FORTEO (teriparatide injection) Efficacy: In a median of 19 months, FORTEO significantly reduced the risk of vertebral and nonvertebral fractures*†2

In a median of 19 months, FORTEO Significantly Reduced the Risk of Vertebral and Nonvertebral Fractures

Number needed to treat11= 11
n=448 (placebo); with ≥1 new vertebral fracture(s): 64
n=444 (FORTEO); with ≥1 new vertebral fracture(s): 22
(RR, 0.35; 95% CI, 0.22—0.55)
(AR: placebo 14.3%; FORTEO 5.0%, P≤0.001)

Number needed to treat12 = 34
n=544 (placebo); with ≥1 new nonvertebral fracture(s): 30
n=541 (FORTEO); with ≥1 new nonvertebral fracture(s): 14
(RR, 0.47; 95% CI, 0.25—0.88)
(AR: placebo 5.5%; FORTEO 2.6%, P<0.05)

Approximately 90% of patients in the Fracture Prevention Trial had a prevalent vertebral fracture2

*Fracture Prevention Trial: Multicenter, prospective, double-blind trial of FORTEO 20 mcg/day (n=541) vs. placebo (n=544). 1,637 postmenopausal women with osteoporosis, of whom 90% had a prevalent vertebral fracture at baseline, were evaluated. Mean age: 69. Median duration of exposure to therapy: 19 months (maximum 24 months). All received 1,000 mg/day of calcium and 400-1,200 IU/day of vitamin D.2,9

**A post hoc analysis of the vertebral fracture data from the Fracture Prevention Trial using a combination of quantititive vertebral morphometry measurements (QM) and qualitative visual semiquantitative (SQ) grading to assess lateral spine radiographs showed that vertebral fracture relative risk reduction for FORTEO was 84%§14

§A post hoc analysis was conducted on a subset of 892 women who had a baseline and endpoint spine radiograph (FORTEO n-444, placebo n=448). Primary analysis was the comparison of the proportions of women with new vertebral fractures as defined by the combination of group-blinded quantitative vertebral morphometry measurements and confirmation of the results of qualitative visual semiquantitative grading by Neer et al, using a Fishers’ exact test.14

Nonvertebral fracture risk reduction was obtained from pooling data from the following sites: ankle/foot, hip, humerus, pelvis, ribs, wrist, and other sites.

Fragility fractures were defined as fractures occurring with minimal trauma (eg, falling from standing height).

FORTEO Select Safety Information

Osteosarcoma has been reported in patients treated with FORTEO in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. Avoid use in patients with increased baseline risk of osteosarcoma including patients with open epiphyses (pediatric and young adult patients), metabolic bone diseases including Paget’s disease of the bone, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. There is limited data assessing the risk of osteosarcoma beyond 2 years.

FORTEO may help increase bone mineral density

In postmenopausal women with osteoporosis treated with FORTEO2*:

  • Hip and femoral neck BMD were significantly increased at endpoint
  • 96% had an increase in lumbar spine BMD
  • Lumbar spine BMD was significantly increased above baseline at 3 months through end point
Forteo increased lumbar spine BMD in postmenopausal women with osteoporosis
  • In a population of patients for whom data were available at every time point (FORTEO [n=129], placebo [n=137]), FORTEO significantly increased lumbar spine BMD by 11.8% at 18 months†10
  • In a separate analysis of the data using the last observation carried forward (FORTEO [n=541], placebo [n=544]), FORTEO significantly increased lumbar spine BMD by 9.7%‡2

Study Design

*Fracture Prevention Trial: Multicenter, prospective, double-blind trial of FORTEO 20 mcg/day (n=541) vs. placebo (n=544). 1,637 postmenopausal women with osteoporosis, of whom 90% had a prevalent vertebral fracture at baseline, were evaluated. Mean age: 69. Median duration of exposure to therapy: 19 months (maximum 24 months). All received 1,000 mg/day of calcium and 400—1,200 IU/day of vitamin D.2,9

P<0.001 for FORTEO vs. placebo at each post baseline time point.

P<0.001 for FORTEO compared with placebo at endpoint.

