These Highlights Do Not Include All The Information Needed To Use Teriparatide Injection Safely And Effectively. See Full Prescribing Information For Teriparatide Injection.

Hypercalcemia

Teriparatide Injection has not been studied in patients with pre-existing hypercalcemia. Teriparatide Injection may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia [see Adverse Reactions (6.1, 6.3)]. Avoid Teriparatide Injection in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

PACKAGE LABEL – Teriparatide 20 mcg per dose, 2.4 mL

Do NOT transfer contents to a syringe

ATTENTION PHARMACIST: Medication Guide and device User Manual for patient inside carton

NDC 66993-495-28

Teriparatide Injection

20 mcg per dose (given once daily subcutaneously)

Each single-patient-use prefilled pen will deliver 28 subcutaneous doses.

560 mcg/2.24 mL (250 mcg/mL)

For Single-Patient-Use Only

REFRIGERATE / DO NOT FREEZE

For subcutaneous use / Rx only

Needles not included

Becton, Dickinson and Company pen needles are recommended for use with this device

Prasco

Teriparatide [ter-i-par-a-tide] Injection

User Manual

Important: First read the Medication Guide that comes inside your Teriparatide carton.

Before you use your new Teriparatide delivery device, please read the entire front and back of this User Manual completely. Follow the directions carefully when using the Teriparatide delivery device.

Do not share your delivery device or needles because infection or disease can be spread from one person to another.

The Teriparatide delivery device contains 28 days of medicine. Throw away the Teriparatide delivery device 28 days after first use, even if it is not completely empty. Do not inject more than one dose of Teriparatide in the same day.

Do not transfer Teriparatide to a syringe.

Wash your hands before every injection. Prepare the injection site as your healthcare provider instructed.

For more information, or if you have any questions, turn to the back of this page.

Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide Injection may transiently increase serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide Injection is used in patients receiving digoxin [see Warnings and Precaution (5.5) and Clinical Pharmacology (12.3)].

In postmarketing spontaneous reports, there have been cases of medication errors in which the entire contents (up to 800 mcg) (40 times the recommended dose) of the Teriparatide Injection prefilled delivery device (pen) have been administered as a single dose. Transient events reported have included nausea, weakness/lethargy and hypotension. No fatalities associated with overdose have been reported. Additional signs, symptoms, and complications of Teriparatide Injection overdosage may include a delayed hypercalcemic effect, vomiting, dizziness, and headache.

Teriparatide Injection is a recombinant human parathyroid hormone analog (PTH 1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone.

The molecular formula of Teriparatide is C₁₈₁H₂₉₁N₅₅O₅₁S₂ and molecular weight is 4117.8 daltons. Its amino acid sequence is shown below:

Teriparatide is manufactured using a strain of Escherichia coli modified by recombinant DNA technology.

Teriparatide Injection is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a single-patient-use delivery device (pen) for subcutaneous injection. Each delivery device (pen) is filled with volume to allow delivery of 2.24 mL. Each mL contains 250 mcg of Teriparatide (as a free base), 0.41 mg of glacial acetic acid, 0.1 mg of sodium acetate (anhydrous), 45.4 mg of mannitol, 3 mg of Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the pH to 4.

Each prefilled delivery device (pen) delivers 20 mcg of Teriparatide per dose for up to 28 days. Each device contains additional volume to allow troubleshooting of the device 2 times.

An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with Teriparatide. Osteosarcoma has been reported in patients treated with Teriparatide Injection in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of Teriparatide Injection use [see Dosage and Administration (2.3), Adverse Reactions (6.3), and Nonclinical Toxicology (13.1)].

Avoid Teriparatide Injection use in patients with (these patients are at increased baseline risk of osteosarcoma):

• Open epiphyses (pediatric and young adult patients) (Teriparatide Injection is not approved in pediatric patients) [see Use in Specific Populations (8.4)].
• Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone.
• Bone metastases or a history of skeletal malignancies.
• Prior external beam or implant radiation therapy involving the skeleton.
• Hereditary disorders predisposing to osteosarcoma.

Teriparatide Injection is a clear and colorless solution, available as single-patient-use prefilled delivery device (pen) in the following package size:

• 560 mcg/2.24 mL (250 mcg/mL) [intended to deliver 28 daily doses of 20 mcg] NDC 66993-989-28.

