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

After mixing the contents of the vial with the solvent, a ready-made injection solution is prepared, the I ml of which contains 5.83 mg of somatropin.

* 1 mg corresponds to 3 ME

Description:

Lyophilizate: lyophilized powder or porous mass of white or almost white color.

Solvent: clear, colorless or slightly yellowish liquid

Pharmacotherapeutic group:growth hormone

ATX: & nbsp

H.01.A.C Somatropin and its analogues

H.01.A.C.01 Somatropin

Pharmacodynamics:

Pharmacodynamics

Sizen® is a recombinant human growth hormone (GH), obtained by genetic engineering using the mammalian cell line. Identical to its composition and action to the pituitary gland of human somatropin (a single-chain polypeptide consisting of 191 amino acid residues).

It has anabolic and anti-catabolic properties, affecting not only growth, but also metabolic processes. Influencing the epiphysis of the tubular bones, stimulates the growth of the bones of the skeleton. Regulates protein metabolism, stimulates the transport of amino acids into the cell and protein synthesis.

Pharmacokinetics:

Pharmacokinetics in doses greater than 8 IU (2.67 mg) are linear, at higher doses linearity is disrupted without any clinical manifestations. Absolute bioavailability with subcutaneous injection is 70-90%. The maximum concentration in the blood is observed after 4 hours and returns to the original level 24 hours after the administration. The effect of cumulation is not observed. After intravenous administration, the volume of distribution is 7 l / kg, the total clearance is 15 l / h.Metabolized in the kidneys and liver. It is excreted through the intestine. The half-life is 2-4 hours.

Indications:

- Growth retardation in children due to GH deficiency.

Lack of growth in girls with Shereshevsky-Turner syndrome.

- The growth retardation in children in the pripubertal period, caused by chronic renal failure.

- The growth retardation in children is 4 years and older in the presence of intrauterine growth retardation in the anamnesis.

Confirmed congenital or acquired GH deficiency in adults (as substitution therapy).

Contraindications:

Hypersensitivity to somatropin and / or to any other component of the drug or to the m-cresol that is part of the solvent.

Signs of active malignant neoplasm (before treatment with somatrolium, antitumor therapy must be completed). Proliferative or pre-proliferative diabetic retinopathy. Proved progression or relapse of an existing tumor. Stimulation of growth in children after the closure of epiphyseal growth zones.

Use in children with chronic renal failure at the time of kidney transplantation.

In acute emergency conditions, developed as a result of complications of open heart surgery, in the abdominal cavity; multiple injuries as a result of an accident, acute respiratory failure, or other similar conditions.

Pregnancy and the period of breastfeeding.

Carefully:

diabetes mellitus, intracranial hypertension, hypothyroidism (including when carrying out thyroid hormone replacement therapy), concomitant glucocorticosteroid (GKO) therapy, Pradsra-Willi syndrome.

Pregnancy and lactation:

Pregnancy

Clinical experience with the use of somatropin in pregnant women is inadequate. Therefore, the use of the drug in pregnant women is contraindicated.

Breast-feeding

Studies of the use of somatropin in women during the period of breastfeeding have not been conducted. At the present time, it is not known whether somatropin in mother's milk. In this regard, the use of the drug in women during breastfeeding is contraindicated.

Dosing and Administration:

Treatment should take place under conditions of regular monitoring by a doctor who has sufficient experience in diagnosing and treating patients with GH deficiency or with Shereshevsky-Ternsr's syndrome.

The preparation Sisen® in a dosage of 8 mg (24 ME) is designed for repeated subcutaneous injection.

The dosage regimen is determined by the doctor individually for each patient, taking into account the patient's body surface area (PPT) and body weight (MT).

The preparation Sizen® is recommended to be administered in the evening. Depending on the indications, the following schemes are recommended:

Children:

Growth retardation caused by GH deficiency:

0.7-1 mg / m2 of PPT per day or 0.025-0.035 mg / kg MT per day subcutaneously.

