Teriparatide

Class: Parathyroid Agents
ATC Class: H05AA02
VA Class: HS600
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
Brands: Forteo

Medically reviewed by Drugs.com on Apr 5, 2022. Written by ASHP.

Warning

Increased risk of osteosarcoma in rats receiving high doses of teriparatide; dependent on dose and treatment duration.
Use only in patients for whom the benefits outweigh the risks.
Do not use in patients with an increased baseline risk for osteosarcoma (i.e., patients with Paget disease of bone or unexplained increases in serum alkaline phosphatase concentrations, pediatric patients or young adults with open epiphyses, and patients who received prior external beam or implant radiation therapy involving the skeleton).

Introduction

A biosynthetic (rDNA origin) fragment of human parathyroid hormone (parathormone, PTH), stimulates bone formation.

Uses for Teriparatide

Osteoporosis

Treatment of osteoporosis in postmenopausal women who are at high risk for fractures (including those with a history of osteoporotic fracture, those with multiple risk factors for fractures, and those intolerant of or failing to respond to prior therapy for osteoporosis). Reduces the risk of new vertebral fractures and nonvertebral fractures. Increases total body bone mass density (BMD) and BMD in the lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and Ward’s triangle.

Used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fractures (including those with a history of osteoporotic fracture, those with multiple risk factors for fractures, and those intolerant of or failing to respond to prior therapy for osteoporosis). Increases lumbar spine and femoral neck BMD in such patients.

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 that pharmacologic therapy for osteoporosis be considered in postmenopausal women and men (≥50 years of age) with high risk of fractures (generally those who have experienced a previous hip or vertebral fracture or who have low BMD); pharmacologic therapy also may be considered in postmenopausal women and men (≥50 years of age) with low bone mass, although there is less evidence supporting overall fracture risk reduction in such patients.

Use of a drug with proven antifracture efficacy is recommended; experts generally recommend teriparatide in patients with very high fracture risk or those in whom bisphosphonate therapy has been ineffective.

Individualize choice of therapy based on potential benefits (with respect to fracture risk reduction) and adverse effects of therapy, patient preferences, comorbidities, and risk factors.

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 (including those with a history of osteoporotic fracture, those with multiple risk factors for fractures, and those intolerant of or failing to respond to prior therapy for osteoporosis). Increases lumbar spine, femoral neck, and total hip BMD in such patients.

American College of Rheumatology (ACR) recommends 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 recommended in patients at moderate-to-high risk of fracture. Oral bisphosphonates are preferred because of their demonstrated antifracture benefits, safety, and cost; teriparatide is suggested as an alternative.

Teriparatide Dosage and Administration

General

Because safety and efficacy of teriparatide beyond 2 years have not been established, use of the drug for more than 2 years is not recommended.
Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate.
Administer initially in an environment in which the patient can assume a supine or sitting position if orthostatic hypotension occurs.

Administration

Sub-Q Administration

Administer sub-Q into the thigh or abdominal wall; 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.

If a dose is missed, administer missed dose as soon as it is remembered on that day, followed by resumption of the regular daily schedule. Do not inject more than one dose per day.

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.

Cautions for Teriparatide

Contraindications

Known hypersensitivity to teriparatide or any ingredient in the formulation.

Warnings/Precautions

Warnings

Carcinogenicity

Teriparatide caused a dose- and duration-related increase in the incidence of osteosarcoma in rats. Relevance of these findings to humans not known; use only in patients for whom potential benefits outweigh potential risks.

Do not use in patients at increased baseline risk for osteosarcoma. (See Boxed Warning.) In addition, do not use in patients with bone metastases, a history of skeletal malignancy, or a metabolic bone disease other than osteoporosis.

A registry has been established to monitor and evaluate potential risk of osteosarcoma in patients receiving teriparatide. Encourage patients to enroll in registry by calling 866-382-6813 or visiting www.forteoregistry.rti.org.

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions, including angioedema and anaphylaxis, reported. (See Contraindications under Cautions.)

Antibody Formation

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.

Other Warnings/Precautions

Renal Effects

If active urolithiasis is suspected, consider measurement of urinary calcium. Use with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

Patients with Hypercalcemia

Not studied in patients with preexisting hypercalcemia (e.g., primary hyperparathyroidism); do not use in such patients because of the possibility of exacerbating hypercalcemia.

Cardiovascular Effects

Orthostatic hypotension, generally occurring within 4 hours of a dose and resolving spontaneously within a few minutes to a few hours, reported.

Relieve transient orthostatic hypotension (occurring within the first several doses) by reclining. (See General under Dosage and Administration.)

Specific Populations

Pregnancy

Category C. Not indicated for use in pregnancy.

Lactation

Not known whether distributed into milk; discontinue nursing or drug.

Pediatric Use

Not indicated in pediatric patients; safety and efficacy not established.

Geriatric Use

No substantial differences in efficacy and safety relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

No studies in patients with hepatic impairment.

Renal Impairment

Limited data indicate possible changes in pharmacokinetics in patients with severe renal impairment. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Pain, arthralgia, rhinitis, asthenia, nausea, dizziness, headache, hypertension, increased cough, pharyngitis, constipation, dyspepsia, diarrhea, rash, insomnia, depression, pneumonia, vertigo, dyspnea, neck pain, vomiting, syncope, leg cramps, angina pectoris, GI disorder, sweating, tooth disorder.

Interactions for Teriparatide

Specific Drugs

Drug	Interaction	Comments
Digoxin	Hypercalcemia may predispose patients to digoxin toxicity	Use concomitantly with caution
Furosemide	Small increases in serum and urinary calcium with concurrent use	Not considered clinically important
Hydrochlorothiazide	Small reduction in urinary calcium excretion	Not considered clinically important

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.

Distribution

Extent

Following IV administration†, volume of distribution is approximately 0.12 L/kg.

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 heart failure (NYHA class I–III), pharmacokinetics not affected.

In patients with hepatic insufficiency, pharmacokinetics not studied.

Stability

Storage

Parenteral

Solution for Injection

2–8°C; do not freeze.

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

Provide patients a copy of the user manual provided by the manufacturer.
Instruct carefully in the use of the injection pen, including priming of the pen.
Inform patients that osteosarcoma was found in rats and that the clinical relevance is unknown. (See Boxed Warning.)
Importance of sitting or lying down if symptoms of lightheadedness or palpitations occur following sub-Q injection. If symptoms persist or worsen, importance of contacting a clinician before continuing treatment.
Importance of contacting a clinician if symptoms of hypercalcemia persist (e.g., nausea, vomiting, constipation, lethargy, muscle weakness).
Importance of other measures (e.g., diet, weight-bearing exercise, reduction in smoking and alcohol use) to retard further bone loss.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of advising patients of other important precautionary information. (See Cautions.)

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.