Mechanism of Action: Treatment with FORTEO (teriparatide [rDNA origin] injection) stimulates an increase in remodeling with positive bone balance2,3

See the difference FORTEO can make in postmenopausal women with osteoporosis

  • To listen to the indication and full important safety information, including boxed warning regarding osteosarcoma, please click here
  • For a complete list of references and study descriptions from the video, please click here

FORTEO Select Safety Information

The safety and efficacy of FORTEO has not been evaluated beyond 2 years of treatment. The use of FORTEO for more than 2 years during a patient’s lifetime is, therefore, not recommended. Do not use FORTEO in patients with hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

FORTEO is a Pro-Remodeling Anabolic Agent2,3

  • Bone remodeling is a coupled process by which osteoclasts remove existing or damaged bone matrix (resorption), and then osteoblasts refill the resorption cavities with new bone (formation).4
  • This coupled process of continuous renewal helps to maintain mechanical strength of the skeleton4
  • In postmenopausal osteoporosis, increased bone turnover results in increased resorption, underfilling of resorption sites, and a deficit of bone with every cycle5
  • This can result in thinning of bone trabeculae, loss of connectivity, and a reduction in bone strength5
FORTEO is a Pro-Remodeling Anabolic Agent
FORTEO is a Pro-Remodeling Anabolic Agent
FORTEO is a Pro-Remodeling Anabolic Agent

Treatment with FORTEO stimulates an increase in remodeling with positive bone balance,2,3 resulting in renewal of bone by:2,3

  • Removing older or fatigued bone
  • Adding more bone than was present prior to treatment

FORTEO Select Safety Information

FORTEO may increase serum calcium, urinary calcium, and serum uric acid. In clinical trials, neither sustained hypercalcemia nor hypercalciuria were observed.

Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered. Patients receiving digoxin should use FORTEO with caution because FORTEO may transiently increase serum calcium and hypercalcemia may predispose patients to digitalis toxicity.

The effect of FORTEO on markers of bone turnover

FORTEO significantly increased both markers of bone remodeling 8,9

  • Concentrations of P1NP increased 129% above baseline at 1 month and plateaued between 6 and 12 months at about 290%
  • The increases in CTX reached significance after 3 months of treatment at 86% above baseline and plateaued between 6 and 12 months at about 146%

Please see study design for SHOTZ study.

The effect of Forteo on markers of Bone Turnover

*P<0.001 for percent change from baseline. SE=standard error. P1NP=procollagen type 1 N-terminal propeptide. CTX= Carboxy-Terminal cross-linked telopeptide of type 1 collagen.

FORTEO Select Safety Information

The most common adverse reactions in clinical trials include: arthralgia (10.1% FORTEO vs. 8.4% placebo), pain (21.3% FORTEO vs. 20.5% placebo), and nausea (8.5% FORTEO vs. 6.7% placebo). Other adverse reactions include: dizziness, leg cramps, joint aches, and injection site reactions.

FORTEO helped stimulate early and sustained bone formation in 2 randomized clinical studies

FORTEO helped stimulate new bone formation in cancellous and cortical bone as early as 3 months*, and sustained new bone formation throughout 24 months* of treatment 6,7

*3-month data are from the AVA study, 6- and 24-month data are from the SHOTZ study.

AVA Study 3 mo cancellous
AVA Study 3 mo cortical
SHOTZ Study 6 mo cancellous
SHOTZ Study 6 mo cortical
SHOTZ Study 24 mo cancellous
SHOTZ Study 24 mo cortical

Continuous and statistically significant bone formation demonstrated that anabolic action continued through 24 months of treatment with FORTEO.7

Please see study designs for AVA and SHOTZ studies.

FORTEO Select Safety Information

FORTEO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal studies, FORTEO may cause fetal harm. It is not known whether teriparatide is excreted in human milk. Breastfeeding mothers should discontinue nursing or FORTEO, taking into account the importance of treatment to the mother.

In a clinical study, FORTEO helped stimulate new bone with mineral properties consistent with younger bone age*10

FORTEO treatment increased the amount of newly formed bone matrix with lower, more heterogeneous mineral content (blue arrows), a property consistent with younger bone age.*

*Younger bone age is characterized by newly formed bone matrix with lower, more heterogeneous bone mineral content.

Analysis of mineralization at the tissue level shows that FORTEO promotes ongoing formation of new bone

Forteo helped stimulate new bone with mineral properties

FORTEO Select Safety Information

In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. The clinical relevance of the rat osteosarcoma finding to humans is unknown.