Growth retardation in girls with Shereshevsky-Turner syndrome:

1.4 mg / m2 of PPT per day or 0.045-0.05 mg / kg MT per day subcutaneously.

Simultaneous administration of paedrogenic anabolic steroids can enhance the rate of growth.

The delay in the growth of g of children in the prepubertal period, caused by chronic renal failure:

1.4 mg / m2 of PPT per day or 0.045-0.05 mg / kg MT per day subcutaneously.

Growth retardation in children 4 years and older with intrauterine growth retardation in history:

I mg / m2 PPT per day or 0.035 mg / kg MT per day subcutaneously.

Treatment is terminated after the patient's growth reaches values corresponding to the growth of an adult or after the closure of the epiphyseal growth zones.

Adults:

Treatment is recommended to start with a low dose of 0.15-0.3 mg per day subcutaneously.The dose should be increased strictly under the supervision of the doctor. The recommended final dose usually does not exceed 1 mg per day. In general, small doses are effective. In elderly patients, the dose should be reduced.

Instructions for patients on the preparation and use of the drug

The injection solution is prepared using a lyophilizate (dry matter in a vial) and an attached bacteriostatic solvent containing a 0.3% solution of metacresol in water for injection using the Click. A prepared solution for subcutaneous injection should be clear and free of visible particles. The use of a solution containing visible particles for injections is not allowed. The prepared solution contains 8 mg of Sisen preparation (5.83 mg / ml). Patients should receive detailed instructions on how to properly perform the procedure for dilution of the drug. Please read the instructions for using the Click.

Children should prepare the solution under the guidance of adults.

Wash your hands with soap and water.

If you have questions regarding solution preparation, contact your doctor, nurse or pharmacist.

A colored insert with illustrations illustrating the procedure for preparing the solution using the Click. ™ device is embedded in the pack.

- Place the device to mix the Click.TM ™ vertically on a flat surface with the vial down and the cap (G) up.

- Press the cap all the way down. (Caution: The control visible sign on the ClickMouse ™ device will now be broken).

- Turn the cap slowly clockwise until the green indicator (E) moves to the vertical window.

- Continue slowly pressing on the cap until then. until all of the solvent has passed from the cartridge to the vial (Caution: The control visible sign on the cap will now be broken). It is very important to press the cap slowly to prevent the formation of bubbles. Make sure that all the solvent has passed into the vial.

- Dissolve the powder in the solvent with gentle circular motions.

(Caution: Do not shake the Quick Click device, as foam or bubbles may form, allow the solution to settle until the powder completely dissolves).

- Turn the ClickMix ™ device upside down.Slowly pull the cap down until it stops completely until the solution has completely moved back into the cartridge. Make sure that no more than 1-2 drops of solution remain in the vial.

If more than 1-2 drops of solution remain in the vial, push the cap slowly again until the solution goes back into the vial. Then reposition the solution in the cartridge, as described above. Remove air from the cartridge by slowly pressing the cap. (Caution: Do not pull the cap too fast, as air may enter the cartridge.)

- While holding the Click.Make ™ device in the upright position, unscrew the cap and remove it. While holding the Click Lock ™ in the same position, remove the cartridge from the prepared solution from the Click.

Carefully remove the top label from the cartridge. Write the date of preparation of the solution on the lower label of the cartridge.

Dispose of the Click.com device in accordance with the rules.

The cartridge containing the prepared Sisen® solution is ready for use with the injectors used to inject the drug. The injectors are supplied separately and a separate instruction is attached to them.

Injections should be made in different parts of the body.Do not administer the drug to places where swelling, dense knots, dents, or pain has occurred: report all your symptoms to your doctor. The skin at the injection site is allowed to be washed with soap and water.

What if you missed a dose or injected a large dose?

