Genotropin lyophilized powder for solution for injection 16 IU (5.3 mg) pre-filled pen No. 1

Instructions Genotropin lyophilized powder for solution for injection 16 IU (5.3 mg) pre-filled pen No. 1

Composition

active ingredient: somatropin;

anterior chamber: somatropin 6.1 mg or 13.8 mg;

1 ml of reconstituted solution contains 16 IU (5.3 mg) or 36 IU (12 mg) of somatropin;

excipients: glycine, mannitol (E 421), sodium dihydrogen phosphate anhydrous, sodium hydrogen phosphate (dodecahydrate);

Rear chamber (solvent): m-cresol, mannitol (E 421), water for injections.

Dosage form

Lyophilized powder and solvent for solution for injection.

Main physicochemical properties: lyophilized homogeneous substance of white color. The solvent should be practically free from mechanical inclusions.

Pharmacotherapeutic group

Anterior pituitary hormones and their analogues. Somatropin and somatropin agonists. Somatropin. ATC code H01A C01.

Pharmacological properties

Pharmacodynamics

Somatropin is a potent metabolic hormone that plays an important role in the metabolism of lipids, carbohydrates and proteins. Somatropin is produced in Escherichia coli cells by recombinant DNA technology. In children with endogenous growth hormone deficiency, somatropin accelerates linear skeletal growth and growth velocity. In both adults and children, somatropin maintains normal body composition by increasing nitrogen uptake, accelerating skeletal muscle growth and mobilizing body fat. Visceral adipose tissue is particularly sensitive to somatropin. In addition to stimulating lipolysis, somatropin reduces the entry of triglycerides into fat depots. Serum concentrations of IGF-1 (insulin-like growth factor, type 1) and IGF-3 (insulin-like growth factor binding protein, type 3) are increased by somatropin. In addition, the following actions have been demonstrated.

- Lipid metabolism. Somatropin stimulates low-density lipoprotein (LDL) cholesterol receptors in the liver and affects the lipid and lipoprotein profile in serum. In general, the use of somatropin in patients with growth hormone deficiency leads to a decrease in LDL and apolipoprotein B concentrations. A decrease in total cholesterol levels is also possible.

- Carbohydrate metabolism. Somatropin increases insulin levels, but fasting glucose levels are usually unchanged. Fasting hypoglycemia may occur in children with hypopituitarism. Somatropin reverses this condition.

- Water-salt metabolism. Growth hormone deficiency is associated with a decrease in blood plasma and tissue fluid volumes. Both of these indicators increase rapidly after treatment with somatropin. Somatropin promotes the retention of sodium, potassium, and phosphorus in the body.

- Bone metabolism. Somatropin stimulates skeletal bone turnover. In patients with growth hormone deficiency and osteoporosis, long-term treatment with somatropin leads to an increase in bone mineral content and density in the supporting areas.

- Physical performance. Long-term treatment with somatropin increases muscle strength and physical endurance. Somatropin also increases cardiac output, but the mechanism of this effect is not yet clear. A decrease in peripheral vascular resistance may play a role in this.

In clinical trials in short-for-gestational-age infants, doses ranging from 0.033 to 0.067 mg/kg body weight per day were used until final height was reached. In 56 patients who were continuously treated and reached (almost) final height, the standard deviation (SD) of the mean change in height from baseline was +1.90 SD for the 0.033 mg/kg/day dose and +2.19 SD for the 0.067 mg/kg/day dose. Published data in untreated SGA infants who failed to spontaneously achieve normal height suggest a delayed growth of 0.5 SD.

Pharmacokinetics

Absorption: The bioavailability of somatropin administered subcutaneously is approximately 80% in both healthy volunteers and growth hormone deficient patients. A dose of 0.035 mg/kg of somatropin administered subcutaneously results in plasma Cmax and tmax ranges of 13–35 ng/ml and 3–6 hours, respectively.

Elimination: The mean terminal elimination half-life after intravenous administration of somatropin to growth hormone deficient adults is approximately 0.4 hours. However, after subcutaneous administration, the half-life may be as long as 2-3 hours. The observed difference may be due to slower absorption from the injection site after subcutaneous administration.

Subpopulations: The absolute bioavailability of somatropin following subcutaneous administration is similar in males and females.

Information on the pharmacokinetics of somatropin in elderly and pediatric patients, in patients of different races, and in patients with impaired renal and hepatic function or heart failure is missing or incomplete.

Preclinical safety data.

No clinically relevant effects were observed in general toxicity, local tolerability and reproductive toxicity studies.

In one in vitro study, lymphocytes from patients treated with long-term somatropin followed by the additional radiomimetic bleomycin were found to have increased chromosome fragility. The clinical significance of this finding is unclear.

