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 on March 26, 2018

Introduction

A biosynthetic (rDNA origin) fragment of human parathyroid hormone (parathormone, PTH), stimulates bone formation.^{1 2 3 4 5}

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).¹ Reduces the risk of new vertebral fractures and nonvertebral fractures.^{1 3} Increases total body bone mass density (BMD) and BMD in the lumbar spine, femoral neck, total hip, trochanter, intertrochanter, and Ward’s triangle.^{1 3}

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).^{1 5} Increases lumbar spine and femoral neck BMD in such patients.^{1 5}

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.^{105 106}

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.^{105 106}

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.^{105 106}

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).^{1 7} Increases lumbar spine, femoral neck, and total hip BMD in such patients.^{1 7}

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.⁶²² Oral bisphosphonates are preferred because of their demonstrated antifracture benefits, safety, and cost; teriparatide is suggested as an alternative.⁶²²

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.^{1 6}

• Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate.¹

• Administer initially in an environment in which the patient can assume a supine or sitting position if orthostatic hypotension occurs.^{1 6}

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.^{1 2}

Commercially available as a prefilled injection pen that delivers 20 mcg of teriparatide per actuation.¹ 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.¹

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.² Do not inject more than one dose per day.²

Dosage

Adults

Treatment of Osteoporosis in Postmenopausal Women at High Risk of Fracture

Sub-Q

20 mcg once daily.¹

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

Sub-Q

20 mcg once daily.¹

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

Sub-Q

20 mcg once daily.¹

Cautions for Teriparatide

Contraindications

• Known hypersensitivity to teriparatide or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

Carcinogenicity

Teriparatide caused a dose- and duration-related increase in the incidence of osteosarcoma in rats.^{1 3 4} Relevance of these findings to humans not known;^{1 3 4} use only in patients for whom potential benefits outweigh potential risks.¹

Do not use in patients at increased baseline risk for osteosarcoma.^{1 6} (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.¹

A registry has been established to monitor and evaluate potential risk of osteosarcoma in patients receiving teriparatide.¹ Encourage patients to enroll in registry by calling 866-382-6813 or visiting www.forteoregistry.rti.org.¹

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions, including angioedema and anaphylaxis, reported.¹ (See Contraindications under Cautions.)

Antibody Formation

Development of anti-teriparatide antibodies observed; however, no evidence of associated hypersensitivity or allergic reactions.^{1 6} Antibody formation did not appear to affect response to the drug.¹

Other Warnings/Precautions

Renal Effects

If active urolithiasis is suspected, consider measurement of urinary calcium.¹ Use with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.¹

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.¹

Cardiovascular Effects

Orthostatic hypotension, generally occurring within 4 hours of a dose and resolving spontaneously within a few minutes to a few hours, reported.¹

Relieve transient orthostatic hypotension (occurring within the first several doses) by reclining.¹ (See General under Dosage and Administration.)

Specific Populations

Pregnancy

Category C.¹ Not indicated for use in pregnancy.¹

Lactation

Not known whether distributed into milk; discontinue nursing or drug.¹

Pediatric Use

Not indicated in pediatric patients; safety and efficacy not established.¹

Geriatric Use

No substantial differences in efficacy and safety relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hepatic Impairment

No studies in patients with hepatic impairment.¹

Renal Impairment

Limited data indicate possible changes in pharmacokinetics in patients with severe renal impairment.¹ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Pain,¹ arthralgia,¹ rhinitis,¹ asthenia,¹ nausea,^{1 3 5} dizziness,^{1 3} headache, ^{1 3} hypertension,¹ increased cough,¹ pharyngitis,¹ constipation,¹ dyspepsia,¹ diarrhea,¹ rash,¹ insomnia,¹ depression,¹ pneumonia,¹ vertigo,¹ dyspnea,¹ neck pain,¹ vomiting,¹ syncope,¹ leg cramps,^{1 3} angina pectoris,¹ GI disorder,¹ sweating,¹ tooth disorder.¹

Interactions for Teriparatide

Specific Drugs

Teriparatide Pharmacokinetics

Absorption

Bioavailability

Approximately 95%.¹ Following sub-Q administration, peak serum drug concentrations usually attained at about 30 minutes.¹

Onset

Maximal increases in serum calcium observed at 4–6 hours following sub-Q administration.¹

Duration

Serum calcium concentrations return to or near baseline by 16–24 hours following sub-Q administration.¹

Special Populations

In men, systemic exposure is 20–30% lower than that in women; no dosage adjustments are necessary.¹

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.¹

Distribution

Extent

Following IV administration†, volume of distribution is approximately 0.12 L/kg.¹

Elimination

Metabolism

Metabolized by nonspecific proteolytic enzymes in the liver (possibly Kupffer cells).¹

Elimination Route

Excreted via the kidneys.¹

Half-life

Following sub-Q administration, approximately 1 hour.¹

Special Populations

In geriatric patients, no age-related differences observed.¹

In patients with severe renal insufficiency (Cl_cr <30 mL/minute), the half-life was increased by 77%.¹ Pharmacokinetics not studied in patients undergoing dialysis for chronic renal failure.¹ Pharmacokinetics not affected by mild to moderate renal insufficiency (Cl_cr 30–72 mL/minute).¹

In patients with heart failure (NYHA class I–III), pharmacokinetics not affected.¹

In patients with hepatic insufficiency, pharmacokinetics not studied.¹

Stability

Storage

Parenteral

Solution for Injection

2–8°C; do not freeze.¹

Actions

• Same physiologic actions as PTH on bone and the kidneys.^{1 3}

• Increases serum calcium and decreases serum phosphorus.¹ Increases urinary calcium excretion.¹ Produces transient phosphaturia, but hypophosphatemia not observed in clinical trials.¹

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

• Increases serum uric acid concentrations.¹

• Stimulates new bone formation on trabecular and cortical bone surfaces by preferentially stimulating osteoblastic activity over osteoclastic activity.^{1 3 5}

• Increases bone turnover (markers of bone formation and resorption).¹

• Increases BMD.¹

Advice to Patients

• Provide patients a copy of the user manual provided by the manufacturer.¹

• Instruct carefully in the use of the injection pen, including priming of the pen.¹

• Inform patients that osteosarcoma was found in rats and that the clinical relevance is unknown.¹ (See Boxed Warning.)

• Importance of sitting or lying down if symptoms of lightheadedness or palpitations occur following sub-Q injection.¹ If symptoms persist or worsen, importance of contacting a clinician before continuing treatment.¹

• Importance of contacting a clinician if symptoms of hypercalcemia persist (e.g., nausea, vomiting, constipation, lethargy, muscle weakness).¹

• Importance of other measures (e.g., diet, weight-bearing exercise, reduction in smoking and alcohol use) to retard further bone loss.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of advising patients of other important precautionary information.¹ (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.

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