Instruction for use: Omnitrope

ATX Code H01AC01 Somatropin

Active substance: Somatropin

Pharmacological group

Growth hormone [Hormones of the hypothalamus, pituitary gland, gonadotropins and their antagonists]

Nosological classification (ICD-10)

E34.3 Low-growth [dwarfism], not elsewhere classified

Growth retardation, Growth retardation in children, Dwarfism, Nanism hypophyseal, Inadequate endogenous growth hormone, Growth Hormone Deficiency, Pituitary Nanism, Low height, Growth disorder, Disturbance of the growth process, Pituitary dwarfism, Disruption of endogenous hormone secretion with growth retardation, Growth disorders, Naniz disproportionate, Nanism associated with external factors

N18 Chronic Renal Failure

Congestive kidney failure, Renal failure chronic, Chronic Renal Failure, CRF, Chronic kidney failure in children

Q87.1 Syndromes of congenital anomalies, manifested mainly by dwarfism

Arskog-Scott dysplasia, Arskoga-Scott syndrome, Face-genital dysplasia, Facial genital syndrome, Face-finger-genital dysplasia, Face-finger-genital syndrome, Laron's dwarfism, COCCINE SYNDROME, The Prader-Willy / Engelman Syndrome, Noonan syndrome

Q96 Turner Syndrome

Turner syndrome, Gonadal Dysgenesis, Mixed gonadal dysgenesis, Shereshevsky-Turner Syndrome

Composition

Name of substance Amount in solution for subcutaneous administration

3.3 mg / ml 6.7 mg / ml

Active substance:

Somatropin

5 mg (15 IU) 10 mg (30 IU)

Excipients:

Sodium hydrogen phosphate heptahydrate, mg 1.33 1.7

Sodium dihydrogen phosphate dihydrate, mg 1.57 1.35

Poloxamer, mg 3 3

Benzyl alcohol (preservative), mg 13.5 -

Phenol (preservative), mg - 4,5

Mannitol, mg 52.51 -

Glycine, mg - 27.75

Phosphoric acid q.s. To pH (6.2 ± 0.2) q.s. To pH (6.2 ± 0.2)

Sodium hydroxide q.s. To pH (6.2 ± 0.2) q.s. To pH (6.2 ± 0.2)

Water for injection, ml up to 1.5 to 1.5

To the beginning ^

Description of dosage form

Transparent or slightly opalescent colorless solution.

pharmachologic effect

Pharmacological action - somatotropic.

Pharmacodynamics

Somatropin has a pronounced effect on the metabolism of fats, proteins and carbohydrates. In children with a deficiency of growth hormone (GH), somatropin stimulates the growth of the bones of the skeleton in length, affecting the plates of the epiphysis of tubular bones. In both adults and children, somatropin helps normalize the structure of the body by increasing muscle mass and reducing body fat. Visceral adipose tissue is especially sensitive to the action of somatropin. In addition to enhancing lipolysis, somatropin reduces the flow of triglycerides into body fat. Under the action of somatropin, the concentration of insulin-like growth factor I (IGF-I) and its binding protein (IGF-SB3, insulin-like growth factor binding protein) increases.

In addition, the following effects were demonstrated

Exchange of fats. Somatropin activates the LDL receptor in the liver and changes the profile of lipids and lipoproteins in the blood. In general, the appointment of somatropin to patients with GH deficiency leads to a decrease in blood levels of LDL and apolipoprotein B. A decrease in the concentration of cholesterol is also observed.

Exchange of carbohydrates. Somatropin increases the release of insulin, but the glucose concentration is usually unchanged. Children with hypopituitarism may develop fasting hypoglycemia. This condition is reversible upon administration of somatropin.

Water-mineral exchange. Deficiency of GH is associated with a decrease in the volume of plasma and extracellular fluid. The administration of somatropin leads to a rapid increase in both parameters. Somatropin promotes retention of sodium, potassium and phosphorus.

Metabolism of bone tissue. Somatropin stimulates bone metabolism. Long-term treatment with children with somatropin deficiency of GH and osteoporosis leads to normalization of mineral composition and bone density.

Physical activity. Long-term substitution therapy with somatropin leads to an increase in muscle strength and physical endurance. Cardiac output is also increased, although the mechanism of this action is not fully understood. Reduction of peripheral vascular resistance, perhaps, partially explains this action of somatropin.

Pharmacokinetics

Absorption

After the SC administration, the bioavailability of somatropin is approximately 80% in both healthy individuals and in patients with GH deficiency. With the introduction of Omnithrop® at a dose of 5 mg to healthy volunteers Cmax of somatropin in plasma and its Tmax were respectively (72 ± 28) μg / l and (4 ± 2) h.

