Teriparatide is subcutaneously administered recombinant parathyroid hormone that is identical to the 34 N-terminal amino acids of human parathyroid hormone (PTH). Teriparatide is indicated for the treatment of osteoporosis is recommended only in patients at a high risk of fracture, which is defined as those with history of osteoporotic fracture, those with multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Teriparatide reduces the incidence of new vertebral and nonvertebral fragility fractures in osteoporotic patients. In clinical trials of postmenopausal women, lumber spine and total hip bone density increased by 9.5% and 2.6% with 18 to 19 months of teriparatide therapy. Vetebral and nonveterbral fracture risks were reduced by 65% and 35%, respectively. The risk of veterbral fracture was reduced by 56% in women at high fracture risk. Avoid use in patients with increased risk of osteosarcoma or hereditary risk factors for osteosarcoma. Teriparatide has been investigated off-label for the treatment of hypoparathyroidism, but the role of the drug for treatment of these patients is not established.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Teriparatide solution should be clear and colorless.
-Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture.
-Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended.
Subcutaneous Administration
-Administer subcutaneously only. Do not inject intramuscularly or intravenously.
-Administer the first dose under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur.
-Patients and/or caregivers who administer teriparatide should receive appropriate training and instruction on the proper use of the prefilled delivery device (pen) from a qualified health care professional.
Subcutaneous Administration (Forteo or Bonsity Pen)
-Inject subcutaneously into the thigh or abdomen.
-Lightly pinch a fold of skin; insert the needle at a 90-degree angle. Push in the pen injection button until it stops. Hold it in and count to 5 slowly. Wait until the count of 5 to make sure the correct dose is administered. Then pull the needle from skin.
-Properly dispose of used pen needles.
-Rotate administration sites with each injection to prevent lipodystrophy.
-The pen should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients; reserve the use of any pen for 1 patient only.
-Storage: Store the pen under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) at all times except when administering the product. Do not freeze. Do not use if the device has been frozen. Do not store the pen with the needle on, as the medication may leak out or air bubbles may form in the cartridge. Recap the delivery device when not in use to protect the cartridge from physical damage and light. During each use, time out of the refrigerator should be minimized; the dose may be delivered immediately following removal from the refrigerator. Each pen can be used for up to 28 days after the first injection. After 28 days, discard the pen, even if it still contains unused solution.
Hypercalcemia and hypercalciuria have been reported in patients treated with teriparatide; the frequency of at least 1 episode of hypercalcemia within 4 to 6 hours of the teriparatide dose was 11% in females and 6% in males with 3% of females and 1% of males having hypercalcemia verified on consecutive calcium measurement. The serum and urine concentrations of calcium are transiently increased in patients treated with teriparatide but typically remain within the normal range (or return to the normal range following a decrease in either teriparatide dose or daily calcium supplement dosage) and cause no associated adverse effects. Increases in serum uric acid concentrations have been reported but were typically asymptomatic and rarely resulted in hyperuricemia or gout, the incidence of which was not different than placebo. Serum calcitriol concentrations significantly increased compared with baseline while receiving teriparatide. Hypomagnesemia requiring daily supplementation has been reported in patients receiving teriparatide for hypoparathyroidism. In single-dose studies, teriparatide produced transient phosphaturia and mild transient reductions in serum phosphorus concentrations, although, hypophosphatemia was not observed in clinical trials. Calciphylaxis and worsening of previously stable cutaneous calcification have been reported during postmarketing experience with teriparatide. Discontinue teriparatide in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification. Risk factors for development of calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use.
Patients reported an injection site reaction associated with teriparatide subcutaneous injections, consisting mainly of injection site pain, swelling, and bruising at the site.
Dizziness (8%), vertigo (3.8%), and syncope (2.6%) have been reported in patients receiving teriparatide at incidences greater than with placebo. Transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients during clinical trials of teriparatide. An event typically began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours. When transient orthostatic hypotension occurred, it happened within the first several doses and was relieved by placing the patient in a reclining position.
Nausea (8.5% to 14%), vomiting (3%), constipation (5.4%), diarrhea (5.1%), and dyspepsia (5.2%) were reported in patients taking teriparatide at higher incidence rates vs. placebo. Nausea, vomiting, and/or constipation may also be symptoms of hypercalcemia.
In postmarketing experience, rare cases of hypersensitivity and anaphylactoid reactions including anaphylaxis, anaphylactic shock, angioedema, and urticaria have been reported in patients taking teriparatide. Also, dyspnea (3.6 to 6%) and rash (unspecified) (4.9%) have been reported at incidences greater than with placebo.
During clinical trials, leg muscle cramps were reported in 2.6% of patients and appeared to be related to teriparatide. Arthralgia was noted in 10.1% of patients. Additionally, during postmarketing surveillance, muscle spasms of both the leg and back have been reported relatively commonly (1 to 10 patients of every 100 patients treated); sometimes the reports of the muscle spasms occur shortly after the first dose. Severe back pain or back muscle spasms are rare and reported in less than 1 patient out of every 10,000 treated.
