Rastan – description, instructions for use Rastan, indications, contraindications
Rastan description of the drug: composition and instructions for use, contraindications. Doctors of the Russian Federation. For healthcare professionals only.
It is produced in a dosage form of a solution for subcutaneous administration in dosages of 5.0 mg (15 IU) and 1.33 mg (4 IU). 2 instructions are provided:
INSTRUCTIONS for the use of the drug for medical use RASTAN® (5.0 mg (15 IU))
Registration number:
Trade name of the drug: Rastan®
International non-proprietary name: somatropin.
Dosage form: solution for subcutaneous administration.
Composition for 1 ml
active substance: somatropin 5.0 mg (15 IU)
excipients: 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) – up 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: somatotropic hormone.
ATX code: [Н01АС01].
Pharmacological properties
Rastan® contains somatoropin, a human growth hormone produced by recombinant DNA biotechnology. Somatropin is an anabolic peptide, contains 191 amino acid residues and has a molecular weight of approximately 22,000 Da. Amino acid sequences 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 bones of the skeleton, acting on the epiphysis plates of tubular bones, bone metabolism in children. Contributes to the normalization of body structure by increasing muscle mass and reducing body fat. Most of the effects of somatropin are realized through insulin-like growth factor I (IGF-I), which is produced in all cells of the body (mainly liver cells). More than 90% of IGF-I is bound to proteins (IGFBP), of which IGFBP-3 is the most important.
In patients with GH deficiency and osteoporosis, replacement therapy leads to the normalization of bone mineral composition and density. Increases the number and size of muscle cells, liver, thymus, gonads, adrenal glands, thyroid gland. It stimulates the transport of amino acids into the cell and protein synthesis, reduces the concentration of cholesterol, affecting the profile of lipids and lipoproteins. Suppresses insulin release. Promotes the retention of sodium, potassium and phosphorus. Increases body weight, muscle activity and physical endurance.
Pharmacokinetics.
Suction
Absorption of somatropin after subcutaneous administration is approximately 80%, the maximum concentration in blood plasma is reached after 3-6 hours.
Distribution
Penetrates into well-perfused organs, especially the liver and kidneys. The volume of distribution of somatropin – 0.49-2.11 l / kg.
Metabolism
Metabolized in the liver and kidneys.
Withdrawal
It is excreted by the kidneys and through the intestines (including 0.1% unchanged). The half-life after subcutaneous administration is 3-5 hours.
Indications for use
Children
Growth retardation in children due to insufficient secretion of growth hormone.
Growth retardation in girls with Shereshevsky-Turner syndrome.
Growth retardation in chronic renal failure (CRF) (decreased kidney function by more than 50%).
Intrauterine growth retardation (in children who have not reached the normative growth indicators by the age of 2 years)
Growth retardation in patients with Prader-Willi syndrome (PWS).
Adults
Confirmed severe congenital or acquired growth hormone deficiency (as replacement therapy) in patients who meet one of the following two criteria:
– manifestation of the disease in adults: patients who have only a deficiency of growth hormone or in combination with a deficiency of other hormones (hypopituitarism) as a result of diseases of the pituitary gland, hypothalamus, surgery, radiation therapy, or trauma.
– manifestation of the disease in adults: patients who have only a deficiency of growth hormone or in combination with a deficiency of other hormones (hypopituitarism), as a result of diseases of the pituitary gland, hypothalamus, surgery, radiation therapy, or trauma.
– manifestation of the disease in children: patients with congenital, genetic, acquired or idiopathic causes.
Contraindications
– Hypersensitivity to any component of the drug.
– Brain tumors (by the beginning of treatment, the intracranial tumor must be inactive and antitumor therapy completed).
– Active malignant neoplasms of any location.
– Urgent conditions (including conditions after operations on the heart, abdominal cavity, acute respiratory failure, multiple injuries as a result of accidents). If, during growth hormone replacement therapy, a patient develops a critical condition for some reason, the ratio of the potential risk and benefits of continuing treatment in this case should be assessed..
– Stimulation of growth in patients after the closure of the epiphyseal growth zones of tubular bones.
– Severe obesity (body weight / height ratio exceeds 200%) or severe respiratory impairment (see section “Special instructions”) in patients with PWS.
– Pregnancy.
With caution: diabetes mellitus, intracranial hypertension, concomitant therapy with glucocorticosteroids (GCS), hypothyroidism (including during thyroid hormone replacement therapy), breastfeeding period, PWS.
Application during pregnancy and during breastfeeding
Currently, there is limited clinical experience with the use of somatropin during pregnancy. Studies of somatropin on animals did not reveal a negative effect on the fetus, from which, however, it does not follow that similar results will be obtained when using Rastan® in humans, therefore, the use of Rastan® during pregnancy is contraindicated. During normal pregnancy, the level of pituitary growth hormone decreases markedly after 20 weeks, being almost completely replaced by placental ones by 30 weeks, therefore the need for replacement therapy with Rastan® in the third trimester of pregnancy seems unlikely.
There is no reliable information about the possibility of penetration of somatropin into breast milk, however, in any case, the absorption of intact protein in the gastrointestinal tract of the child is extremely unlikely. However, if it is necessary to use somatropin during breastfeeding, precautions should be taken.