If you skip the next dose or inject an excessive amount of Saizen®, you should tell your doctor about it, because minor changes in the recommended dose may be necessary to compensate for the disorder. The administration of an increased dose will result in a change in the glucose level in the patient's blood, and the patient may experience shivering and dizziness. The use of high doses can cause excessive growth of bones, mainly the bones of the hands, feet and jaw.

Side effects:

Like other Sizen® medications, it may have side effects, but most patients tolerate the drug well.

In adult patients with GH deficiency. which was diagnosed in childhood, there are fewer side effects compared to those who have a GR deficiency in adulthood.

Antibodies to somatropium can rarely be formed.The clinical significance of these antibodies is not established.

There is information about cases of leukemia in a small number of patients with GH deficiency and those receiving co-administration with somatropin. However, there were no cases when the amount of leukemia increased due to the use of somatropin.

Cases of pancreatitis have been reported against the background of the drug.

The listed undesirable reactions are classified according to the frequency of occurrence as follows: very often> 1/10. often> 1/100 - <1/10, infrequently> 1/1000 - <1/100. rarely> 1/10 000 - <1/1000. very rarely <1/10 000. The frequency is unknown.

Impaired nervous system:

Infrequently: idiopathic intracranial hypertension (benign), tunnel syndrome of the wrist.

Frequency unknown: headache.

Disturbances from the musculoskeletal system and connective tissue:

Very rarely: ephmphysiolysis of the head of the femur.

Disorders from the endocrine system:

Very rarely: hypothyroidism.

Disorders from the metabolism and nutrition

Often in adult patients, infrequently in children: fluid retention with development

peripheral edema, stiffness, joint pain, muscle pain and paresthesia, which appeared at the beginning of treatment and usually disappeared during treatment.

The frequency is unknown: insulin resistance (hyperglycemia).

General disorders and disorders at the site of administration:

Often: local reactions in the field of injection (soreness, hyperemia, lipoatrophy, swelling, pruritus), which can be avoided by changing the injection site.

Attention! The following side effects have been described in the literature with somatroin, however, they have not been observed to date with the use of Sizen *: weakness, fatigue, gynaecomastia, edema of the optic nerve (usually seen during the first 8 weeks of treatment, most often in patients with Sheres- wski-Turner syndrome), otitis media and hearing impairment (in patients with Shereshevsky-Terper syndrome), subluxation of the hip in children (limping, pain in the thigh and knee), acceleration of the growth of the previously existing nevus (possible malignancy); Progression of scoliosis (in patients with excessively rapid growth); Allergic reactions: skin rash, itching; Increase in the content in the blood of inorganic phosphorus, parathyroid hormone and alkaline phosphatase activity.

If these or any other undesirable phenomena have arisen, be sure to inform your doctor.

Overdose:

There are no reports of acute overdose cases.However, the use of the drug in a dose exceeding the recommended dose can lead to hypoglycemia followed by the development of hyperglycemia. Overdosing of somatropin can lead to severe manifestations of fluid retention.

With prolonged overdose, signs and symptoms characteristic of an excess of growth hormone - active growth of bone tissue, especially of the hands, feet and jaw, as well as the development of hypothyroidism, a decrease in corizisol in the blood may appear.

Treatment: withdrawal of the drug, symptomatic therapy.

Interaction:

Currently, drugs that are incompatible with Sisen® are not known.

Simultaneous application of GCS can suppress growth and, thus, interfere with the growth effect of the preparation Sizen. If necessary, the replacement therapy of GCS should carefully adjust the dose of the drug.

The effectiveness of the drug (in terms of final growth) may also be affected by concomitant therapy with other hormones, for example, gonadotropin, anabolic steroids, estrogens and thyroid hormones.

If the preparation Saizen® is prescribed together with the preparations for which it is established,that they are metabolized with the participation of CYP P450 for 4 dependent liver enzymes, it is recommended to monitor the clinical efficacy of these drugs.

Special instructions:

Treatment with Sisen® should be carried out with constant monitoring by a doctor experienced in the diagnosis and treatment of patients with GH deficiency.

