Parathyroid hormone (injection)

Parathyroid hormone (injection)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shivani Chaparala M.B.B.S [2]

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Black Box Warning

WARNING See full prescribing information for complete Boxed Warning. POTENTIAL RISK OF OSTEOSARCOMA: In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. A risk to humans could not be excluded. Because of the potential risk of osteosarcoma, prescribe NATPARA 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. Avoid use of NATPARA in patients who are at increased baseline risk for osteosarcoma (including those 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 history of prior external beam or implant radiation therapy involving the skeleton). NATPARA is available only through a restricted program called the NATPARA REMS Program.

Overview

Parathyroid hormone (injection) is a parathyroid hormone that is FDA approved for the treatment of hypocalcemia in patients with hypoparathyroidism, as an adjunct to calcium and vitamin D.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include * Paresthesia

• Hypocalcemia
• Headache
• Hypercalcemia
• Nausea
• Hypoaesthesia
• Diarrhea
• Vomiting
• Arthralgia
• Hypercalciuria and
• Pain in extremity..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

INDICATIONS AND USAGE

NATPARA is a parathyroid hormone indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism.

Limitations of Use

• Because of the potential risk of osteosarcoma, NATPARA is recommended only for patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone.
• NATPARA was not studied in patients with hypoparathyroidism caused by calcium-sensing receptor mutations.
• NATPARA was not studied in patients with acute post-surgical hypoparathyroidism.

DOSAGE AND ADMINISTRATION

• The dose of NATPARA should be individualized to achieve a serum calcium level in the lower half of the normal range.
• Confirm vitamin D stores are sufficient and serum calcium is above 7.5 mg/dL before starting NATPARA.
• The starting dose of NATPARA is 50 mcg injected once daily in the thigh. When starting NATPARA, decrease dose of active vitamin D by 50%, if serum calcium is above 7.5 mg/dL.
• Monitor serum calcium levels every 3 to 7 days after starting or adjusting NATPARA dose and when adjusting either active vitamin D or calcium supplements dose while using NATPARA.

DOSAGE FORMS AND STRENGTHS

• NATPARA is supplied as a multiple-dose, dual-chamber glass cartridge containing a sterile lyophilized powder and a sterile diluent for reconstitution in four dosage strengths.
• For injection: 25 mcg, 50 mcg, 75 mcg, or 100 mcg.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Parathyroid hormone (Injection) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Parathyroid hormone (Injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Parathyroid hormone (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Parathyroid hormone (Injection) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Parathyroid hormone (Injection) in pediatric patients.

Contraindications

There is limited information regarding Parathyroid hormone (injection) Contraindications in the drug label.

Warnings

WARNING See full prescribing information for complete Boxed Warning. POTENTIAL RISK OF OSTEOSARCOMA: In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. A risk to humans could not be excluded. Because of the potential risk of osteosarcoma, prescribe NATPARA 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. Avoid use of NATPARA in patients who are at increased baseline risk for osteosarcoma (including those 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 history of prior external beam or implant radiation therapy involving the skeleton). NATPARA is available only through a restricted program called the NATPARA REMS Program.

Potential Risk of Osteosarcoma

• In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor).
• The occurrence of osteosarcoma was observed to be dependent on parathyroid hormone dose and treatment duration.
• This effect was observed at parathyroid hormone exposure levels ranging from 3 to 71 times the exposure levels for humans receiving a 100 mcg dose of NATPARA.
• These data could not exclude a risk to humans.
• Because of a potential risk of osteosarcoma, use NATPARA only in patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone and for whom the potential benefits are considered to outweigh this potential risk.
• To further mitigate the potential risk of osteosarcoma, avoid use of NATPARA in patients who are at increased 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.
• Instruct 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.
• NATPARA is available only through a restricted program under a REMS.

NATPARA REMS Program

• Because of the potential risk of osteosarcoma associated with NATPARA therapy, NATPARA is available only through a restricted REMS program called the NATPARA REMS Program.
• Under the NATPARA REMS Program, only certified healthcare providers can prescribe and only certified pharmacies can dispense NATPARA.
• Further information is available at www.NATPARAREMS.com or by telephone at 1-800-828-2088.

Hypercalcemia

• Severe hypercalcemia has been reported with NATPARA.
• In the pivotal trial, 3 patients randomized to NATPARA required administration of IV fluids to correct hypercalcemia during treatment with NATPARA.
• The risk is highest when starting or increasing the dose of NATPARA, but can occur at any time.
• Monitor serum calcium and patients for signs and symptoms of hypercalcemia.
• Treat hypercalcemia per standard practice and consider holding and/or lowering the dose of NATPARA if severe hypercalcemia occurs.

