Dosing & Uses
Dosage Forms & Strengths
SC injection cartridge
- 25 mcg/dose
- 50 mcg/dose
- 75 mcg/dose
- 100 mcg/dose
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 (ie, 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 >7.5 mg/dL
Initiating rhPTH
- Initial: 50 mcg SC qDay; 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 >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 (ie, 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 (ie, 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 >ULN (10.6 mg/dL): Decrease or discontinue vitamin D; decrease calcium supplement
- Serum calcium >9 mg/dL and
- Serum calcium ≤9 mg/dL and >8 mg/dL: No change for vitamin D and calcium supplements
- Serum calcium <8 mg/dL: Increase vitamin D and calcium supplements
rhPTH dose adjustment
- May increase dose in increments of 25 mcg q4wk; not to exceed 100 mcg/day if serum calcium cannot be maintained >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 >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 (ie, ~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 (CrCl 30-90 mL/min): No dose adjustment required
- Severe (CrCl <30 mL/min), 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
<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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (5)
- alendronate
alendronate decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
- etidronate
etidronate decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
- ibandronate
ibandronate decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
- risedronate
risedronate decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
- zoledronic acid
zoledronic acid decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
Serious - Use Alternative (1)
- digoxin
human parathyroid hormone, recombinant, digoxin. Other (see comment). Avoid or Use Alternate Drug. Comment: rhPTH causes transient increase in calcium and therefore, concomitant use with cardiac glycosides may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy is reduced if hypocalcemia is present. If coadministered, carefully monitor serum calcium and digoxin levels, and patients for signs and symptoms of digoxin toxicity. Adjustment of digoxin and/or rhPTH dose may be needed.
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Paraesthesia (31%)
Hypocalcemia (27%)
Headache (25%)
Hypercalcemia (19%)
Nausea (18%)
Hypoaesthesia (14%)
Diarrhea (12%)
Vomiting (12%)
Arthralgia (11%)
Hypercalciuria (11%)
1-10%
Pain in extremity (10%)
Upper respiratory tract infection (8%)
Abdominal pain upper (7%)
Sinusitis (7%)
Blood 25-hydroxycholecalciferol decreased (6%)
Hypertension (6%)
Hypoaesthesia facial (6%)
Neck pain (6%)
Postmarketing Reports
Hypersensitivity reactions
Seizures (due to hypocalcemia)
Warnings
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; further information is available at www.NATPARAREMS.com or by telephone at 1-855-NATPARA (1-855-628-7272)
Avoid with 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 prior external beam or implant radiation therapy involving the skeleton
Contraindications
Hypersensitivity to drug or excipients
Cautions
Potential increased risk of osteosarcoma (see Black Box Warnings)
Hypersensitivity reactions, including anaphylaxis, dyspnea, angioedema, urticaria, and rash reported; if signs or symptoms of serious hypersensitivity reaction occur, discontinue treatment and treat hypersensitivity reaction according to standard of care; monitor until signs and symptoms resolve; monitor for hypocalcemia if therapy discontinued
Severe hypercalcemia 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 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 a 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 coadministered; 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 dose
Coadministration with alendronate leads to 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 potential risk of osteosarcoma associated with therapy, drug is available only through 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 & Lactation
Pregnancy
Available data with injection use in pregnant women are insufficient to inform a drug-associated risk of birth defects, miscarriage or adverse maternal or fetal outcomes; there are no adequate and well-controlled studies in pregnant women
Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia
Infants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal 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
Animal Data
- Because animal reproduction studies are not always predictive of human response, use during pregnancy only if the potential benefit justifies the potential risk to the fetus
- No adverse developmental effects were observed when pregnant rats and rabbits were administered parathyroid hormone subcutaneously during period of organogenesis at doses resulting in 123 times and 8 times, respectively, the human exposure at the 100 mcg/day clinical dose
- Developmental effects were observed in a perinatal/postnatal study in pregnant rats given SC doses of 100, 300, 1000 mcg/kg/day from organogenesis through lactation, entire stillborn litters were observed in the 300-mcg/kg/day group (34 times the 100-mcg/day clinical dose based on AUC)
- Increased incidence of morbidity associated with dehydration, broken palate, and palate injuries related to incisor misalignment and mortality were found in pups from litters given 100 mcg/kg/day (10 times the 100-mcg/day clinical dose based on AUC)
Lactation
There are no data available on presence of parathyroid hormone in breast milk, effects on breastfed infant or on milk production; parathyroid hormone is present in the milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk
The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition
Infants exposed to parathyroid hormone through breast milk should be monitored for signs and symptoms of hypercalcemia or hypocalcemia; monitoring of serum calcium in the infant should be considered
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Bioengineered replica of human parathyroid hormone 1-84 (rhPTH 1-84)
Parathyroid hormone raises serum calcium by increasing renal tubular calcium reabsorption, increasing intestinal calcium absorption (ie, by converting 25 OH vitamin D to 1,25 OH2 vitamin D), and increasing bone turnover, which releases calcium into the circulation
Absorption
Bioavailability: 53%
Peak plasma concentration: 5-30 min; second small peak at 1-2 hr
Distribution
Vd: 5.35 L (steady state)
Metabolism
Primarily via hepatic clearance; most of the intact PTH is cleaved by cathepsins
Elimination
Half-life: ~3 hr
Excretion: A small amount of PTH binds to physiologic PTH-1 receptors, but most is filtered at the glomerulus; C-terminal fragments are also cleared efficiently by glomerular filtration
Administration
SC Preparation
Supplied as a multiple dose, dual-chamber glass cartridge containing a sterile powder and diluent in 4 dosage strengths
Reconstitute each cartridge using the mixing device for reconstitution Inspect visually for particulate matter and discoloration prior to administration
Discard the needle in a puncture-resistant container following administration
After reconstitution, each medication cartridge can be used for 14 SC injections
SC Administration
Administer SC by using the pen delivery device (ie, Q-Cliq pen)
Administer in thigh, rotating between thighs for each dose
Storage
The mixing device and empty Q-Cliq pen can be stored at room temperature
Store away from heat and light; avoid exposure to elevated temperatures
Do not freeze or shake; do not use if it has been frozen or shaken
Unreconstituted cartridges
- Refrigerate at 36-46°F (2-8°C)
- Store away from heat and light; avoid exposure to elevated temperatures
- Do not freeze or shake
- Do not use if it has been frozen or shaken
Reconstituted cartridge
- Refrigerate (36-46°F [2-8°C]) the remaining reconstituted doses in the Q-Cliq pen for up to 14 days
- After the 2-wk use period, only the cartridge should be discarded (ie, do not discard Q-Cliq pen)
- The Q-Cliq pen can be used for up to 2 years by replacing the reconstituted medication cartridges q2wk
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