Omnitrop - instructions for use, dose, side effects, contraindications

The name of the substance.	Quantity in solution for subcutaneous administration
The name of the substance.	3.3 mg / ml	6.7 mg / ml
Active substance:
Somatropin	5.0 mg (15.0 ME)	10.0 mg (30.0 ME)
Excipients:
sodium hydrogen phosphate heptahydrate	1.33 mg	1.70 mg
sodium dihydrogen phosphate dihydrate.	1.57 mg	1.35 mg
poloxamer	3.00 mg	3.00 mg
benzyl alcohol (preservative)	13.50 mg	-
phenol (preservative)	-	4.50 mg
mannitol	52.51 mg	-
glycine	-	27.75 mg
phosphoric acid	q.s. to a pH of 6.2 ± 0.2	q.s. to a pH of 6.2 ± 0.2
sodium hydroxide	q.s. to a pH of 6.2 ± 0.2	q.s. to a pH of 6.2 ± 0.2
water for injections	up to 1.5 ml	up to 1.5 ml

Description:

transparent or slightly opalescent colorless solution

Pharmacotherapeutic group:growth hormone

ATX: & nbsp

H.01.A.C Somatropin and its analogues

H.01.A.C.01 Somatropin

Pharmacodynamics:

Somatropin has a pronounced effect on the metabolism of fats, proteins and carbohydrates. In children with growth hormone deficiency (GH) somatropin stimulates the growth of the bones of the skeleton in length, affecting the plates of the epiphysis of tubular bones. Both adults and children somatropin contributes to the normalization of body structure by increasing muscle mass and ■ reduction in body fat. Visceral adipose tissue is especially sensitive to the action of somatropin. In addition to enhancing lipolysis, somatropin reduces the flow of triglycerides in body fat. Under the action of somatropin, the concentration of insulin-like growth factor I (IRP-1) and its binding protein (IGF-DBC, insulin-like growth factor binding protein) increases.

In addition, the following effects were demonstrated:, ^:

Fat exchange

Somatropin activates low-density lipoprotein (LDL) receptors 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.There is also a decrease in cholesterol concentration.

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 with the 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 the retention of sodium, potassium and phosphorus.

Metabolism of bone tissue

Somatropin stimulates bone metabolism. Long-term treatment with children with somatropin deficiency GH and osteoporosis leads to the 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. -

The cardiac output is also increased, although the mechanism of this action is not completely clear. Reduction of peripheral vascular resistance, perhaps, partially explains this action of somatropin.

Pharmacokinetics:

Absorption

After subcutaneous administration, the bioavailability of somatropin is approximately 80% in both healthy individuals and in patients with GH deficiency. With subcutaneous administration of Omnithrop® in a dose of 5 mg to healthy volunteers, the maximum concentration somatropin in plasma (cmax) and time to reach C_max (T_max) respectively, were 72 ± 28 μg / l and 4.0 ± 2.0 hours, respectively.

Excretion

The mean half-life of somatropin after iv administration to adult patients with GH deficiency is about 0.4 hours. However, after subcutaneous administration, the half-life of the drug reaches 3 hours.

Individual patient groups

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

There is no evidence of an effect on age, race, liver, kidney or heart function on the pharmacokinetic parameters of somatropin.

Indications:

Children

Growth retardation:
due to insufficient secretion of GH;
with Shereshevsky-Turner syndrome;

. - with Prader-Willi syndrome (SLE);

in chronic renal failure (CRF) with a decrease in renal function 'by more than 50%)
in children born with low growth rates for this gestational age.

In adults, as a substitute therapy:

with confirmed expressed congenital or acquired deficiency of GH.

Contraindications:

- hypersensitivity to anyone from the components of the preparation;

- malignant neoplasms;

- Urgent conditions (including in complications after

operations on the heart and abdominal cavity, multiple injuries in

result of accidents, acute respiratory

insufficiency);

- stimulation of growth in patients with Closed epiphyseal growth zones;

Pregnancy and the period of breastfeeding (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;
Signs of brain tumor activity (before starting treatment, the drug must be convinced of the absence of brain tumor activity and that the antitumor therapy has been completed). Treatment with somatropin should be discontinued if signs of tumor growth appear.

Carefully:

Diabetes mellitus, craniocerebral hypertension, concomitant therapy with glucocorticosteroids, hypothyroidism (including with substitution therapy hormones of the thyroid gland).

Dosing and Administration:Comatropin is administered subcutaneously, 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 with taking into account the severity of GR deficiency, mass or surface area body, efficiency in the process

therapy.

- In children with insufficient GH secretion recommended dose

0.025-0.035 mg / kg / day or 0.7-1 mg / m / day. Treatment begins as can be at an earlier age and continue until sexual maturation and / or before the closure of zones growth of bones. maybe discontinuation of treatment with achieve the desired result.

- With the syndrome of Shereshevsky-Turner a dose of 0.045-

0.050 mg / kg / day or 1.4 mg / m² / day.

- With SLE (Prader-Willie) to increase growth and

improvement of body composition children recommended dose is 0.035 mg / kg / day or 1.0 mg / m2 / day. The daily dose of the drug should not exceed 2.7 mg.

