human parathyroid hormone recombinant

Recombinant human parathyroid hormone (rhPTH) is a biological product structurally similar to the natural human parathyroid hormone, bioengineered in the laboratory using DNA recombinant technology. Recombinant human parathyroid hormone is used, in addition to calcium and vitamin D therapy, to restore normal calcium levels in people with low calcium (hypocalcemia) associated with underactive parathyroid glands (hypoparathyroidism).

Human parathyroid hormone (PTH) is a natural hormone produced by the parathyroid glands. Patients with hypoparathyroidism are deficient in PTH. Recombinant parathyroid hormone supplements the natural PTH deficiency. Parathyroid hormone is responsible for the maintenance of a stable balance (homeostasis) of calcium and phosphorus in blood. Parathyroid hormone increases calcium absorption in the intestines and reabsorption in the kidneys, and also mobilizes calcium from the bones and releases into the blood circulation.

• Do not use it in patients with known hypersensitivity to any component of recombinant human parathyroid hormone.
• There have been reports of hypersensitivity reactions including rash, hives, shortness of breath, angioedema and anaphylaxis. Discontinue recombinant human parathyroid hormone if a patient develops serious hypersensitivity reactions and treat appropriately. Monitor for hypocalcemia if rhPTH is discontinued.
• Animal studies show rhPTH can increase the risk for osteosarcoma, a type of malignant bone cancer. Because of the potential risk of osteosarcoma:
  • Use rhPTH therapy only for patients for whom treatment with calcium supplements and active forms of vitamin D alone are not adequate and potential benefits outweigh the potential risk of osteosarcoma.
  • Avoid use in patients with an increased risk of osteosarcoma including:
    • Paget’s disease of bone
    • Unexplained elevations of alkaline phosphatase
    • Pediatric and young adult patients with open epiphyses
    • Hereditary disorders predisposing to osteosarcoma
    • History of prior external beam or implant radiation therapy involving the skeleton
  • Recombinant parathyroid hormone is available only through a restricted program called the NATPARA REMS Program. Further information is available at www.NATPARAREMS.com or call 1-855-NATPARA (1-855-628-7272).
• Recombinant parathyroid hormone treatment can lead to hypercalcemia that requires treatment with intravenous (IV) fluids. Hypercalcemia can occur any time, however, the risk is highest when initiating or increasing dosage. Monitor patients and treat hypercalcemia with standard care and withhold or lower rhPTH, if required.
• There have been reports of severe hypocalcemia, including cases that resulted in seizures. The risk of hypocalcemia is highest when rhPTH is withheld, missed or abruptly discontinued. Monitor patients and resume treatment or increase the dosage of an active form of D, calcium supplements or both if required to prevent hypocalcemia.
• Concurrent use with digoxin can increase the toxicity of digoxin. The effects of digoxin are influenced by calcium levels and rhTPH can increase calcium levels. Monitor calcium and digoxin levels more frequently in patients taking both, particularly when initiating or adjusting dose.
• Do not use concurrently with alendronate, it can reduce its calcium-sparing effect and interfere with the normalization of serum calcium levels.

Common side effects of human parathyroid hormone, recombinant include:

• Abnormal skin sensations including prickling, burning, tingling and numbness (paresthesia)
• Headache
• Diminished skin sensation (hypoesthesia)
• Facial hypoesthesia
• Low blood calcium (hypocalcemia)
• High blood calcium (hypercalcemia)
• Excessive calcium in urine (hypercalciuria)
• Nausea
• Vomiting
• Diarrhea
• Upper abdominal pain
• Antibody development
• High blood pressure (hypertension)
• Upper respiratory tract infection
• Sinus inflammation (sinusitis)
• Joint pain (arthralgia)
• Pain in extremity
• Neck pain
• Decrease in 25-hydroxy vitamin D (25-hydroxycholecalciferol) in blood

Less common side effects of human parathyroid hormone, recombinant include:

• Seizure from hypocalcemia
• Hypersensitivity reactions including:
  • Rash
  • Hives (urticaria)
  • Shortness of breath (dyspnea)
  • Swelling beneath the skin and mucous tissue (angioedema)
  • Severe allergic reaction (anaphylaxis)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Subcutaneous (SC) Injection Cartridge

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

Adult:

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-hour 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 above 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 above 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 above upper limit normal (ULN - 10.6 mg/dL): Decrease or discontinue vitamin D; decrease calcium supplement
  • Serum calcium above 9 mg/dL and 9 mg/dL to 8 mg/dL: No change for vitamin D and calcium supplements
  • Serum calcium below 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 above 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 above 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

• Maintenance dose should be the lowest dose that achieves a total serum calcium (albumin-corrected) within the lower half of the normal total serum calcium range (i.e., 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 required
• Severe (Child-Pugh C): Data are not available

Renal impairment

• Mild-to-moderate (creatinine clearance [CrCl] 30-90 mL/minute): No dose adjustment required
• Severe (CrCl below 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

Pediatric:

• Children below 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

Overdose

There is limited information on overdose. One accidental overdose in an individual who received 150 mcg caused mild palpitations. In the event of overdose, the patient must be monitored for hypercalcemia by a medical professional.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of human parathyroid hormone, recombinant include:
  • alendronate
  • etidronate
  • ibandronate
  • risedronate
  • 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.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies in pregnant women. Available data on the use of recombinant human parathyroid hormone in pregnant women are insufficient to identify a drug-related risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
• Use recombinant human parathyroid hormone during pregnancy only if potential benefits outweigh potential risks to the fetus.
• Hypocalcemia during pregnancy can increase the risk for spontaneous abortion, premature and dysfunctional labor, and possibly, preeclampsia.
• Hypocalcemia during pregnancy can result in fetal and neonatal hyperparathyroidism, which can cause fetal and neonatal conditions such as skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures.
• Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability (ranging from myotonic jerks to seizures), apnea, cyanosis and cardiac rhythm disorders.
• There is no information on the presence of human parathyroid hormone in the breastmilk, or its effects on milk production or the breastfed infant. Parathyroid hormone is present in animal milk, and it is likely also present in human milk.
• Decision to breastfeed should be based on the mother’s clinical need for the drug, the developmental and health benefits of breastfeeding, and the risks to the breastfed infant from exposure to the drug or because of the mother’s underlying condition.
• Infants exposed to parathyroid hormone in breast milk should be monitored for signs and symptoms of hypocalcemia or hypercalcemia.

• Follow the directions exactly for administration of recombinant human parathyroid hormone. Do not reuse needles. Dispose of used needles as per instructions.
• Recombinant human parathyroid hormone carries a risk for osteosarcoma, a type of bone cancer. Report to your physician immediately if you develop symptoms such as persistent localized pain or occurrence of new soft tissue mass that is tender to palpation.
• Recombinant human parathyroid hormone is available only through a restricted program called the Natpara REMS Program, because of the risk for osteosarcoma. You will need to go through the required procedure to obtain your prescription of rhPTH.
• You will need regular monitoring of calcium levels. Follow up with your physician and do not miss your tests. Report immediately if you develop symptoms of hypercalcemia, which may include increased thirst and urination, digestive symptoms and muscle weakness, or signs of hypocalcemia which include prickling, tingling or other abnormal sensations, muscle spasms, cramps and seizures.
• Report immediately if you develop hypersensitivity reactions such as rash, hives, breathing difficulties, swelling or other severe reactions.
• Store safely out of reach of children.
• In case of overdose, seek immediate medical help or contact Poison Control.