Hypocalcemia

• Severe hypocalcemia has been reported with NATPARA.
• The risk is highest when NATPARA 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 form of vitamin D or calcium supplements or both if indicated in patients interrupting or discontinuing NATPARA to prevent severe hypocalcemia.

Risk of Digoxin Toxicity with Concomitant Use of Digitalis Compounds

• The inotropic effects of digoxin are affected by serum calcium levels.
• Hypercalcemia of any cause may predispose to digoxin toxicity.
• In patients using NATPARA concomitantly with digitalis compounds, monitor serum calcium and digoxin levels and patients for signs and symptoms of digitalis toxicity.
• Adjustment of digoxin and/or NATPARA may be needed.
• No drug-drug interaction study has been conducted with digoxin and NATPARA.

Adverse Reactions

Clinical Trials Experience

Adverse Reactions in Clinical Trials for Hypoparathyroidism

• Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
• NATPARA was studied in a placebo-controlled trial.
• The data described in Table 1 below reflect exposure to NATPARA in 84 patients, including 78 exposed for 24 weeks.
• The mean age of the trial population was 47 years and ranged from 19 to 74 years old.
• Seventy-nine percent (79%) were females.
• Ninety-six percent (96%) were Caucasian, 0.8% were Black, and 1.6% were Asian.
• Patients had had hypoparathyroidism for on average 15 years and hypoparathyroidism was caused by post-surgical complications in 71% of cases, idiopathic hypoparathyroidism in 25% of cases, DiGeorge Syndrome in 3% of cases, and auto-immune hypoparathyroidism in 1% of cases.
• Prior to trial enrollment, participants were receiving a median (interquartile range) daily oral calcium dose of 2000 (1250, 3000) mg and a median daily oral active vitamin D dose equivalent to 0.75 (0.5, 1) mcg of calcitriol.
• The mean eGFR at baseline was 97.4 mL/min/1.73 m2 and 45%, 10% and 0% had mild, moderate and severe renal impairment, respectively, at baseline.
• During the trial, most patients received 100 mcg and the dose range was 50 to 100 mcg administered subcutaneously once daily in the thigh.
• Table 1 lists common adverse reactions associated with NATPARA use in the clinical trial.
• Common adverse reactions were reactions that occurred in ≥5% of subjects and occurred more commonly on NATPARA than on placebo.

TABLE 1:

Hypercalcemia

• In the overall pivotal trial a greater proportion of patients on NATPARA had albumin-corrected serum calcium above the normal range (8.4 to 10.6 mg/dL).
• During the entire trial duration 3 patients on NATPARA and 1 patient on placebo had a calcium level above 12 mg/dL.
• Table 2 displays the number of subjects who had albumin-corrected serum calcium levels above the normal range (8.4 to 10.6 mg/dL) by study treatment period in the placebo-controlled study based on routine monitoring at each trial visit.
• More patients randomized to NATPARA had hypercalcemia in both phases of the study (note: all trial participants underwent a 50% reduction in active vitamin D dose at randomization).

Table 2

Hypocalcemia

• Table 3 displays the number of subjects who had albumin-corrected serum calcium levels below 8.4 mg/dL by treatment period in the placebo-controlled study based on routine monitoring at each trial visit.
• More patients randomized to placebo had hypocalcemia of less than 7 mg/dL in the titration phase (note: all trial participants underwent a 50% reduction in active vitamin D dose at randomization).
• More patients randomized to NATPARA had hypocalcemia of less than 7 mg/dL in the dose maintenance phase.

Table 3:

• The risk of hypocalcemia increases when NATPARA is withdrawn.
• At the end of the trial, NATPARA and placebo were withdrawn, calcium and active vitamin D were returned to baseline doses and subjects were followed for 4 weeks.
• During this withdrawal phase, more patients previously randomized to NATPARA experienced an albumin-corrected serum calcium value of less than 7 mg/dL (5.0% versus 17% for previous treatment with placebo and NATPARA respectively).
• Twenty subjects (24%) previously randomized to NATPARA experienced adverse reactions of hypocalcemia in the post-treatment phase compared to three subjects (8%) previously randomized to placebo.
• Five subjects previously randomized to NATPARA with albumin-corrected serum calcium below 7 mg/dL required treatment with IV calcium gluconate to correct hypocalcemia.

Hypercalciuria

• Treatment with NATPARA did not lower 24-hour urinary calcium excretion in the placebo-controlled trial.
• The proportion of subjects with hypercalciuria (defined as urine calcium levels of >300 mg/24 hours) was similar at baseline and trial end in the NATPARA and placebo groups.
• The median (IQR) 24-hour Urine Calcium at trial end was similar between NATPARA [231 (168-351) mg/24 hours], and placebo [232 (139-342) mg/24 hours].
• At trial end, serum calcium values between NATPARA and placebo were also similar.
• Risk of hypercalciuria throughout the trial was related to serum calcium levels.
• To minimize the risk of hypercalciuria, NATPARA should be dosed to a target albumin-corrected total serum calcium within the lower half of the normal range (i.e., between 8 and 9 mg/dL).