The safety and effectiveness of Teriparatide Injection have not been established in pediatric patients. Pediatric patients are at higher baseline risk of osteosarcoma because of open epiphyses [see Warnings and Precautions (5.1)].

Of the patients who received Teriparatide Injection in the osteoporosis trial of 1637 postmenopausal women, 75% were 65 years of age and older and 23% were 75 years of age and older. Of the patients who received Teriparatide Injection in the trial of 437 men with primary or hypogonadal osteoporosis, 39% were 65 years of age and over and 13% were 75 years of age and over. Of the 214 patients who received Teriparatide Injection in the glucocorticoid induced osteoporosis trial, 28% were 65 years of age and older and 9% were 75 years of age and older. No overall differences in safety or effectiveness of Teriparatide Injection have been observed between patients 65 years of age and older and younger adult patients.

As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other Teriparatide products may be misleading.

In the clinical trial of postmenopausal women with osteoporosis [see Clinical Studies (14.1)], antibodies that cross reacted with Teriparatide were detected in 3% of women (15/541) who received Teriparatide Injection. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no evidence of hypersensitivity reactions among these patients. Antibody formation did not appear to have effects on serum calcium, or on bone mineral density (BMD) response.

Teriparatide Injection is contraindicated in patients with hypersensitivity to Teriparatide or to any of its excipients. Hypersensitivity reactions have included angioedema and anaphylaxis [see Adverse Reactions (6.3)].

Most common adverse reactions (>10%) include: arthralgia, pain, and nausea (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Digoxin: Transient hypercalcemia may predispose patients to digitalis toxicity (5.5, 7.1)

In 5 patients with severe renal impairment (CrCl<30 mL/minute), the AUC and T_1/2 of Teriparatide were increased by 73% and 77%, respectively. Maximum serum concentration of Teriparatide was not increased. It is unknown whether Teriparatide Injection alters the underlying metabolic bone disease seen in chronic renal impairment [see Clinical Pharmacology (12.3)].

In single-dose rodent studies using subcutaneous injection of Teriparatide, no mortality was seen in rats given doses of 1000 mcg/kg (540 times the human dose based on surface area, mcg/m²) or in mice given 10,000 mcg/kg (2700 times the human dose based on surface area, mcg/m²).

In a long-term study, skeletally mature ovariectomized female monkeys (N=30 per treatment group) were given either daily subcutaneous Teriparatide injections of 5 mcg/kg or vehicle. Following the 18-month treatment period, the monkeys were removed from Teriparatide treatment and were observed for an additional 3 years. The 5 mcg/kg dose resulted in systemic exposures that were approximately 6 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Bone tumors were not detected by radiographic or histologic evaluation in any monkey in the study.

The recommended dosage is 20 mcg per dose given subcutaneously once a day. Instruct patients to take supplemental calcium and vitamin D if daily dietary intake is inadequate.

No studies have been performed in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

Teriparatide Injection is indicated:

• For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Teriparatide Injection reduces the risk of vertebral and nonvertebral fractures.
• To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
• For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.

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 microarchitecture 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.

In clinical trials, the frequency of urolithiasis was similar in patients treated with Teriparatide Injection and patients treated with placebo. However, Teriparatide Injection has not been studied in patients with active urolithiasis. If Teriparatide Injection-treated patients have pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion. Consider the risks and benefits of use in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

• Store Teriparatide Injection under refrigeration at 2° to 8°C (36° to 46°F) at all times except when administering the product.
• Recap the delivery device (pen) when not in use to protect the cartridge from physical damage and light.
• When using Teriparatide Injection, minimize the time out of the refrigerator; deliver the dose immediately following removal from the refrigerator.
• Do not freeze. Do not use Teriparatide Injection if it has been frozen.
• Throw away the device 28 days after first use.

• Osteosarcoma: Avoid use in patients with increased risk of osteosarcoma including patients with open epiphyses, metabolic bone diseases including Paget's disease, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. (5.1)
• Hypercalcemia and Cutaneous Calcification: Avoid in patients known to have an underlying hypercalcemic disorder. Discontinue in patients developing worsening of previously stable cutaneous calcification. (5.2)
• Risk of Urolithiasis: Consider the risk/benefit in patients with active or recent urolithiasis because of risk of exacerbation (5.3)
• Orthostatic Hypotension: Transient orthostatic hypotension may occur with initial doses of Teriparatide Injection (5.4)

• Recommended dosage is 20 mcg subcutaneously once a day (2.1)
• Consider supplemental calcium and Vitamin D based on individual patient needs (2.1)
• Administer as a subcutaneous injection into the thigh or abdominal region (2.2)
• Administer initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur (2.2)
• Use of Teriparatide Injection 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 (2.3)

Teriparatide Injection 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 of Teriparatide Injection in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers. Typically, these events began within 4 hours of dosing and resolved (without treatment) 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.

