Forteo Information
Forteo (Teriparatide) 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) only for patients for whom the potential benefits are considered to outweigh the potential risk. Forteo (Teriparatide) 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) .
Forteo (Teriparatide) Indications And Usage
[see Clinical Studies ()].
Forteo (Teriparatide) Dosage Forms And Strengths
Multi-dose prefilled delivery device (pen) for subcutaneous injection containing 28 daily doses of 20 mcg.
Forteo (Teriparatide) Contraindications
Do not use Forteo (Teriparatide) in patients with:
Forteo (Teriparatide) Warnings And Precautions
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 . Forteo (Teriparatide) should not be prescribed for patients at increased baseline risk of osteosarcoma.
These include:
Patients should be encouraged to enroll in the voluntary Forteo (Teriparatide) Patient Registry, which is designed to collect information about any potential risk of osteosarcoma in patients who have taken Forteo (Teriparatide) . Enrollment information can be obtained by calling 1-866-382-6813, or by visiting
Forteo (Teriparatide) Adverse Reactions
The following adverse reactions have been identified during postapproval use of Forteo (Teriparatide) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse events reported since market introduction that were temporally (but not necessarily causally) related to Forteo (Teriparatide) therapy include the following:
Forteo (Teriparatide) Use In Specific Populations
Pregnancy Category C — There are no adequate and well-controlled studies of Forteo (Teriparatide) in pregnant women. In animal studies, teriparatide increased skeletal deviations and variations in mouse offspring at doses more than 60 times the equivalent human dose and produced mild growth retardation and reduced motor activity in rat offspring at doses more than 120 times the equivalent human dose. Forteo (Teriparatide) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In animal studies, pregnant mice received teriparatide during organogenesis at subcutaneous doses 8 to 267 times the human dose. At doses ≥ 60 times the human dose, the fetuses showed an increased incidence of skeletal deviations or variations (interrupted rib, extra vertebra or rib). When pregnant rats received subcutaneous teriparatide during organogenesis at doses 16 to 540 times the human dose, the fetuses showed no abnormal findings.
In a perinatal/postnatal study, pregnant rats received subcutaneous teriparatide from organogenesis through lactation. Mild growth retardation in female offspring at doses ≥120 times the human dose (based on surface area, mcg/m). Mild growth retardation in male offspring and reduced motor activity in both male and female offspring occurred at maternal doses 540 times the human dose. There were no developmental or reproductive effects in mice or rats at doses 8 or 16 times the human dose, respectively.
Exposure multiples were normalized based on body surface area (mcg/m). Actual animal doses: mice (30 to 1000 mcg/kg/day); rats (30 to 1000 mcg/kg/day).
Forteo (Teriparatide) Overdosage
Incidents of overdose in humans have not been reported in clinical trials. Teriparatide has been administered in single doses of up to 100 mcg and in repeated doses of up to 60 mcg/day for 6 weeks. The effects of overdose that might be expected include a delayed hypercalcemic effect and risk of orthostatic hypotension. Nausea, vomiting, dizziness, and headache might also occur.
In postmarketing spontaneous reports, there have been cases of medication errors in which the entire contents (up to 800 mcg) of the Forteo (Teriparatide) delivery device (pen) have been administered as a single dose. Transient events reported have included nausea, weakness/lethargy and hypotension. In some cases, no adverse events occurred as a result of the overdose. No fatalities associated with overdose have been reported.
Forteo (Teriparatide) Description
Forteo (Teriparatide) (teriparatide [rDNA origin] injection) contains recombinant human parathyroid hormone (1-34), and is also called rhPTH (1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone.
Teriparatide has a molecular weight of 4117.8 daltons and its amino acid sequence is shown below:
Teriparatide (rDNA origin) is manufactured using a strain of modified by recombinant DNA technology. Forteo (Teriparatide) is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.
Each cartridge, pre-assembled into a delivery device, delivers 20 mcg of teriparatide per dose each day for up to 28 days.