Method of administration and dosage
Rastan® is injected subcutaneously, slowly, once a day, usually at night. Injection sites should be changed to prevent the development of lipoatrophy.
Doses are selected individually, taking into account the severity of GH deficiency, body mass or surface area, effectiveness in the course of therapy.
If there is insufficient GH secretion, treatment is started as early as possible and continued until puberty and / or until the bone growth zones are closed. It is possible to stop treatment when the desired result dbol steroid for sale the ultimate home six pack is achieved. In case of insufficient growth dynamics, dose adjustment may be required.
Recommended dosage for adults with growth hormone deficiency
With GH deficiency in adults, the initial dose is 0.15-0.3 mg / day (which corresponds to 0.45-0.9 IU / day) with a subsequent increase, depending on the effect. In dose titration, plasma IGF-I concentration can be used as a reference. The maintenance dose is selected individually, but does not exceed, as a rule, 1.3 mg / day, which corresponds to 4 IU / day. Women may need a higher dose than men. Since normal physiological production of growth hormone decreases with age, the dose may be reduced according to age. Clinical and side effects, and serum IGF-1 concentration can be used as a guideline in dose selection..
Side effect
A feature of patients with GH deficiency is a deficit in the volume of extracellular fluid. With the start of treatment with somatropin, this deficiency is corrected. Adverse reactions associated with fluid retention, such as peripheral edema, joint stiffness, arthralgia, myalgia, and paresthesias, are common in adult patients. As a rule, the severity of these reactions varies from moderate to moderate, they develop in the first months of treatment and disappear spontaneously or when the dose is reduced. 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 rare.
Below is a summary of adverse reactions identified in clinical trials of somatropin in accordance with the systemic organ classification (MedDRA) and the WHO classification by frequency of occurrence.
Post-registration data.
From the immune system: rarely – hypersensitivity reactions, including anaphylactic reactions; increased titer of antibodies to somatropin.
Metabolic and nutritional disorders: infrequently – type 2 diabetes mellitus in children.
Vascular disorders: often – increased blood pressure in adults; very rarely – increased blood pressure in children.
From the respiratory system, chest and mediastinal organs: often – dyspnea (in adults), cessation of breathing during sleep (in adults).
Benign, malignant and unspecified neoplasms: There is evidence that a small number of children treated with somatropin, including both pituitary GH preparations and DNA-recombinant GH preparations, developed leukemia. The relationship between leukemia and somatropin treatment is still unclear..
There is evidence of the development of femoral head epiphysis, Legg-Calve-Perthes disease during therapy with somatropin (see the section “Special instructions”).
Increases in the upper and lower extremities have been reported in children with Shereshevsky-Turner syndrome during treatment with somatropin.
There was a tendency to an increase in the incidence of otitis media in children with Shereshevsky-Turner syndrome who received high doses of somatropin.
The following side effects are described in the literature with the use of somatropin: edema of the optic nerve head (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 hip and knee); acceleration of the growth of a preexisting nevus (malignancy is possible); increased blood concentration of inorganic phosphate, parathyroid hormone and alkaline phosphatase activity.
Overdose
Overdose cases are unknown.
Acute overdose can lead to hypoglycemia in the beginning, and then to hyperglycemia. With prolonged overdose, there may be signs and symptoms characteristic of an excess of human GH – 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.
Treatment: drug withdrawal, symptomatic therapy.
Interaction with other medicinal products
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Patients diagnosed with diabetes mellitus receiving somatropin therapy may require 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 stimulating growth. In patients receiving treatment with somatropin, previously undiagnosed secondary adrenal insufficiency may be detected, which may require replacement therapy with GCS. In addition, patients receiving GCS replacement therapy for a previously diagnosed adrenal cortex insufficiency may need to increase the maintenance dose of GCS or the dose required 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, such as gonadotropin, anabolic steroids, estrogens and thyroid hormones.
Incompatibility.
No incompatibility studies have been carried out, therefore Rastan® cannot be mixed with other drugs..
special instructions
Treatment with somatropin should be carried out by physicians experienced in diagnosing and treating patients with GH deficiency or Shereshevsky-Turner syndrome.
Do not exceed the maximum recommended daily dose (see section “Dosage and Administration”).
Stimulation of longitudinal growth can be carried out in children before the closure of the epiphyseal growth zones.
Growth hormone deficiency in adults persists throughout life and needs appropriate treatment, however, there are currently no results of long-term therapy in adults.
Shereshevsky-Turner syndrome
In patients with Shereshevsky-Turner syndrome during treatment with somatropin, it is recommended to monitor the proportional growth of the upper and lower extremities, and if an increased growth is detected, 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 should be monitored by an otolaryngologist.
Chronic renal failure
Growth impairment in children with CRF should be accurately established before starting treatment with somatropin by monitoring growth against the background of optimal CRF therapy for one year. During therapy with somatropin, conservative treatment of chronic renal failure with traditional drugs and, if necessary, dialysis should be continued. During kidney transplantation, somatropin therapy should be discontinued.
