Composition, form of production and packaging
Liofilizate for the preparation of a solution for s / c introduction of white color; the solvent is a clear, colorless liquid.
1 cartridge 1 ml of finished r-ra
somatropin recombinant 18.4 IU (6.1 mg) 16 IU (5.3 mg)
Excipients: glycine, mannitol, sodium dihydrophosphate anhydrous, sodium hydrophosphate anhydrous.
The composition of the solvent: m-cresol, mannitol, water d / u.
Cartridges two-section for injectors Genotropin В® Pen 5.3 with solvent (1) - packs cardboard.
Cartridges two-section for injectors Genotropin В® Pen 5.3 with solvent (5) - packs cardboard.
Liofilizate for the preparation of a solution for s / c introduction of white color; the solvent is a clear, colorless liquid.
1 cartridge 1 ml of finished r-ra
somatropin recombinant 41.4 IU (13.8 mg) 36 IU (12 mg)
Excipients: glycine, mannitol, sodium dihydrophosphate anhydrous, sodium hydrophosphate anhydrous.
The composition of the solvent: m-cresol, mannitol, water d / u.
Cartridges two-section for injectors Genotropin В® Pen 12 with solvent (1) - packs cardboard.
Cartridges two-section for injectors Genotropin В® Pen 12 with solvent (5) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
The drug is a growth hormone. It is a somatropin, synthesized with the help of recombinant technologies, identical to the human growth hormone.
In children with deficiency of endogenous growth hormone and Prader-Willi syndrome, somatropin enhances and accelerates the linear growth of the skeleton.
In both adults and children, somatropin maintains a normal body structure, stimulating muscle growth and facilitating the mobilization of fat. Visceral adipose tissue is particularly sensitive to somatropin. In addition to stimulating lipolysis, somatropin reduces the flow of triglycerides to the fat stores. Somatropin increases the concentration of insulin-like growth factor (IRP-1) and IRP-binding protein (IRFSB-3) in serum.
In addition, the drug has an effect on fat, carbohydrate and water-salt metabolism.
Somatropin stimulates liver receptors to LDL and affects the profile of lipids and lipoproteins in the serum. In general, the appointment of somatropin to patients with a deficiency of growth hormone leads to a decrease in the concentration of LDL and apolipoprotein B in the blood serum. There may also be a decrease in the level of total cholesterol.
Somatropin increases the level of insulin, however, the fasting glucose level usually does not change. In children with hypopituitarism, hypoglycemia may be observed on an empty stomach, stopping on the background of taking the drug.
Somatropin restores the volume of plasma and tissue fluid, reduced with a lack of growth hormone; promotes the retention of sodium, potassium and phosphorus.
Somatropin stimulates bone metabolism. In patients with growth hormone deficiency and osteoporosis, prolonged treatment with somatropin leads to the restoration of mineral composition and bone density.
Treatment with somatropin increases muscle strength and physical endurance.
Somatropin also increases cardiac output, but the mechanism of this effect has not yet been elucidated. A certain role in this may play a decrease in peripheral vascular resistance.
In patients with growth hormone deficiency, there may be a decrease in mental abilities and changes in mental status. Somatropin increases vitality, improves memory and affects the balance of neurotransmitters in the brain.
PHARMACOKINETICS
Suction and distribution
Both in healthy individuals and in patients with growth hormone deficiency, about 80% of the injected Genotropin is absorbed. After sc administration of the drug at a dose of 0.1 IU / kg body weight C max is 13-35 ng / ml and is achieved after 3-6 hours.
V d is 0.5-2.1 l / kg.
Metabolism and excretion
Biotransformed in the kidneys and liver. The mean T 1/2 after intravenous administration of Genotropin in patients with growth hormone deficiency is about 0.4 hours. With the introduction of the drug, T 1/2 reaches 2-3 hours. The observed difference is probably associated with a slower absorption of the drug at Рї / Рє injections.About 0.1% of the injected drug is excreted unchanged in the bile.
Pharmacokinetics in special clinical cases
Absolute bioavailability of Genotropin with p / to the introduction is the same in males and females.
INDICATIONS
For children
- Growth disorder with insufficient growth hormone secretion;
- Growth disorder in Shereshevsky-Turner syndrome;
- Dysplasia in chronic renal failure;
intrauterine growth retardation;
- Prader-Willi syndrome.
For adults
- confirmed insufficiency of growth hormone.
DOSING MODE
The dose of the drug should be selected individually. The drug is administered sc, to prevent lipoatrophy, the injection site should be changed.
