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

auxiliary substances: sodium chloride - 8.7 mg, sodium citrate dihydrate - 2.94 mg, polysorbate - 20 - 4.0 mg, phenol - 2.5 mg, citric acid (1 M solution) to pH 6.0- 6.5, water for injection - up to 1.0 ml.

Description:

colorless or slightly colored, transparent or opalescent liquid.

Pharmacotherapeutic group:growth hormone

ATX: & nbsp

H.01.A.C Somatropin and its analogues

H.01.A.C.01 Somatropin

Pharmacodynamics:

Rastan® contains in its composition somatropin - human growth hormone, produced by the method of biotechnology of recombinant DNA. Somatropin is an anabolic peptide, contains 191 amino acid residues and has a molecular weight of approximately 22,000 Da.The amino acid sequence in the somatropin molecule is identical to the amino acid sequence of human growth hormone (GH) produced by the pituitary gland.

Pharmacodynamics

Stimulates skeletal and somatic growth, and also has a pronounced effect on metabolic processes. Stimulates the growth of the bones of the skeleton, affecting the plate epiphysis tubular bones, bone metabolism in children. Helps normalize body structure by increasing muscle mass and reducing body fat. Most effects of somatropin are realized through insulin-like growth factor I (IGF-1), which is produced in all cells of the body (mainly by liver cells). More than 90% of IGF-1 is associated with proteins (IGRB), of which IFDB-3 is the most important.

In patients with GH deficiency and osteoporosis, substitution therapy results in normalization of mineral composition and bone density. Increases the number and size of cells of muscles, liver, thymus gland, gonads, adrenals, thyroid gland. Stimulates the transport of amino acids into the cell and the synthesis of proteins, reduces the concentration of cholesterol, affecting the profile of lipids and lipoproteins. Suppresses the release of insulin. Promotes the retention of sodium, potassium and phosphorus.Increases body weight, muscle activity and physical endurance.

Pharmacokinetics:

Suction

The absorption of somatropin after subcutaneous administration is approximately 80%, the maximum concentration in the blood plasma is achieved in 3-6 hours.

Distribution

Penetrates into well perfused organs, especially the liver and kidneys. The volume of distribution of somatropin is 0.49-2.11 l / kg.

Metabolism

Metabolised in the liver and kidneys.

Excretion

It is excreted by the kidneys and through the intestine (including 0.1% unchanged). The half-life after subcutaneous administration is 3-5 hours.

Indications:

Retarded growth in children due to insufficient secretion of GH.

Growth retardation in girls with Shereshevsky-Turner syndrome.

Growth retardation in chronic renal failure (CRF) in the prepubertal period (decreased renal function by more than 50%).

In adults with confirmed expressed congenital or acquired deficiency of GH as a substitution therapy.

Contraindications:

⦁ Hypersensitivity to any component of the drug.

⦁ Tumors of the brain (at the beginning of treatment, the intracranial tumor should be inactive and antitumor therapy completed).

⦁ Active malignant neoplasms of any localization.

⦁ Urgent conditions (including conditions after heart surgery, abdominal cavity, acute respiratory failure, multiple injuries as a result of accidents).

⦁ Stimulation of growth in patients after the closure of epiphyseal growth zones.

⦁ The Prader-Willi syndrome with pronounced obesity and breathing disorder.

⦁ Pregnancy and the period of breastfeeding.

Carefully:

: diabetes mellitus, intracranial hypertension, concomitant glucocorticosteroid therapy (GCS), hypothyroidism (including thyroid hormone replacement therapy), Prader-Willi syndrome.

Pregnancy and lactation:

It is not known whether somatropin to influence reproductive function or whether it can cause damage to the fetus when administered to pregnant women. Therefore, the use of somatropin is contraindicated during pregnancy.

Possible secretion of somatropin with breast milk is not excluded. Therefore, when it is necessary to use somatropin during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

Rastay® is administered subcutaneously, slowly, once a 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.

In children with insufficient GH secretion, a dose of 25-35 μg / kg / day (0.07-0.1 IU / kg / day) is recommended, which corresponds to 0.7-1 mg / m2 / day (2-3 IU / m2 / day). 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.

In Shereshevsky-Turner syndrome, a dose of 50 μg / kg / day (0.14 IU / kg / day) is recommended, which corresponds to 1.4 mg / m2 / day (4.3 IU / m2 / day). If the dynamics of growth is insufficient, a dose adjustment of up to 67 μg / kg / day (0.2 IU / kg / day) may be required, which corresponds to 2.0 mg / m2 / day (6 IU / m2 / day).