Prader-Willi syndrome
There have been reports of deaths in children with PWS with GH deficiency who received somatropin therapy and had at least one of the following risk factors: severe obesity, a history of respiratory failure, sleep apnea, or unidentified respiratory tract infection. A possible risk factor could be the patient’s male gender. Patients with PWS in the presence of one or more of the listed factors are at high risk when using somatropin.
Before prescribing somatropin in patients with GH deficiency in combination with PWS, the risk-benefit ratio should be considered.
In patients with PWV, treatment with somatropin must necessarily be associated with a calorie-restricted diet. Patients with PWS should actively monitor their body weight both before and during somatropin use..
Tumors
Patients with a history of malignant neoplasms should be carefully examined for recurrence. In case of occurrence or recurrence of malignant neoplasm, somatropin therapy should be discontinued.
Patients with GH deficiency secondary to the presence of brain neoplasms should undergo more frequent examinations to exclude the progression and recurrence of the underlying disease. Somatropin should not be prescribed if any signs of active tumor growth are detected. Before the appointment of somatropin, the tumor process should be in an inactive phase and antitumor therapy should be completed. If signs of tumor resumption appear, the drug should be discontinued.
The development of secondary benign and malignant neoplasms has been reported in patients with childhood cancer and receiving somatropin therapy. The most common complication was the development of intracranial tumors, in particular, meningiomas in patients who had previously received head radiotherapy for primary neoplasms. However, no recurrence of primary neoplasms was reported in this category of patients..
Leukemia
Reported the development of leukemia in children treated with somatropin. The relationship between the occurrence of leukemia and somatropin therapy has not been established..
Benign intracranial hypertension
In the event of severe or recurrent headaches, visual impairment, nausea and / or vomiting, a fundoscopy is recommended to detect possible swelling of the optic nerve head. Upon confirmation of the diagnosis, the presence of benign intracranial hypertension should be assessed and, upon confirmation of the diagnosis, somatropin therapy should be discontinued.
To date, there are no clear guidelines for the use of growth hormone 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 recurrence of intracranial hypertension. If the use of somatropin has been resumed, careful monitoring is necessary for the possible appearance of symptoms of intracranial hypertension.
Epiphyseolysis
In patients with endocrine disorders, including GH deficiency, epiphyseolysis of the tubular heads may be more common. It is necessary to conduct a thorough examination if the child develops lameness during treatment.
Hypopituitarism
Patients with hypopituitarism (deficiency of several pituitary hormones) in the case of standard hormone replacement therapy with the introduction of somatropin should be under strict supervision.
Thyroid function
During the treatment with somatropin, an increased conversion of thyroxine (T4) to triiodothyronine (T3) was revealed, which may cause a decrease in the concentration of T4 and an increase in the concentration of T3 in the blood plasma. In healthy volunteers, as a rule, the concentration of thyroid hormones in the blood plasma remained within the normal range. The effect of somatropin on thyroid hormone concentration may be of clinical relevance in patients with central subclinical hypothyroidism who may potentially develop hypothyroidism. 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 starting therapy with somatropin, as well as at each change in its dose. Lack of adequate therapy for hypothyroidism may prevent optimal results from treatment with somatropin.
Formation of antibodies to somatropin
The formation of antibodies to somatropin is possible. The study of the titer of antibodies to somatropin should be carried out in cases where the patient does not respond to therapy.
Insulin sensitivity
Somatropin reduces insulin sensitivity, especially in high doses in patients with high sensitivity, which can cause the development of hyperglycemia in patients with inadequate insulin secretion.
Thus, previously undiagnosed impairment of 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 mellitus: in patients with obesity, Shereshevsky-Turner syndrome, a family history of diabetes mellitus, while taking GCS or a pre-existing impaired glucose tolerance. During treatment with somatropin, more careful monitoring is necessary in patients with diagnosed type 1 or 2 diabetes mellitus or with impaired glucose tolerance (see the section “Interaction with other medicinal products”). In such patients, the need for dose adjustment of hypoglycemic drugs should be assessed when prescribing somatropin.
Scoliosis
In some children, during the period of excessively rapid growth (especially often in children with PWS), scoliosis may progress. During the entire period of treatment with somatropin, monitoring should be carried out to detect signs of scoliosis. However, available evidence suggests that somatropin therapy does not affect the incidence or severity of scoliosis..
Pancreatitis
Compared with adults, pediatric patients receiving somatropin therapy may have an increased risk of developing pancreatitis. Despite the rarity of this complication, increased attention should be paid to pediatric patients with abdominal pain.
Obesity
Obese patients are more likely to experience adverse events with weight-based doses.
Hyperestrogenism in women
Women with hyperestrogenism or women taking oral estrogens may need higher doses of somatropin than men.
Elderly age
Elderly patients may be more sensitive to the action of somatropin and, therefore, the likelihood of side effects increases. Therefore, it is advisable to use a lower initial dose and a slower increase in the dose of the drug. There is no experience with somatropin treatment in patients over 60 years old.
Urgent states
Safety of continuation of somatropin therapy in patients with severe diseases associated with complications after open heart or abdominal surgery, multiple injuries associated with accidents, as well as patients with acute respiratory failure receiving replacement therapy according to registered indications, in whom during therapy the mentioned diseases appeared, it is not established. Therefore, the ratio of the potential risk and benefit of continuing somatropin therapy in patients in an urgent state should be carefully assessed..