Recommended doses for children are presented in the table
Indications Daily dose
mg / kg body weight IU / kg body weight mg / m 2 body surface area ME / m 2 body surface area
Insufficient secretion of growth hormone 0.025 - 0.035 0.07-0.1 0.7-1.0 2.1-3.0
Syndrome Shereshevsky-Turner 0.045-0.05 0.14 1.4 4.3
Chronic renal failure 0.045-0.05 0.14 1.4 4.3
The Prader-Willi syndrome 0.035 0.1 1.0 3.0
Intrauterine growth retardation 0.033-0.067 0.1-0.2 1.0-2.0 3.0-6.0
The initial dose for adults with growth hormone deficiency is 0.15-0.3 mg (0.45-0.9 IU) / day. The maintenance dose is selected individually according to age and sex.It rarely exceeds 1.3 mg (4 IU) / day. Women may need a higher dose than men. Since the normal physiological production of growth hormone decreases with age, the dose corresponding to age can be reduced.
Clinical and side effects, as well as the determination of the serum level of IGF-1, can be used as a guide in the selection of a dose.
GenotropinВ® 5.3 mg (16 IU) and 12 mg (36 IU) are injected with generic injectors GenotropinВ® Pen 5.3 and GenotropinВ® Pen 12, respectively. After the cartridge is inserted into the injector, dilution of the drug occurs automatically. When diluting the drug, the solution should not be shaken.
SIDE EFFECT
Side effects due to fluid retention: in adults (> 1% and <10%) - peripheral edema, lower extremities pastostess, arthralgia, myalgia and paresthesia. These phenomena are usually mild or moderate, manifest during the first months of treatment and decrease spontaneously or after a decrease in the dose of the drug. The frequency of these side effects depends on the dose of Genotropin, the age of the patients and, possibly, inversely proportional to the age at which growth hormone deficiency arose. In children, these side effects are rare (> 0.1% and <1%).
From the side of the central nervous system: rarely (> 0.01% and <0.1%) - benign intracranial hypertension, the development of edema of the optic nerve is possible.
On the part of the endocrine system: rarely (> 0.01% and <0.1%) - the development of type 2 diabetes. Also, a decrease in the level of cortisol in the serum is detected. The clinical significance of this phenomenon is limited.
From the musculoskeletal system: dislocations and subluxations of the femoral head, accompanied by limping, pain in the thigh and knee; Patients with Prader-Willi syndrome may develop scoliosis (since Genotropin В® enhances growth rate); very rarely - myositis, which can be caused by the action of the preservative m-cresol, which is part of Genotropin.
Allergic reactions: skin rash and itching.
Local reactions: at the injection site (> 1% and <10%) - rash, itching, soreness, numbness, hyperemia, swelling, lipoatrophy.
Other: in single cases (<0.01%) - the development of leukemia in children, but the incidence of leukemia does not differ from that in children without growth hormone deficiency.
CONTRAINDICATIONS
- the presence of symptoms of tumor growth, including uncontrolled growth of a benign intracranial tumor (antitumor therapy should be completed before the initiation of Genotropin treatment);
- a critical condition, acute development in patients as a result of open heart or abdominal surgery, multiple trauma and acute respiratory failure;
- severe forms of obesity (weight / height ratio exceeds 200%) or severe respiratory disorders in patients with Prader-Willi syndrome;
- Closure of the growth zones of the epiphyses of tubular bones;
- Hypersensitivity to any of the components of the drug.
With caution should prescribe the drug for diabetes, intracranial hypertension, hypothyroidism.
PREGNANCY AND LACTATION
Clinical experience with the use of Genotropin in pregnancy is limited. Therefore, during pregnancy should clearly assess the need for prescribing the drug and the possible risks associated with this. At normal course of pregnancy the level of pituitary growth hormone noticeably decreases after 20 weeks, replaced almost completely by placental by 30 weeks, and therefore the need for continuing substitution therapy with Genotropin in the III trimester of pregnancy seems unlikely.
Experimental studies in animals have not revealed a negative effect on the fetus, but it does not follow that similar results will be obtained with the use of Genotropin in humans.
There is no reliable information on excretion of somatropin with breast milk, however, in any case, the absorption of intact protein in the child's gastrointestinal tract is extremely unlikely.
APPLICATION FOR FUNCTIONS OF THE LIVER
Treatment Genotropinom appoint only those patients with chronic renal failure, in which the kidney function is reduced by more than 50%. To confirm violations of growth, this indicator should be monitored within a year. During treatment with generotropin should continue to conduct conservative treatment of kidney failure.Treatment should be discontinued with kidney transplantation.
APPLICATION FOR CHILDREN
Recommended doses for children are presented in the table
Indications Daily dose
mg / kg body weight IU / kg body weight mg / m 2 body surface area ME / m 2 body surface area
Insufficient secretion of growth hormone 0.025 - 0.035 0.07-0.1 0.7-1.0 2.1-3.0
Syndrome Shereshevsky-Turner 0.045-0.05 0.14 1.4 4.3
Chronic renal failure 0.045-0.05 0.14 1.4 4.3
The Prader-Willi syndrome 0.035 0.1 1.0 3.0
Intrauterine growth retardation 0.033-0.067 0.1-0.2 1.0-2.0 3.0-6.0
SPECIAL INSTRUCTIONS
If, during any substitution therapy with Genotropin, for any reason, a critical condition arises, before continuing treatment, the risk / benefit ratio of the individual patient should be assessed.