The recommended maximum daily dose of ns should be exceeded.

Bone age

During the period of therapy with Saizen®, bone age should be periodically evaluated, especially in pubertal children and / or receiving concomitant therapy with thyroid hormones. In these conditions, a rapid progression of the maturation of the epiphyses is possible. When closing the epiphyseal growth zone, it is recommended to re-confirm the presence of GR deficiency with the help of endocrinological tests. If GH deficiency is maintained, therapy should be continued at the doses shown with GH deficiency in adults.

Local Reactions

It is necessary to change the injection site to prevent the development of localized lipoatrophy, especially in cases of prolonged subcutaneous administration of Sizen.

Fluid retention

In the period of substitution therapy with somatropin in adults, fluid retention is possible. Clinical manifestations of fluid retention may include swelling, swelling of the joints, arthralgia, myalgia, paresthesia, carpal tunnel syndrome and benign intracranial hypertension; the development of these symptoms is most likely in elderly Nazis with the onset of the disease in adulthood. At the same time, these symptoms / signs are usually transient and depend on the dose of the drug.

Severe condition

Since there is insufficient information on the safety of taking somatroin, in patients who are in serious condition as a result of complications that develop after surgery on the open heart, abdominal cavity, polytrauma or acute respiratory failure, the use of somatroin is contraindicated.

Prader-Willi syndrome

Sisen® is not indicated for long-term therapy of children with short stature due to genetically confirmed Prader-Willi syndrome, except in cases of diagnosed GH deficiency. There were described cases of sleep apnea and sudden death after the initiation of somatropin therapy in children with the syndrome

Prader-Willy in the presence of one or more of the following risk factors: severe obesity, upper airway obstruction or sleep apnea, and an unidentified respiratory infection.

Leukemia

The cases of development of leukemia in a small number of patients with GH deficiency were described; some of them received somatropin therapy. Currently, there are no data confirming an increase in the incidence of leukemia in patients receiving somatropip, in the absence of predisposing factors. However, given the limited data available, patients receiving somatropin therapy should be closely monitored.

Jesus Resistance

During the period of therapy with Sizen, patients should be monitored for signs of impaired glucose tolerance. The drug should be used with caution in patients with diabetes mellitus (there may be a need for correction of hypoglycemic therapy), as well as a burdened family history of diabetes mellitus. Despite the fact that somatropip causes a decrease in insulin sensitivity, the vast majority of patients do not develop glucose homeostasis.Most of the available data did not show an increase in the incidence of type 1 or type 2 diabetes in children treated with somatropin, compared with the general population.

Hypothyroidism

Prior to the initiation of Sisen® therapy, thyroid function should be examined and regular reevaluation should be performed during treatment at a frequency of at least once a year. If during the period of therapy with Sizen® the patient was diagnosed with hypothyroidism, it is necessary to prescribe appropriate substitution therapy with thyroid hormone preparations.

Idiopathic intracranial hypertension

Before starting therapy with Sisen, it is necessary to carry out fundoscopy in an established manner in order to eliminate the previously existing edema of the optic disc. This examination should be repeated in the event of any clinical suspicion (severe or recurrent headache, visual impairment, nausea and / or vomiting). If the results of fundoscopy have confirmed the presence of edema of the optic nerve disc, therapy with Sisen® should be discontinued.Treatment can be resumed using a lower dose of the drug after resolving idiopathic intracranial hypertension, which quickly passes after the withdrawal of therapy. In this case, it is necessary to carefully monitor the symptoms of intracranial hypertension and discontinue therapy if it recurs.

Pancreatitis

In the treatment with somatropin it is rare, but pancreatitis can develop, especially in children who experience abdominal pain.

The formation of antibodies

As with any drug containing somatropia. a small proportion of patients may form antibodies to somatropin. The ability of these antibodies to interact is low, and they do not affect the rate of growth. In all patients with no response to therapy, it is necessary to perform a test for the presence of antibodies to somatropin.