Influence on the ability to drive vehicles, mechanisms
Rastan® does not affect the ability to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.
Release form
Solution for subcutaneous administration 5 mg / ml (15 IU / ml).
3 ml in a bottle of colorless neutral glass with a capacity of 5 ml, sealed with a combined cap. 5 vials are placed in a blister strip made of polyvinyl chloride film, without foil. 1 bottle or 1 blister strip together with instructions for medical use is placed in a carton box.
3 ml of the drug in a cartridge of colorless neutral glass, sealed with a combined cap. 1 or 5 cartridges are placed in a blister strip made of polyvinyl chloride film and aluminum foil. 1 blister strip along with instructions for medical use is placed in a cardboard box.
3 ml of the drug in a cartridge of colorless neutral glass, sealed with a combined cap. The cartridge is mounted in a disposable BiomaticPen®2 syringe pen. 5 disposable syringe pens BiomaticPen®2 with cartridges are placed in a blister strip packaging. 1 blister strip with syringe pens or 1 or 5 syringe pens BiomaticPen®2 disposable with cartridges together with instructions for medical use and instructions for use of syringe pen BiomaticPen®2 are placed in a cardboard box.
Storage conditions
In the dark place at a temperature of 2 ºFrom to 8 ºFROM.
Do not freeze.
Store the used bottle (cartridge) at a temperature of 2 ° C to 8 ° C for 28 days.
Store a disposable syringe pen with a cartridge 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.
Vacation conditions
On prescription.
Manufacturer / organization accepting customer claims:
OJSC “Pharmstandard-UfaVITA”
450077, Russia, Ufa, st. Khudayberdin, 28,
phone / fax (347) 272 92 85, www.pharmstd.ru
Injection technique when using the drug Rastan® in vials
1. Disinfect the rubber membrane of the vial with alcohol or other antiseptic to prevent microorganisms from entering the vial, which is especially important when carrying out multiple injections.
2. For injections, use sterile syringes and needles. The syringe must be of sufficient volume to take the required amount of the drug and inject.
3. Draw air into the syringe in the amount corresponding to the required dose of the drug. Introduce air into the vial.
4. Turn the vial with the syringe upside down and draw the required dose of the drug into the syringe. Remove the needle from the vial and remove the air from the syringe. Check the correct dose of the drug.
5. Inject immediately.
Injection technique when using Rastan® in cartridges
For injecting Rastan® in cartridges, use the BiomaticPen® syringe pen or any other syringe pen designed for use with Rastan® cartridges.
For the correct administration of Rastan®, you must carefully follow the instructions in the instructions for use of the syringe pen.
1. Before use, make sure that the Rastan® cartridge is not damaged (eg cracks). Do not use the cartridge if there is any visible damage or change in the appearance of the solution (change in color, transparency, presence of sediment, etc.).
2. Treat the rubber cap of the cartridge with alcohol or other antiseptic to prevent the ingress of microorganisms.
3. Install the cartridge into the pen in accordance with the instructions for use of the pen.
4. Use a new sterile, replaceable needle for each injection of Rastan® in cartridges..
5. After injection, the needle should remain under the skin for at least 6 seconds. The button should be kept pressed until the needle is completely removed from under the skin, thus ensuring the correct dose administration and limiting the possibility of blood or lymph getting into the needle or into the cartridge with the Rastan® drug.
If the drug continues to flow out of the needle after injection, keep the needle in the skin longer for subsequent injections..
6. The Rastan® cartridge is intended for individual use only, cannot be refilled..
To administer the dose of the drug prescribed by the doctor, use the table for converting the indications of the dosage indicator of the syringe pen into the dose of the drug.
Conversion table of the readings of the dosage indicator of the syringe pen BiomaticPen® in the dose of Rastan®, solution for subcutaneous administration, 5 mg / ml (15 IU), 3 ml cartridges:
INSTRUCTIONS FOR INJECTION OF THE MEDICINAL PREPARATION Rastan®, solution for subcutaneous administration 5 mg / ml (15 IU) USING THE SYRINGE-PEN BiomaticPen®2 (single-use for multiple injections)
The appearance and parts of the BiomaticPen®2 syringe pen
1 – cap, 2 – body, 3 – dosage indicator window, 4 – dose setting ring, 5 – start button
Ensuring asepsis during injection
Wash your hands before injecting. It is very important that the hands and all equipment needed for the injection are clean. Choose an injection site. Wipe the skin at the injection site with an alcohol wipe only after the dose of somatropin has been set in the pen. Allow the alcohol to dry at the injection site before injection.
Additional Information
Sound and tactile signals
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In the process of operation, the syringe pen BiomaticPen®2 produces the following sound and tactile signals:
– setting the required dose
When the dose setting ring is rotated, a certain physical resistance is felt and clicks are heard as each dose unit is dialed.
– injection
The process of drug injection from the BiomaticPen®2 syringe pen is accompanied by a sound signal (ratchet), which stops when the drug is completely injected (to the value “0” in the dosage indicator window).