In controlled trials, early discontinuation due to adverse effects occurred in 5.6% of patients assigned to placebo and 7.1% of patients assigned to teriparatide. Adverse effects that occurred during clinical trials in teriparatide-treated and placebo treated-patients, respectively, included: pain (21.3% vs. 20.5%), headache (7.5% vs 7.4%), asthenia (8.7 vs. 6.8%), neck pain (3 vs 2.7%), hypertension (7.1% vs. 6.8%), angina (2.5% vs. 1.6%), depression (4.1% vs. 2.7%), insomnia (4.3% vs. 3.6%), rhinitis (9.6% vs. 8.8%), cough (6.4% vs. 5.5%), pharyngitis (5.5% vs. 4.8%), pneumonia (3.9% vs. 3.3%), and diaphoresis (2.2% vs. 1.7%).
In clinical trials, antibodies that cross-reacted with teriparatide were detected in 3% of females receiving the drug. Antibody formation appears to occur in the first 12 months of treatment, with diminished presence of antibodies following withdrawal of therapy. Among these patients, there was no evidence of hypersensitivity reactions, allergic reactions, effects on serum calcium, or effects on bone mineral density response reported. During a 24-week trial comparing the effects of 2 teriparatide products (n = 181), 2.2% of patients in each treatment group had detectable antibodies to teriparatide. One patient developed neutralizing antibodies to teriparatide.
Teriparatide may increase the risk of osteogenic sarcoma (osteosarcoma), a new primary malignancy. Rarely cases of osteosarcoma have been reported in postmarketing experience; however, an increased risk of osteosarcoma was not detected in observational studies in humans. Osteosarcoma was observed in 3 of 379,283 and in zero of 153,316 teriparatide-treated patients in 2 observational surveillance safety studies. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use. Use in rats has been associated with an increased incidence of osteosarcoma. This increased incidence was dependent on dose and duration of treatment; systemic exposure to teriparatide in the rats ranged from 3 to 60 times the exposure given to humans on a 20 mcg daily dose. The relevance of these rat osteosarcoma findings is uncertain relative to humans.
Teriparatide is contraindicated in patients with a hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.
Rare cases of osteogenic sarcoma (osteosarcoma) have rarely been reported postmarketing in patients on teriparatide therapy; however, an increased risk of osteosarcoma was not detected in observational studies in humans. An increase in the incidence of osteosarcoma was observed during animal studies in male and female rats treated with teriparatide. Consider the potential risk of this new primary malignancy before treating patients with teriparatide. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use. Use of teriparatide for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Avoid prescribing teriparatide to patients who are at an increased risk for osteosarcoma (i.e., those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses or lack of epiphyseal closure, patients with prior external beam or implant radiation therapy involving the skeleton, or hereditary disorders predisposing to osteosarcoma). Patients with bone metastases or a history of skeletal malignancies and those with metabolic bone disorders other than osteoporosis should also not receive treatment with teriparatide.
Teriparatide is the amino-terminal fragment of parathyroid hormone and has actions similar to parathyroid hormone. Teriparatide may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia. Patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, should not be treated with teriparatide. Measure serum calcium at least 16 hours after drug administration if indicated. There have been serious reports of calciphylaxis and worsening of previously stable cutaneous calcification from teriparatide use. Risk factors for calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue teriparatide in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification.
Teriparatide has not been studied in patients with active nephrolithiasis. In clinical trials, the frequency of urolithiasis was similar in patients treated with teriparatide and placebo. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered. Use the drug with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.
Teriparatide should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur. In short-term clinical pharmacology studies with teriparatide, transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients. Typically, an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours. When transient orthostatic hypotension occurred, it happened within the first several doses, it was relieved by placing the person in a reclining position, and it did not preclude continued treatment.
Consider discontinuing teriparatide when pregnancy is recognized. There are no available data regarding the use of teriparatide in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, teriparatide increased skeletal deviations and variations in mouse offspring at subcutaneous doses equivalent to more than 60 times the recommended 20 mcg human daily dosage (based on body surface area), and the drug produced mild growth retardation and reduced motor activity in rat offspring at subcutaneous doses equivalent to more than 120 times the human dose.
It is not known whether teriparatide is excreted in human milk, affects human milk production, or has effects on the breastfed infant. Because of the potential for osteosarcoma shown with teriparatide in animal studies, advise patients that breast-feeding is not recommended during treatment.
The safety and efficacy of teriparatide have not been established in any pediatric population (adolescents, children, infants). The drug should not be prescribed in patients at an increased baseline risk of osteosarcoma which includes pediatric and young adult patients with open epiphyses. Therefore, teriparatide is not indicated for use in pediatric or young adult patients with open epiphyses.
Recommendations for calcium and vitamin D intake:
-To promote general bone health, guidelines for the prevention and treatment of osteoporosis recommend a target daily intake of 1,200 mg of elemental calcium for females older than 50 years. Daily vitamin D intake of 25 to 25 mcg (800 to 1,000 international units) is recommended for patients 50 years of age and older.