Excretion

The average T1 / 2 somatropin after iv introduction to adult patients with GH deficiency is about 0.4 hours. However, after the SC administration of T1 / 2 the drug reaches 3 hours.

Individual patient groups

Absolute bioavailability of somatropin after SC administration does not differ between men and women.

There is no evidence that age, race, liver, kidney or heart function has been affected by pharmacokinetic parameters of somatropin.

Indications

In children with growth retardation as a result of the following diseases and conditions:

Insufficient growth hormone secretion;

Shereshevsky-Turner syndrome;

Prader-Willi syndrome (SLE);

Chronic renal failure (CRF) with a decrease in kidney function by more than 50%;

Children born with low growth rates for this gestational age.

In adults, as a substitute therapy:

Confirmed pronounced congenital or acquired deficiency of growth hormone.

Contraindications

Hypersensitivity to any component of the drug;

Malignant neoplasms;

Urgent conditions (including conditions after operations on the heart, abdominal cavity, acute respiratory failure);

Stimulation of growth in patients with closed epiphyseal growth zones;

Pregnancy and lactation (during the period of treatment it is necessary to refuse breastfeeding);

The period of newborns (including premature infants) due to the presence of benzyl alcohol in the composition.

With caution: diabetes mellitus; Craniocerebral hypertension; Concomitant therapy with SCS; Hypothyroidism (including when carrying out substitution therapy with thyroid hormones).

Side effects

The following summarizes the adverse events reported in accordance with the system-organ classification (MedDRA) and the WHO classification by frequency: very often (≥1 / 10); Often (≥1 / 100, <1/10); Infrequently (≥1 / 1000, <1/100); Rarely ≥1 / 10000, <1/1000) and very rarely (<1/10000).

A feature of patients with GH deficiency is the lack of volume of extracellular fluid. With the appointment of somatropin, this deficit is quickly eliminated.

Adult patients often experience adverse reactions associated with fluid retention, such as peripheral edema, limb stiffness, arthralgia, myalgia, and paresthesia. Typically, the severity of these reactions varies from moderate to moderate, they develop in the first months of treatment and are spontaneous or with a decrease in dose. The probability of these reactions depends on the dose of the drug, the age of the patient; And they are probably irreversibly related to age when GH deficiency occurs. In children these side effects are unknown.

Benign, malignant and unspecified neoplasms: very rarely - leukemia. In very rare cases, cases of leukemia with GH deficiency in treatment with somatropin were noted in children, but it was found that this frequency is similar to that of children with normal GH concentration.

From the immune system: often - the formation of antibodies to somatropin. In the appointment of somatropin, approximately 1% of patients develop antibodies to it. The binding ability of these antibodies is small, and clinical manifestations of such antibody production have not been noted.

From the endocrine system: rarely - type 2 diabetes mellitus.

From the nervous system: often - paresthesia (in adults); Infrequently - carpal tunnel syndrome (in adults), paresthesia (in children); Rarely - benign intracranial hypertension.

From the musculoskeletal and connective tissue: often - rigidity of the limbs, arthralgia, myalgia (in adults); Infrequently - stiff limbs, arthralgia, myalgia (in children).

General disorders and disorders at the site of administration: often - peripheral edema (in adults), transient skin reactions at the injection site (in children); Infrequently, peripheral edema (in children).

Interaction

The results of the study of drug interaction in adult patients with GH deficiency suggest that the appointment of somatropin increases the clearance of drugs metabolized by microsomal isoenzymes of cytochrome P450 in the liver, especially those metabolized by the isoenzyme 3A4 - sex hormones, GCS, anticonvulsants and cyclosporine, which can lead to Decrease in their concentration in plasma. The clinical significance of this effect has not yet been determined.

GCS inhibits the stimulating effect of somatropin on growth processes. The effectiveness of the drug (with respect to final growth) may also be influenced by concomitant therapy with other hormones, for example gonadotropin, anabolic steroids, estrogens and thyroid hormones.

Dosing and Administration

P / to, slowly, 1 time per day, usually at night. It is necessary to change the injection site to prevent the development of lipoatrophy.

Doses are selected individually, taking into account the severity of GH deficiency, mass or body surface area, efficiency in the therapy process.

Children

- with insufficient GH secretion, a dose of 0.025-0.035 mg / kg / day or 0.7-1 mg / m2 / day is recommended;

Treatment begins as early as possible and continues until puberty and / or until the bone growth zones are closed. It is possible to stop treatment when the desired result is achieved.

