Parathyroid Hormone (Monograph)

Brand name: Natpara
Drug class: Parathyroid Agents
Chemical name: Parathormone (human recombinant)
Molecular formula: C₄₀₈H₆₇₄N₁₂₆O₁₂₆S₂
CAS number: 9002-64-6

Medically reviewed by Drugs.com on Apr 5, 2024. Written by ASHP.

Introduction

Biosynthetic (recombinant DNA origin) preparation of human parathyroid hormone (parathormone, PTH); structurally identical to the full-length (84-amino acid) endogenous hormone.

Uses for Parathyroid Hormone

Hypoparathyroidism

Adjunct to calcium and vitamin D for management of hypocalcemia in patients with hypoparathyroidism; designated an orphan drug by FDA for this use.

Has been shown to maintain serum calcium concentrations within the normal physiologic range, while substantially reducing (sometimes even eliminating) supplemental calcium and activated vitamin D requirements.

Because of potential risk of osteosarcoma (see Boxed Warning), recommended only in patients who cannot be well controlled with calcium and activated vitamin D supplementation alone and for whom potential benefits are considered to outweigh such potential risk.

Safety and efficacy not established in patients with hypoparathyroidism caused by calcium-sensing receptor mutations or in patients with acute postsurgical hypoparathyroidism.

Parathyroid Hormone Dosage and Administration

General

• Prior to initiating therapy, evaluate 25-hydroxyvitamin D stores, and replace to sufficient levels if deficient; also ensure serum calcium concentration >7.5 mg/dL.

• Adjust vitamin D and calcium supplementation during therapy; goal is to reduce or completely discontinue the supplements. (See Calcium and Vitamin D Supplementation under Dosage and Administration.) Abrupt interruption or discontinuance of parathyroid hormone therapy may cause severe hypocalcemia; resume or increase dosage of calcium and/or activated vitamin D, if necessary, in these situations. (See Hypocalcemia under Cautions.)

• Routinely monitor serum calcium concentrations to assess therapeutic response and adverse effects (e.g., hyper- or hypocalcemia).

Restricted Distribution Program

• Available only through a restricted distribution program (Natpara REMS program) because of potential risk of osteosarcoma. (See Osteosarcoma under Cautions.)

• Clinicians and pharmacies must be certified with the program before they can prescribe or dispense the drug.

• Additional information available at 855-628-7272.

Administration

Sub-Q Administration

Administer by sub-Q injection; using Q-Cliq pen delivery device (supplied by manufacturer).

Administer once daily.

Inject sub-Q into thigh; alternate thighs daily.

If dose is missed, administer missed dose as soon as reasonably possible. In the event of hypocalcemia resulting from a missed dose, administer additional calcium supplementation.

May be self-administered after patient and/or caregiver is properly trained.

Commercially available as a dual-chambered cartridge containing lyophilized drug and sterile diluent; when used as directed, each cartridge delivers 14 doses of parathyroid hormone.

Never transfer contents of delivery device to syringe.

Reconstitution

Reconstitute directly in cartridge by using mixing device supplied by manufacturer.

Mix contents by slowly moving cartridge back and forth about 10 times; do not shake.

The reconstituted solution should be colorless; however, it is normal for small particles to be present.

Each cartridge containing reconstituted drug may be used for up to 14 days if stored under recommended conditions. (See Storage under Stability.)

Mixing device may be used up to 6 times (i.e., to reconstitute 6 medication cartridges).

Dosage

Individualize dosage according to albumin-corrected serum calcium concentration and 24-hour urinary calcium excretion. Goal is to administer lowest dosage that will prevent both hypocalcemia and hypercalciuria. To minimize risk of hypercalciuria, target serum calcium concentrations should be in the lower half (i.e., 8–9 mg/dL) of normal range.

Adults

Hypoparathyroidism

Initial Dosage

Sub-Q

Initially, 50 mcg once daily in conjunction with activated vitamin D and calcium supplementation.

If baseline serum calcium concentration >7.5 mg/dL, reduce dosage of activated vitamin D by 50% upon initiation of parathyroid hormone therapy. Maintain current calcium dosage.

Measure serum calcium concentrations within 3–7 days of initiating parathyroid hormone therapy and adjust vitamin D and calcium supplementation accordingly (see Calcium and Vitamin D Supplementation under Dosage and Administration).

