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 C 181 H 291 N 55 O 51 S 2 and the molecular weight is 4117.8 daltons. Its amino acid sequence is shown below: Teriparatide is manufactured using a strain of Pseudomonas fluorescens 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 pen is filled with volume to allow delivery of 2.24 mL. Each mL contains 250 mcg teriparatide (as a free base), 0.41 mg glacial acetic acid, 0.10 mg sodium acetate, 45.4 mg mannitol, 3 mg metacresol, and water for injection. The drug product is a pH 4.0 solution. Each cartridge, pre-assembled into a delivery device, delivers 20 mcg of teriparatide per dose each day for up to 28 days. Each device contains additional volume to allow troubleshooting of the device 2 times. amino-acid-sequence

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. Teriparatide injection is a parathyroid hormone analog, (PTH 1-34), indicated for: Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy

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

Recommended dosage is 20 mcg subcutaneously once a day Consider supplemental calcium and Vitamin D based on individual patient needs Administer as a subcutaneous injection into the thigh or abdominal region Administer initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur 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 2.1 Recommended Dosage The recommended dosage is 20 mcg given subcutaneously once a day. Instruct patients to take supplemental calcium and vitamin D if daily dietary intake is inadequate

Administration Instructions 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 . 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 delivery device from a qualified health professional

Recommended Treatment Duration 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 .

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. Hypercalcemia and Cutaneous Calcification : Avoid in patients known to have an underlying hypercalcemic disorder. Discontinue in patients developing worsening of previously stable cutaneous calcification. Risk of Urolithiasis : Consider the risk/benefit in patients with active or recent urolithiasis because of risk of exacerbation Orthostatic Hypotension : Transient orthostatic hypotension may occur with initial doses of teriparatide injection 5.1 Osteosarcoma 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 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 use . 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) . 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

Hypercalcemia and Cutaneous Calcification Hypercalcemia Teriparatide has not been studied in patients with pre-existing hypercalcemia. Teriparatide may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia . Avoid teriparatide injection in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism. Risk of Cutaneous Calcification Including Calciphylaxis Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking teriparatide. Risk factors for development of calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue teriparatide injection in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification

Risk of Urolithiasis In clinical trials, the frequency of urolithiasis was similar in patients treated with teriparatide and patients treated with placebo. However, teriparatide 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

Orthostatic Hypotension 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 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

Risk of Digoxin Toxicity Hypercalcemia may predispose patients to digitalis toxicity because teriparatide transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when teriparatide injection is used in patients receiving digoxin .

Digoxin: Transient hypercalcemia may predispose patients to digitalis toxicity 7.1 Digoxin Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide 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 .