- With Shereshevsky-Turner syndrome, a dose of 0.045-0.05 mg / kg / day or 1.4 mg / m2 / day is recommended;

- With SPS to increase growth and improve body composition in children, the recommended dose is 0.035 mg / kg / day or 1 mg / m2 / day. The daily dose of the drug should not exceed 2.7 mg. Treatment should not be given to children who have an increase in growth of less than 1 cm per year and with practically closed epiphyseal bone growth zones;

- In chronic renal failure accompanied by growth retardation, a dose of 0.045-0.05 mg / kg / day is recommended. If the growth dynamics are insufficient, higher doses of the drug may be required. Revision of the optimal dose is possible after 6 months of treatment;

- in case of growth disorders in children born with low growth rates for a given gestational age, a dose of 0.035 mg / kg / day or 1 mg / m2 / day is recommended until the desired growth is achieved. Treatment should be discontinued if, after the first year of therapy, the increase in growth does not exceed 1 cm.

The therapy should also be discontinued if the increase in growth does not exceed 2 cm per year and on the basis of the condition of the epiphyseal growth zones, if necessary, it is confirmed that the bone age is> 14 years (for girls) or> 16 years (for boys).

In adults with severe GH deficiency, it is recommended to start substitution therapy with low doses, 0.15-0.3 mg / day, followed by a gradual increase depending on the serum concentration of IGF-I. This indicator should be within 2 deviations from the average for a given age. In patients with normal initial concentration of IGF-I, the dose of the drug should be selected so that the IGF-I values are on the VGN, within 2 standard deviations from the mean.

The maintenance dose is selected individually, but does not exceed, as a rule, 1 mg / day, which corresponds to 3 IU / day. Elderly, lower doses are recommended.

Overdose

Cases of overdose are unknown.

Symptoms: Acute overdose may lead to hypoglycemia first, and then to hyperglycemia. With prolonged overdose, signs and symptoms characteristic of excess of human GR (the development of acromegaly and / or gigantism, as well as the development of hypothyroidism, a decrease in the concentration of cortisol in the blood serum) may be noted.

Treatment: withdrawal of the drug, symptomatic therapy.

special instructions

Somatropin can cause insulin resistance, and in some patients hyperglycaemia, so you should first identify the presence of glucose intolerance. In rare cases, type 2 diabetes may develop with the use of somatropin, but in the vast majority of these cases, patients had risk factors such as obesity (including obesity with SLE), a family history, the use of GCS, or a previously existing impaired glucose tolerance. In patients with existing diabetes mellitus, when administering somatropin, a dosage adjustment of hypoglycemic drugs may be necessary.

In the treatment with somatropin, an enhanced conversion of thyroxine (T4) to triiodothyronine (T3) has been identified, which can cause a decrease in T4 concentration and an increase in T3 concentration in the plasma. In healthy volunteers, as a rule, the concentration of thyroid hormones in the blood remained within normal limits. The effect of somatropin on the concentration of thyroid hormones can be of clinical significance in patients with central subclinical hypothyroidism, in whom hypothyroidism can potentially develop. On the other hand, patients receiving thyroxine as hormone replacement therapy may develop hyperthyroidism. Proceeding from this, it is strongly recommended to monitor the function of the thyroid gland after the initiation of somatropin therapy, and also with each change in its dose.

It was noted that somatropin reduces the concentration of cortisol in the plasma, possibly by acting on carrier proteins or by increasing hepatic clearance. The clinical significance of these observations can be limited, nevertheless, the replacement GCS-therapy before the appointment of Omnitrop® should be optimized.

In case of GH deficiency, which appeared after antitumor therapy, it is necessary to pay attention to possible signs of recurrence of malignant neoplasm.

In patients with endocrine disorders, incl. Deficiency of GH, the displacement of the epiphyses of the femur can be noted more often than in the general population.

Detection of lameness on the background of somatropin therapy requires clinical examination and careful observation.

In the event of severe or recurrent headaches, visual impairment, nausea and / or vomiting, it is recommended that a fundoscopy be performed to diagnose a possible edema of the optic nerve disc. When confirming the diagnosis, you should evaluate the presence of benign intracranial hypertension and, if necessary, cancel the drug.

To date, there is no clear guidance on the use of GH in patients with corrected intracranial hypertension. Nevertheless, the experience of clinical use indicates that the resumption of treatment with somatropin in many cases does not lead to a relapse of intracranial hypertension. If the use of GH has been resumed, careful monitoring of the possible appearance of symptoms of intracranial hypertension is necessary. Experience in people over 60 years of age is limited.

In patients with SLE, treatment should necessarily be associated with a calorie-restricted diet.

There have been reports of lethal cases associated with the use of GH in children with SLE who have at least one of the following risk factors: severe obesity, a history of respiratory failure, nocturnal sleep apnea, or an unidentified respiratory infection. Patients with SLE in the presence of one or more of the listed factors may be at greater risk. Patients with SLE should be screened for upper airway obstruction, nighttime apnea, and respiratory infections before commencing somatropine.