Storage, use and disposal rules
The pen is intended for individual use and cannot be used by multiple persons.
Handle the BiomaticPen®2 syringe pen carefully.
Do not allow dust and moisture to enter the BiomaticPen®2 syringe pen.
Close the pen cap with the cap after each use. Always keep the BiomaticPen®2 syringe pen individually wrapped without a needle.
Store the BiomaticPen®2 syringe pen, observing the instructions for storing the medicinal product.
You can clean the BiomaticPen®2 syringe pen with a damp cloth. Do not use alcohol, thinners or other cleaning agents.
Never immerse the BiomaticPen®2 syringe pen in water, as this may damage it..
Warnings
Use the BiomaticPen®2 syringe pen only with the pen-compatible needles recommended by your doctor..
Rastan® should be used as part of the therapy prescribed by your doctor and in the dosage prescribed for you. Any changes must be made under medical supervision.
If you have any questions about the length of the needle, please consult your doctor or medical staff..
Do not expose the BiomaticPen®2 syringe pen to extreme temperatures, do not leave it in direct sunlight or in the cold (for example, in a freezer).
Keep the BiomaticPen®2 syringe pen, needles for the pen out of the reach of children and other persons who are not familiar with the correct handling method. In cases of inadvertent injection of the drug or injury from a needle stick, seek immediate medical attention!
The needles of the pen should only be used by one person to prevent the transmission of infectious diseases.
Use a new pen needle for each injection to ensure sterility. Remove the needle of the pen after injection to prevent drug leakage, air ingress and possible clogging of the pen needle.
Dispose of the used pen needles together with the protective cap put on them, following the 300mg ml manufacturer’s instructions so that they cannot harm other people.
Never use the BiomaticPen®2 syringe pen if you have doubts about its correct operation..
Disposal rules
The BiomaticPen®2 syringe pen does not contain components that are dangerous to the environment and can be disposed of with ordinary household waste.
The used syringe pen BiomaticPen®2 should be disposed of only with the needle disconnected.
Conversion table of the indications of the dosage indicator of the syringe pen BiomaticPen®2 in the dose of Rastan®, solution for subcutaneous administration
5 mg / ml (15 IU):
INSTRUCTIONS for the medical use of Rastan® (1.33 mg (4 IU))
Registration number:
Trade name of the drug: Rastan®
International non-proprietary name: Somatropin.
Dosage form: lyophilisate for preparation of a solution for subcutaneous administration.
Composition of one bottle
active substance: human somatropin 1.33 mg (4 IU)
excipients: mannitol, glycine, sodium dihydrogen phosphate dihydrate, sodium hydroxide.
Solvent: 0.3% solution of metacresol in water for injection.
Description: freeze-dried mass of white or white with a yellowish sheen.
Solvent – a clear, colorless or weakly colored liquid with a specific odor.
Pharmacotherapeutic group: Growth hormone.
ATX code: [H01AC01]
Pharmacological properties
Rastan® contains somatropin, a human growth hormone (GH) produced by recombinant DNA biotechnology. 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 the human growth hormone produced by the pituitary gland.
Pharmacodynamics.
Stimulates skeletal and somatic growth, and also has a pronounced effect on metabolic processes. Stimulates the growth of bones of the skeleton, acting on the epiphysis plates of tubular bones, bone metabolism in children. Helps to normalize body structure by increasing muscle mass and reducing body fat.
Most of the effects of somatropin are realized through insulin-like growth factor I (IGF-I), which is produced in all cells of the body (mainly liver cells). More than 90% of IGF-I is bound to proteins (IGFBP), of which IGFBP-3 is the most important.
In patients with growth hormone deficiency and osteoporosis, replacement therapy leads to the normalization of bone mineral composition and density. Increases the number and size of muscle cells, liver, thymus, gonads, adrenal glands, thyroid gland. It stimulates the transport of amino acids into the cell and protein synthesis, reduces the concentration of cholesterol, affecting the profile of lipids and lipoproteins. Suppresses insulin release. Promotes the retention of sodium, potassium and phosphorus. Increases body weight, muscle activity and physical endurance.
Pharmacokinetics.
Suction
Absorption of somatropin after subcutaneous administration is approximately 80%, the maximum concentration in blood plasma is reached after 3-6 hours.
Distribution
Penetrates into well-perfused organs, especially the liver and kidneys. The volume of distribution of somatropin – 0.49-2.11 l / kg.
Metabolism
Metabolized in the liver and kidneys.
Withdrawal
It is excreted by the kidneys and through the intestines (including 0.1% unchanged). The half-life after subcutaneous administration is 3-5 hours.
Indications for use
Children
Growth retardation in children due to insufficient secretion of growth hormone.
Growth retardation in Shereshevsky-Turner syndrome.
Growth retardation in chronic renal failure (CRF) (decreased kidney function by more than 50%).
Intrauterine growth retardation (in children who have not reached the normative growth indicators by the age of 2 years).
Growth retardation in patients with Prader-Willi syndrome (PWS).
