily requirements.
Doses of active forms of vitamin D and calcium supplements will need to be adjusted when using NATPARA.
DOSAGE FORMS AND STRENGTHS
NATPARA is supplied as a multiple-dose, dual-chamber glass cartridge containing a sterile powder and diluent in 4 dosage strengths.
For injection: 25 mcg per dose strength (0.4 mg for reconstitution with 1.13 mL)
For injection: 50 mcg per dose strength (0.8 mg for reconstitution with 1.13 mL)
For injection: 75 mcg per dose strength (1.21 mg for reconstitution with 1.13 mL)
For injection: 100 mcg per dose strength (1.61 mg for reconstitution with 1.13 mL)
DESCRIPTION
The active ingredient in NATPARA, parathyroid hormone, is produced by recombinant DNA technology using a modified strain of Escherichia coli. Parathyroid hormone has 84 amino acids and a molecular weight of 9425 daltons; the amino acid sequence for parathyroid hormone is shown below.
Figure 1: Amino Acid Sequence of Parathyroid Hormone
Figure 1
(click image for full-size original)
NATPARA (parathyroid hormone) for injection for subcutaneous use is supplied as a medication cartridge, which is comprised of a multiple-dose, dual-chamber glass cartridge containing a sterile lyophilized powder and a sterile diluent, within a plastic cartridge holder. The sterile lyophilized powder contains either 0.4 mg or 0.8 mg or 1.21 mg or 1.61 mg of parathyroid hormone, depending on dosage strength, and 4.5 mg sodium chloride, 30 mg mannitol, and 1.26 mg citric acid monohydrate. The volume of the sterile diluent is 1.13 mL and the diluent contains a 3.2 mg/mL aqueous solution of m-cresol.
The disposable NATPARA medication cartridge is designed for use with a reusable mixing device for product reconstitution and a reusable Q-Cliq pen for drug delivery. The Q-Cliq pen delivers a fixed volumetric dose of 71.4 �L. Using the Q-Cliq pen, each NATPARA dual chamber cartridge delivers 14 doses of NATPARA [see Dosage Forms and Strengths (3)].
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
NATPARA is a parathyroid hormone. Parathyroid hormone raises serum calcium by increasing renal tubular calcium reabsorption, increasing intestinal calcium absorption (i.e., by converting 25-OH vitamin D to 1,25-OH2 vitamin D) and by increasing bone turnover which releases calcium into the circulation.