Treatment should not be prescribed children who have an increase in growth less than 1 cm per year and practically closed epiphyseal zones premains of bones.

When CRF y_ children, accompanied by a delay in growth, a dose of 0.045-0.050 mg / kg / day is recommended. When insufficient growth dynamics may require more high doses of the drug.Revision of the optimal dose is possible after 6 months of treatment.

When growth is disturbed the children, born with a low for a given gestational age growth indicators, a dose of 0.035 mg / kg / day or 1.0 mg / m / day is recommended until the desired growth is achieved. Treatment should be discontinued if, after the first year of therapy with the drug, the increase in height does not exceed 1 cm. Also, therapy should be discontinued if the increase in growth does not exceed 2 cm per year if it is found that bone age> 14 years (for girls) or > 16 years (for boys), are observed closed growth zones.

Doses of the drug, for children

Indications	mg / kg masses body / day	mg / m²surfaces body / day
GH deficiency	0,025- 0,035	0,7-1,0
Syndrome Pradera Willi	0,035	1,0
Syndrome Shereshevsky- Turner	0,045- 0,050	1,4
Chronic renal failure	0,045- 0,050	1,4
Children with low birth height	0,035	1,0

In adults with severe GH deficiency, it is recommended to start substitution therapy with a low dose, 0.15-0.3 mg / day, followed by a gradual increase depending on the concentration of IGF-I in the blood serum. In patients with normal baseline IHF concentration-I The dose of the drug should be selected as follows:brazeme, so that the values of IGF-1 were at the upper limit of the norm, without going beyond the 2 standard deviations from the mean. The maintenance dose is selected individually, but, as a rule, does not exceed 1 mg / day (3 IU / day). Higher doses may be required for women than for men, as men have been increasing over time

sensitivity to IGF-I. In this regard, in women, especially those receiving oral

substitution therapy with estrogen, there is a risk of receiving treatment with somatropin in an insufficient dose, while men can receive somatropin treatment in an excessive dose. Therefore, the optimality of the somatropin dose should be monitored every 6 months. Patients older than 60 years of therapy should start with a starting dose of 0.1-0.2 mg / day, and then slowly increase to individually necessary.

You should use the minimum eThe effective dose (rarely more than 0.5 mg)

Side effects:

Side effects According to the World Health Organization (WHO), the undesirable effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100 to <1/10),infrequently (from> 1 / 1,000 to <1/100), rarely (> 1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence. A feature of patients with GH deficiency is A feature of patients with GH deficiency is a deficiency of extracellular fluid volume. With the appointment of somatropin, this deficit is quickly eliminated. Adult patients often experience adverse reactions associated with fluid retention, such as peripheral edema, rigidity of the limbs, 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 lower dose. The likelihood of these reactions depends on the dose of the drug, the age of the patient and is probably irreversibly related to age when GH deficiency appears. 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 somatotropin have been reported in children, but it was found that this frequency is similar to that of children with normal GH concentration. Immune system disorders

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 no clinical manifestations of such antibody production have been reported.

Disorders from the endocrine system

rarely: type 2 diabetes.

Disturbances from the nervous system

often: in adults, paresthesia. infrequently: in adults - a syndrome

carpal tunnel, in children paresthesia;

rarely: benign intracranial hypertension.

Disturbances from the gastrointestinal tract infrequent: in children - pancreatitis Disturbances from the musculoskeletal and connective tissue often: in adults, stiffness

extremities, arthralgia, myalgia. infrequently: children - rigidity

extremities, arthralgia, myalgia. General disorders and disorders at the site of administration

often: in adults - peripheral edema. In children, transient skin reactions at the injection site; infrequently: in children, peripheral edema.

Overdose:

Cases of overdose are unknown.

Acute overdose can 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.

Interaction:

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, glucocorticosteroids, anticonvulsants and cyclosporine, which can lead to a decrease in ₍their concentration, in the plasma. The clinical significance of this effect has not yet been determined.

Glucocorticosteroids inhibit the stimulating effect of somatropin on growth processes, and the concomitant therapy with other hormones, for example, gonadotropin, anabolic steroids, estrogens and thyroid hormones, can also influence the effectiveness of the drug (with respect to final growth).

Special instructions:ANDinsulin resistance:

Somatropin can cause insulin resistance, and in some patients hyperglycaemia, therefore Preliminary it is necessary to reveal the presence of a violation of glucose tolerance. In rare cases, with the appointment of somatropin, type 2 diabetes can develop, but in the vast majority of these cases, patients had risk factors such as obesity (including obesity with SLE), family history, glucocorticosteroids, or an earlier violation of glucose tolerance. In patients with existing diabetes mellitus, when administering somatropin, a dosage adjustment of hypoglycemic drugs may be necessary.

Children with an increased risk of developing diabetes mellitus (family history of diabetes, obesity, severe insulin resistance, acanthokeratodermia), should be tested for glucose tolerance. When diagnosing diabetes, somatropin is not allowed.

