Parathyroid horomone (ORPHAN DRUG) to control low blood calcium levels in patients with hypoparathyroidism- approved by USFDA.

Date of approval- January 23, 2015

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The U.S. Food and Drug Administration approved Natpara (parathyroid horomone) to control hypocalcemia (low blood calcium levels) in patients with hypoparathyroidism.

  • Hypoparathyroidism occurs when the body secretes abnormally low levels of parathyroid hormone, which helps regulate calcium and phosphorus levels in the body.
  • Hypoparathyroidism is caused by loss of function of the parathyroid glands and occurs most commonly as a result of surgical removal of the parathyroid glands and more rarely as a result of autoimmune or congenital diseases.
  • Symptoms include numbness, tingling, muscle twitching, spasms or cramps, abnormal heart rhythm, and seizures as a consequence of low blood calcium levels. Hypoparathyroidism is also associated with long-term complications such as kidney damage, kidney stones, development of cataracts and calcification of soft tissues.
  • NATPARA is a parathyroid hormone indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism.
  • NATPARA is not a parathyroid hormone replacement .

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

NATPARA

  • 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 0.40 mg or 0.80 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 μL. Using the Q-Cliq pen, each NATPARA dual chamber cartridge delivers 14 doses of NATPARA.

CLINICAL PHARMACOLOGY

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.

DOSAGE AND ADMINISTRATION

  • The dose of NATPARA should be individualized to achieve a serum  calcium level in the lower half of the normal range.
  • Confirm vitamin D stores are sufficient and serum calcium is above 7.5  mg/dL before starting NATPARA.
  • The starting dose of NATPARA is 50 mcg injected once daily in the thigh. When starting NATPARA, decrease dose of active vitamin D by 50%, if serum calcium is above 7.5 mg/dL.
  • Monitor serum calcium levels every 3 to 7 days after starting or adjusting NATPARA dose and when adjusting either active vitamin D or calcium supplements dose while using NATPARA.

DOSAGE FORMS AND STRENGTHS

  • NATPARA is supplied as a multiple dose, dual-chamber glass cartridge containing a sterile lyophilized powder and a sterile diluent for reconstitution in four dosage strengths.
  • For injection: 25 mcg, 50 mcg, 75 mcg, or 100 mcg.

Safety Data

  • The safety and effectiveness of Natpara were evaluated in a clinical trial of 124 participants who were randomly assigned to receive Natpara or a placebo.
  • The trial was designed to determine whether Natpara can be used as a substitute for, or be used to help reduce the amount of, active forms of vitamin D or oral calcium taken by participants.
  • Results showed 42 percent of Natpara-treated participants achieved normal blood calcium levels on reduced doses of calcium supplements and active forms of vitamin D, compared to three percent of placebo-treated participants.

Limitations of Use

  • Natpara carries a boxed warning that bone cancer (osteosarcoma) has been observed in rat studies with Natpara.
  • It is unknown whether Natpara causes osteosarcoma in humans, but because of a potential risk of osteosarcoma, Natpara is only recommended for use in patients whose hypocalcemia cannot be controlled on calcium supplementation and active forms of vitamin D, and for whom the potential benefits are considered to outweigh this potential risk.
  • Natpara is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). 
  • 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.
  • The most common side effects observed in Natpara-treated participants were sensations of tingling, tickling, pricking, or burning of the skin (paraesthesia); low blood calcium; headache; high blood calcium; and nausea.
  • Natpara is manufactured by NPS Pharmaceuticals, Inc., based in Bedminster, New Jersey.

 Reference:

  1. Press Release
  2. Drug Trials Snapshot
  3. Natpara Medication Guide