In another study, no chromosomal abnormalities were found in lymphocytes taken from patients after long-term treatment with somatropin.

Indication

Children.

Growth failure due to insufficient secretion of growth hormone (growth hormone deficiency).

Growth failure associated with Turner syndrome or chronic renal failure.

Growth failure (standard deviation of current height less than –2.5 and standard deviation of genetically determined height less than –1) in short children who were born smaller than normal for their gestational age, with a standard deviation of weight and/or length less than –2, and failed to achieve age-appropriate height (standard deviation of growth velocity less than 0 during the last year) by the time they were 4 years old or older.

Prader-Willi syndrome, to improve growth and body structure. The diagnosis of Prader-Willi syndrome should be confirmed by appropriate genetic testing.

Adults.

Replacement therapy for adults with severe growth hormone deficiency.

Adult onset growth hormone deficiency. Patients with severe growth hormone deficiency associated with multiple hormone deficiencies due to known hypothalamic or pituitary pathology, as well as patients who have a deficiency of at least one pituitary hormone, with the exception of prolactin. These patients should undergo an appropriate dynamic test to determine whether or not growth hormone deficiency is present.

Onset of growth hormone deficiency in childhood. Patients who developed growth hormone deficiency in childhood due to hereditary, genetic, acquired, or unknown causes. For patients with growth hormone deficiency that developed in childhood, a repeat test of hormone secretory capacity should be performed after the end of longitudinal growth. For patients with a high probability of permanent growth hormone deficiency (e.g., due to hereditary causes or secondary growth hormone deficiency due to hypothalamic-pituitary disease or stroke), a mean deviation of insulin-like growth factor type 1 (IGF-1) less than -2 without growth hormone treatment for at least 4 weeks should be considered sufficient grounds for the diagnosis of growth hormone deficiency.

For all other patients, an IGF-1 assay and one growth hormone stimulation test should be performed.

Contraindication

Hypersensitivity to the active substance or any excipient included in the medicinal product.

Somatropin should not be administered if there is any evidence of tumor activity. Intracranial tumors must be inactive, and antitumor therapy must be completed before initiating growth hormone therapy. Treatment should be discontinued if there is any evidence of tumor growth.

Genotropin® should not be used to stimulate growth in children with closed epiphyseal growth plates.

Treatment with Genotropin® is contraindicated in patients who are in acute critical condition due to complications of open heart surgery, abdominal surgery, multiple trauma, acute respiratory failure or other similar conditions (for information on patients receiving replacement therapy, see the section "Special instructions for use").

Interaction with other medicinal products and other types of interactions

Concomitant use with glucocorticoids inhibits the stimulatory effect of somatropin preparations on growth rate. Glucocorticoid replacement therapy should be carefully selected in patients with adrenocorticotropic hormone deficiency to avoid any growth-suppressive effect.

Therefore, it is necessary to carefully monitor the growth of patients receiving glucocorticoid treatment to be able to assess the potential impact of glucocorticoid use on growth.

Growth hormone reduces the conversion of cortisone to cortisol and may lead to the manifestation of previously undiagnosed central adrenal hypofunction or render the use of low doses of glucocorticoids for replacement therapy ineffective (see section "Special instructions").

Data from a drug interaction study in adult patients with growth hormone deficiency suggest that somatropin may increase the clearance of compounds metabolized by cytochrome P450 isoenzymes. The clearance of compounds metabolized by cytochrome P450 3A4 (such as sex steroid hormones, corticosteroids, anticonvulsants, and cyclosporine) may be increased, leading to decreased plasma concentrations of these substances. The clinical significance of this finding is unknown.

For additional information regarding diabetes mellitus and thyroid dysfunction, see the Precautions section.

Women receiving oral estrogen replacement therapy may require a higher dose of growth hormone to achieve the treatment goal (see section "Special warnings and precautions for use").

Diagnosis, initiation of therapy with Genotropin® and subsequent monitoring should be performed by qualified physicians who have experience in diagnosing and treating patients according to the indications for use.

Myositis is a very rare side effect that may be caused by the preservative m-cresol in the preparation. In case of myalgia or increased pain at the injection site, myositis should be suspected. If confirmed, a form of Genotropin® that does not contain m-cresol should be used.

The maximum recommended daily dose should not be exceeded (see section “Method of administration and dosage”).

Insulin sensitivity.

Somatropin may reduce insulin sensitivity. Patients with diabetes mellitus may require adjustment of insulin dosage after initiation of somatropin therapy. Patients with diabetes mellitus, glucose intolerance, or additional risk factors for diabetes mellitus should be monitored during somatropin therapy.

Thyroid function.