Injection: 560 mcg/2.24 mL (250 mcg/mL) clear, colorless solution in a single-patient-use prefilled delivery device (pen) intended to deliver 28 daily doses of 20 mcg.

Hypercalcemia may predispose patients to digitalis toxicity because Teriparatide Injection transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide Injection is used in patients receiving digoxin [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

• Pregnancy: Consider discontinuing when pregnancy is recognized (8.1)
• Lactation: Breastfeeding is not recommended (8.2)
• Pediatric Use: Safety and effectiveness not established. Avoid use due to increased baseline risk of osteosarcoma (5.1, 8.4)

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

• Administer Teriparatide Injection as a subcutaneous injection into the thigh or abdominal region. Teriparatide Injection is not approved for intravenous or intramuscular use.
• Teriparatide Injection should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur [see Warnings and Precautions (5.4)].
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration (Teriparatide Injection is a clear and colorless liquid). Do not use if solid particles appear or if the solution is cloudy or colored.
• Patients and/or caregivers who administer Teriparatide Injection should receive appropriate training and instruction on the proper use of the Teriparatide Injection prefilled delivery device (pen) from a qualified health professional.
• Discard the delivery device 28 days after first use.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and the User Manual) before starting Teriparatide Injection and each time the prescription is renewed. Failure to follow the instructions may result in inaccurate dosing.

Use of Teriparatide Injection 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 [see Warnings and Precautions (5.1)].

The safety and efficacy of once-daily Teriparatide Injection, median exposure of 19 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 1637 postmenopausal women with osteoporosis. In this study 541 postmenopausal women were treated with 20 mcg Teriparatide Injection subcutaneously once daily.

All women received 1000 mg of calcium and at least 400 IU of vitamin D per day. Baseline and endpoint spinal radiographs were evaluated using the semiquantitative scoring. Ninety percent of the women in the study had 1 or more radiographically diagnosed vertebral fractures at baseline. The primary efficacy endpoint was the occurrence of new radiographically diagnosed vertebral fractures defined as changes in the height of previously undeformed vertebrae. Such fractures are not necessarily symptomatic.

The efficacy of Teriparatide Injection for treating glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥5 mg/day prednisone or equivalent for a minimum of 3 months. The duration of the trial was 18 months. In the trial 214  patients were treated with Teriparatide Injection 20 mcg given subcutaneously once daily. In the Teriparatide Injection group, the baseline median glucocorticoid dose was 7.5 mg/day and the baseline median duration of glucocorticoid use was 1.5 years. The mean (SD) baseline lumbar spine BMD was 0.85 ± 0.13 g/cm² and lumbar spine BMD T-score was –2.5 ± 1 (number of standard deviations below the mean BMD value for healthy adults). A total of 30% of patients had prevalent vertebral fracture(s) and 43% had prior non-vertebral fracture(s). The patients had chronic rheumatologic, respiratory or other diseases that required sustained glucocorticoid therapy. All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.

Because of differences in mechanism of action (anabolic vs. anti-resorptive) and lack of clarity regarding differences in BMD as an adequate predictor of fracture efficacy, data on the active comparator are not presented.

The safety and efficacy of once-daily Teriparatide Injection, median exposure of 10 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 437 men with either primary (idiopathic) or hypogonadal osteoporosis. In this study, 151 men received 20 mcg of Teriparatide Injection given subcutaneously once daily. All men received 1000 mg of calcium and at least 400 IU of vitamin D per day. The primary efficacy endpoint was change in lumbar spine BMD.

Teriparatide Injection increased lumbar spine BMD in men with primary or hypogonadal osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. Teriparatide Injection was effective in increasing lumbar spine BMD regardless of age, baseline rate of bone turnover, and baseline BMD. The effects of Teriparatide Injection at additional skeletal sites are shown in Table 4.

Teriparatide Injection treatment for a median of 10 months increased lumbar spine BMD from baseline in 94% of men treated. Fifty-three percent of patients treated with Teriparatide Injection achieved at least a 5% increase in spine BMD, and 14% gained 10% or more.