Immunogenicity

• NATPARA may trigger the development of antibodies.
• In the placebo-controlled study in adults with hypoparathyroidism, the incidence of anti-PTH antibodies was 8.6% (3/35) and 5.9% (1/17) in subjects who received subcutaneous administration of 50 to 100 mcg NATPARA or placebo once daily for 24 weeks, respectively.
• Across all clinical studies in subjects with hypoparathyroidism following treatment with NATPARA for up to 2.6 years, the immunogenicity incidence rate was 16.1% (14/87).
• These 14 subjects had low titer anti-PTH antibodies and, of these, 3 subjects subsequently became antibody negative.
• One of these subjects had antibodies with neutralizing activity; this subject maintained a clinical response with no evidence of immune-related adverse reactions.
• Anti-PTH antibodies did not appear to affect efficacy or safety during the clinical trials but their longer-term impact is unknown.
• Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying diseases.
• For these reasons, comparison of the incidence of antibodies to NATPARA with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

There is limited information regarding Parathyroid hormone (injection) Postmarketing Experience in the drug label.

Drug Interactions

Alendronate

• Co-administration of alendronate and NATPARA leads to reduction in the calcium-sparing effect, which can interfere with the normalization of serum calcium.
• Concomitant use of NATPARA with alendronate is not recommended.

Digoxin

• NATPARA causes transient increase in calcium and therefore, concomitant use of NATPARA and cardiac glycosides (e.g., digoxin) may predispose patients to digitalis toxicity if hypercalcemia develops.
• Digoxin efficacy is reduced if hypocalcemia is present.
• In patients using NATPARA concomitantly with digoxin, carefully monitor serum calcium and digoxin levels, and patients for signs and symptoms of digoxin toxicity.
• Adjustment of digoxin and/or NATPARA may be needed.
• No drug-drug interaction study has been conducted with digoxin and NATPARA.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Developmental effects were observed in a peri-/post-natal study in pregnant rats given subcutaneous doses of 100, 300, 1000 mcg/kg/day from organogenesis through lactation, while 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).
• Because animal reproduction studies are not always predictive of human response, NATPARA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Parathyroid hormone (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Parathyroid hormone (injection) during labor and delivery.

Nursing Mothers

• It is unknown whether NATPARA is excreted in human milk. * In rats, mean parathyroid hormone concentration in milk was approximately 10 ng/mL at a dose of 1000 mcg/kg/day, 42 times lower in milk than in plasma.
• For nursing mothers, consideration should be made whether discontinuing nursing or NATPARA is warranted, taking into account the importance of the drug to the mother.

Pediatric Use

• Safety and efficacy in patients less than 18 years of age has not been established.
• Avoid use of NATPARA in patients who are at increased baseline risk for osteosarcoma including pediatric and young adult patients with open epiphyses.

Geriatic Use

• Clinical studies of NATPARA did not include sufficient numbers of subjects aged 65 and over to determine whether response in these subjects is different from younger subjects.
• In general, dose selection for elderly individuals should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Gender

There is no FDA guidance on the use of Parathyroid hormone (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Parathyroid hormone (injection) with respect to specific racial populations.

Renal Impairment

• Clinical studies of NATPARA did not include sufficient numbers of subjects with moderate and severe renal impairment to determine whether they respond differently from subjects with mild renal impairment or normal renal function.
• Some of the mechanisms of action of NATPARA (e.g., conversion of 25-OH vitamin D to 1,25-OH2 vitamin D) are dependent on renal function.
• NATPARA is eliminated by the kidney and maximum drug levels increased with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Parathyroid hormone (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Parathyroid hormone (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Parathyroid hormone (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Parathyroid hormone (injection) Administration in the drug label.

Monitoring

There is limited information regarding Parathyroid hormone (injection) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Parathyroid hormone (injection) and IV administrations.

Overdosage

There is limited information regarding Parathyroid hormone (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Parathyroid hormone (injection) Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Parathyroid hormone (injection) Mechanism of Action in the drug label.

Structure

There is limited information regarding Parathyroid hormone (injection) Structure in the drug label.

Pharmacodynamics

There is limited information regarding Parathyroid hormone (injection) Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Parathyroid hormone (injection) Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Parathyroid hormone (injection) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Parathyroid hormone (injection) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Parathyroid hormone (injection) How Supplied in the drug label.

Storage

There is limited information regarding Parathyroid hormone (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Parathyroid hormone (injection) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Parathyroid hormone (Injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Parathyroid hormone (injection) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Parathyroid hormone (injection) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.