Growth hormone accelerates the peripheral conversion of T4 to T3, which can lead to a decrease in serum T4 concentrations and an increase in serum T3 concentrations. While peripheral thyroid hormone concentrations remain normal in most healthy volunteers, hypothyroidism is theoretically possible in patients with subclinical hypothyroidism. Therefore, thyroid function should be monitored in all patients. In patients with hypopituitarism receiving standard replacement therapy, the possible effect of growth hormone therapy on thyroid function should be carefully monitored.

Adrenal hypofunction.

Initiation of somatropin treatment may result in inhibition of 11βHSD-1 and a decrease in serum cortisol concentrations. Patients treated with somatropin may develop previously undiagnosed central (secondary) adrenal insufficiency and may require glucocorticoid replacement therapy. In addition, patients receiving glucocorticoid replacement therapy for previously diagnosed adrenal insufficiency may require increased maintenance or titration doses after initiation of somatropin treatment (see section 4.5).

Concomitant use with oral estrogen therapy.

If a woman using somatropin starts oral estrogen therapy, her somatropin dose may need to be increased to maintain serum IGF-1 levels within the age-appropriate range. Conversely, if a woman using somatropin stops oral estrogen therapy, her somatropin dose may need to be reduced to avoid growth hormone excess and/or side effects (see section 4.5).

In cases of secondary growth hormone deficiency following treatment for malignancy, it is recommended to be alert for signs of recurrence of the malignancy. In patients with a history of childhood malignancy, an increased risk of developing a secondary malignancy has been reported in patients treated with somatropin after the primary malignancy.

The most common such secondary neoplasms in patients who received radiation treatment to the head for a primary neoplasm were intracranial tumors, particularly meningiomas.

Patients with endocrine disorders, particularly growth hormone deficiency, may experience dislocations of the femoral head more frequently than in the general population. Children who develop a limp during somatropin therapy should undergo clinical evaluation.

Benign intracranial hypertension.

In case of severe or frequent headache, visual disturbances, nausea and/or vomiting, ophthalmoscopy is recommended to detect optic disc edema. If optic disc edema is confirmed, a diagnosis of benign intracranial hypertension should be considered and, if necessary, growth hormone treatment should be discontinued. There is currently insufficient information to make recommendations on the continuation of growth hormone therapy in patients after resolution of intracranial hypertension. After resumption of growth hormone therapy, careful monitoring for symptoms of intracranial hypertension is required.

Leukemia.

Cases of leukemia have been reported in a small number of patients with growth hormone deficiency, some of whom received somatropin therapy. However, there is no evidence of an increased incidence of leukemia in patients receiving growth hormone who are not predisposed to the disease.

Antibodies.

As with all somatropin preparations, a small proportion of patients may develop antibodies to Genotropin®. Approximately 1% of patients develop antibodies after taking Genotropin®. These antibodies are characterized by weak binding capacity and do not affect growth rate. In case of insufficient response to treatment (which cannot be explained by other reasons), the patient should be tested for the presence of antibodies to somatropin.

Experience in patients over 80 years of age is limited. Elderly patients may be more sensitive to the effects of Genotropin® and therefore more likely to develop adverse reactions.

Acute critical conditions.

The efficacy of Genotropin® during recovery was studied in two placebo-controlled studies in 522 critically ill patients following complications of open heart surgery, abdominal surgery, multiple trauma or acute respiratory failure. Mortality was higher in patients receiving 5.3 or 8 mg of Genotropin® per day than in the placebo group: 42% versus 19%. Based on this information, such patients should not be treated with Genotropin®. Since there is no information on the safety of growth hormone replacement therapy in patients with acute critical conditions, the benefits of continued treatment should be weighed against the potential risks in this situation.

For all patients who have another or similar acute critical condition, the potential benefit of treatment with Genotropin® should be weighed against the associated potential risk.

Pancreatitis.

Although pancreatitis may occur rarely, the possibility of its development should be considered in any patient treated with somatropin, especially in children who develop abdominal pain.

Prader-Willi syndrome.

Treatment of patients with Prader-Willi syndrome should always be combined with a low-calorie diet.

Fatalities have been reported in association with the use of growth hormone in children with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity (patients with a weight-for-height ratio greater than 200%), a history of respiratory failure or sleep apnea, or an unidentified respiratory infection. Patients with one or more of the following factors may be at increased risk.

Before initiating treatment with somatropin, patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction, sleep apnea, or respiratory infections.

If the assessment of upper airway patency reveals pathology, the child should be referred to an otolaryngologist for treatment and resolution of the respiratory disorder before initiating growth hormone treatment.

Before initiating growth hormone therapy, sleep apnea should be assessed using standard polysomnography or nocturnal oximetry and monitored for possible development.

If patients develop symptoms of upper airway obstruction (including new or worsening snoring) during treatment with somatropin, treatment should be discontinued and a new ENT examination should be performed.