Hypercalcemia

Teriparatide Injection has not been studied in patients with pre-existing hypercalcemia. Teriparatide Injection may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia [see Adverse Reactions (6.1, 6.3)]. Avoid Teriparatide Injection in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

PACKAGE LABEL – Teriparatide 20 mcg per dose, 2.4 mL

Do NOT transfer contents to a syringe

ATTENTION PHARMACIST: Medication Guide and device User Manual for patient inside carton

NDC 66993-495-28

Teriparatide Injection

20 mcg per dose (given once daily subcutaneously)

Each single-patient-use prefilled pen will deliver 28 subcutaneous doses.

560 mcg/2.24 mL (250 mcg/mL)

For Single-Patient-Use Only

REFRIGERATE / DO NOT FREEZE

For subcutaneous use / Rx only

Needles not included

Becton, Dickinson and Company pen needles are recommended for use with this device

Prasco

Teriparatide [ter-i-par-a-tide] Injection

User Manual

Important: First read the Medication Guide that comes inside your Teriparatide carton.

Before you use your new Teriparatide delivery device, please read the entire front and back of this User Manual completely. Follow the directions carefully when using the Teriparatide delivery device.

Do not share your delivery device or needles because infection or disease can be spread from one person to another.

The Teriparatide delivery device contains 28 days of medicine. Throw away the Teriparatide delivery device 28 days after first use, even if it is not completely empty. Do not inject more than one dose of Teriparatide in the same day.

Do not transfer Teriparatide to a syringe.

Wash your hands before every injection. Prepare the injection site as your healthcare provider instructed.

For more information, or if you have any questions, turn to the back of this page.

Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide Injection may transiently increase serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide Injection is used in patients receiving digoxin [see Warnings and Precaution (5.5) and Clinical Pharmacology (12.3)].

In postmarketing spontaneous reports, there have been cases of medication errors in which the entire contents (up to 800 mcg) (40 times the recommended dose) of the Teriparatide Injection prefilled delivery device (pen) have been administered as a single dose. Transient events reported have included nausea, weakness/lethargy and hypotension. No fatalities associated with overdose have been reported. Additional signs, symptoms, and complications of Teriparatide Injection overdosage may include a delayed hypercalcemic effect, vomiting, dizziness, and headache.

Teriparatide Injection is a recombinant human parathyroid hormone analog (PTH 1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone.

The molecular formula of Teriparatide is C₁₈₁H₂₉₁N₅₅O₅₁S₂ and molecular weight is 4117.8 daltons. Its amino acid sequence is shown below:

Teriparatide is manufactured using a strain of Escherichia coli modified by recombinant DNA technology.

Teriparatide Injection is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a single-patient-use delivery device (pen) for subcutaneous injection. Each delivery device (pen) is filled with volume to allow delivery of 2.24 mL. Each mL contains 250 mcg of Teriparatide (as a free base), 0.41 mg of glacial acetic acid, 0.1 mg of sodium acetate (anhydrous), 45.4 mg of mannitol, 3 mg of Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the pH to 4.

Each prefilled delivery device (pen) delivers 20 mcg of Teriparatide per dose for up to 28 days. Each device contains additional volume to allow troubleshooting of the device 2 times.

An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with Teriparatide. Osteosarcoma has been reported in patients treated with Teriparatide Injection in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of Teriparatide Injection use [see Dosage and Administration (2.3), Adverse Reactions (6.3), and Nonclinical Toxicology (13.1)].

Avoid Teriparatide Injection use in patients with (these patients are at increased baseline risk of osteosarcoma):

• Open epiphyses (pediatric and young adult patients) (Teriparatide Injection is not approved in pediatric patients) [see Use in Specific Populations (8.4)].
• Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone.
• Bone metastases or a history of skeletal malignancies.
• Prior external beam or implant radiation therapy involving the skeleton.
• Hereditary disorders predisposing to osteosarcoma.

Teriparatide Injection is a clear and colorless solution, available as single-patient-use prefilled delivery device (pen) in the following package size:

• 560 mcg/2.24 mL (250 mcg/mL) [intended to deliver 28 daily doses of 20 mcg] NDC 66993-989-28.

The safety and effectiveness of Teriparatide Injection have not been established in pediatric patients. Pediatric patients are at higher baseline risk of osteosarcoma because of open epiphyses [see Warnings and Precautions (5.1)].