Adults
Confirmed severe congenital or acquired growth hormone deficiency (as replacement therapy) in patients who meet one of the following two criteria:
– manifestation of the disease in adults: patients who have only a deficiency of growth hormone or in combination with a deficiency of other hormones (hypopituitarism), as a result of diseases of the pituitary gland, hypothalamus, surgery, radiation therapy or injury;
– manifestation of the disease in children: patients with congenital, genetic, acquired or idiopathic causes.
Contraindications
– Hypersensitivity to any component of the drug.
– Brain tumors (by the beginning of treatment, the intracranial tumor must be inactive and antitumor therapy completed).
– Active malignant neoplasms of any location.
– Urgent conditions (including conditions after operations on the heart, abdominal cavity, acute respiratory failure, multiple injuries as a result of accidents). If, during growth hormone replacement therapy, a patient develops a critical condition for some reason, the ratio of the potential risk and benefits of continuing treatment in this case should be assessed..
– Stimulation of growth in patients after the closure of the epiphyseal growth zones of tubular bones.
– Severe obesity (body weight / height ratio exceeds 200%) or severe respiratory impairment (see section “Special instructions”) in patients with PWS.
– Pregnancy.
With caution: diabetes mellitus, intracranial hypertension, concomitant therapy with glucocorticosteroids (GCS), hypothyroidism (including during thyroid hormone replacement therapy), breastfeeding period, PWS.
Application during pregnancy and during breastfeeding
Currently, there is limited clinical experience with the use of somatropin during pregnancy. Studies of somatropin on animals did not reveal a negative effect on the fetus, from which, however, it does not follow that similar results will be obtained when using Rastan® in humans, therefore, the use of Rastan® during pregnancy is contraindicated. During normal pregnancy, the level of pituitary growth hormone decreases markedly after 20 weeks, being almost completely replaced by placental ones by 30 weeks, therefore the need for replacement therapy with Rastan® in the third trimester of pregnancy seems unlikely.
There is no reliable information about the possibility of penetration of somatropin into breast milk, however, in any case, the absorption of intact protein in the gastrointestinal tract of the child is extremely unlikely. However, if it is necessary to use somatropin during breastfeeding, the drug should be used with caution..
Method of administration and dosage
Rastan® is injected subcutaneously, slowly, once a day, usually at night. Injection sites should be changed to prevent the development of lipoatrophy.
It is recommended to dissolve the contents of the bottle in 1 ml of the supplied solvent, based on the calculated dose. To do this, select the solvent with a syringe and inject it into the vial with the drug through the stopper. Shake gently until the contents of the vial are completely dissolved. Sudden shaking is unacceptable. The prepared solution is stored in a bottle for no more than two weeks at a temperature of 2 to 8 ºFROM.
Doses are selected individually, taking into account the severity of GH deficiency, body mass or surface area, effectiveness in the course of therapy.
If there is insufficient GH secretion, treatment is started as early as possible and continued until puberty and / or until the bone growth zones are closed. It is possible to stop treatment when the desired result is achieved. In case of insufficient growth dynamics, dose adjustment may be required.
Recommended dosage for adults with growth hormone deficiency
With GH deficiency in adults, the initial dose is 0.15-0.3 mg / day (which corresponds to 0.45-0.9 IU / day) with a subsequent increase, depending on the effect. For dose titration, plasma IGF-I concentration can be used as a reference. The maintenance dose is selected individually, but does not exceed, as a rule, 1.3 mg / day, which corresponds to 4 IU / day. Women may need a higher dose than men. Since normal physiological production of growth hormone decreases with age, the dose may be reduced according to age. Clinical and side effects, as well as determination of serum IGF-I concentration can be used as a guide in dose selection..
Side effect
Patients with GH deficiency are characterized by a deficiency of extracellular fluid. After the start of treatment with Rastan®, this deficiency is quickly restored. In general, fluid retention side effects such as peripheral edema, skeletal muscle rigidity, arthralgia, myalgia, and paresthesia are common in adult patients. These phenomena are usually mild or moderate, appear during the first months of treatment and subside spontaneously or after reducing the dose of the drug. The frequency of these side effects depends on the dose of Rastan®, the age of the patients and, possibly, is inversely proportional to the age at which GH deficiency occurs..
Transient reactions at the injection site may occur: rash, itching, soreness, numbness, hyperemia, swelling, lipoatrophy.
A decrease in the concentration of cortisol in the blood serum is revealed. The clinical significance of this phenomenon appears to be limited.
There are rare cases of leukemia in children with GH deficiency receiving Rastan® therapy, but the incidence of leukemia does not differ from that in children without GH deficiency.
The following are undesirable reactions distributed by systemic organ classes and frequency separately for children and adults: very often (≥1/10), often (≥1/100 but
Benign, malignant and unspecified neoplasms (including cysts and polyps): rarely – leukemia (children).
Metabolic and nutritional disorders: frequency unknown – type 2 diabetes mellitus.
Nervous system disorders: often – paresthesia (adults), carpal tunnel syndrome (adults); infrequently – paresthesia (children); rarely – benign intracranial hypertension (children); frequency unknown – benign intracranial hypertension (adults).
Musculoskeletal and connective tissue disorders: very often – arthralgia (adults); often – myalgia (adults), skeletal muscle rigidity (adults), arthralgia (children); rarely – myalgia (children); frequency unknown – skeletal muscle stiffness (children).
