Parathyroid Hormone- Natpara -@- (Jan 2015) - Thyroid hormone
Drug Name:Parathyroid Hormone- Natpara -@- (Jan 2015) - Thyroid hormone
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No drug-drug interaction study has been conducted with digoxin and NATPARA
Indication:
HIGHLIGHTS OF PRESCRIBING INFORMATION
Indication- Indicated as an Adjunct to Calcium and Vitamin D to
control Hypocalcemia in Patients with Hypothyrodism
Initial U.S. Approval: 2015
Proprietary Name- NATPARA*
Established Name- Parathyroid hormone
Applicant- NPS Pharmaceuticals INC
Indication- Indicated as an Adjunct to Calcium and Vitamin D to
control Hypocalcemia in Patients with Hypothyrodism
Approval Date- 1/23/2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.3
Drug Name - Parathyroid Hormone
Active Ingredient- Natpara
Date of approval - 1/23/2015
FDA-approved use - To control hypocalcemia (low calcium levels)
in patients with hypoparathyroidism
Approved by US FDA on 1/23/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
ADVERSE REACTIONS
• The most common adverse reactions associated with NATPARA and skeleton) occurring in greater than 10% of individuals were: paresthesia,
Contra-Indications:
CONTRAINDICATIONS
• None
WARNINGS AND PRECAUTIONS
1.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 wellcontrolled 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
2. Hypercalcemia
Severe hypercalcemia has been reported with NATPARA. In the pivotal trial, 2 patients randomized to NATPARA required administration of IV fluids to correct hypercalcemia.
The risk is highest when starting or increasing the dose of NATPARA.
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
3. 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
4.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
Dosages/ Overdosage Etc:
Indication- Indicated as an Adjunct to Calcium and Vitamin D to
control Hypocalcemia in Patients with Hypothyrodism
DOSAGE FORMS AND STRENGTHS
These highlights do not include all the information needed to use NATPARA is supplied as a multiple-dose, dual-chamber glass cartridge NATPARA safely and effectively. See full prescribing information for containing a sterile lyophilized powder and a sterile diluent for reconstitution NATPARA. in four dosage strengths.
NATPARA® (parathyroid hormone) for injection, for subcutaneous use For injection: 25 mcg, 50 mcg, 75 mcg, or 100 mcg.
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
1. Dosing Guidelines
The dose of NATPARA should be individualized based on total serum calcium (albumin-corrected) and 24-hour urinary calcium excretion. The recommended NATPARA dose is the minimum dose required
NATPARA® (parathyroid hormone) for injection 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 (i.e., between 8 and 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.
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide and Instructions for Use)
General Counseling Information-
Prior to treatment, patients should fully understand the risks and benefits of NATPARA. Ensure that all patients receive the Medication Guide and Instructions for Use document prior to initiating NATPARA therapy.
1. Potential Risk of Osteosarcoma-
Advise patients that the active ingredient in NATPARA, parathyroid hormone, caused an increase in the incidence of osteosarcoma (a malignant bone tumor) in male and female rats in dedicated lifelong carcinogenicity studies and that the risk of osteosarcoma in rats was dependent on parathyroid hormone dose administered, on treatment duration and occurred at exposure levels close to the clinical exposure range.
Based on these findings NATPARA may carry a potential risk to humans.
Patients should be advised that because of a potential risk of osteosarcoma, NATPARA is only recommended for patients who cannot be well-controlled on oral calcium supplementation and on active forms of Vitamin D. In addition, use of NATPARA should be avoided in patients who have risk factors for osteosarcoma unless the benefits of using NATPARA in these patients are determined to outweigh this potential risk.
3. Severe Hypercalcemia-
Instruct patients that severe hypercalcemia can occur when starting or adjusting NATPARA dose and/or when making changes to co-administered drugs known to raise serum calcium.
Instruct patients to: report symptoms of hypercalcemia promptly, report any changes to co-administered drug(s) known to influence calcium levels and follow recommended serum calcium monitoring.
Manufactured for:
NPS Pharmaceuticals, Inc.
550 Hills Drive
Bedminster, NJ 07921
Manufactured for:
NPS Pharmaceuticals, Inc.
550 Hills Drive
Bedminster, NJ 07921
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
NATPARA is a parathyroid hormone. Parathyroid hormone raises serum calcium by increasing renal tubular calcium reabsorption, increasing intestinal calcium absorption (i.e., by converting 25 OH vitamin D to 1,25 OH2 vitamin D) and by increasing bone turnover which releases calcium into the circulation.
2. Pharmacokinetics
Following single subcutaneous injections of NATPARA at 50 mcg and 100 mcg in subjects with hypoparathyroidism, peak plasma concentrations (mean Tmax) of NATPARA occurs within 5 to 30 minutes and a second usually smaller peak at 1 to 2 hours.
The plasma AUC increased in a dose proportional manner from 50 mcg to 100 mcg. The apparent terminal half-life (t1/2) was 3.02 and 2.83 hours for the 50 and 100 mcg dose, respectively.
Distribution:
NATPARA has a volume of distribution of 5.35 L at steady state.
Metabolism:
In vitro and in vivo studies demonstrated that the clearance of parathyroid hormone is primarily a hepatic process with a lesser role played by the kidneys.
Excretion:
In the liver, most of the intact parathyroid hormone is cleaved by cathepsins. In the kidney, a small amount of parathyroid hormone binds to physiologic PTH-1 receptors, but most is filtered at the glomerulus. C-terminal fragments are also cleared efficiently by glomerular filtration.
Hepatic Impairment:
A pharmacokinetic study was conducted in 6 men and 6 women with moderate hepatic impairment (Child-Pugh Classification of 7-9 [Grade B]) as compared with a matched group of 12 subjects with normal hepatic function
There were no apparent differences in the serum total calcium concentration-time profiles between the 2 hepatic function groups. No dose adjustment for NATPARA is recommended in patients with mild to moderate hepatic impairment.
Renal Impairment:
Pharmacokinetics following a single NATPARA 100 mcg subcutaneous dose was evaluated in 16 subjects with normal renal function (creatinine clearance (CLcr) > 90 mL/min) and 16 subjects with renal impairment.
The mean maximum concentration (Cmax) of parathyroid hormone following administration of 100 mcg NATPARA in subjects with mild (CLcr 60 to 90 mL/min) and moderate (CLcr 30 to 60 mL/min) renal impairment was approximately 22% higher than that observed in subjects with normal renal function.
No studies were conducted in patients with severe renal impairment or in renal impairment patients on dialysis.
Age, Sex, Race, and Weight:
Based on population pharmacokinetic analysis, age, sex, race, and body weight did not significantly affect the NATPARA pharmacokinetics.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS-
1.Pregnancy Category C:
There are no adequate and well-controlled studies in pregnant women.
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 ).
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
3. 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.
4. 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
5 Geriatric 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
6 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
OVERDOSAGE
Accidental overdose in studies in hypoparathyroidism occurred in 1 subject who received a 150 mcg dose and experienced mild palpitations. Serum calcium 24 hours later was 10.3 mg/dL.
In the event of overdose, the patient should be carefully monitored for hypercalcemia by a medical professional