If an OBD obstruction is detected, it must be cleverly cleared before using somatropin.

Diagnosis of nocturnal sleep apnea is carried out before the application of the drug with the help of approved methods such as polysomnography or night oximetry, and if suspicion of this syndrome appears, careful monitoring should be carried out. If during treatment with somatropin signs of OBD obstruction (including the appearance or strengthening of snoring) are observed, treatment should be discontinued and an unplanned otolaryngological examination should be conducted.

All patients with SLE should be observed for an overnight apnea, and if suspected, their condition should be monitored. In addition, all patients with SLE should monitor the occurrence of respiratory infections, diagnose them as early as possible, and carry out massive antimicrobial therapy. All patients with SLE should actively monitor their body weight, both before the application of somatropin, and during it.

Scoliosis - a frequent phenomenon in SLE, it can progress in any child with rapid growth of the body. Therefore, during treatment with somatropin, it is necessary to monitor possible signs of scoliosis. Despite this, the use of GR does not increase the likelihood of development or severity of scoliosis. Long-term experience in adults and patients with SLE is limited. In children and adolescents with growth deficiency and low weight for gestational age at birth (MWGV), other causes of growth failure and the possibility of using other treatments should be evaluated before starting somatropin therapy. In children and adolescents with WBG it is recommended to measure the concentration of insulin and blood glucose on an empty stomach before the start of therapy and then - annually. In patients with an increased risk of developing diabetes (a family history of diabetes, obesity, severe insulin resistance, acanthokeratodermia), a glucose tolerance test should be performed. With obvious symptoms of diabetes, the use of GH is not allowed.

In children and adolescents with WBG it is recommended to measure the concentration of IGF-I before treatment and 2 times a year after its onset. If in repeated measurements the concentration of IGF-I exceeds 2 standard deviations relative to typical values for a given age and the degree of sexual development, then the ratio of concentrations of IGF-I to IRF-SB3 should be taken into account for correcting the dose of somatropin.

The experience of therapy in patients with MWVB during puberty is limited, so starting treatment during this period is not recommended. The experience of use in patients with the syndrome of Silver-Russell is also limited.

When treating children and adolescents with MHIF, it should be borne in mind that with the cessation of therapy until the maximum possible growth, part of the increase in growth may be lost.

With CRF, the functional activity of the kidneys before the start of therapy should be less than 50% of normal. To confirm the violation of growth, it is necessary to monitor growth in dynamics during the year preceding therapy. During this period, prescribe conservative treatment (including the control of acidosis, hyperparathyroidism, and nutrition status), which continues with the beginning of the main therapy. When kidney transplantation treatment should be discontinued.

At present, there is no data on the magnitude of the growth gain in the appointment of Omnitrop® to patients with CRF.

The reparative effects of somatropin in adult patients critically ill due to complications after open heart and abdominal operations, multiple accidental injuries, and acute respiratory failure were evaluated in two placebo-controlled studies.

Mortality in patients who received 5.3 or 8 mg / day of somatropin was higher than in the placebo group (42 and 19%, respectively). According to these results, the listed patient groups should not be assigned somatropin, since the safety of prescribing GH in patients in an acute critical condition is unknown, the intended benefit from the appointment should be correlated with the possible risk in such patients.

It is necessary to change the places of hypodermic injections in connection with the possibility of lipoatrophy development.

This preparation contains less than 1 mmol sodium (23 mg) in 1 ml, which is a negligible amount.

As part of Omnitropa, benzyl alcohol is present, it should not be given to premature infants or newborns, since This component can cause toxic and anaphylactic reactions in children under 3 years old.

Special precautions when destroying an unused preparation. There is no need for special precautions when destroying an unused preparation.

Form of issue

A solution for subcutaneous administration, 3.3 mg / ml, 6.7 mg / ml. For 1.5 ml of the drug in cartridges of transparent colorless borosilicate glass type I (Hebrew F.), sealed with siliconized bromobutyl rubber rod-piston on one side and combi (aluminum cap with brombutyl rubber gasket) on the other.

For 1, 5 or 10 cartridges are placed in a contour package of transparent colorless plastic plastic (correx). One copy is placed in a cardboard box.

Terms of leave from pharmacies

On prescription.

Storage conditions

At a temperature of 2-8 ° C (do not freeze).

Keep out of the reach of children.

Shelf life

Solution for subcutaneous administration 3.3 mg / ml - 2 years.

Solution for subcutaneous injection 6.7 mg / ml - 1.5 years.

Do not use after the expiry date printed on the package.