General disorders and disorders at the injection site: very often – peripheral edema (adults); often – transient reactions at the injection site (rash, itching, soreness, numbness, hyperemia, swelling, lipoatrophy, pain at the injection site) (children); infrequently – peripheral edema (children); frequency unknown – transient reactions at the injection site (rash, pruritus, soreness, numbness, hyperemia, swelling, lipoatrophy, pain at the injection site) (adults).
Laboratory and instrumental data: the frequency is unknown – a decrease in the concentration of cortisol in the blood plasma.
Allergic reactions may occur, including skin rash and itching, myositis (caused by the action of m-cresol), progression of scoliosis, the formation of antibodies to the drug, headache, insomnia, glucosuria, a decrease in T4 concentration and an increase in serum T3 concentration, limping, pain in the hip and knee (see the section “Special instructions”).
There are reports of the development of optic nerve edema.
During the post-marketing study, there were rare cases of sudden death of patients with PWS treated with somatropin, although a direct relationship between these cases and taking the drug has not been established.
Cases of femoral head epiphysis and Legg-Calve-Perthes disease have been reported in children treated with somatropin. A causal relationship with somatropin has not been demonstrated.
Overdose
Acute overdose can lead first to hypoglycemia, and then to hyperglycemia. With prolonged overdose, there may be signs and symptoms characteristic of an excess of human growth hormone – 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.
Treatment: drug withdrawal, symptomatic therapy.
Interaction with other medicinal products
Patients diagnosed with diabetes mellitus receiving somatropin therapy may require dose adjustment of insulin and / or other hypoglycemic drugs.
Glucocorticosteroids (GCS), when used simultaneously with GH, reduce the stimulating effect on the growth process. 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 stimulating growth. In patients receiving treatment with somatropin, previously undiagnosed secondary adrenal insufficiency may be detected, which may require replacement therapy with GCS. In addition, patients receiving trenbolone become stronger leaner and faster with GCS replacement therapy for a previously diagnosed adrenal cortex insufficiency may need to increase the maintenance dose of GCS or the dose required 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, such as gonadotropin, anabolic steroids, estrogens, and thyroid hormones. Moderate hypothyroidism may develop in patients receiving levothyroxine sodium as replacement therapy. In this regard, it is recommended to investigate the function of the thyroid gland after starting treatment with Rastan® and after changing its dose..
Incompatibility.
No incompatibility studies have been carried out, therefore Rastan® cannot be mixed with other drugs..
special instructions
Treatment with somatropin should be carried out by physicians experienced in diagnosing and treating patients with GH deficiency or Shereshevsky-Turner syndrome.
Do not exceed the maximum recommended daily dose (see section “Dosage and Administration”).
Stimulation of longitudinal growth can be carried out in children before the closure of the epiphyseal growth zones.
Growth hormone deficiency in adults persists throughout life and needs appropriate treatment, however, there are currently no results of long-term therapy in adults.
Shereshevsky-Turner syndrome
In patients with Shereshevsky-Turner syndrome during treatment with somatropin, it is recommended to monitor the proportional growth of the upper and lower extremities, and if an increased growth is detected, 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 should be monitored by an otolaryngologist.
Chronic renal failure
Growth impairment in children with CRF should be accurately established before starting treatment with somatropin by monitoring growth against the background of optimal CRF therapy for one year. During therapy with somatropin, conservative treatment of chronic renal failure with traditional drugs and, if necessary, dialysis should be continued. During kidney transplantation, somatropin therapy should be discontinued.
Prader-Willi syndrome
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There have been reports of deaths in children with PWS with GH deficiency who received somatropin therapy and had at least one of the following risk factors: severe obesity, a history of respiratory failure, sleep apnea, or unidentified respiratory tract infection. A possible risk factor could be the patient’s male gender. Patients with PWS in the presence of one or more of the listed factors are at high risk when using somatropin.
Before prescribing somatropin to patients with GH deficiency in combination with PWV, the ratio of potential risk and benefit should be considered.
In patients with PWV, treatment with somatropin must necessarily be associated with a calorie-restricted diet. Patients with PWS should actively monitor their body weight both before and during somatropin use..
Tumors
Patients with a history of malignant neoplasms should be carefully examined for recurrence. In case of occurrence or recurrence of malignant neoplasm, somatropin therapy should be discontinued.
Patients with GH deficiency secondary to the presence of brain neoplasms should undergo more frequent examinations to exclude the progression and recurrence of the underlying disease. Somatropin should not be prescribed if any signs of active tumor growth are detected. Before the appointment of somatropin, the tumor process must be in an inactive phase and antitumor therapy must be completed. If signs of tumor resumption appear, the drug should be discontinued.
The development of secondary benign and malignant neoplasms has been reported in patients with childhood cancer and receiving somatropin therapy. The most common complication was the development of intracranial tumors, in particular, meningiomas in patients who had previously received head radiotherapy for primary neoplasms. However, no recurrence of primary neoplasms was reported in this category of patients..
Leukemia
Reported the development of leukemia in children treated with somatropin. The relationship between the occurrence of leukemia and somatropin therapy has not been established..