In chronic kidney failure in children accompanied by growth retardation, a dose of 45-50 μg / kg / day (0.14 IU / kg / day) is recommended, which corresponds to 1.4 mg / m2 / day (4.3 IU / m2 / day) . If the dynamics of growth is insufficient, a dose adjustment may be required.

With a GH deficiency in adults, the initial dose is 0.15-0.3 mg / day (corresponding to 0.45-0.9 IU / day), followed by an increase, depending on the effect.When the dose is titrated, the concentration of insulin-like growth factor (IRP-1) in blood plasma can be used as a reference indicator. 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.

The technique of injection with Rastan® in vials

1. Disinfect the rubber membrane of the vial with alcohol or other antiseptic to prevent the entry of microorganisms into the vial, which is especially important when carrying out multiple injections.

2. For injections, sterile syringes and needles should be used. The syringe should be of sufficient volume to take the right amount of the drug and to carry out the injection.

3. Put the air in the syringe in the volume corresponding to the desired dose of the drug. Enter the air into the vial.

4. Turn the bottle with the syringe upside down and draw the desired dose of the drug into the syringe. Remove the needle from the vial and remove air from the syringe. Check the correct dose set.

5. Immediately make an injection.

Injection technique with Rastay® in cartridges

For injections of Rastan ^ in cartridges, you should use the BiomatikPen® pen or any other syringe-pen designed for use with Rastan® cartridges.

For the correct administration of Rastan®, you should carefully follow the instructions in the instructions for using the syringe pen.

1. Before use, make sure that there is no damage (for example, cracks) on the Rastan® cartridge. Do not use the cartridge if there is any visible damage or change in the appearance of the solution (discoloration, transparency, the presence of sediment, etc.).

2. Treate the rubber cap of the cartridge with alcohol or other antiseptic to prevent ingestion of microorganisms.

3. Install the cartridge in the syringe pen according to the instructions for using the syringe pen.

4. For each injection of Rastan in the cartridges, use a new sterile replaceable needle.

5. After the injection, the needle should remain under the skin for a minimum of 6 seconds. Keep the button depressed until the needle is completely removed from the skin, thus ensuring the correct dose administration and limiting the possibility of blood or lymph flow into the needle or the Rastay® cartridge.

If the drug continues to flow out of the needle after the injection, hold the needle in the skin for longer injections.

6. The cartridge with Rastan® is for individual use only, it can not be refilled.

For the introduction of a dose prescribed by the doctor, use the table for transferring the indication of the dosage indicator of the syringe-pen to the dose of the drug.

A table for transferring the indication of the dosage indicator of the Biomatick Pen® pen to the dose of Rastan®, a solution for subcutaneous administration,

5 mg / ml (15 IU) cartridges 3 ml:

Dosing indication Dose of Rastan®, mg

1 0,05

2 0,10

3 0,15

4 0,20

5 0,25

6 0,30

7 0,35

8 0,40

9 0,45

10 0,50

11 0,55

12 0,60

13 0,65

Dosing indication Dose of Rastay®, mg

14 0,70

15 0,75

16 0,80

17 0,85

18 0,90

19 0,95

20 1,00

21 1,05

22 1,10

23 1,15

24 1,20

25 1,25

26 1,30

27 1,35

28 1,40

29 1,45

30 1,50

31 1,55

32 1,60

33 1,65

34 1,70

35 1,75

36 1,80

37 1,85

38 1,90

39 1,95

40 2,00

41 2,05

42 2,10

43 2,15

44 2,20

45 2,25

46 2,30

47 2,35

48 2,40

Dosing indication Dose of Rastay®, mg

49 2,45

50 2,50

51 2,55

52 2,60

53 2,65

54 2,70

55 2,75

56 2,80

57 2,85

58 2,90

59 2,95

60 3,00

Side effects:

A feature of patients with GH deficiency is a deficiency of extracellular fluid volume. With the start of treatment with somatropin, this deficit is corrected. Adult patients often experience adverse reactions associated with fluid retention, such as peripheral edema, joint 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 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 occurs.

Adverse reactions in children are rare or infrequent.

The summarized data on adverse reactions identified in clinical studies of somatropin according to the systemic organ classification (MedDRA) and the WHO classification by frequency of occurrence are presented below.

