Human Parathyroid Hormone, Recombinant

Human parathyroid hormone, recombinant is used as an adjunct to calcium and vitamin D to control low blood calcium (hypocalcemia) in patients with hypoparathyroidism.

Human parathyroid hormone, recombinant is available under the following different brand names: Natpara.

Dosages of Human Parathyroid Hormone, Recombinant:

Dosage Forms and Strengths

Subcutaneous (SC) Injection Cartridge

• 25 mcg/dose
• 50 mcg/dose
• 75 mcg/dose
• 100 mcg/dose

Dosage Considerations – Should be Given as Follows:

Hypocalcemia

Indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism

Dosing guidelines

• Individualize dose based on total serum calcium (albumin-corrected) and 24-hr urinary calcium excretion
• The recommended dose is the minimum 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., 8-9 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 recombinant human parathyroid hormone (rhPTH)

Before initiating rhPTH

• Confirm 25-hydroxyvitamin D stores are sufficient; if insufficient, replace to sufficient levels per standard of care
• Confirm serum calcium is greater than 7.5 mg/dL

Initiating rhPTH

• Initial: 50 mcg subcutaneously (SC) once daily; administer in the thigh (alternate thigh each day)
• In patients using active forms of vitamin D, decrease the dose of active vitamin D by 50%, if serum calcium is greater than 7.5 mg/dL
• In patients using calcium supplements, maintain calcium supplement dose
• Measure serum calcium concentration within 3-7 days
• Adjust dose of active vitamin D or calcium supplement or both based on serum calcium value and clinical assessment (i.e., signs and symptoms of hypocalcemia or hypercalcemia)
• Suggested adjustments to active vitamin D and calcium supplement based on serum calcium levels are provided below; repeat steps 4 and 5 until target serum calcium levels are within the lower half of the normal range (i.e., 8-9 mg/dL), active vitamin D has been discontinued, and calcium supplementation is sufficient to meet daily requirements
• Vitamin D and calcium dose adjustment
  • Adjust active vitamin D forms first and calcium supplement second
  • Serum calcium greater than ULN (10.6 mg/dL): Decrease or discontinue vitamin D; decrease calcium supplement
  • Serum calcium greater than 9 mg/dL and less than ULN (10.6 mg/dL): Decrease vitamin D; decrease calcium supplement
  • Serum calcium up to 9 mg/dL and greater than 8 mg/dL: No change for vitamin D and calcium supplements
  • Serum calcium less than 8 mg/dL: Increase vitamin D and calcium supplements

rhPTH dose adjustment

• May increase dose in increments of 25 mcg every 4 weeks; not to exceed 100 mcg/day if serum calcium cannot be maintained greater than 8 mg/dL without an active form of vitamin D and/or oral calcium supplementation
• May decrease dose to as low as 25 mcg/day if total serum calcium is repeatedly greater than 9 mg/dL after the active form of vitamin D has been discontinued and calcium supplement has been decreased to a dose sufficient to meet daily requirements
• Monitor clinical response and serum calcium levels after a dosage change
• Adjust active vitamin D and calcium supplements (as described above) if indicated

rhPTH maintenance dose

• The maintenance dose should be the lowest dose that achieves total serum calcium (albumin-corrected) within the lower half of the normal total serum calcium range (i.e., approximately 8-9 mg/dL), without the need for active forms of vitamin D and with calcium supplementation sufficient to meet daily requirements
• Monitor serum calcium and 24-hour urinary calcium per standard of care once a maintenance dose is achieved

rhPTH dose interruption or discontinuation

• Abrupt interruption or discontinuation of rhPTH can result in severe hypocalcemia
• Resume treatment with, or increase the dose of, an active form of vitamin D and calcium supplements if indicated in patients interrupting or discontinuing rhPTH
• Monitor for signs and symptoms of hypocalcemia and serum calcium levels
• In the case of a missed dose, the next rhPTH dose should be administered as soon as reasonably feasible, and additional exogenous calcium should be taken in the event of hypocalcemia

Dosage Modifications

Hepatic impairment

• Mild-to-moderate (Child-Pugh A or B): No dose adjustment is required
• Severe (Child-Pugh C): Data are not available

