Composition, form of production and packaging
Liofilizate for the preparation of solution for injection from white to almost white.
1 cartridge
somatropine 6 mg
Excipients: glycine, mannitol, sodium phosphate dibasic, phosphoric acid (r-p 10%), sodium hydroxide r-p 10%.
Solvent : m-cresol 3 mg / ml, glycerol, water d / i, phosphoric acid (r-p 10%) sodium hydroxide solution 10% (for pH adjustment).
Cartridges in volume of 3 ml (1) complete with a solvent (a syringe of 3 ml) - packs cardboard.
Liofilizate for the preparation of a solution for injections of white to almost white.
1 cartridge
somatropine 12 mg
Excipients: glycine, mannitol, sodium phosphate dibasic, phosphoric acid (rp 10%), sodium hydroxide solution 10% (for pH adjustment).
Solvent : m-cresol 3 mg / ml, glycerol, water d / i, phosphoric acid (r-p 10%) sodium hydroxide solution 10% (for pH adjustment).
Cartridges in volume of 3 ml (1) complete with a solvent (a syringe of 3 ml) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Biosynthetic human DNA-recombinant growth hormone, which is a polypeptide hormone. Somatropin contains 191 amino acid residues and has a molecular weight of about 22 125 Da. The amino acid sequence of the preparation is identical to the amino acid sequence of human growth hormone produced by the pituitary.Somatropin is synthesized by the Escherichia coli strain, which was modified by the addition of the human growth hormone gene. It is a highly purified product.
Somatropin stimulates linear growth in children with an endogenous growth hormone deficiency and in children with growth retardation in Turner's syndrome. A marked increase in the linear length of the body after the administration of somatropin occurs as a result of exposure to growth plates of tubular bones. Treatment of a growth hormone deficiency in children with somatropin causes an increase in the growth rate and an increase in the concentrations of IGF-I (insulin-like growth factor / Somatomedin-C). In addition, somatropin enhances intracellular protein synthesis and causes nitrogen retention. Somatropin, according to the therapeutic effect, is equivalent to the pituitary hormone of human growth and has an equivalent pharmacokinetic profile in healthy adults.
PHARMACOKINETICS
Suction
After the introduction of the drug to adult volunteers at a dose of 100 mcg / kg body weight C max is achieved in 3-6 h and is about 55 ng / ml. Absorption after SC or IM injection - 63% and 75%, respectively.
Distribution and Metabolism
AUC is about 475 ng x h / ml. Somatropin penetrates well-perfused organs, especially the liver and kidneys.
Metabolized in the kidneys and liver.
Excretion
T 1/2 is about 4 hours. It is excreted by the kidneys and with bile (including 0.1% unchanged).
INDICATIONS
For children
- long-term treatment of children with growth retardation as a result of deficiency of endogenous growth hormone;
- treatment of short stature in children with Turner syndrome;
- treatment of growth retardation in pre-pubertal children suffering from chronic renal insufficiency.
For adults
- Substitution therapy in adults with a pronounced growth hormone deficiency. Patients must meet the following two criteria:
1. In patients in whom growth hormone deficiency arose in childhood, stimulation tests should be performed to confirm the failure of growth hormone before initiating substitution therapy with somatropin.
2. In patients in whom growth hormone deficiency arose in adulthood (patients with the syndrome of both isolated growth hormone deficiency and deficiency of other pituitary hormones / hypopituitarism) that developed as a result of pituitary disease, hypothalamus, surgery, radiation therapy, or trauma) , biochemical confirmation of the diagnosis of a growth hormone deficiency should also be made on the basis of an inadequately reduced response to dynamic tests to stimulate hormone secretion Ost.
DOSING MODE
The dosage and administration of somatropin is determined individually.
Depending on the indications, the following schemes are recommended:
If the growth hormone deficiency in children is recommended, the recommended dose is 0.18-0.3 mg (0.5-0.9 IU) / kg body weight per week. This weekly dose should be divided into 6-7 injections (0.07-0.1 IU / kg body weight / day), which are administered daily w / w. It is also permissible for the / m introduction.
