Questions about Rheumatoid Arthritis? Get answers from our expert.

Generic Name: Teriparatide
Class: Parathyroid
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

Warning(s)

  • Increased risk of osteosarcoma in rats receiving high doses of teriparatide; dependent on dose and treatment duration.1

  • Use only in patients for whom the benefits outweigh the risks.1

  • Do not use in patients with an increased baseline risk for osteosarcoma (i.e., patients with Paget’s disease of bone or unexplained increases in serum alkaline phosphatase concentrations, pediatric patients or young adults with open epiphyses, and patients who received prior radiation therapy involving the skeleton).1

REMS:

FDA approved a REMS for teriparatide to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of teriparatide and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

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

Uses for Forteo

Osteoporosis in Postmenopausal Women

Used in the 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

Slideshow: Flashback: FDA Drug Approvals 2013

Should not be used to prevent osteoporosis or treat patients not considered to be at high risk for fracture.c

Osteoporosis in Men

Used in the treatment of osteoporosis 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 In men with primary or hypogonadal osteoporosis, increases lumbar spine and femoral neck BMD.1

Should not be used to prevent osteoporosis or treat patients not considered to be at high risk for fracture.c

Forteo 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

  • Use adjunctively with other measures (e.g., weight-bearing exercise, reduction in smoking and alcohol use) to retard further bone loss.1 c

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

Administration

Sub-Q Administration

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

Administer into the thigh or abdominal wall.1

Dosage

Adults

Osteoporosis in Postmenopausal Women
Sub-Q

20 mcg once daily.1 c

Osteoporosis in Men
Sub-Q

20 mcg once daily.1 c

Cautions for Forteo

Contraindications

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

  • Bone metastases, a history of skeletal malignancy, or metabolic bone disease other than osteoporosis.1

  • Not studied in patients with preexisting hypercalcemia (e.g., primary hyperparathyroidism).1 Should not be used because of the possibility of exacerbation of hypercalcemia.1

  • Difficulty with injection and a caregiver is not available.1

Warnings/Precautions

Warnings

Endocrine and Metabolic Effects

Possible transient hypercalcemia; discontinue pending further evaluation if persistent hypercalcemia is detected.1

If preexisting hypercalcemia is suspected, consider measurement of urinary calcium.1 (See Contraindications.)

Sensitivity Reactions

Although hypersensitivity to teriparatide has not been reported to date, antibodies to parathyroid hormone that cross-react with teriparatide are first detected following 12 months of treatment.1 Antibody titers decrease following discontinuance of therapy.1

General 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

Cardiovascular Effects

Relieve transient orthostatic hypotension (occurring within the first several doses) by reclining.1 In clinical studies, did not preclude continued treatment.1

Specific Populations

Pregnancy

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

Lactation

Not indicated in nursing women; not studied.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

Limited information on safety available.1

Renal Impairment

Limited information on safety available.1

Common Adverse Effects

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

Interactions for Forteo

Specific Drugs

Drug

Interaction

Comments

Digoxin

Hypercalcemia may predispose patients to digoxin toxicity1

Use concomitantly with caution1

Furosemide

Small increases in serum and urinary calcium with concurrent use1

Not considered clinically important1

Hydrochlorothiazide

Small reduction in urinary calcium excretion1

Not considered clinically important1

Forteo 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 (Clcr <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 (Clcr <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 (Clcr 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

  • 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

  • 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 c

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

  • 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.

Teriparatide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

250 mcg/mL (750 mcg)

Forteo (with metacresol in multiple-dose pen)

Lilly

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Forteo 600MCG/2.4ML Solution (LILLY): 2/$1,019.03 or 7/$2,996.87

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 1, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Eli Lilly and Company. Forteo (teriparatide recombinant DNA origin) injection. Indianapolis, IN; 2002 Nov.

2. Reeve J. Recombinant human parathyroid hormone: osteoporosis is proving amenable to treatment. BMJ. 2002; 324:435-6. [PubMed 11859030]

3. Neer RM, Arnaud CD, Zanchetta JR et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001; 344:1434-41. [IDIS 463195] [PubMed 11346808]

a. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 2003.

b. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition with selected updates for 2003. Endocrine Practice. 2003; 9:545-64.

c. Eli Lilly and Company. Forteo (teriparatide recombinant DNA orgin) injection mediation guide. Indianapolis, IN; 2002 Nov.

d. Eli Lilly and Company. Forteo (teriparatide recombinant DNA orgin) user manual. Indianapolis, IN; 2003 Oct 20.

Hide
(web3)