Of the patients who received Teriparatide Injection in the osteoporosis trial of 1637 postmenopausal women, 75% were 65 years of age and older and 23% were 75 years of age and older. Of the patients who received Teriparatide Injection in the trial of 437 men with primary or hypogonadal osteoporosis, 39% were 65 years of age and over and 13% were 75 years of age and over. Of the 214 patients who received Teriparatide Injection in the glucocorticoid induced osteoporosis trial, 28% were 65 years of age and older and 9% were 75 years of age and older. No overall differences in safety or effectiveness of Teriparatide Injection have been observed between patients 65 years of age and older and younger adult patients.

As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other Teriparatide products may be misleading.

In the clinical trial of postmenopausal women with osteoporosis [see Clinical Studies (14.1)], antibodies that cross reacted with Teriparatide were detected in 3% of women (15/541) who received Teriparatide Injection. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no evidence of hypersensitivity reactions among these patients. Antibody formation did not appear to have effects on serum calcium, or on bone mineral density (BMD) response.

Teriparatide Injection is contraindicated in patients with hypersensitivity to Teriparatide or to any of its excipients. Hypersensitivity reactions have included angioedema and anaphylaxis [see Adverse Reactions (6.3)].

Most common adverse reactions (>10%) include: arthralgia, pain, and nausea (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Digoxin: Transient hypercalcemia may predispose patients to digitalis toxicity (5.5, 7.1)

In 5 patients with severe renal impairment (CrCl<30 mL/minute), the AUC and T_1/2 of Teriparatide were increased by 73% and 77%, respectively. Maximum serum concentration of Teriparatide was not increased. It is unknown whether Teriparatide Injection alters the underlying metabolic bone disease seen in chronic renal impairment [see Clinical Pharmacology (12.3)].

In single-dose rodent studies using subcutaneous injection of Teriparatide, no mortality was seen in rats given doses of 1000 mcg/kg (540 times the human dose based on surface area, mcg/m²) or in mice given 10,000 mcg/kg (2700 times the human dose based on surface area, mcg/m²).

In a long-term study, skeletally mature ovariectomized female monkeys (N=30 per treatment group) were given either daily subcutaneous Teriparatide injections of 5 mcg/kg or vehicle. Following the 18-month treatment period, the monkeys were removed from Teriparatide treatment and were observed for an additional 3 years. The 5 mcg/kg dose resulted in systemic exposures that were approximately 6 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Bone tumors were not detected by radiographic or histologic evaluation in any monkey in the study.

The recommended dosage is 20 mcg per dose given subcutaneously once a day. Instruct patients to take supplemental calcium and vitamin D if daily dietary intake is inadequate.

No studies have been performed in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

Teriparatide Injection is indicated:

• For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Teriparatide Injection reduces the risk of vertebral and nonvertebral fractures.
• To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
• For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.

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 microarchitecture 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.

In clinical trials, the frequency of urolithiasis was similar in patients treated with Teriparatide Injection and patients treated with placebo. However, Teriparatide Injection has not been studied in patients with active urolithiasis. If Teriparatide Injection-treated patients have pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion. Consider the risks and benefits of use in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

• Store Teriparatide Injection under refrigeration at 2° to 8°C (36° to 46°F) at all times except when administering the product.
• Recap the delivery device (pen) when not in use to protect the cartridge from physical damage and light.
• When using Teriparatide Injection, minimize the time out of the refrigerator; deliver the dose immediately following removal from the refrigerator.
• Do not freeze. Do not use Teriparatide Injection if it has been frozen.
• Throw away the device 28 days after first use.

• Osteosarcoma: Avoid use in patients with increased risk of osteosarcoma including patients with open epiphyses, metabolic bone diseases including Paget's disease, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. (5.1)
• Hypercalcemia and Cutaneous Calcification: Avoid in patients known to have an underlying hypercalcemic disorder. Discontinue in patients developing worsening of previously stable cutaneous calcification. (5.2)
• Risk of Urolithiasis: Consider the risk/benefit in patients with active or recent urolithiasis because of risk of exacerbation (5.3)
• Orthostatic Hypotension: Transient orthostatic hypotension may occur with initial doses of Teriparatide Injection (5.4)

• Recommended dosage is 20 mcg subcutaneously once a day (2.1)
• Consider supplemental calcium and Vitamin D based on individual patient needs (2.1)
• Administer as a subcutaneous injection into the thigh or abdominal region (2.2)
• Administer initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur (2.2)
• Use of Teriparatide Injection 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 (2.3)

Teriparatide Injection 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 of Teriparatide Injection in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers. Typically, these events began within 4 hours of dosing and resolved (without treatment) 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.

