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

Osteoporosis

Treatment of osteoporosis in postmenopausal women; treatment of primary osteoporosis or osteoporosis due to hypogonadism in men.

Active ingredient

Teriparatide

Composition

1 ml of a solution for subcutaneous injection contains:

the active ingredient:

teriparatide 250 mcg,

auxiliary substances:

icy acetic acid – 0.41 mg,

sodium acetate anhydrous – 0.1 mg,

mannitol – 45.4 mg,

methacresol – 3 mg,

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

d/i water – q.s. to 1 ml

How to take, the dosage

The drug Forsteo is administered to adults. The dose does not depend on the age of the patient.

The recommended dose of Forsteo is 20 mcg administered once daily subcutaneously in the thigh or abdomen.

The maximum duration of treatment with Forsteo is 18 months. If there is a break in treatment with Forsteo, patients may continue treatment with other drugs.

The patient must be trained in the technique of administering the medication (see Syringe Pen Instructions for Use).

The rules for using the syringe pen

Forsteo is a solution in a syringe pen designed for individual use. A new sterile needle is required for each injection. Each package of Forsteo contains a “Patient Guide” detailing how to use the syringe pen.

Injection needles are not included. The syringe pen can be used with insulin syringe needles (Becton Dickinson).
The drug should be injected immediately after the syringe is removed from the refrigerator.
The syringe pen should be placed in the refrigerator after each injection.

Interaction

Clinically significant interaction with hydrochlorothiazide, furosemide, digoxin, atenolol, as well as with drugs with delayed release – diltiazem, nifidipine, phelodipine, nisoldipine has not been observed.

The co-administration of teriparatide with raloxifene or hormone replacement therapy has no effect on serum and urinary calcium levels.

Single administration of teriparatide has no effect on the pharmacodynamics of digoxin.

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

Special Instructions

The effect of teriparatide in patients with hypercalcemia has not been studied, therefore the drug should not be prescribed in these patients because of the possibility of exacerbation of hypercalcemia.

Hypercalcemia should be excluded before initiating treatment with teriparatide; however, regular monitoring of serum calcium concentrations is not necessary.

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

Blood sampling for determination of blood calcium should not be performed earlier than 16 hours after the last injection of Forsteo, because a transient increase in serum calcium after teriparatide injection may be observed. Continuous monitoring of calcium concentration during treatment is not necessary.

In administration of Forsteo, rare episodes of transient orthostatic hypotension may be observed that occur within 4 hours after drug administration and subside on their own within several minutes to several hours when the patient is placed in supine position and are not contraindications to further treatment.

In view of the paucity of clinical data for long-term treatment with teriparatide, the recommended duration of treatment should not exceed 18 months.

Forsteo should not be used if the solution in the syringe pen is cloudy, stained or contains foreign particles.

Pediatric use

The effect of teriparatide in pediatric patients has not been studied. Teriparatide should not be used in pediatric patients, adolescents, or young adults with open epiphyseal growth areas.

Contraindications

• previous hypercalcemia;
• severe renal insufficiency;
• increased ALP activity of unclear genesis;
• previous radiation therapy of skeletal bones;
• bone metastases or bone tumors in history;
• pregnancy;
• age below 18 years of age;
• high sensitivity to the components of Forsteo.

With caution:

• in patients in the phase of exacerbation of urolithiasis or who have recently had it, because of the possible worsening of the condition; urinary calcium excretion should be monitored;
• in patients with moderate renal dysfunction;
• hypovitaminosis D, clinically significant hypocalcemia.

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Side effects

Musculoskeletal system disorders:very common (≥10%) – limb pain; common (≥1%,

Hematopoietic system disorders:often (≥1%,

Metabolic disorders:often (≥1%,

Nervous system disorders:often (≥1%,

Mental disorders:often (≥1%,

Cardiovascular system:often (≥1%,

Respiratory system disorders:often (≥1%,

Digestive system disorders:often (≥1%,

Skin and subcutaneous tissue disorders:often (≥1%,

Urinary system disorders:rarely (≥0.1%,

Allergic reactions are very rare (< 0.1%) – acute dyspnea, oral/face swelling, and generalized rash occur shortly after injection.

General reactions:common (≥1%,

Local reactions: rare (≥0.1%,

Overdose

Symptoms: overdose may manifest as prolonged hypercalcemia and development of orthostatic collapse. Nausea, vomiting, dizziness, headache are also possible.

Treatment: there is no special antidote. In case of suspected overdose it is recommended to cancel the drug Forsteo, control serum calcium and conduct symptomatic therapy.

Pregnancy use

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

The drug should not be administered in pregnancy.

There have been no clinical studies to determine whether teriparatide is excreted with breast milk.

Teriparatide should not be prescribed to nursing mothers.