Cases of deaths have been reported against the use of growth hormone in children with Prader-Willi syndrome with one or more of the following risk factors: severe obesity, respiratory disorders, sleep apnea, or unidentified respiratory infections. Another possible risk factor may be the male sex of the patient. Patients with Prader-Willi syndrome should be examined for obstruction of the upper respiratory tract. If signs of obstruction of the upper respiratory tract (including the appearance and / or strengthening of snoring, obstructive apnea or similar clinical symptoms) appear during treatment, treatment should be discontinued. All patients with Prader-Willi syndrome should be examined for sleep apnea and be closely monitored if suspected. These patients also need to control body weight and the symptoms of respiratory infections, the development of which should be as soon as possible to begin the most active therapy.
As a result of treatment with Genotropin, the transition of the hormone T 4 to T 3 is activated, which leads to a decrease in T 4 concentration and an increase in serum T 3 concentration. Usually, the level of these hormones in the peripheral blood remains within normal limits. However, this effect of Genotropin may cause hypothyroidism in patients with a hidden subclinical form of central hypothyroidism. It is recommended to investigate the function of the thyroid gland after the initiation of treatment with Genotropin and after changing its dose.
In secondary insufficiency of growth hormone, caused by the treatment of malignant neoplasm, a more thorough observation is recommended for the development of symptoms of tumor recurrence.
Treatment Genotropinom appoint only those patients with chronic renal failure, in which the kidney function is reduced by more than 50%. To confirm violations of growth, this indicator should be monitored throughout the year. During treatment with generotropin should continue to conduct conservative treatment of kidney failure. Treatment should be discontinued with kidney transplantation.
Genotropin В® may reduce the sensitivity of peripheral receptors to insulin and, therefore, patients should be examined for glucose tolerance before starting Genotropin. The risk of developing type 2 diabetes mellitus during treatment with generotropin is greatest in patients with other risk factors, such as overweight, cases of diabetes mellitus among relatives, GCS therapy or a previously known impairment of glucose tolerance. In patients with diabetes mellitus against the background of Genotropin treatment, a dose change of hypoglycemic drugs may be required.
In the case of myalgia or increased pain in the place of injection of Genotropin, the development of myositis should be assumed. In case of confirmation of the diagnosis, it is necessary to use the form of somatropin without m- cresol.
Dislocations and subluxations of the femoral head (limping, pain in the thigh and knee) can be more often observed in patients with endocrine disorders, including a deficiency of growth hormone. Children receiving growth hormone, who are lame, should be carefully examined.
In case of development of severe or repeated headaches, visual disturbances, nausea and / or vomiting with Genotropin, it is recommended to examine the fundus for the detection of edema of the optic disc. In case of confirmation of the edema of the optic nerve disc, it is necessary to assume the presence of benign intracranial hypertension. If necessary, treatment with Genotropin should be temporarily discontinued. When the treatment is resumed, careful monitoring of the patient's condition is necessary.
Perhaps the formation of antibodies to the drug, the study of antibody titer to somatropin should be carried out in the absence of a therapeutic response.
The drug is not effective if the body does not synthesize growth factors or lacks receptors for growth factors.
The patient may be stored for 1 month at room temperature before the dilution (not above 25 В° C).
Impact on the ability to drive vehicles and manage mechanisms
Genotropin В® does not affect the ability to drive vehicles and work with mechanisms.
OVERDOSE
Cases of an overdose of Genotropin В® are unknown.
Symptoms: with acute overdose hypoglycemia is possible, and then hyperglycemia. A prolonged overdose may be manifested by known symptoms of excess human growth hormone (acromegaly, gigantism).
Treatment: withdrawal of the drug, symptomatic therapy.
DRUG INTERACTION
GCS, when combined, reduces the stimulating effect of Genotropin on the growth process.
With the simultaneous use of generotropin with thyroxine, moderate hyperthyroidism may develop.
Genotropin В®, when used simultaneously, can increase the clearance of compounds metabolized by the isoenzyme CYP3A4 (sex hormones, corticosteroids, anticonvulsants, cyclosporine). The clinical significance of this effect has not been studied.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of the reach of children, in a dark place at a temperature of 2 В° to 8 В° C. Shelf life - 3 years.
The finished solution can be stored in the refrigerator (at a temperature of 2 В° to 8 В° C) for 4 weeks. Do not freeze the cartridge, nor the finished solution.