Thyroid:

In the treatment with somatropin, increased conversion of thyroxine (T₄) into triiodothyronine (T₃), which can cause the corresponding changes in blood plasma.Despite the fact that in healthy volunteers, as a rule, the concentration of thyroid hormones in the blood remained within normal limits, theoretically, a clinical manifestation of subclinical hypothyroidism is possible. On the other hand, in patients receiving levothyroxine sodium as a hormone replacement therapy, hyperthyroidism may develop. Proceeding from this, it is strongly recommended to monitor the function thyroid gland after the initiation of somatropin therapy, and also with each change in its dose.

Adrenal Function:

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

Malignant neoplasms:

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, including GH deficiency, the femoral epiphysis shift may be observed more often than in the general population.

ABOUTthe detection of lameness on the background of somatropin therapy requires clinical examination and careful follow-up.

Benign intracranial hypertension:

In the event of severe or recurrent headaches, visual impairment, nausea and / or vomiting, fundus examination is recommended to diagnose a possible edema of the optic nerve disc. It should, however, be remembered that at first the rise in intracranial pressure may not be accompanied by edema of the optic nerve disc. Thus, the absence of edema of the optic disc does not exclude intracranial hypertension. When confirming the diagnosis, you should, if necessary, cancel the drug.

Today, there are no clear indications on the scheme of somatropin in patients with corrected intracranial hypertension. Nevertheless, the experience of clinical application shows that the resumption of treatment with somatropin in many cases does not lead to relapse of intracranial hypertension.If the use of somatropin has been resumed, careful monitoring of possible symptoms of intracranial hypertension is necessary.

Elderly patients: experience in people over 80 years of age is limited.

WSP: v patients with SPV treatment should necessarily be associated with a calorie-restricted diet.

There have been reports of lethal cases associated with the use of somatropin 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 nThese factors can have a greater risk. Patients with SLE should be screened for upper airway obstruction, nighttime apnea, and respiratory infections before commencing somatropin.

If an OBD obstruction is detected, an ENT doctor should be consulted to treat obstruction before starting somatropin. Diagnosis of nocturnal sleep apnea is performed before the application of the drug with the help of approved methods, such as polysomnography or night oximetry, and, if suspicion of this syndrome arises, the patient's condition should be carefully monitored.If during treatment with somatropin there are signs of OBD obstruction (including the appearance or strengthening of snoring), treatment should be discontinued and an unplanned otolaryngological examination should be conducted.

All patients with SLE should be observed for the nightand, if suspected, their condition should be controlled. 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 and during somatropin. 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 somatropin 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 a shortage of growth and low weight for gestational age at birth (MWVH), before the Silver-Russell syndrome also is limited.

In the treatment of children and adolescents with MWIA should be borne in mind that when discontinuation of therapy until maximum possible growth, part of the increase in growth can be lost.

Dysplasia in chronic renal failure:

In chronic renal failure, functional activity of the kidneys before therapy should be less than 50% of the normal. For confirmation of growth disruption, it is necessary to monitor growth in dynamics during the year preceding therapy. During this period, conservative treatment is prescribed (including control of acidosis, hyperparathyroidism, and nutritional status), which continues with the onset of primary therapy. When kidney transplantation treatment should be discontinued.

Currently, there is no data on increase in growth the appointment of Omnithrop patients with CRF.

Since Omnitrop® contains benzene alcohol, it should not be given to premature infants or newborns, as this component can cause toxic and anaphylactic reactions in children under 3 years of age.

Antibodies: a small number of patients can form antibodies to somatropin, which, due to low affinity, these antibodies do not affect the growth process.However, the determination of the presence of antibodies to somatropin should be performed in all patients with an inexplicable decrease / absence of the effect.

Dysplasia in children born with low growth rates for this gestational age: Before the start of treatment, all other reasons for the lack of growth should be excluded. Similarly, these children are recommended to monitor blood glucose levels.

Pancreatitis in children: increased risk of pancreatitis. Despite the fact that this complication is rare, pancreatitis should be excluded in all children, with abdominal pain appeared.

Leukemia: a small number of patients with GH deficiency who were treated with somatropin described cases of leukemia. However, at the moment there is no evidence that the risk of developing leukemia is increased in the absence of other risk factors

Form release / dosage:A solution for subcutaneous administration, 3.3 mg / ml, 6.7 mg / ml.

Packaging:For 1.5 ml of the drug in cartridges of transparent colorless borosilicate glass type I (Hebrew F.), sealed with siliconized bromobutyl rubber piston rod on one side and combi (aluminum cap with brombutyl rubber gasket) on the other.
For 1.5 or 10 cartridges are placed in a contoured package of transparent colorless plastic sheet (correx). One correction together with the instruction for use is placed in a cardboard box.

Storage conditions:

Store at a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Special precautions when destroying an unused preparation

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

Shelf life:

Cartridges 5 mg / 1.5 ml: 2 years.

Cartridges 10 mg / 1.5 ml: 1,5 years.

Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001262

Date of registration:23.11.2011

The owner of the registration certificate:Sandoz GmbHSandoz GmbH Austria

Manufacturer: & nbsp

SANDOZ, GmbH Austria

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp16/08/2015

Illustrated instructions

Instructions

Omnitrop® (Omnitrope®)