Maintenance Dosage

Sub-Q

Titrate dosage based on total albumin-corrected serum calcium concentrations. Goal is to achieve the minimum dosage that will maintain total albumin-corrected serum calcium concentrations at 8–9 mg/dL without the need for activated vitamin D and with only the minimum amount of calcium supplementation necessary to meet daily requirements.

Increase by 25 mcg every 4 weeks up to 100 mcg once daily if serum calcium concentration cannot be maintained above 8 mg/dL without activated vitamin D and/or calcium supplementation.

May reduce to as low as 25 mcg once daily if total serum calcium concentration is repeatedly >9 mg/dL after activated vitamin D has been discontinued and calcium supplementation has been reduced to a dosage sufficient to meet daily requirements.

Monitor serum calcium concentrations and clinical response after each dosage adjustment. Adjust daily dosages of activated vitamin D and calcium accordingly. (See Calcium and Vitamin D Supplementation under Dosage and Administration.)

Once a maintenance dosage of parathyroid hormone has been achieved, monitor serum calcium concentrations and 24-hour urinary calcium excretion according to the standard of care.

Calcium and Vitamin D Supplementation

During parathyroid hormone therapy, adjust vitamin D and calcium supplementation based on serum calcium concentrations and clinical response (i.e., manifestations of hypo- or hypercalcemia). Monitor serum calcium concentrations within 3–7 days of initiating parathyroid hormone therapy, and adjust dosage of the supplements accordingly (see Table 1). Repeat process until serum calcium concentration is 8–9 mg/dL, activated vitamin D is discontinued, and calcium supplementation is sufficient to meet patient's daily requirements.

Discontinue in patients receiving the lowest available dose of vitamin D.

Prescribing Limits

Adults

Hypoparathyroidism

Sub-Q

Maximum 100 mcg daily.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustments not needed. (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild or moderate renal impairment: Dosage adjustments not needed. (See Renal Impairment under Cautions.)

Severe renal impairment and patients receiving dialysis: Dosage recommendations not available; safety and efficacy not established.

Geriatric Patients

Select dosage with caution (at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Cautions for Parathyroid Hormone

Contraindications

• Manufacturer states none known.

Warnings/Precautions

Warnings

Osteosarcoma

In rat carcinogenicity studies, a dose- and duration-dependent increase in osteosarcoma observed; occurred at systemic exposures ranging from 3–71 times those achieved in humans at recommended doses.

Use of parathyroid hormone recommended only in selected patients. (See Boxed Warning.)

Avoid use in patients with increased baseline risk of osteosarcoma.

Other Warnings and Precautions

Hypercalcemia

Risk of severe hypercalcemia, particularly when drug is initiated or dosage is increased.

Monitor serum calcium concentrations and patients for hypercalcemia; symptoms may include nausea, vomiting, constipation, fatigue, and muscle weakness.

If hypercalcemia occurs, manage according to standard practice; consider withholding and/or decreasing dosage of parathyroid hormone.

Hypocalcemia

Risk of severe hypocalcemia, particularly when drug is withheld, missed, or abruptly discontinued.

Monitor serum calcium concentrations and patients for hypocalcemia; symptoms may include tingling, cramping or twitching of muscles, seizures, depression, and cognitive impairment.

Resume or increase dosage of calcium and/or vitamin D supplements, if indicated.

Concomitant Use of Digoxin

Risk of digoxin toxicity in patients with hypercalcemia.

In patients receiving concomitant digoxin and parathyroid hormone therapy, monitor serum calcium and digoxin concentrations more frequently, particularly when initiating or adjusting dosage of parathyroid hormone. Monitor for signs and symptoms of digoxin toxicity and adjust dosage of the drugs, if necessary. (See Specific Drugs under Interactions.)

Immunogenicity

Antibodies to parathyroid hormone (including neutralizing antibodies) detected. Such antibodies do not appear to affect efficacy and safety; however, long-term implications unknown.

Specific Populations

Pregnancy

Category C.

Developmental toxicity observed in animal reproduction studies; no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefits justify potential risk to fetus.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in pediatric patients. Avoid use in individuals at increased risk of osteosarcoma, including pediatric and young adult patients with open epiphyses. (See Osteosarcoma under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Increased plasma concentrations observed in patients with moderate hepatic impairment (Child-Pugh class B). (See Hepatic Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Renal Impairment

Since parathyroid hormone is eliminated by the kidneys, plasma concentrations may be increased in patients with renal impairment. (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Not evaluated in patients with severe renal impairment or in patients undergoing dialysis.

