Forsteo,extract 250 mcg/ml 2.4ml syringe pen cartridges

Pharmgroup:

Parathyroid hormone analog.

Pharmic action:

Forsteo is an analog of parathyroid hormone. Recombinant human parathyroid hormone (PTH) produced using a strain of Escherichia coli (using DNA recombination technology). Endogenous PTH, which is a sequence of 84 amino acid residues, is a major regulator of calcium and phosphorus metabolism in the bones and kidneys. Forsteo® (recombinant human PTH (1-34)) is an active fragment of endogenous human PTH. Physiological effect of PTH is stimulation of bone formation by direct influence on osteoblasts. PTH indirectly increases intestinal absorption and tubular reabsorption of calcium as well as renal excretion of phosphate.

The biological action of PTH is accomplished through binding to specific PTH receptors on the surface of cells. Teriparatide binds to these same receptors and has the same effect on bone and kidney as PTH. Daily single administration of teriparatide stimulates new bone formation on the trabecular and cortical (periosteal and/or endosteal) bone surfaces with preferential stimulation of osteoblast activity in relation to osteoclast activity. This is confirmed by an increase in the content of markers of bone formation in the blood serum: bone-specific alkaline phosphate and procollagen-I carboxyterminal propeptide (PICP). The increase of the content of bone formation markers is accompanied by a secondary increase of the level of bone resorption markers in the urine: N-telopeptide (NTX) and deoxypyridinoline (DPD), which reflects the physiological interaction of the processes of bone formation and resorption in skeletal remodeling.

In 2 h after the administration of teriparatide a transient increase in serum calcium concentration is observed, which reaches maximum values after 4-6 h and returns to baseline values within 16-24 h. In addition, transient phosphaturia and slight transient decrease of serum phosphorus concentration may be observed.

Teriparatide treatment increases bone mineral density (BMD) of the whole body by 5-10% (including lumbar spine, femoral neck and thigh bone).

The processes of mineralization occur without signs of toxic effect on bone tissue cells, and the bone tissue formed under the effect of teriparatide has normal structure (without formation of reticulofibrous bone tissue and bone marrow fibrosis).
Teriparatide reduces risk of fractures regardless of age, initial indices of bone metabolism or value of BMD (relative decrease of risk of new fractures is 65%).

Pharmacokinetics:

Teriparatide is well absorbed when given by injection. Absolute bioavailability of the drug is approximately 95%. Cmax of teriparatide is reached 30 min after 20 mcg i.v. i.v. injection and exceeds by 4-5 times the IGN level of PTH, with following reduction of concentration to undetectable values during 3 hours.

Vd is approximately 1.7 L/kg.

Like endogenous PTH, teriparatide does not accumulate in bones or other tissues.

The1/2 of teriparatide when given by injection is about 1 h, which reflects the time required for absorption.

Peripheral metabolism of PTH occurs primarily in the liver through non-specific enzymatic mechanisms with subsequent excretion by the kidneys.

Pharmacokinetics in special clinical cases:

No effect of age (age group from 31 to 85 years) on the pharmacokinetics of teriparatide was noted.

In patients with mild to moderate renal insufficiency (CKR of 30 to 72 ml/min) the drug pharmacokinetics is not altered.

Indications

Treatment of osteoporosis in postmenopausal women; treatment of primary osteoporosis or osteoporosis caused by hypogonadism in men.

Pharmacological effect

Pharmaceutical group:

parathyroid hormone analogue.

Pharmaceutical action:

Forsteo is an analogue of parathyroid hormone. Recombinant human parathyroid hormone (PTH) produced using a strain of Escherichia coli (using DNA recombination technology). Endogenous PTH, which is a sequence of 84 amino acid residues, is the main regulator of calcium and phosphorus metabolism in the bones and kidneys. Forsteo® (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.

The biological action of PTH occurs through 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 content of markers of bone tissue formation in the blood serum: bone-specific ALP and procollagen-I carboxy-terminal propeptide (PICP). The increase in the content of markers of bone tissue formation is accompanied by a secondary increase in the level of markers of bone resorption in urine: N-telopeptide (NTX) and deoxypyridinoline (DPD), which reflects the physiological interaction of the processes of formation and resorption of bone tissue in skeletal remodeling.

2 hours after administration of teriparatide, a short-term increase in the concentration of serum calcium is observed, which reaches maximum values ​​after 4-6 hours and returns to initial values ​​within 16-24 hours. In addition, transient phosphaturia and a slight short-term decrease in the phosphorus content in the blood serum may be observed.

During treatment with teriparatide, bone mineral density (BMD) of the whole body increases by 5-10% (including in the lumbar spine, femoral neck and femur).

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 reduction in the risk of new fractures is 65%).

Pharmacokinetics:

Teriparatide is well absorbed when administered subcutaneously. The absolute bioavailability of the drug is approximately 95%. Cmax of teriparatide is achieved 30 minutes after subcutaneous administration of the drug at a dose of 20 mcg and exceeds the PTH level by 4-5 times the ULN, followed by a decrease in concentration to undetectable values ​​within 3 hours.