Renal impairment

• Mild-to-moderate (CrCl 30-90 mL/minute): No dose adjustment required
• Severe (CrCl less than 30 mL/minute), end-stage renal disease (ESRD), dialysis: Data are not available

Dosing Considerations

• 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
• Not studied in patients with hypoparathyroidism caused by surgery or calcium-sensing receptor mutations
• Children under 18 years: Safety and efficacy not established
• Avoid use in patients who are at increased baseline risk for osteosarcoma, including pediatric and young adult patients with open epiphyses

Common side effects of human parathyroid hormone, recombinant include:

• Numbness, tingling, pricking, burning sensation
• Low blood calcium (hypocalcemia)
• Headache
• High blood calcium (hypercalcemia)
• Nausea
• Diarrhea
• Vomiting
• Joint pain
• High levels of calcium in urine
• Pain in extremities
• Upper respiratory tract infection
• Abdominal pain upper
• Sinusitis
• Blood 25-hydroxycholecalciferol decreased
• High blood pressure (hypertension)
• Facial numbness
• Neck pain

Postmarketing side effects of human parathyroid hormone, recombinant reported include:

• Hypersensitivity reactions
• Seizures (due to hypocalcemia)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe interactions of human parathyroid hormone, recombinant include:
  • alendronate
  • etidronate
  • ibandronate
  • risedronate
  • tiludronate
  • zoledronic acid
• Serious interactions of human parathyroid hormone, recombinant include:
  • digoxin
• Human parathyroid hormone, recombinant has no listed moderate interactions with other drugs.
• Human parathyroid hormone, recombinant has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains the human parathyroid hormone, recombinant. Do not take Natpara if you are allergic to human parathyroid hormone, recombinant, or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Black Box Warnings

• Because of the potential risk of osteosarcoma, prescribe only to patients who cannot be well-controlled on calcium and active forms of vitamin D and for whom the potential benefits are considered to outweigh the potential risk
• Available only through a restricted program called the NATPARA REMS Program

Avoid increased osteosarcoma risk

• Paget disease of bone or unexplained elevations of alkaline phosphatase
• Pediatric and young adult patients with open epiphyses
• Hereditary disorders predisposing to osteosarcoma
• History of the prior external beam or implant radiation therapy involving the skeleton

Contraindications

• Hypersensitivity to drug or excipients

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Human Parathyroid Hormone, Recombinant?”

Long-Term Effects

• See "What Are Side Effects Associated with Using Human Parathyroid Hormone, Recombinant?”

Cautions

• Potential increased risk of osteosarcoma
• Hypersensitivity reactions, including anaphylaxis, shortness of breath, angioedema, hives, and rash reported; if signs or symptoms of a serious hypersensitivity reaction occur, discontinue treatment and treat hypersensitivity reaction according to the standard of care; monitor until signs and symptoms resolve; monitor for hypocalcemia if therapy discontinued
• Severe hypercalcemia was reported; the risk is highest when starting or increasing the dose; monitor serum calcium and patients for signs and symptoms of hypercalcemia; monitor serum calcium when starting or adjusting the dose and when making changes to co-administered drugs known to raise serum calcium
• Severe hypocalcemia that resulted in seizures reported; the risk is highest when an rhPTH dose is withheld, missed, or abruptly discontinued, but can occur at any time; monitor for signs and symptoms of hypocalcemia
• Monitor digoxin levels if co-administered; the inotropic effects of digoxin are affected by serum calcium levels; hypercalcemia of any cause may predispose to digoxin toxicity; monitor serum calcium more frequently and increase monitoring when initiating or adjusting the dose
• Coadministration with alendronate leads to a reduction in the calcium sparing effect, which can interfere with the normalization of serum calcium; concomitant use with alendronate is not recommended

REMS Program

• Because of the potential risk of osteosarcoma associated with therapy, the drug is available only through a restricted REMS program; under the program, only certified healthcare providers can prescribe and only certified pharmacies can dispense the drug; further information is available at www.NATPARAREMS.com or by telephone at 1-800-828-2088

Pregnancy and Lactation

• There are no adequate and well-controlled studies of human parathyroid hormone, recombinant in pregnant women. Consult your doctor.
• It is unknown if human parathyroid hormone, recombinant is distributed in human breast milk. Consult your doctor before breastfeeding.