Teriparatide (Monograph)

Brand name: Forteo
Drug class: Parathyroid Agents
Chemical name: l-Seryl-l-valyl-l-seryl-l- α-glutamyl-l-isoleucyl-l-glutaminyl-l-leucyl-l-methionyl-l-histidyl-l-asparaginyl-l-leucylglycyl-l-lysyl-l-histidyl-l-leucyl-l-asparaginyl-l-seryl-l-methionyl-l-α-glutamyl-l-arginyl-l-valyl-l-α-glutamyl-l-tryptophyl-l-leucyl-l-arginyl-l-lysl-l-lysl-l-leucyl-l-glutaminyl-l-α-aspartyl-l-valyl-l-histidyl-l-asparaginyl-l-phenylalanine
Molecular formula: C₁₈₁H₂₉₁N₅₅O₅₁S₂
CAS number: 52232-67-4

Medically reviewed by Drugs.com on Apr 25, 2023. Written by ASHP.

Introduction

A biosynthetic (recombinant DNA origin) fragment of human parathyroid hormone (parathormone, PTH); osteoanabolic agent.

Uses for Teriparatide

Osteoporosis in Postmenopausal Women

Treatment of osteoporosis in postmenopausal women who are at high risk for fractures (defined as having a history of osteoporotic fracture or multiple risk factors for fracture) or those who have failed or are intolerant to other therapy for osteoporosis. Has been shown to reduce the risk of new vertebral fractures and nonvertebral fractures in such patients.

Because of potential risk of osteosarcoma, 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.

In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend pharmacologic therapy for osteoporosis in postmenopausal women at high risk of fractures. Choice of therapy should be individualized based on potential benefits (with respect to fracture risk reduction) and adverse effects of therapy as well as patient preferences, comorbidities, drug availability, and costs.

Clinical practice guidelines generally recommend parathyroid hormone and parathyroid hormone–related protein analogs (e.g., teriparatide, abaloparatide) in postmenopausal women with osteoporosis who are at very high risk of fracture (e.g., those with several or multiple vertebral fractures). Treatment duration should be limited to 2 years. In such women who have completed a course of teriparatide or abaloparatide, treatment with antiresorptive osteoporosis therapies is recommended to maintain bone density gains.

Osteoporosis in Men

Used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fractures (defined 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. Has been shown to increase lumbar spine and femoral neck bone mineral density (BMD) in such patients.

Because of potential risk of osteosarcoma, 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.

In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), the Endocrine Society guidelines recommend that men at high risk of fracture be treated with an approved pharmacologic agent. Selection of therapy should be individualized based on factors such as fracture history, severity of osteoporosis (T-scores), risk of hip fracture, patterns of BMD, comorbid conditions, and cost.

Glucocorticoid-induced Osteoporosis

Treatment of glucocorticoid-induced osteoporosis (associated with long-term use of a glucocorticoid at a daily dosage equivalent to ≥5 mg of prednisone) in men and women who are at high risk for fractures (defined 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. Increases lumbar spine, femoral neck, and total hip BMD in such patients.

Because of potential risk of osteosarcoma, 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.

The American College of Rheumatology (ACR) guidelines recommend optimizing calcium and vitamin D intake and lifestyle modifications (e.g., diet, smoking cessation, weight-bearing or resistance-training exercise) in all patients receiving long-term glucocorticoid therapy; in addition, pharmacologic therapy with an oral bisphosphonate is strongly recommended in adults ≥40 years of age at high risk of fracture. Oral bisphosphonates are preferred because of their demonstrated antifracture benefits, safety, and cost. Parathyroid hormone and parathyroid hormone-related protein analogs (e.g., teriparatide, abaloparatide) are options that may be considered; however, these agents are conditionally recommended due to the lack of fracture prevention data in this patient population.

Teriparatide Dosage and Administration

General

Pretreatment Screening

• Evaluate patient's risk of osteosarcoma. Avoid use of teriparatide in patients at increased baseline risk (e.g., patients with open epiphyses, metabolic bone diseases other than osteoporosis including Paget's disease of the bone, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, or hereditary disorders predisposing to osteosarcoma).

• Evaluate patients for hypercalcemia; avoid use of teriparatide in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

• Consider the risks and benefits of teriparatide use in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

Patient Monitoring

• In patients with pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion.

Other General Considerations

• Patients should receive supplemental calcium and vitamin D while receiving teriparatide if dietary intake is inadequate.

Administration

Sub-Q Administration

Administer sub-Q into the thigh or abdominal region; no data available on safety or efficacy of IV or IM administration.

Commercially available as a prefilled injection pen that delivers 20 mcg of teriparatide per actuation. Use each injection pen for up to 28 days after the first injection and then dispose of properly, even if the pen is not empty.

Dosage

Adults

Treatment of Osteoporosis in Postmenopausal Women at High Risk of Fracture

Sub-Q

20 mcg once daily.

Treatment in Men with Primary or Hypogonadal Osteoporosis at High Risk of Fracture

Sub-Q

20 mcg once daily.

Treatment of Men or Women with Glucocorticoid-induced Osteoporosis at High Risk of Fracture

Sub-Q

20 mcg once daily.

Special Populations

No special population dosage recommendations at this time.

Cautions for Teriparatide

Contraindications

• Known hypersensitivity to teriparatide or any ingredient in the formulation.

Warnings/Precautions

Osteosarcoma

Increased incidence of osteosarcoma in male and female rats; effect was dose dependent. Osteosarcoma reported in patients treated with teriparatide during postmarketing experience; however, an increased risk of osteosarcoma was not observed in observational studies in humans.

Limited data assessing risk of osteosarcoma beyond 2 years of teriparatide use.

