parathyroid hormone [SC]

Adult Dosing

To control hypocalcemia in patients with hypoparathyroidism

Dosing guidelines

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

Before initiating recombinant human parathyroid hormone (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

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

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

Contraindications ⬆ ⬇

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

Black Box Warnings ⬆ ⬇

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

Dosing Adjustment ⬆ ⬇

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

Warnings/Precautions ⬆ ⬇

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

Caution: Use cautiously in

Patients receiving digitalis compounds

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:C

Breastfeeding: Unknown if distributed in human breast milk

Adverse Reactions ⬆ ⬇

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

Clinical Pharmacology ⬆ ⬇

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

Brands and Availability ⬆ ⬇