Forteo (Teriparatide) Clinical Pharmacology
Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.
The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.
Forteo (Teriparatide) Nonclinical Toxicology
In single-dose rodent studies using subcutaneous injection of teriparatide, no mortality was seen in rats given doses of 1000 mcg/kg (540 times the human dose based on surface area, mcg/m) or in mice given 10,000 mcg/kg (2700 times the human dose based on surface area, mcg/m).
In a long-term study, skeletally mature ovariectomized female monkeys (N=30 per treatment group) were given either daily subcutaneous teriparatide injections of 5 mcg/kg or vehicle. Following the 18-month treatment period, the monkeys were removed from teriparatide treatment and were observed for an additional 3 years. The 5 mcg/kg dose resulted in systemic exposures that were approximately 6 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Bone tumors were not detected by radiographic or histologic evaluation in any monkey in the study.
Forteo (Teriparatide) Clinical Studies
The safety and efficacy of once-daily Forteo (Teriparatide) , median exposure of 19 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 1637 postmenopausal women with osteoporosis (Forteo (Teriparatide) 20 mcg, n=541).
All women received 1000 mg of calcium and at least 400 IU of vitamin D per day. Baseline and endpoint spinal radiographs were evaluated using the semiquantitative scoring. Ninety percent of the women in the study had 1 or more radiographically diagnosed vertebral fractures at baseline. The primary efficacy endpoint was the occurrence of new radiographically diagnosed vertebral fractures defined as changes in the height of previously undeformed vertebrae. Such fractures are not necessarily symptomatic.
The safety and efficacy of once-daily Forteo (Teriparatide) , median exposure of 10 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 437 men with either primary (idiopathic) or hypogonadal osteoporosis (Forteo (Teriparatide) 20 mcg, n=151). All men received 1000 mg of calcium and at least 400 IU of vitamin D per day. The primary efficacy endpoint was change in lumbar spine BMD.
Forteo (Teriparatide) increased lumbar spine BMD in men with primary or hypogonadal osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. Forteo (Teriparatide) was effective in increasing lumbar spine BMD regardless of age, baseline rate of bone turnover, and baseline BMD. The effects of Forteo (Teriparatide) at additional skeletal sites are shown in .
Forteo (Teriparatide) treatment for a median of 10 months increased lumbar spine BMD from baseline in 94% of men treated. Fifty-three percent of patients treated with Forteo (Teriparatide) achieved at least a 5% increase in spine BMD, and 14% gained 10% or more.
The efficacy of Forteo (Teriparatide) for treating glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥5 mg/day prednisone or equivalent for a minimum of 3 months. The duration of the trial was 18 months with 214 patients exposed to Forteo (Teriparatide) . In the Forteo (Teriparatide) group, the baseline median glucocorticoid dose was 7.5 mg/day and the median duration of glucocorticoid use was 1.5 years. The mean (SD) baseline lumbar spine BMD was 0.85 ± 0.13 g/cm and lumbar spine BMD T-score was –2.5 ± 1 (number of standard deviations below the mean BMD value for healthy adults). A total of 30% of patients had prevalent vertebral fracture(s) and 43% had prior non-vertebral fracture(s). The patients had chronic rheumatologic, respiratory or other diseases that required sustained glucocorticoid therapy. All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.
Because of differences in mechanism of action (anabolic vs. anti-resorptive) and lack of clarity regarding differences in BMD as an adequate predictor of fracture efficacy, data on the active comparator are not presented.
Forteo (Teriparatide) Patient Counseling Information
See .
Patients and caregivers who administer Forteo (Teriparatide) should be instructed on how to properly use the delivery device (refer to ), properly dispose of needles, and be advised not to share their delivery device with other patients. The contents of the delivery device should NOT be transferred to a syringe.
Each Forteo (Teriparatide) delivery device can be used for up to 28 days including the first injection from the delivery device. After the 28-day use period, discard the Forteo (Teriparatide) delivery device, even if it still contains some unused solution.
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