Benign intracranial hypertension
In the event of severe or recurrent headaches, visual impairment, nausea and / or vomiting, a fundoscopy is recommended to detect possible swelling of the optic nerve head. Upon confirmation of the diagnosis, the presence of benign intracranial hypertension should be assessed and, upon confirmation of the diagnosis, somatropin therapy should be discontinued.
To date, there are no clear guidelines for the use of growth hormone 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 recurrence of intracranial hypertension. If the use of somatropin has been resumed, careful monitoring is necessary for the possible appearance of symptoms of intracranial hypertension.
Epiphyseolysis
In patients with endocrine disorders, including GH deficiency, epiphyseolysis of the tubular heads may be more common. It is necessary to conduct a thorough examination if the child develops lameness during treatment.
Hypopituitarism
Patients with hypopituitarism (deficiency of several pituitary hormones) in the case of standard hormone replacement therapy with the introduction of somatropin should be under strict supervision.
Thyroid function
During the treatment with somatropin, an increased conversion of thyroxine (T4) to triiodothyronine (T3) was revealed, which may cause a decrease in the concentration of T4 and an increase in the concentration of T3 in the blood plasma. In healthy volunteers, as a rule, the concentration of thyroid hormones in the blood plasma remained within the normal range. The effect of somatropin on thyroid hormone concentration may be of clinical relevance in patients with central subclinical hypothyroidism who may potentially develop hypothyroidism. 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 starting therapy with somatropin, as well as at each change in its dose. Lack of adequate therapy for hypothyroidism may prevent optimal results from treatment with somatropin.
Formation of antibodies to somatropin
The formation of antibodies to somatropin is possible. The study of the titer of antibodies to somatropin should be carried out in cases where the patient does not respond to therapy.
Insulin sensitivity
Somatropin reduces insulin sensitivity, especially in high doses in patients with high sensitivity, which can cause the development of hyperglycemia in patients with inadequate insulin secretion.
Thus, previously undiagnosed impairment of 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 mellitus: in patients with obesity, Shereshevsky-Turner syndrome, a family history of diabetes mellitus, while taking GCS or a pre-existing impaired glucose tolerance. During treatment with somatropin, more careful monitoring is necessary in patients with diagnosed type 1 or 2 diabetes mellitus or with impaired glucose tolerance (see the section “Interaction with other medicinal products”). In such patients, the need for dose adjustment of hypoglycemic drugs should be assessed when prescribing somatropin.
Scoliosis
In some children, during the period of excessively rapid growth (especially often in children with PWS), scoliosis may progress. During the entire period of treatment with somatropin, monitoring should be carried out to detect signs of scoliosis. However, available evidence suggests that somatropin therapy does not affect the incidence or severity of scoliosis..
Pancreatitis
Compared with adults, pediatric patients receiving somatropin therapy may have an increased risk of developing pancreatitis. Despite the rarity of this complication, increased attention should be paid to pediatric patients with abdominal pain.
Obesity
Obese patients are more likely to experience adverse events with weight-based doses.
Hyperestrogenism in women
Women with hyperestrogenism or women taking oral estrogens may need higher doses of somatropin than men.
Elderly age
Elderly patients may be more sensitive to the action of somatropin and, therefore, the likelihood of side effects increases. Therefore, it is advisable to use a lower initial dose and a slower increase in the dose of the drug. There is no experience with somatropin treatment in patients over 60 years old.
Urgent states
Safety of continuation of somatropin therapy in patients with severe diseases associated with complications after open heart or abdominal surgery, multiple injuries associated with accidents, as well as patients with acute respiratory failure receiving replacement therapy according to registered indications, in whom during therapy the mentioned diseases appeared, it is not established. Therefore, the ratio of the potential risk and benefit of continuing somatropin therapy in patients in an urgent state should be carefully assessed..
Influence on the ability to drive vehicles, mechanisms
Rastan® does not affect the ability to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.
Release form
Lyophilisate for the preparation of a solution for subcutaneous administration of 4 IU (1.33 mg).
1.33 mg (4 IU) of active substance in vials, sealed with stoppers for freeze drying and rolled in with combined caps.
1 ml of solvent in bottles, sealed with combined caps made of aluminum and plastic with an elastomeric element or sealed with stoppers made of elastomeric material and combined caps made of aluminum and plastic.
1 bottle with the drug, complete with 1 bottle of solvent, together with instructions for use, are placed in a carton box.
Or 1 bottle with the drug, complete with 1 bottle of solvent, is placed in a blister strip along with instructions for use, placed in a cardboard box.
Storage conditions
In the dark place at a temperature of 2 ºFrom to 8 ºC. Do not freeze.
Store the reconstituted form of the drug in a dark place at a temperature of 2 to 8 ºFrom within 2 weeks.
Keep out of the reach of children.
Shelf life
2 years. Do not use after the expiration date printed on the package.
Terms of dispensing from pharmacies
On prescription.
Manufacturer and organization accepting claims:
OJSC “Pharmstandard-UfaVITA”
450077, Russia, Ufa, st. Khudayberdin, 28,
telephone / fax (347) 272 92 85
www.pharmstd.ru
