HSE P&T Portfolio--Forteo

February 17, 2003

Forteo

 

HEALTH-SYSTEM EDITION
P & T PORTFOLIO

Generic name

Teriparatide injection

Proprietary name/manufacturer

Forteo/Lilly

FDA-approved indications

Teriparatide is approved for treating postmenopausal women with osteoporosis who are at high risk for fracture, including those with a history of osteoporotic fracture, those with multiple risk factors for fracture, or those who have failed or are intolerant of previous osteoporosis therapy based upon physician assessment. The agent is also indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture, including men with a history of osteoporotic fracture, those with multiple risk factors for fracture, or those who have failed or are intolerant of previous osteoporosis therapy based upon physician assessment.

Pharmacology

Teriparatide is a synthetic polypeptide hormone that is the biologically active N-terminal region of the human parathyroid hormone (PTH). Teriparatide contains recombinant PTH (1-34), which has an identical sequence to the 34-N-terminal amino acids of the 84-amino acid human PTH. The actions of teriparatide mimic those of endogenous PTH, the primary regulator of calcium and phosphate metabolism in bone and kidney, and are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide stimulates bone formation and resorption and can increase or decrease bone density, depending on the mode of administration. Once-daily administration stimulates new bone formation on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. The anabolic effects of teriparatide result in an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. In contrast, continuous excess of endogenous PTH may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.

Pharmacokinetics

Bioavailability (subcutaneous)95%
Volume of distribution (IV)0.12 L/kg
MetabolismPTH undergoes rapid metabolism in liver via nonspecific enzymatic mechanisms. Teriparatide undergoes very little metabolism.
ExcretionUrine (PTH)
Half-life (subcutaneous)1 hour

Warnings

• Teriparatide has caused an increase in the incidence of osteosarcoma in rats and should not be prescribed for patients at increased baseline risk for osteosarcoma.

• Teriparatide should not be prescribed for patients with bone metastases or a history of skeletal malignancies, or metabolic bone diseases other than osteoporosis.

• Teriparatide should not be prescribed for patients with preexisting hypercalcemia.

Adverse effects

The most common adverse effects, occurring in 8% to 21% of patients, were: pain, transient hypercalcemia, arthralgia, rhinitis, asthenia, nausea, and dizziness.

Dose

20 mcg once daily as a subcutaneous injection into the thigh or abdominal wall

Note: Teriparatide should initially be administered under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur. Use of teriparatide for more than two years is not recommended.

Conclusion/comments

Teriparatide (human PTH [1-34] recombinant origin) is a synthetic polypeptide hormone that is the biologically active N-terminal region of the human parathyroid hormone. When administered once daily subcutaneously, teriparatide increases bone density by stimulating new bone formation. Studies demonstrate efficacy in the treatment of postmenopausal women with osteoporosis and men with primary or hypogonadal osteoporosis. Teriparatide is the first osteoporosis drug designed to promote the growth of new bone rather than slow down the breakdown of old bone. Teriparatide appears to be more effective than alendronate for the treatment of postmenopausal women with osteoporosis, but comparative studies with other agents used to treat osteoporosis are not available. In rats, high doses of recombinant PTH have induced osteosarcoma and the manufacturer will develop a postmarketing surveillance program to collect and assess information regarding the potential for this adverse effect. Because of the concern over osteosarcoma, teriparatide was approved with restrictions.

Published February 2003. Content based on medical literature and product information available at that time.

 

 

HSE P&T Portfolio--Forteo. Drug Topics 2003;4:HSE13.