Injection: 560 mcg/2.24 mL (250 mcg/mL) clear, colorless solution in a single-patient-use prefilled delivery device (pen) intended to deliver 28 daily doses of 20 mcg.

Hypercalcemia may predispose patients to digitalis toxicity because Teriparatide Injection transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide Injection is used in patients receiving digoxin [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

• Pregnancy: Consider discontinuing when pregnancy is recognized (8.1)
• Lactation: Breastfeeding is not recommended (8.2)
• Pediatric Use: Safety and effectiveness not established. Avoid use due to increased baseline risk of osteosarcoma (5.1, 8.4)

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

• Administer Teriparatide Injection as a subcutaneous injection into the thigh or abdominal region. Teriparatide Injection is not approved for intravenous or intramuscular use.
• Teriparatide Injection should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur [see Warnings and Precautions (5.4)].
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration (Teriparatide Injection is a clear and colorless liquid). Do not use if solid particles appear or if the solution is cloudy or colored.
• Patients and/or caregivers who administer Teriparatide Injection should receive appropriate training and instruction on the proper use of the Teriparatide Injection prefilled delivery device (pen) from a qualified health professional.
• Discard the delivery device 28 days after first use.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and the User Manual) before starting Teriparatide Injection and each time the prescription is renewed. Failure to follow the instructions may result in inaccurate dosing.

Use of Teriparatide Injection 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 [see Warnings and Precautions (5.1)].

The safety and efficacy of once-daily Teriparatide Injection, median exposure of 19 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 1637 postmenopausal women with osteoporosis. In this study 541 postmenopausal women were treated with 20 mcg Teriparatide Injection subcutaneously once daily.

All women received 1000 mg of calcium and at least 400 IU of vitamin D per day. Baseline and endpoint spinal radiographs were evaluated using the semiquantitative scoring. Ninety percent of the women in the study had 1 or more radiographically diagnosed vertebral fractures at baseline. The primary efficacy endpoint was the occurrence of new radiographically diagnosed vertebral fractures defined as changes in the height of previously undeformed vertebrae. Such fractures are not necessarily symptomatic.

The efficacy of Teriparatide Injection for treating glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥5 mg/day prednisone or equivalent for a minimum of 3 months. The duration of the trial was 18 months. In the trial 214  patients were treated with Teriparatide Injection 20 mcg given subcutaneously once daily. In the Teriparatide Injection group, the baseline median glucocorticoid dose was 7.5 mg/day and the baseline median duration of glucocorticoid use was 1.5 years. The mean (SD) baseline lumbar spine BMD was 0.85 ± 0.13 g/cm² and lumbar spine BMD T-score was –2.5 ± 1 (number of standard deviations below the mean BMD value for healthy adults). A total of 30% of patients had prevalent vertebral fracture(s) and 43% had prior non-vertebral fracture(s). The patients had chronic rheumatologic, respiratory or other diseases that required sustained glucocorticoid therapy. All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.

Because of differences in mechanism of action (anabolic vs. anti-resorptive) and lack of clarity regarding differences in BMD as an adequate predictor of fracture efficacy, data on the active comparator are not presented.

The safety and efficacy of once-daily Teriparatide Injection, median exposure of 10 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 437 men with either primary (idiopathic) or hypogonadal osteoporosis. In this study, 151 men received 20 mcg of Teriparatide Injection given subcutaneously once daily. All men received 1000 mg of calcium and at least 400 IU of vitamin D per day. The primary efficacy endpoint was change in lumbar spine BMD.

Teriparatide Injection increased lumbar spine BMD in men with primary or hypogonadal osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. Teriparatide Injection was effective in increasing lumbar spine BMD regardless of age, baseline rate of bone turnover, and baseline BMD. The effects of Teriparatide Injection at additional skeletal sites are shown in Table 4.

Teriparatide Injection treatment for a median of 10 months increased lumbar spine BMD from baseline in 94% of men treated. Fifty-three percent of patients treated with Teriparatide Injection achieved at least a 5% increase in spine BMD, and 14% gained 10% or more.