Class of organ system	Very often> 1/10	Often> 1/100; <1/10	Infrequently> 1/1000; <1/100	Rarely> 1/10000; <1/1000	Very rarely <1/10000
Immune system disorders		Hypersensitivity reactions, including allergic reactions
Disorders from the endocrine system	Hypothyroidism
Disorders from the metabolism and nutrition	In adults, peripheral and local edema	Children - peripheral and local edema	In adults, type 2 diabetes mellitus. Children have hyperglycemia, including impaired glucose tolerance.
Disturbances from the nervous system	Head pain	In adults - insomnia, paresthesia, tunnel syndrome		Benign intracranial hypertension, paresthesia (in children)	Children have insomnia
Disorders from the gastrointestinal tract				Pancreatitis

Class of organ system	Very often> 1/10	Often> 1/100; <1/10	Infrequently> 1/1000; <1/100	Rarely> 1/10000; <1/1000	Very rarely <1/10000
Disturbances from the skin and subcutaneous tissues			In adults itching	Children have a rash
Disturbances from musculoskeletal and connective tissue	In adults - arthralgia Violations from gastro- intestinal tract	In adults, myalgia; in children - progression of scoliosis	In adults - rigidity muscles	Children - myalgia
Violations of the genitals and mammary gland			In adults - gynecomastia		Children - gynecomastia
General disorders and disorders at the site of administration		Local reactions at the injection site, including pain at the injection site	Weakness
Laboratory and instrumental data				In adults, glucosuria	Children - Glucosuria

Post-registration data.

On the part of the immune system: rarely - hypersensitivity reactions, including anaphylactic reactions; increase the antibody titer to somatropin.

Disorders from the metabolism and nutrition: infrequently - type 2 diabetes in children.

Vascular disorders: often - increased blood pressure in adults; very rarely - increased blood pressure in children.

On the part of the respiratory system, chest and mediastinal organs: often - dyspnea (in adults), stopping breathing in sleep (in adults). Benign, malignant and unspecified neoplasms:

there is evidence that a small number of children treated with somatropin, including both the preparations of the pituitary gland, and the preparations of DNA-recombinant GR, developed leukemia. The relationship between leukemia and treatment with somatropin is still unclear.

There are data on the development of epiphysiolysis of the head of the femur, Legg-Calve-Perthes disease against somatropin therapy (see section "Special instructions").

Upper and lower extremities were reported in children with Shereshevsky-Turner syndrome during treatment with somatropin.

There was a tendency to increase the incidence of otitis media in children with Shereshevsky-Turner syndrome receiving high doses of somatropin.

The following side effects are described in the literature with the use of somatropin: edema of the optic disc (usually observed during the first 8 weeks of treatment, most often in patients with Shereshevsky-Turner syndrome); subluxation of the hip in children (limping,pain in the thigh and knee); acceleration of the growth of the previously existing nevus (malignancy is possible); an increase in the concentration in the blood of inorganic phosphate, parathyroid hormone and the activity of alkaline phosphatase.

Overdose:

Cases of overdose are unknown.

Acute overdose can lead in the beginning to hypoglycemia, and then to hyperglycemia. With prolonged overdose, there may be signs and symptoms characteristic of excess 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 serum.

Treatment: withdrawal of the drug, symptomatic therapy.

Interaction:

Patients with a diagnosis of diabetes mellitus receiving co-administration with somatropin may require a dose adjustment of insulin and / or other hypoglycemic drugs.

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 the effect of growth stimulation. Patients treated with somatropin may be diagnosed with a previously unrecognized secondary adrenal insufficiency, which may require replacement therapy with GCS.In addition, patients receiving SCS replacement therapy for a previously diagnosed adrenal cortex deficiency may need an increase in the maintenance dose of GCS or the dose needed for stress.

Somatropin can increase the enzymatic activity of cytochrome P450 isoenzymes, which can cause a decrease in plasma concentration and the effectiveness of drugs metabolized with the participation of the CYP3A isoenzyme, such as steroid sex hormones, GCS, cyclosporins and some antiepileptic drugs. The clinical significance of this effect has not yet been determined.

The effectiveness of somatropin may be influenced by concomitant therapy with other hormonal drugs, for example gonadotropin, anabolic steroids, estrogens and thyroid hormones.

Incompatibility.

Studies on incompatibility have not been conducted, so the drug Rastan® can not be mixed with other drugs.

