Teriparatide

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.

• Recommended dosage is 20 mcg subcutaneously once a day (
  2.1 Recommended Dosage

  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.
  )
• Consider supplemental calcium and Vitamin D based on individual patient needs (
  2.1 Recommended Dosage

  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.
  )
• Administer as a subcutaneous injection into the thigh or abdominal region (
  2.2 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
    [see Warnings and Precautions ]
    .
  • 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.
  )
• Administer initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur (
  2.2 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
    [see Warnings and Precautions ]
    .
  • 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.
  )
• 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 Recommended Treatment Duration

  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 ]

  .
  )

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.

• Pregnancy: Consider discontinuing when pregnancy is recognized (
  8.1 Pregnancy

  Risk Summary

  There are no available data on Teriparatide Injection use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Consider discontinuing Teriparatide Injection when pregnancy is recognized.

  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 dose (based on body surface area, mcg/m²), and produced mild growth retardation and reduced motor activity in rat offspring at subcutaneous doses equivalent to more than 120 times the human dose (see

  Data

  ).

  The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk in the US general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

  Data

  Animal Data

  In animal reproduction studies, pregnant mice received Teriparatide during organogenesis at subcutaneous doses equivalent to 8 to 267 times the human dose (based on body surface area, mcg/m²). At subcutaneous doses ≥60 times the human dose, the fetuses showed an increased incidence of skeletal deviations or variations (interrupted rib, extra vertebra or rib). When pregnant rats received Teriparatide during organogenesis at subcutaneous doses 16 to 540 times the human dose, the fetuses showed no abnormal findings.

  In a perinatal/postnatal study in pregnant rats dosed subcutaneously from organogenesis through lactation, mild growth retardation was observed in female offspring at doses ≥120 times the human dose. Mild growth retardation in male offspring and reduced motor activity in both male and female offspring were observed at maternal doses of 540 times the human dose. There were no developmental or reproductive effects in mice or rats at doses 8 or 16 times the human dose, respectively.
  )
• Lactation: Breastfeeding is not recommended (
  8.2 Lactation

  Risk Summary

  It is not known whether Teriparatide is excreted in human milk, affects human milk production, or has effects on the breastfed infant. Avoid Teriparatide Injection use in women who are breastfeeding.
  )
• Pediatric Use: Safety and effectiveness not established. Avoid use due to increased baseline risk of osteosarcoma (
  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 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 , Adverse Reactions , and Nonclinical Toxicology ]

  .

  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 ]
    .
  • 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.
  ,
  8.4 Pediatric Use

  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 ]

  .
  )

• 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 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 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 , Adverse Reactions , and Nonclinical Toxicology ]

  .

  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 ]
    .
  • 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
  : Avoid in patients known to have an underlying hypercalcemic disorder. Discontinue in patients developing worsening of previously stable cutaneous calcification. (
  5.2 Hypercalcemia and Cutaneous Calcification

  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 ]

  . 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 Injection. Risk factors for development of calciphylaxis include underlying auto-immune 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
  : Consider the risk/benefit in patients with active or recent urolithiasis because of risk of exacerbation (
  5.3 Risk of Urolithiasis

  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.
  )
• Orthostatic Hypotension
  : Transient orthostatic hypotension may occur with initial doses of Teriparatide Injection (
  5.4 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 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.
  )