Common Adverse Effects

Paresthesia, hypocalcemia, headache, hypercalcemia, nausea, hypoesthesia, diarrhea, vomiting, arthralgia, hypercalciuria, extremity pain, upper respiratory tract infection, upper abdominal pain, sinusitis, decreased 25-hydroxycholecalciferol concentration, hypertension, facial hypoesthesia, neck pain.

Drug Interactions

Specific Drugs

Parathyroid Hormone Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 53% after sub-Q injection.

Peak plasma concentrations generally attained in a biphasic manner; initial peak within 5–30 minutes and second (usually smaller) peak at 1–2 hours.

Dose-proportional increases in exposure observed with usual dosages.

Duration

Longer duration of calcemic effect compared with teriparatide; duration of calcemic response is 24 hours in patients with hypoparathyroidism following a 100-mcg dose.

Special Populations

In patients with moderate hepatic impairment (Child-Pugh class B), peak plasma concentrations increased by approximately 18–20% compared with individuals with normal hepatic function.

In patients with mild (Cl_cr 60–90 ml/minute) or moderate (Cl_cr 30–60 mL/minute) renal impairment, peak plasma concentrations and systemic exposure increased by 22 and 3.9%, respectively, compared with individuals with normal renal function.

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.

Elimination

Metabolism

Cleaved in liver by cathepsins into N- and C-terminal fragments. N-terminal fragments are further degraded, while C-terminal fragments are released into the circulation and eliminated by the kidneys.

Elimination Route

Any intact parathyroid hormone mostly cleared through glomerular filtration; small amounts bind to parathyroid hormone receptors. C-terminal fragments are filtered at the glomerulus.

Half-life

Following sub-Q administration of 50 or 100 mcg, apparent half-life approximately 3 hours.

Stability

Storage

Parenteral

Powder for Injection

Store cartridges containing lyophilized drug and sterile diluent at 2–8°C; do not freeze or shake. Store in original package. Store mixing device and empty Q-Cliq pen delivery device at room temperature.

Store reconstituted cartridge in the Q-Cliq pen at 2–8°C for up to 14 days. Protect from light and heat; avoid exposure to elevated temperatures.

Actions

• Structurally identical to full-length, 84-amino acid endogenous human parathyroid hormone.

• Binds and activates parathyroid hormone receptors in the kidney and bone.

• Responsible for calcium and phosphate homeostasis and maintenance of bone health.

• Increases serum calcium concentrations through reabsorption of calcium in the distal renal tubules, stimulation of renal 1-α-hydroxylase (to facilitate conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and increase intestinal calcium absorption), and release of calcium from bone into circulation from increased bone turnover.

• Also promotes phosphate excretion.

Advice to Patients

• Importance of providing patients with a copy of the manufacturer's patient information (medication guide and instructions for use) prior to initiating parathyroid hormone therapy, and of ensuring that patients fully understand the risks and benefits of therapy.

• Potential risk of osteosarcoma; importance of informing patients that parathyroid hormone caused a dose- and duration-dependent increase in osteosarcoma in rats and that a potential risk also may exist in humans. Advise patients to promptly report manifestations of possible osteosarcoma (e.g., persistent localized pain, new soft tissue mass that is tender to palpation).

• Importance of advising patients that parathyroid hormone is available only through a restricted distribution program (Natpara REMS Program). Inform patients of the requirements of the program and provide them with information on how they can obtain the drug (e.g., through certified pharmacies).

• Importance of informing patients that severe hypercalcemia can occur when initiating or adjusting parathyroid hormone therapy. Advise patients to promptly report any symptoms of hypercalcemia or changes in concurrently administered medications known to influence serum calcium concentration. Importance of informing patients that severe hypocalcemia can occur if parathyroid hormone therapy is abruptly discontinued or interrupted. Advise patients to promptly report any symptoms of hypocalcemia or interruptions in therapy, including missed doses. Recommendations for monitoring serum calcium concentration should be followed.

• Importance of instructing patients and/or their caregivers regarding proper preparation and administration of parathyroid hormone, including use of aseptic technique, and proper storage and disposal of the delivery device (Q-Cliq pen) and related supplies (e.g., used needles). Importance of not sharing the Q-Cliq pen with other patients.

• Importance of advising patients of common adverse effects (e.g., paresthesia, hypocalcemia, headache, hypercalcemia, nausea, hypoesthesia, diarrhea, vomiting, arthralgia, hypercalciuria, extremity pain).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., digoxin) and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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