Special instructions:

Treatment with somatropin should be conducted by physicians with experience in diagnosis and treatment of patients with GH deficiency or with a syndromeShereshevsky-Turner.

Do not exceed the maximum recommended daily dose (see section "Method of administration and dose").

Stimulation of longitudinal growth can be carried out in children before the closure of epiphyseal growth zones.

Adult growth hormone deficiency persists throughout life and needs appropriate treatment, but there are currently no results of prolonged adult therapy.

Sheregievsky-Turner Syndrome

In patients with the syndrome of Shereshevsky-Turner during treatment with somatropin, it is recommended to monitor the proportional growth of the upper and lower extremities, and when detecting increased growth, the dose of the drug should be reduced to the lower limit of the dose range.

Girls with Shereshevsky-Turner syndrome usually have an increased risk of developing otitis media, and therefore an otolaryngologist should be monitored.

Chronic Renal Failure

Dysplasia in children with CRF should be accurately established before starting treatment with the drug somatropin by monitoring growth against the background of optimal therapy for chronic renal failure within one year.During somatropin therapy, conservative treatment of chronic renal failure with conventional drugs and, if necessary, dialysis should be continued. During kidney transplantation, therapy with somatropin should be discontinued.

Prader-Willi syndrome

There were reports of deaths in children with Prader-Willi syndrome (SLE) with GH deficiency who received somatropin therapy and who had 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 these factors belong to the high-risk group when using somatropin.

Before prescribing somatropin, patients with GH deficiency in combination with SLE should consider the benefit / risk ratio.

In patients with SLE, the treatment with somatropin should necessarily be associated with a calorie-restricted diet. Patients with SLE should actively monitor their body weight both before and during somatropin.

Tumors

Patients with a history of malignant neoplasms should be carefully examined for their relapse.In case of occurrence or relapse of a malignant neoplasm, therapy with somatropin should be discontinued.

Patients with GH deficiency, which arose secondary in the presence of brain tumors, should be conducted more frequent examinations to exclude the progression and recurrence of the underlying disease. Somatropin Should not be appointed in case of detection of any signs of active growth of the tumor. Before the appointment of somatropin, 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.

It was reported about the development of secondary benign and malignant neoplasms in patients with childhood cancer and receiving therapy with somatropin. The most common complication was the development of intracranial tumors, in particular, meningiomas in patients who previously received head radiotherapy for primary neoplasms. However, no recurrence of primary neoplasms was reported in this category of patients.

It was reported on the development of leukemia in children treated with somatropin. The relationship between the onset of leukemia and therapy with somatropin has not been established.

Benign intracranial hypertension

In case of severe or recurrent headaches, visual disturbances, nausea and / or vomiting, fundus examination is recommended to detect possible edema of the optic disc. When confirming the diagnosis, the presence of benign intracranial hypertension should be assessed and, with confirmation of the diagnosis, somatropin therapy should be discontinued.

To date, there is no clear guidance on the use of growth hormone in patients with corrected intracranial hypertension. Nevertheless, the experience of clinical application suggests 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.

Epiphysiolysis

In patients with endocrine disorders, including GH deficiency, epiphysiolysis of tubular bony heads may be more frequent.It is necessary to conduct a thorough examination if during the treatment the child has limp.

Hypopituitarism

Patients with hypopituitarism (deficiency of several pituitary hormones) in the case of standard hormonal replacement therapy with the administration of somatropin should be under strict supervision.

Thyroid function

In the treatment with somatropin, increased conversion of thyroxine (T4) to triiodothyronine (T3) has been identified, which can cause a decrease in T4 concentration and an increase in plasma T3 concentration. 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. Based on this, it is recommended to monitor the function of the thyroid gland after the initiation of somatropin therapy, and also with each change in its dose.Lack of adequate therapy for hypothyroidism may prevent optimal results of treatment with somatropin.

Formation of antibodies to somatropin

It is possible the formation of antibodies to somatropin. An antibody titer to somatropin should be investigated in cases where the patient does not respond to therapy.

Sensitivity to insulin

Somatropin decreases sensitivity to insulin, especially in high doses in patients with high sensitivity, which can cause the development of hyperglycemia in patients with inadequate insulin secretion.