References

2. FORTEO Prescribing Information, 3. Riggs BL, Parfitt AM. J Bone Miner Res. 2005;20:177-184., 4. Raggatt LJ, Partridge NC. J Biol Chem. 2010;285:25103-25108., 5. Seeman E. Rheumatology (Oxford). 2008;47:iv2-iv8., 6. Dempster DW, et al. J Clin Endocrinol Metab. 2016;101:1353-1363., 7. Dempster DW, et al. J Bone Miner Res. 2016;31:1429-1439., 8. Dempster D, et al. J Clin Endocrinol Metab. 2012;97(8):2799-2808., 9. Data on file, Lilly Research Laboratories (FOR20161208A)., 10. Dempster DW, et al. J Bone Miner Res. 2016; 31(8):1527-1535.

Indications and Important Safety Information Warning: Potential Risk of Osteosarcoma
Warning: Potential Risk of Osteosarcoma
Indications and Usage

FORTEO is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, and for the treatment of men and women with osteoporosis associated with sustained, systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture.

High risk for fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

FORTEO is administered as a 20-microgram once-daily dose and is available in a 2.4-mL prefilled delivery device for subcutaneous injection over 28 days.

It is not known if FORTEO reduces the risk of fracture in men. Consistent with the FORTEO Prescribing Information, fracture data in patients with glucocorticoid-induced osteoporosis are not shown.

Important Safety Information

WARNING: POTENTIAL RISK OF OSTEOSARCOMA

In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe FORTEO® (teriparatide [rDNA origin] injection) only for patients for whom the potential benefits are considered to outweigh the potential risk. FORTEO should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton).

CONTRAINDICATIONS

Hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

The following categories of patients have increased baseline risk of osteosarcoma and therefore should not be treated with FORTEO: Paget’s disease of bone, pediatric populations and young adults with open epiphyses, or prior external beam or implant radiation therapy.

Patients should be encouraged to enroll in the voluntary FORTEO Patient Registry, which is designed to collect information about any potential risk of osteosarcoma in patients who have taken FORTEO. Enrollment information can be obtained by calling 1-866-382-6813, or by visiting www.forteoregistry.rti.org.

Cases of bone tumor and osteosarcoma have been reported rarely in people taking FORTEO in the post-marketing period. The causality to FORTEO use is unclear.

The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. The use of FORTEO for more than 2 years during a patient’s lifetime is, therefore, not recommended.

Patients with the following conditions also should not receive FORTEO: bone metastases or a history of skeletal malignancies, metabolic bone diseases other than osteoporosis, or hypercalcemic disorders.

FORTEO may increase serum calcium, urinary calcium, and serum uric acid.

Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered.

Transient orthostatic hypotension may occur with initial doses of FORTEO. In short-term clinical pharmacology studies, transient episodes of symptomatic orthostatic hypotension were observed in 5% of patients. FORTEO should be administered initially under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur.

Patients receiving digoxin should use FORTEO with caution because FORTEO may transiently increase serum calcium and hypercalcemia may predispose patients to digitalis toxicity.

ADVERSE REACTIONS

The most common adverse reactions in clinical trials include: arthralgia (10.1% FORTEO vs. 8.4% placebo), pain (21.3% FORTEO vs. 20.5% placebo), and nausea (8.5% FORTEO vs. 6.7% placebo). Other adverse reactions include: dizziness, leg cramps, joint aches, and injection site reactions.

USE IN PREGNANCY/NURSING MOTHERS

FORTEO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal studies, FORTEO may cause fetal harm.

It is not known whether teriparatide is excreted in human milk. Breastfeeding mothers should discontinue nursing or FORTEO, taking into account the importance of treatment to the mother.

INSTRUCTIONS FOR FORTEO USE

FORTEO is provided as a fixed-dose, prefilled delivery device that can be used for up to 28 days, including the first injection. The delivery device contains 28 daily doses of 20 mcg each. Do not transfer the contents of the delivery device into a syringe. The FORTEO delivery device should be stored under refrigeration at 36° to 46° F (2° to 8° C) at all times. Do not use FORTEO if it has been frozen.

For more safety information, please see Medication Guide and Full Prescribing Information, including Boxed Warning regarding osteosarcoma. See Full User Manual that accompanies the delivery device.

Forteo is a registered trademark owned or licensed by Eli Lilly & Company, its subsidiaries, or affiliates.
TE HCP ISI 24SEP2012