FORSTEO
Pharmacodynamics
| Mechanism of action |
Teriparatide is a recombinant human parathyroid hormone produced using a strain of Escherichia coli (using DNA recombination technology).
Endogenous parathyroid hormone (PTH), which is a sequence of 84 amino acid residues, is the main regulator of calcium and phosphorus metabolism in the bones and kidneys. Teriparatide (recombinant human PTH (1-34)) is an active fragment of endogenous human PTH. The physiological effect of PTH is to stimulate bone formation through a direct effect on osteoblasts. PTH indirectly increases intestinal absorption and tubular reabsorption of calcium, as well as renal excretion of phosphate. Pharmacodynamic properties The biological effect of PTH is due to binding to specific PTH receptors on the surface of cells. Teriparatide binds to the same receptors and has the same effects on bones and kidneys as PTH.
Single daily administration of teriparatide stimulates the formation of new bone tissue on the trabecular and cortical (periosteal and/or endosteal) surfaces of bones with preferential stimulation of osteoblast activity relative to osteoclast activity. This is confirmed by an increase in the levels of markers of bone tissue formation in the blood serum: bone-specific alkaline phosphatase and carboxy-terminal propeptide of type I procollagen (PICP). The increase in the content of bone tissue formation markers is accompanied by a secondary increase in the level of bone resorption markers in urine: N-telopeptide (NTX) and deoxypyridinoline (DPD), which reflects the physiological interaction of the processes of bone tissue formation and resorption in skeletal remodeling. 2 hours after administration of teriparatide, a short-term increase in serum calcium concentration is observed, which reaches maximum values after 4-6 hours and returns to baseline values within 16-24 hours. In addition, transient phosphaturia and a slight short-term decrease in serum phosphorus levels may occur.
Clinical effectiveness
Postmenopausal osteoporosis
The main clinical trial of teriparatide included 1637 patients with postmenopausal osteoporosis, with a mean age of 69.5 years.
At the start of the study, 90% of patients had suffered 1 or more vertebral fractures and the mean vertebral bone mineral density (BMD) was equivalent to a T-score of -2.6. All patients took 1000 mg of calcium daily and. at least 400 IU vitamin D.
Results of teriparatide therapy for up to 24 months (mean duration of therapy was 19 months) indicate a statistically significant reduction in the incidence of fractures. The incidence of new vertebral fractures (>1 fracture, as measured by radiography at the beginning and end of the study) in the teriparatide group and in the placebo group was 5.0% and 14.3%, respectively (p < 0.001 compared with the placebo group, a relative decrease risk - 65%).
The incidence of multiple vertebral fractures (>2 fractures, as determined by radiography at the beginning and end of the study) in the teriparatide group and in the placebo group was 1.1% and 4.9%, respectively (p < 0.001 compared with the placebo group, relative risk reduction - 77%).
The incidence of nonvertebral low-energy fractures (minimal trauma fractures) in the teriparatide group and placebo group was 2.6% and 5.5%, respectively (p < 0.025 compared with placebo group, relative risk reduction 53%).
The incidence of major nonvertebral low-energy fractures (femur, radius, humerus, ribs, pelvis) in the teriparatide group and placebo group was 1.5% and 3.9%, respectively (p < 0.025 compared with the placebo group, decreased relative risk - 62%).
After 19 months of treatment (median duration of therapy), there was an increase in BMD at the lumbar spine and proximal femur compared to placebo by 9% and 4%, respectively (p < 0.001). Post-therapy follow-up: After completion of teriparatide therapy, 1262 women with postmenopausal osteoporosis from the main study were included in a follow-up study. The primary objective of the study was to collect data on the safety of teriparatide. During this observation period, other osteoporosis therapy was permitted and additional evaluation of vertebral fractures was performed. At an average of 18 months after discontinuation of teriparatide therapy, the number of patients with at least one new vertebral fracture in the teriparatide-experienced group was 41% lower than in the placebo group (p=0.004).
| In an open-label study, 503 patients with postmenopausal severe osteoporosis and fragility fractures (minimal trauma fractures) within the previous three years (83% had previously received treatment for osteoporosis) received teriparatide for 24 months. After 24 months, BMD at the lumbar spine, proximal femur, and femoral neck increased from baseline by an average of 10.5%, 2.6%, and 3.9%, respectively. From 18 to 24 months, BMD at the lumbar spine, proximal femur, and femoral neck increased by 1.4%, 1.2%, and 1.6%, respectively. Osteoporosis in men |
In a clinical study of men with osteoporosis due to hypogonadism (defined by low morning free testosterone or elevated follicle-stimulating hormone or luteinizing hormone concentrations) or
| 437 patients with idiopathic osteoporosis took part, with an average age of 58.7 years. At the start of the study, the BMD of the vertebrae and femoral neck according to the T-criterion ranged from -2.2 to -2.1, respectively. At the start of the study, 35% of patients had a history of vertebral fractures, and 59% of patients had fractures of other locations. All patients took 1000 mg calcium and at least 400 IU vitamin D daily. Significant increases in lumbar spine bone mineral density were noted after 3 months. After 12 months of therapy, BMD at the lumbar spine and proximal femur increased by 5% and 1%, respectively, compared with placebo. |
Osteoporosis with long-term therapy
| glucocorticosteroids The effectiveness of teriparatide in osteoporosis caused by long-term treatment with glucocorticosteroids was proven in an 18-month randomized, double-blind clinical trial with an active comparator (alendronate 10 mg/day; 428 patients, mean age 57 years). At the start of the study, 28% of patients had 1 or more vertebral fractures. All patients took 1000 mg of calcium and 800 IU of vitamin D daily. The study included 277 postmenopausal women, 67 premenopausal women and 83 men. After 18 months of therapy, BMD of the lumbar spine increased by 7.2% (by 3.4% in the alendronate group, p < 0.001), BMD of the proximal femur increased by 3.6% (by 2.2% in the alendronate group, p<0.01), femoral neck BMD increased by 3.7% (by 2.1% in the alendronate group, p<0.05). |
In patients taking teriparatide,
| study period from 18 months to 24 months of therapy, BMD of the lumbar spine, proximal femur, and femoral neck increased by an additional 1.7%, 0.9%, and 0.4%, respectively. In the teriparatide group, after 36 months of therapy, new vertebral fractures were detected in 1.7% of patients (7.7% in the alendronate group, p = 0.01), new non-vertebral fractures were detected in 7.5% of patients (7.0% in the alendronate group, p =0.84). In premenopausal women after 18 months of therapy, the increase in BMD was significantly higher in the teriparatide group compared with alendronate: lumbar spine BMD increased by 4.2% (-1.9% in the alendronate group, p < 0.001), proximal BMD femur increased by 3.8% (0.9% in the alendronate group, p = 0.005). |
Mineralization processes occur without signs of toxic effects on bone tissue cells, and bone tissue formed under the influence of teriparatide has a normal structure (without the formation of reticulofibrous bone tissue and bone marrow fibrosis). Teriparatide reduces the risk of fractures regardless of age, baseline bone turnover, or BMD (relative risk reduction for new fractures is 65%).