With Turner syndrome, the recommended dose is 0.17-0.375 mg (0.5-1.125 IU) / kg body weight per week. This weekly dose should be divided into 6-7 injections.The drug is administered sc, in the evening.
If the growth hormone is inadequate in adults, the recommended dose at the beginning of treatment is 0.04 mg (0.125 IU) / kg body weight per week, daily, p / k. The maximum dose is 0.08 mg (0.25 IU) / kg of body weight per week. Selection of the dose of the drug is carried out gradually, depending on the effectiveness, adverse reactions and the level of insulin-like growth factor (IGF-1). With an increase in the patient's age, the recommended doses can be reduced.
With growth retardation in pre-pubertal children with chronic renal insufficiency, the recommended dose at the beginning of treatment is 0.045-0.05 mg / kg (about 0.14 IU) of body weight daily, p / k.
Rules for the preparation of solution
Cartridge with somatropin can come in 2 sets.
1. Set No. 1 - cartridge with somatropin, syringe with solvent and connecting block.
Each cartridge with somatropin should be diluted with the supplied syringe with solvent and a connecting block. Attach the connection block to the cartridge, and then enter the entire contents of the syringe (solvent) into the cartridge. The connector block will automatically direct the flow of liquid to the glass wall of the cartridge. To completely dissolve the contents, gently turn the cartridge upside down (about 10 times), do not shake. The resulting solution should be clear and free of suspended particles. If the solution is cloudy or contains suspended particles, the contents can not be inserted.
2. Kit No. 2 - cartridge with somatropin and modified syringe with solvent (without connecting block).
Each cartridge with somatropin should be diluted with the supplied modified syringe with a solvent. Connect the cartridge to the syringe with the solvent and enter the entire contents of the syringe (solvent) into the cartridge, directing the flow of liquid to the glass wall of the cartridge. To completely dissolve the contents, gently turn the cartridge upside down (about 10 times), do not shake. The resulting solution should be clear and free of suspended particles. If the solution is cloudy or contains suspended particles, the contents can not be entered.
Terms of use
Cartridges with the finished solution should only be used with the Humatro-Pen injector. For instructions on installing the cartridge, see the Humatro-Pen injector manual. For each administration of somatropin, a sterile needle should be used. In case of increased sensitivity to m-cresol or glycerol, the somatropin solution should not be prepared using the supplied solvent, in this case somatropin can be dissolved in sterile water for injection. When preparing a solution of somatropin in a similar way it follows:
- from the cartridge with the prepared solution to take only one dose;
- if the prepared solution is not used immediately after preparation, it should be stored at a temperature of 2 В° to 8 В° C;
- use the prepared dose for 24 hours;
- unused portion of the prepared solution to drain.
SIDE EFFECT
From the side of the central nervous system: headache, weakness, fatigue, increased intracranial pressure.
On the part of the endocrine system: with prolonged use of the drug in high doses - acromegaly, hypothyroidism, a decrease in the level of cortisol in the blood serum.
From the musculoskeletal system: epiphysis of the head of the femur (limping, pain in the thigh and knee), myalgia.
Allergic reactions: skin rash, itching.
Local reactions: soreness, numbness, hyperemia, swelling, lipoatrophy, itching.
Other: gynecomastia, otitis media (with Turner syndrome), peripheral edema in the first weeks of treatment, pancreatitis; rarely - glycosuria.
There are reports that a small number of children treated with growth hormone, including both pituitary growth hormone and DNA-recombinant growth hormone, developed leukemia. The relationship between leukemia and growth hormone treatment is still unclear.
CONTRAINDICATIONS
- Tumors of the brain, malignant neoplasms of any localization;
- growth stimulation in children with closed growth zones;
- acute critical conditions associated with complications after surgery on the open heart or cavity operations, multiple injuries or with acute respiratory insufficiency;
- established hypersensitivity to one of the components of the preparation or solvent.