Avoid use of teriparatide in patients with an increased baseline risk of osteosarcoma (e.g., patients with open epiphyses, metabolic bone diseases other than osteoporosis including Paget's disease of the bone, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, or hereditary disorders predisposing to osteosarcoma).

Hypercalcemia and Cutaneous Calcification

Risk of hypercalcemia and exacerbation of hypercalcemia in patients with pre-existing hypercalcemia. Teriparatide has not been studied in patients with preexisting hypercalcemia. Avoid use in patients with an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

Serious cases of calciphylaxis and worsening of previously stable cutaneous calcification reported during postmarketing experience with teriparatide. Risk factors 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.

Urolithiasis

Urolithiasis occurred with similar frequency with teriparatide and placebo in clinical studies; however, not studied in patients with active urolithiasis.

In patients with preexisting hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion prior to treatment with teriparatide. Consider risks and benefits of use in patients with active or recent urolithiasis.

Orthostatic Hypotension

Orthostatic hypotension, generally occurring within 4 hours of a dose and resolving spontaneously within a few minutes to a few hours, reported infrequently. Administer teriparatide initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur.

Digoxin Toxicity

Teriparatide transiently increases serum calcium concentrations, which can predispose patients to digoxin toxicity. Consider the potential onset of signs and symptoms of digitalis toxicity when teriparatide is used in patients receiving digoxin.

Immunogenicity

Development of anti-teriparatide antibodies observed; however, no evidence of associated hypersensitivity or allergic reactions. Antibody formation did not appear to affect response to the drug.

Specific Populations

Pregnancy

No available data in pregnant women to determine whether there is a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Skeletal variations, growth retardation, and reduced motor activity observed in animal reproductive studies.

Consider discontinuing teriparatide when pregnancy is recognized.

Lactation

Not known whether distributed into milk or whether the drug has any effects on milk production or the breasted infant; avoid use in women who are breastfeeding.

Pediatric Use

Safety and efficacy not established. Pediatric patients have a higher baseline risk of osteosarcoma because of open epiphyses.

Geriatric Use

No substantial differences in efficacy and safety relative to younger adults.

Hepatic Impairment

No studies in patients with hepatic impairment.

Renal Impairment

Limited data indicate possible changes in pharmacokinetics in patients with severe renal impairment. Not known whether teriparatide alters the underlying metabolic bone disease in chronic renal impairment.

Common Adverse Effects

Most common adverse reactions (>10%): arthralgia, pain, nausea.

Drug Interactions

Specific Drugs

Teriparatide Pharmacokinetics

Absorption

Bioavailability

Approximately 95%. Following sub-Q administration, peak serum drug concentrations usually attained at about 30 minutes.

Onset

Maximal increases in serum calcium observed at 4–6 hours following sub-Q administration.

Duration

Serum calcium concentrations return to or near baseline by 16–24 hours following sub-Q administration.

Special Populations

In men, systemic exposure is 20–30% lower than that in women; no dosage adjustments are necessary.

In patients with severe renal insufficiency (Cl_cr <30 mL/minute), the AUC is increased by 73%, but maximum serum drug concentrations were not increased.

Elimination

Metabolism

Metabolized by nonspecific proteolytic enzymes in the liver (possibly Kupffer cells).

Elimination Route

Excreted via the kidneys.

Half-life

Following sub-Q administration, approximately 1 hour.

Special Populations

In geriatric patients, no age-related differences observed.

In patients with severe renal insufficiency (Cl_cr <30 mL/minute), the half-life was increased by 77%. Pharmacokinetics not studied in patients undergoing dialysis for chronic renal failure. Pharmacokinetics not affected by mild to moderate renal insufficiency (Cl_cr 30–72 mL/minute).

In patients with hepatic insufficiency, pharmacokinetics not studied.

Stability

Storage

Parenteral

Prefilled Injection Pen

2–8°C; do not freeze. When using teriparatide, minimize time out of refrigerator; deliver the dose immediately following removal from refrigerator.

Actions

• Same physiologic actions as PTH on bone and the kidneys.

• Increases serum calcium and decreases serum phosphorus. Increases urinary calcium excretion. Produces transient phosphaturia, but hypophosphatemia not observed in clinical trials.

• Increases the median serum concentration of 1,25-dihydroxyvitamin D.

• Increases serum uric acid concentrations.

• Stimulates new bone formation on trabecular and cortical bone surfaces by preferentially stimulating osteoblastic activity over osteoclastic activity.

• Increases bone turnover (markers of bone formation and resorption).

• Increases BMD.

Advice to Patients

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

• Inform patients about the increased incidence of osteosarcoma in rats receiving teriparatide; Although cases of osteosarcoma have been reported in patients using teriparatide, no increased risk of osteosarcoma was observed in adult humans treated with the drug.

• Instruct patients to contact a health care provider if they develop persistent symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy, muscle weakness).

• Instruct patients and caregivers on use of the injection pen, including proper disposal. Advise patients not to share their prefilled delivery device with other patients and inform them that the contents of the delivery device should not be transferred to a syringe. Inform patients that each delivery device can be used for up to 28 days; the delivery device should be discarded after this period, even if it still contains some unused solution. Instruct patients not to use the drug after the expiration date printed on the delivery device and packaging.

• When initiating teriparatide therapy, instruct patients to be prepared to immediately sit or lie down during or after administration in case they feel lightheaded or have palpitations after the injection. Instruct patients to sit or lie down until the symptoms resolve. If symptoms persist or worsen, instruct patients to consult a healthcare provider before continuing treatment.

• Inform patients about other osteoporosis treatment modalities such as supplemental calcium and/or vitamin D.

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Inform patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

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