In the USA, FORSTEO has been used since 2002. In Europe since 2003. Today, Teriparatide is widely used in all countries, and in 2012, doctors prescribed it to the millionth patient.
In Russia, FORSTEO has been used in all regions since 2014, and more than 300 patients in Russia have already received effective therapy for osteoporosis with FORSTEO.
Teriparatide increases bone density of the spine and proximal femur, reduces the risk of fractures of the vertebral bodies and peripheral bones in women with postmenopausal osteoporosis. It is most effective in patients who have not previously received bisphosphonate therapy. Bisphosphonates are prescribed after a course of treatment with teriparatide, since treatment with teriparatide can only be received once in a lifetime for 18-24 months. Repeated courses of treatment with teriparatide are not carried out.
FORSTEO is the only drug for the treatment of osteoporosis that activates bone tissue synthesis.
This is the most effective drug for the treatment of osteoporosis today.
P is indicated for the treatment of severe forms of osteoporosis. The use of teriparatide within its registered indications is recommended in the following patient groups:
- As first-line therapy in patients with severe osteoporosis (one or more vertebral fractures or fractures of the proximal femur, multiple repeated skeletal bone fractures).
- In patients with ineffectiveness of previous anti-osteoporotic therapy (new fractures that occurred during treatment and/or ongoing decrease in bone density).
- In patients who are intolerant to other drugs for the treatment of osteoporosis or have contraindications for their use.
And the use of bisphosphonates after treatment with teriparatide (sequential therapy regimen) leads to a significant further increase in bone mineral density in postmenopausal women.
To start treatment with FORSTEO, it is necessary to conduct a number of blood tests: total calcium, parathyroid hormone, alkaline phosphatase, creatine, general blood test. The presence of bone metastases should also be excluded if cancer is suspected.
A single daily subcutaneous injection of teriparatide stimulates the formation of new bone tissue.
Evaluation of the effectiveness of FORSTEO therapy
As part of the patient support program (8-800-100-58-33), the patient will be determined free of charge P1NP (Marker of new bone formation) at the beginning of therapy and after 3 months of therapy (You can obtain a patient support program card from your doctor). This P1NP control will help the doctor and the patient understand how much the process of new bone formation has accelerated after 3 months and predict the increase in BMD after a year of therapy.
Also , as part of this program, a nurse will come to your home and teach you how to use a FORSTEO syringe pen. The patient will also be given a cooler bag and a protective case for transporting the drug.
during treatment with teriparatide were pain in the extremities, nausea, headache and dizziness. As a rule, side effects during FORSTEO therapy were mild or moderate in nature and, with continued therapy, decreased and disappeared completely.
Since 2015, FORSTEO has been included in the list of vital drugs in the Russian Federation.
Guidelines for the use of a syringe pen with the drug FORSTEO
- Remove the white cap.
- Attach a new needle: tear off the paper tab, insert the needle directly into the medication cartridge; Screw the needle tightly, remove the outer protective cap and set it aside without throwing it away.
- Set the dose: pull the black trigger button all the way; Make sure the red stripe is visible, remove the inner protective cap and discard it.
- Inject the dose: gently pull back the skin on the thigh or abdomen and insert the needle subcutaneously, press the black trigger button all the way; while holding, slowly count to 5, then remove the needle.
- Check the dose: after removing the needle, make sure that the black trigger button is pressed in all the way; if the yellow rod is not visible, the injection was performed correctly; if the yellow rod is visible after the injection, do not re-inject on the same day; it is necessary to install the syringe pen in its original position.
- Remove the needle; put the outer protective cap on the needle; completely unscrew the needle by turning the outer protective cap 3-5 times; remove the needle and dispose of it in accordance with the recommendations of the attending physician; put the white cap back on; Place the pen in the refrigerator immediately after use.
The drug should be stored in the refrigerator at a temperature of 2° to 8° C. Do not freeze.
In Samara, FORSTEO is presented in the Biomed pharmacy at 28 Moskovskoe Shosse. tel.: 203-80-43.