Vd is approximately 1.7 l/kg.

Like endogenous PTH, teriparatide does not accumulate in bones or other tissues.

T1/2 of teriparatide with subcutaneous administration is about 1 hour, which reflects the time required for absorption.

Peripheral metabolism of PTH occurs primarily in the liver through nonspecific enzymatic mechanisms, followed by excretion by the kidneys.

Pharmacokinetics in special clinical situations:

There was no effect of age (age group from 31 to 85 years) on the pharmacokinetics of teriparatide.

In patients with mild or moderate renal failure (creatinine clearance from 30 to 72 ml/min), the pharmacokinetics of the drug does not change.

Special instructions

The effect of teriparatide in patients with hypercalcemia has not been studied, and therefore the drug should not be prescribed to such patients due to the possibility of exacerbation of hypercalcemia.

Before starting treatment with teriparatide, hypercalcemia should be excluded, however, regular monitoring of serum calcium concentrations is not required.

The effect of teriparatide in patients with active urolithiasis has not been studied. In patients with urolithiasis (acute or recent exacerbation), teriparatide should not be used due to the risk of exacerbation of this disease.

Blood sampling to determine the calcium content in the blood should be done no earlier than 16 hours after the last administration of the drug Forsteo, because A transient increase in serum calcium may occur following injection of teriparatide. Continuous monitoring of calcium concentrations during treatment is not required.

When taking Forsteo, rare episodes of short-term orthostatic hypotension may occur, which occur within 4 hours after administration of the drug and go away on their own within a few minutes to several hours when the patient is placed in a supine position and are not a contraindication to further treatment.

Due to the lack of clinical data on long-term treatment with teriparatide, the recommended duration of treatment should not exceed 18 months.

Forsteo cannot be used if the solution in the syringe pen is cloudy, colored or contains foreign particles.

Use in pediatrics

The effect of teriparatide in pediatric patients has not been studied. Teriparatide should not be used in pediatric, adolescent, or young adult patients with patent epiphyseal growth plates.

Active ingredient

Teriparatide

Composition

1 ml of solution for subcutaneous administration contains:

active ingredient:

teriparatide 250 mcg,

excipients:

glacial acetic acid – 0.41 mg,

sodium acetate anhydrous – 0.1 mg,

mannitol – 45.4 mg,

metacresol – 3 mg,

hydrochloric acid solution 10% and/or sodium hydroxide solution 10% – q.s.,

water d/i – q.s. up to 1 ml

Pregnancy

The effect of teriparatide treatment on fetal development in humans has not been studied.

The drug should not be prescribed during pregnancy.

No clinical studies have been conducted to determine whether teriparatide is excreted in breast milk.

Teriparatide should not be prescribed to nursing mothers.

Contraindications

previous hypercalcemia;
severe renal failure;
metabolic bone diseases, with the exception of primary osteoporosis (including hyperparathyroidism and Paget’s disease);
increased activity of alkaline phosphatase of unknown origin;
previous radiation therapy of skeletal bones;
history of bone metastases or bone tumors;
pregnancy;
lactation;
age under 18 years;
hypersensitivity to the components of the drug Forsteo.

With caution:

in patients in the phase of exacerbation of urolithiasis or those who have recently suffered from it, due to a possible deterioration of the condition; urinary calcium excretion should be monitored;
in patients with moderate renal impairment;
hypovitaminosis D, clinically significant hypocalcemia.

Side Effects

From the musculoskeletal system: very often (≥ 10%) – pain in the extremities; often (≥1%,

From the hematopoietic system: often (≥1%,

Metabolic: often (≥1%,

From the nervous system: often (≥1%,

Psychiatric disorders: often (≥1%,

Cardiovascular system: often (≥1%,

From the respiratory system: often (≥1%,

From the digestive system: often (≥1%,

From the skin and subcutaneous tissues: often (≥1%,

From the urinary system: rarely (≥ 0.1%,

Allergic reactions are very rare (<0.1%) - acute shortness of breath, swelling of the mouth/face, and a generalized rash occur soon after the injection.

General reactions: often (≥1%,

Local reactions: rare (≥ 0.1%,

Interaction

There were no clinically significant interactions with hydrochlorothiazide, furosemide, digoxin, atenolol, as well as with sustained-release drugs – diltiazem, nifidipine, felodipine, nisoldipine.

Co-administration of teriparatide with raloxifene or hormone replacement therapy does not affect calcium levels in serum or urine.

A single administration of teriparatide has no effect on the pharmacodynamics of digoxin.

Hypercalcemia is a predisposing factor for the development of intoxication with digitalis preparations, therefore teriparatide should be used with caution in patients taking digitalis preparations.

Overdose

Symptoms: overdose can be manifested by prolonged hypercalcemia and the development of orthostatic collapse. Nausea, vomiting, dizziness, and headache are also possible.

Treatment: There is no special antidote. If an overdose is suspected, it is recommended to discontinue the drug Forsteo, monitor serum calcium levels and carry out symptomatic therapy.

Storage conditions

At 2–8 °C (do not freeze)

Shelf life

2 years

Manufacturer

Lilly France, France