With caution should prescribe the drug for diabetes, intracranial hypertension, hypothyroidism.
PREGNANCY AND LACTATION
It is not known whether somatropin affects reproductive function or whether fetal damage occurs when administered to pregnant women. Therefore somatropin should not be administered during pregnancy.
It is not known whether this drug is excreted in breast milk. Since many drugs can be excreted in breast milk, if it is necessary to administer somatropin during lactation, breastfeeding should be discontinued.
SPECIAL INSTRUCTIONS
Treatment with somatropin should be done by doctors who have experience in diagnosing and treating patients with growth hormone deficiency or with Turner syndrome.
Patients who, before the end of growth, were treated with growth hormone, before resumption of somatropin replacement therapy at doses recommended for adults, after closure of growth zones, should be re-examined to identify growth hormone deficiency.
Patients with a deficiency of growth hormone, which arose secondary in the presence of brain tumors, should be carried out more frequent examinations to exclude the progression and relapse of the underlying disease. Somatropin should not be prescribed if any signs of active tumor growth are detected. Before the appointment of growth hormone, the tumor process must be in the inactive phase and antitumor therapy must be completed. If signs of resumption of tumor growth appear, the drug should be discontinued.
In case of severe or recurrent headaches, visual impairment, nausea and / or vomiting, examination of the fundus (fundoscopy) is recommended to detect edema of the optic disc, the presence of which suggests the possibility of intracranial hypertension. In this case, it is necessary to stop treatment with growth hormone.
In patients with endocrine disorders, including insufficiency of growth hormone, epiphysiolysis of tubular bone heads can be more often observed. It is necessary to conduct a thorough examination if during the treatment with growth hormone the child has limp.
Patients with hypopituitarism in the case of standard hormone replacement therapy with the administration of somatropin should be under strict supervision.
During treatment with somatropin, hypothyroidism may develop, and the lack of adequate therapy for hypothyroidism may prevent optimal treatment with somatropin.
Perhaps the formation of antibodies to the drug and E. coli proteins.
The study of antibodies to somatropin should be conducted in those cases when the patient does not respond to the therapy.
Since human growth hormone can cause the development of insulin resistance, it is necessary to monitor patients to identify signs of impaired glucose tolerance.
Patients with diabetes during treatment with somatropin should be under constant medical supervision. Against the background of the introduction of somatropin in patients with diabetes mellitus, it may be necessary to correct the dose of insulin.
Prior to the appointment of somatropin treatment for growth retardation due to chronic renal failure, patients should first be observed for one year to confirm a disruption in growth. Conservative treatment of renal failure should be initiated, which should be performed during treatment with somatropin. During kidney transplantation, treatment with somatropin should be discontinued.
The experience of treatment with somatropin in patients older than 60 years is absent.
The experience of prolonged treatment of adults is absent.
OVERDOSE
Acute overdose can lead first to hypoglycemia, and then to hyperglycemia. Chronic overdose can cause the appearance of signs and symptoms of gigantism / acromegaly, which is consistent with the known effects of excess amounts of human growth hormone.
DRUG INTERACTION
With the simultaneous administration of GCS, the inhibitory effect of somatropin on growth is suppressed. If it is necessary to carry out GCS replacement therapy, adequate doses of GCS should be carefully selected to prevent the development of adrenal insufficiency or suppress growth.
It is not established that somatotropin is incompatible with other drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Before dilution (in the cartridge) the drug should be stored in the refrigerator at a temperature of 2 В° to 8 В° C; Do not freeze. Shelf life - 3 years.
The prepared solution should be stored in the refrigerator at a temperature of 2 В° to 8 В° C for not more than 28 days; Do not freeze. Shelf life 28 days. The prepared drug solution can be stored at room temperature for no more than 30 minutes.
List B. The solvent in the syringe should be stored in the refrigerator at a temperature of 2 В° to 8 В° C. Shelf life - 3 years.