Thus, previously not diagnosed impaired glucose tolerance and diabetes mellitus can be detected. In all patients receiving somatropin, periodic monitoring of glucose concentration is necessary, especially in patients with a high risk of diabetes: in obese patients, Shereshevsky-Turner syndrome, family history of diabetes mellitus, with the use of GCS or a previously existing impaired glucose tolerance. In the course of treatment with somatropin, more careful monitoring is necessary for patients with diagnosed type 1 or type 2 diabetes mellitus or with impaired glucose tolerance (see section "Interaction with other drugs").Such patients should assess the need for correcting the dose of hypoglycemic drugs in the administration of somatropin.

Scoliosis

In some children, during the period of excessively rapid growth (especially often in children with SLE) progression of scoliosis can be observed. During the entire treatment period, somatropin should be monitored to identify signs of scoliosis. However, the available data suggest that therapy with somatropin does not affect the frequency or severity of scoliosis.

Pancreatitis

In comparison with adults, the risk of developing pancreatitis may increase in patients of children who receive somatropin therapy. Despite the rarity of this complication, it is necessary to show increased attention to patients of childhood with abdominal pain.

Obesity

In patients with obesity, the occurrence of adverse events is more likely to occur with the administration of doses calculated by body weight.

Hyperestrogenism in e / senses

Women with hyperestrogenia or women taking estrogen orally may need higher doses of somatropin than men.

Elderly age

Elderly patients may be more sensitive to the action of somatropin and, consequently, the likelihood of developing side effects increases. Therefore, it is advisable to use a smaller initial dose and a slower increase in the dose of the drug. There is no experience of treatment with somatropin in patients older than 60 years.

Urgent conditions

The safety of continuation of somatropin therapy in patients with serious diseases associated with complications after open surgery on the heart or abdomen, multiple injuries associated with accidents, as well as patients with acute respiratory failure receiving replacement therapy for registered indications who during therapy there were mentioned diseases, not established. Therefore, the ratio of potential risk and the benefit of continuing therapy with somatropin in patients in the urgent state should be carefully evaluated.

Effect on the ability to drive transp. cf. and fur:

Provided there are no symptoms of increased intracranial pressure (headache, nausea, vomiting, impaired vision),the drug Rastan® does not affect the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Solution for subcutaneous administration 5 mg / ml (15 IU / ml).

3 ml of the drug in a bottle of colorless neutral glass with a capacity of 5 ml, capped with a cap combined. 5 vials are placed in a contour mesh package made of polyvinyl chloride film, without foil. 1 bottle or 1 circuit cell package, along with the instruction for medical use, is placed in a pack of cardboard.

For 3 ml of the drug in a cartridge of colorless neutral glass, capped with a cap combined. 1 or 5 cartridges are placed in a contour mesh box made of polyvinyl chloride film and aluminum foil. 1 circuit cell pack together with instructions for medical use is placed in a pack of cardboard.

For 3 ml of the drug in a cartridge of colorless neutral glass, capped with a cap combined. The cartridge is mounted in the BiomatikPank2 disposable syringe.5 BiomaticPen® 2 disposable syringe pens with cartridges are placed in a contour mesh package. 1 circuit cell pack with syringe handles or 1 or 5 BiomatikPen® 2 disposable syringes with cartridges, along with instructions for medical use and instructions for the use of the BiomatikPen® 2 penstick, are placed in a pack of cardboard.

Packaging:

(5) - cartridges (1) - syringe-pens-packs cardboard
cartridges (1) - packings, cellular, outboard, packs, cardboard
cartridges (1) - syringe-pens-packs cardboard
cartridges (5) - packings, cellular, contour-packs, cardboard
vials (1) - packs cardboard
vials (5) - packings, cell planimetric without cover-packs cardboard

Storage conditions:

In the dark place at a temperature of 2 ° C to 8 ° C.

Do not freeze.

The used vial (cartridge) should be stored at a temperature of 2 ° C to 8 ° C for 28 days.

The disposable disposable syringe pen with the cartridge should be stored at a temperature of 2 ° C to 8 ° C for 28 days.

Keep out of the reach of children.

Shelf life:

2 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006944/10

Date of registration:21.07.2010

The owner of the registration certificate:PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

Manufacturer: & nbsp

FARMSTANDART-UFAVITA, JSC Russia

Representation: & nbspPHARMSTANDART-Ufa-VITA, JSCPHARMSTANDART-Ufa-VITA, JSC

Information update date: & nbsp16/08/2015

Illustrated instructions

Instructions

instruction on the technique of injection

Rastan® (Rastan)