Adult Dosing

To control hypocalcemia in patients with hypoparathyroidism

• The dose should be individualized based on total serum calcium (albumin-corrected) and 24-hr urinary calcium excretion
• Recommended dose is the minimum dose required to prevent both hypocalcemia and hypercalciuria that maintains total serum calcium (albumin-corrected) level of 8-9 mg/dL (i.e., the lower half of the normal range) without the need for active vitamin D form and with calcium supplementation sufficient and individualized to meet the patient’s daily requirements
• Doses of active vitamin D form and calcium need to be adjusted when using recombinant rhPTH

• Levels of 25-hydroxyvitamin D should be sufficient; if insufficient, replace to sufficient levels per standard of care
• Serum calcium levels should be >7.5 mg/dL

Initiating rhPTH

• Step 1: Initial dose: 50 mcg SC qd; administer in the thigh (alternate thigh every day)
• Step 2: Decrease the dose of active vitamin D by 50% in patient using it if serum calcium is >7.5 mg/dL
• Step 3: Maintain calcium supplement dose in patients using it
• Step 4: Measure serum calcium concentration within 3-7 days
• Step 5: Adjust the dose of active vitamin D or calcium supplement or both based on serum calcium value and clinical assessment
• Step 6: Repeat steps 4 and 5 until target serum calcium levels are within the lower half of the normal range, active vitamin D has been discontinued, and calcium supplementation is sufficient to meet daily requirements

Dose adjustments for active vitamin D and calcium supplements based on serum calcium levels

• Serum calcium > ULN (10.6 mg/dL): Decrease the dose of active vitamin D form first and then decrease calcium supplements; in patients receiving the lowest available dose of active vitamin D, discontinue it first and then decrease calcium supplements
• Serum calcium < ULN (10.6 mg/dL) but > 9 mg/dL: Decrease or discontinue active vitamin D form first and do not change or decrease calcium supplement if active vitamin D form has been discontinued; discontinue active vitamin D form in patients receiving the lowest available dose
• Serum calcium 9 mg/dL but > 8 mg/dL: Do not change the doses of active vitamin D form and calcium supplements
• Serum calcium < 8 mg/dL: Increase both active vitamin D form and calcium supplements

rhPTH dose adjustment

• Serum calcium cannot be maintained > 8 mg/dL without an active vitamin D form and/or oral calcium supplementation: Dose may be increased in increments of 25 mcg q4wks up to a maximum dose of 100 mcg/day
• Total serum calcium is repeatedly > 9 mg/dL after discontinuation of active vitamin D form and decreased calcium supplements (dose sufficient to meet daily requirements): Dose may be decreased to 25 mcg/day
• Monitor clinical response and serum calcium levels after a dosage change
• Adjust active vitamin D and calcium supplements (as per steps 4-6 described above) if indicated

rhPTH maintenance dose

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

rhPTH dose interruption or discontinuation

• Abrupt interruption or discontinuation can lead to severe hypocalcemia
• If interruption or discontinuation is indicated, resume treatment active vitamin D form and calcium supplements at the same doses or increase the doses
• Monitor serum calcium levels and signs and symptoms of hypocalcemia
• If a dose is missed, the next dose should be administered as soon as reasonably feasible and additional exogenous calcium should be taken if hypocalcemia occurs

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

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

• Hypersensitivity to any of the ingredients of the product
• Use in patients with Paget’s disease of bone
• Use in patients with unexplained elevations of alkaline phosphatase
• Use in pediatric and young adult patients with open epiphyses
• Use in patients with hereditary disorders predisposing to osteosarcoma
• Use in patients with a prior history of external beam or implant radiation therapy involving the skeleton

• Increased incidence of osteosarcoma has been reported in animal studies involving male and female rats that was dependent on dose and treatment duration; a risk to humans could not be excluded
• Use only in patients who cannot be well-controlled on calcium and active vitamin D forms alone and for whom the potential benefits outweigh potential risk of osteosarcoma
• Do not use 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

Renal Dose Adjustment

• Mild to moderate impairment (CrCl 30-90 mL/min): No dose adjustment
• Severe impairment (CrCl < 30 mL/min), ESRD: Dose adjustments not defined

Hepatic Dose Adjustment

• Mild to moderate impairment (Child-Pugh A or B): No dose adjustment
• Severe impairment (Child-Pugh C): Dose adjustments not defined

• Increased incidence of osteosarcoma has been reported in animal studies involving male and female rats that was dependent on dose and treatment duration; a risk to humans could not be excluded
• Use only in patients who cannot be well-controlled on calcium and active vitamin D forms alone and for whom the potential benefits outweigh potential risk of osteosarcoma
• Do not use 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
• Advise patients to promptly report clinical symptoms (e.g., persistent localized pain) and signs (e.g., soft tissue mass tender to palpation) that could be consistent with osteosarcoma
• Severe hypercalcemia has been reported; highest risk is when starting or increasing the dose; monitor serum calcium and patients for signs and symptoms of hypercalcemia. Treat hypercalcemia as per standard practice and withhold and/or reduce the dose if severe hypercalcemia occurs
• Severe hypocalcemia has been reported; highest risk is when therapy is withheld, missed, or abruptly discontinued, but can occur at any time; monitor serum calcium and patients for signs and symptoms of hypocalcemia. Resume treatment with, or increase the dose of, an active vitamin D form or calcium supplements or both if indicated in patients interrupting or discontinuing therapy to prevent severe hypocalcemia
• If coadministered with digitalis compounds, monitor serum calcium and digoxin levels and patients for signs and symptoms of digitalis toxicity because ionotropic effects of digoxin are affected by serum calcium levels; hypercalcemia may predispose to digoxin toxicity. Dose adjustment of digoxin and/or rhPTH may be needed
• Coadministered with alendronate is not recommended

• Patients receiving digitalis compounds

Pregnancy Category:C

Breastfeeding: Unknown if distributed in human breast milk

• CV: Hypertension
• CNS: Paraesthesia, headache, hypoaesthesia
• METABOLIC: Hypocalcemia, hypercalcemia, hypercalciuria
• GI: Nausea. diarrhea, vomiting, upper abdominal pain
• MUSC: Arthralgia, neck pain
• MISC: Pain in extremity
• RESP: Upper respiratory tract infection
• EENT: Sinusitis
• LABTEST: Decreased blood 25-hydroxycholecalciferol

• Parathyroid hormone analogs; parathyroid hormone increases serum calcium levels by increasing renal tubular calcium reabsorption, intestinal calcium absorption, and bone turnover, thereby releasing calcium into the circulation
• Metabolism: Metabolized in liver; CYP450: unknown
• Excretion: Renal excretion
• Half-life: 2.8-3hrs

US Trade Name(s)

• Natpara

US Availability

Natpara

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

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

Endocrine/Metabolic

Hormones

Parathyroid Hormone Analogs