FORTEO Select Safety Information

FORTEO may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia. Avoid FORTEO in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

VERO – The first trial in osteoporosis research that has shown a significant vertebral fracture risk reduction outcome as a primary endpoint in a head-to-head, active comparator study.13

FORTEO® (teriparatide) demonstrated a statistically significant reduction in the incidence of new vertebral fragility fractures at 24 months vs a bisphosphonate.13

Forteo Vero Study & Incidence of new vertebral fractures graph

The effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO) trial. A multicenter, double-blind, double-dummy, randomized controlled trial of teriparatide (FORTEO) 20mcg/day (n=680) vs. risedronate 35mg once weekly (n=680). 1,366 postmenopausal women with severe osteoporosis (≥1 prevalent vertebral fracture at baseline) of whom 72.1% received at least one prior osteoporosis medication, most commonly a bisphosphonate, were enrolled. The mean age was 72.1. Median (IRQ) duration of therapy was 23.9 (18.8 to 24.1) months for FORTEO and 23.7 (22.8 to 24.0) months for risedronate. All patients received 500 - 1,000 mg/day of calcium and 400 - 800 IU/day of vitamin D.13

There were no statistically significant differences between the 2 groups in the proportion of patients with 1 or more treatment-emergent adverse events in VERO: ≥1 adverse event (72.8% FORTEO vs. 73.5% risedronate).13

The Fracture Prevention Trial, FORTEO’s pivotal trial, showed that, in a median of 19 months, FORTEO 20 mcg/day significantly reduced the risk of vertebral fracture by 9.3% ARR or 65% RRR vs placebo [FORTEO n=444, Placebo n=448]. Mean age: 69; 90% had prevalent vertebral fracture at baseline; all received 1,000 mg/day calcium and 400-1,200 IU/day vitamin D.9

The most common adverse reactions in FORTEO 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).9


References

2. FORTEO package insert. Indianapolis, IN: Eli Lilly and Company; 2012., 9. Neer RM, et al. N Engl J Med. 2001;344:1434-1441., 10. Data on file, Lilly Research Laboratories (FOR20090922A)., 11. Data on file, Lilly Research Laboratories (FOR20110608A)., 12. Data on file, Lilly Research Laboratories (FOR20111019A)., 13. Kendler DL et al. The Lancet 2017. DOI: https://doi.org/10.1016/S0140-6736(17)32137-2, 14. Prevrhal S. Curr Med Res Opin. 2009;25:921-928.

Indications and Important Safety Information
Indications and Usage

FORTEO is indicated:

  • for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures.
  • to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
  • 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 or who have failed or are intolerant to other available osteoporosis therapy.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

FORTEO is contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis.

WARNINGS AND PRECAUTIONS

Osteosarcoma: Osteosarcoma has been reported in patients treated with FORTEO in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. Avoid use in patients with increased baseline risk of osteosarcoma including patients with open epiphyses (pediatric and young adult patients), metabolic bone diseases including Paget’s disease of the bone, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. There is limited data assessing the risk of osteosarcoma beyond 2 years.


Hypercalcemia and Cutaneous Calcification: FORTEO may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia. Avoid FORTEO in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.


Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking FORTEO. Risk factors for development of calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue in patients developing calciphylaxis or worsening of previously stable cutaneous calcification.


Risk of Urolithiasis: Consider the risks and benefits in patients with active or recent urolithiasis because of risk of exacerbation. If FORTEO-treated patients have pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion.


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


Risk of Digoxin Toxicity: Hypercalcemia may predispose patients to digitalis toxicity because FORTEO transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when FORTEO is used in patients receiving digoxin.

ADVERSE REACTIONS

The most common adverse reactions in clinical trials included: 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 included: dizziness, leg cramps, joint aches, and injection site reactions.


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

USE IN SPECIFIC POPULATIONS

Pregnancy & Lactation
There are no available data on FORTEO use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Consider discontinuing FORTEO when pregnancy is recognized. It is not known whether teriparatide is excreted in human milk, affects human milk production, or has effects on the breastfed infant. Avoid FORTEO use in women who are breastfeeding.


Pediatric Use
The safety and effectiveness of FORTEO have not been established in pediatric patients. Pediatric patients are at higher baseline risk of osteosarcoma because of open epiphyses. Avoid use due to increased baseline risk of osteosarcoma.

For more safety information, please click to see Medication Guide and Full Prescribing Information. Click to see Full User Manual that accompanies the delivery device.

Forteo® is a registered trademark owned or licensed by Eli Lilly AND Company, its subsidiaries, or affiliates.
TE HCP ISI 16NOV2020