Epiphysiolysis of the femoral head

Epiphysiolysis of the head of the femur is often associated with endocrine diseases, such as GH deficiency and hypothyroidism, as well as in the period of growth spikes. In children receiving somatropia, epiphysiolysis of the head of the femur can be due to endocrine disease, or an increase in the growth rate associated with therapy.If the child has chronic renal failure, it also needs to be inspected regularly for bone damage. Before starting treatment, a radiograph of the femur should be made. Doctors and parents should be careful about the appearance of lameness or complaints of pain in the thigh or knee (as pain in the thigh may extend to the knee area) in children receiving Sisen®.

Development and recurrence of tumors

Evidence that somatropin therapy increases the risk of developing malignant neoplasms is lacking. Nevertheless, taking into account the limited data available, careful monitoring of patients receiving somatropin therapy should be carried out, especially if there was a brain tumor in the past.

Chronic Renal Failure

Children with chronic kidney failure should stop treatment for the time of kidney transplantation.

Retardation of growth due to intrauterine growth retardation

In children diagnosed with growth retardation due to intrauterine growth retardation, other causes of growth retardation should be excluded before treatment begins.

Children diagnosed with growth retardation as a result of intrauterine growth retardation before starting treatment should be fasted to determine the concentration of insulin and glucose in the blood plasma and conduct these studies annually. In the presence of diabetes, treatment with Sisen® is not recommended.

In children diagnosed with growth retardation as a result of intrauterine growth retardation before starting treatment and then twice a year, it is recommended to determine the concentration of insulin-like growth factor I (IRF-1).

The final growth of children diagnosed with growth retardation as a result of intrauterine growth retardation will not be achieved if treatment with Sisen® is discontinued until the final growth is achieved.

Elderly age

Patients over 60 years of age who receive Sisen® therapy over a long period should be closely monitored, as the experience with Sisen® in elderly patients is insufficient.

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

The drug Sizen does not affect the ability to drive vehicles and other mechanisms.

Form release / dosage:

Lyophilizate for the preparation of a solution for subcutaneous administration of 8 mg.

The amount of lyophilizate, equivalent to 8 mg of somatropin, in a colorless transparent glass bottle of 3 ml volume, closed with a rubber stopper, crimped with an aluminum ring. Solvent - 0.3% methacresol solution in a volume of 1.37 ml in a cartridge of colorless neutral glass, closed at one end with a butyl rubber stopper, crimped with an aluminum ring, and a rubber piston at the other end. On the cartridge are pasted 2 labels, one on the other. The upper one is removed after the preparation of the solution.

I vial with lyophilizate and I solvent cartridge are placed in the device Click.izi ™, consisting of a transparent plastic cylinder, engraved with "Click.easy", and a sterile transitional cannula.

1 or 5 Clickxis ™ devices are placed in a plastic pallet with partitions and then in a cardboard box along with the instruction manual and the colored insert.

Packaging:

(1) - bottles of 3 ml (1) / complete with a solvent: methacresol solution 0.3% (cartridges) 1.37 ml and a device for the preparation of the solution "Click Izi" / - contour plastic containers (pallets)
(1) - bottles of 3 ml (5) / complete with a solvent: methacresol solution 0.3% (cartridges) 1.37 ml and a device for the preparation of the "Click Isi" solution / - packagingcontour plastic (pallets)

Storage conditions:

At a temperature of no higher than 25 ° C in the original packaging.

The reconstituted solution should be stored at a temperature of 2 to 8 ° C for no longer than 28 days.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016125 / 01

Date of registration:18.11.2009

The owner of the registration certificate:Merck Serono SpAMerck Serono SpA Italy

Manufacturer: & nbsp

MERCK SERONO, S.p.A. Italy

Information update date: & nbsp16.08.2015

Illustrated instructions

Instructions

device of click

Saizen® (Saizen® )