For the treatment of osteoporosis:
-for osteoporosis in postmenopausal women or in men with primary or hypogonadal osteoporosis at high risk for fracture:
Subcutaneous dosage:
Adults: 20 mcg subcutaneously once daily. Patients at high risk of fracture are defined as those with history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Supplement calcium and vitamin D if dietary intake is inadequate. Follow teriparatide treatment with a bisphosphonate or denosumab to prevent decline in bone density and loss of efficacy against fracture. Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended. The North American Menopause Society (NAMS) recommends that use of parathyroid analogs in postmenopausal women be reserved for those patients with a high risk of fracture who do not have hypercalcemia, bone metastases, any bone tumor-predisposing disorder, or a history of skeletal irradiation.
-for glucocorticoid-induced osteoporosis in adults at high risk of fracture:
Subcutaneous dosage:
Adults: 20 mcg subcutaneously once daily. Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended. Patients at high risk of fracture are defined as those with history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Supplement calcium and vitamin D if dietary intake is inadequate.
For the treatment of hypoparathyroidism*:
Subcutaneous dosage:
Adults: Teriparatide has been investigated off-label for hypoparathyroidism, but the role of the drug for treatment of these patients is not established. Typical dosage used in open-label trials is 20 mcg subcutaneously once or twice daily. More study is needed to determine if teriparatide has a role in the treatment of these patients.
Maximum Dosage Limits:
-Adults
20 mcg/day subcutaneously for osteoporosis.
-Geriatric
20 mcg/day subcutaneously for osteoporosis.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are necessary.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.
*non-FDA-approved indication
Calcium Acetate: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Carbonate: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Carbonate; Simethicone: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Chloride: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium Gluconate: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium; Vitamin D: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium; Vitamin D: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Chromium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Digoxin: (Minor) Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Because teriparatide increases serum calcium it should be used with caution in patients taking digoxin. Administering a single dose of teriparatide to patients with steady-state digoxin levels did not alter the effect of digoxin on the systolic time interval.
Pyridoxine, Vitamin B6: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Teriparatide is a recombinant amino terminal fragment of parathyroid hormone (PTH), comprised of the first 34 amino acids of PTH which produce most of its chief biologic effects. Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues. The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular micro-architecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.
Teriparatide is administered as a subcutaneous injection. Systemic clearance (approximately 62 L/hour in women and 94 L/hour in men) of teriparatide exceeds the rate of normal liver plasma flow, consistent with both hepatic and extra-hepatic clearance. Volume of distribution following intravenous injection is approximately 0.12 L/kg. Intersubject variability in systemic clearance and volume of distribution is 25% to 50%. The half-life of teriparatide in serum is 5 minutes when administered by intravenous injection and approximately 1 hour when administered by subcutaneous injection. The longer half-life following subcutaneous administration reflects absorption from the injection site. Peripheral metabolism of intact PTH, the 34 N-terminal amino acids, and, presumably, teriparatide, is believed to occur by non-specific enzymatic mechanisms in the liver followed by excretion via the kidneys.
Affected cytochrome P450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Subcutaneous Route
Teriparatide is absorbed after subcutaneous injection; the absolute bioavailability is approximately 95% based on pooled data from 20-, 40-, and 80-mcg doses (1, 2, and 4-times the recommended dosage, respectively). The rates of absorption and elimination are rapid. The peptide reaches peak serum concentrations about 30 minutes after subcutaneous injection of a 20-mcg dose and declines to non-quantifiable concentrations within 3 hours. Pharmacokinetic data from another brand of injection (20-mcg dose) results in a Cmax of 109.5 +/- 62.8 pg/mL (mean +/- SD) at a median Tmax of 0.25 hours (0.12 minimum, 1.08 maximum). Concentrations decline to non-quantifiable within 3 hours.
-Special Populations
Hepatic Impairment
Teriparatide has not been studied in patients with hepatic impairment.
Renal Impairment
Teriparatide administered as a single dose has not been noted to have any pharmacokinetic differences in a limited number of patients with mild to moderate renal insufficiency (i.e., CrCl 30 to 72 mL/minute). In patients with severe renal insufficiency (i.e., CrCl less than 30 mL/minute), the AUC and half-life were increased by 73% and 77% respectively; however, maximum serum concentrations of teriparatide were not increased. No information is available for patients undergoing dialysis for chronic renal failure.
Pediatrics
The pharmacokinetic parameters of teriparatide in children are not available.
Geriatric
The pharmacokinetic parameters of teriparatide appear to be similar across an age range of 31 to 85 years.
Gender Differences
The systemic exposure of teriparatide is 20% to 30% lower in men than women, although the recommended dose for both genders is 20 mcg/day.
Ethnic Differences
The populations included in the pharmacokinetic analyses were 98.5% Caucasian. The influence of race has not been determined.
Other
Heart Failure
The pharmacokinetic parameters of teriparatide appear to be similar in patients with NYHA Class I to Class III heart failure, and no clinically relevant changes in blood pressure or pulse rate were noted.