All patients with Prader–Willi syndrome should be monitored for sleep apnea if it is suspected.

Patients should be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively.

In all patients with Prader-Willi syndrome, body weight should also be carefully monitored before and during growth hormone treatment.

Scoliosis is common in patients with Prader-Willi syndrome. In some children, scoliosis may progress due to rapid growth. During treatment, signs of scoliosis should be monitored.

Experience with long-term use of growth hormone for the treatment of adults and patients with Prader-Willi syndrome is limited.

Children who were born small for their gestational age.

Before starting treatment for children born small for gestational age, the possibility of other medical causes or treatments causing growth failure should be ruled out.

It is recommended that fasting blood glucose and insulin levels be measured before treatment is initiated in children born small for gestational age and that these levels be repeated annually. Patients at high risk of developing diabetes mellitus (e.g., family history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) should have an oral glucose tolerance test. If diabetes mellitus is diagnosed, growth hormone should not be used.

It is recommended that IGF-1 levels be measured before treatment is initiated in children born small for gestational age and that this test be repeated twice a year. If, after re-measurement, the standard deviation of IGF-1 levels exceeds +2 SD compared to the age norm and puberty, the IGF-1/IFN-3 ratio should be considered to determine the need for dose adjustment.

Experience with treatment just before the onset of puberty in children born small for gestational age is limited. Therefore, treatment should not be initiated just before the onset of puberty. Experience with treatment in patients with Silver-Russell syndrome is limited.

Some of the height gain achieved with growth hormone treatment in children born small for gestational age may be lost if treatment is stopped before they reach their final height.

In chronic renal failure, renal function should be less than 50% of normal before treatment. Growth should be monitored for one year before treatment to confirm signs of growth failure. Conservative treatment of renal function (including control of acidosis, hyperparathyroidism and nutrition) should be initiated during this period and continued during growth hormone therapy. Treatment should be discontinued in the event of kidney transplantation.

There are currently no data on the achievement of final height in patients with chronic renal impairment treated with Genotropin®.

Special precautions for handling the drug and disposal of residues.

The solution is prepared by twisting the sections of the pre-filled pen to mix the solvent with the powder in the dual-chamber cartridge. Gently dissolve the powder by slow, twisting movements. Do not shake vigorously. This may cause denaturation of the active substance. The reconstituted solution for injection should be colourless or slightly opalescent. The reconstituted solution for injection should be inspected visually prior to use and only clear, particle-free solutions should be used.

Any unused medicinal product or waste material should be disposed of properly. Empty pre-filled pens should never be refilled and should be disposed of.

Ability to influence reaction speed when driving vehicles or other mechanisms

Genotropin® does not affect the reaction rate when driving or operating other mechanisms.

Use during pregnancy or breastfeeding

Pregnancy.

There are insufficient data from animal studies on the effects of Genotropin® on pregnancy, embryonic development, parturition or postnatal development (see Pharmacokinetics). There are no clinical studies on the use of the drug during pregnancy. Therefore, drugs containing somatropin are not recommended for use in pregnant women and women of childbearing potential not using contraception.

Breast-feeding.

Clinical studies of somatropin preparations in nursing women have not been conducted. It is not known whether somatropin is excreted in human milk, but absorption of intact protein from the infant's gastrointestinal tract is extremely unlikely. Therefore, somatropin preparations should be used with caution in nursing women.

Method of administration and doses

Dosage and regimen should be selected individually.

The injection should be administered subcutaneously and the injection site should be rotated to prevent lipoatrophy.

Growth retardation due to insufficient secretion of growth hormone in children. The usual recommended dose is 0.025–0.035 mg/kg body weight per day or 0.7–1.0 mg/m² body surface area per day. There is experience with even higher doses.

If growth hormone deficiency begins in childhood and persists into adolescence, treatment should be continued until full somatic development (i.e., body composition, bone mass) is achieved. One of the therapeutic goals during the transition period was used as a control: achievement of normal peak bone mass, defined as a T score >–1 (i.e., standardized to the mean peak adult bone mass measured by dual-energy X-ray absorptiometry, taking into account the patient's gender and ethnicity). Dosage instructions for adults are described below.

Prader-Willi syndrome, to improve growth and body composition in children. Usually 0.035 mg/kg body weight per day (1.0 mg/m2 body surface area per day) should be prescribed. The daily dose should not exceed 2.7 mg. Treatment should not be used in children with a growth rate of less than 1 cm per year and at the age when the epiphyseal growth plates begin to close.

Growth retardation due to Turner syndrome: The recommended dose is 0.045–0.050 mg/kg body weight per day or 1.4 mg/m² body surface area per day.

Growth retardation in patients with chronic renal failure. The recommended dose is 0.045–0.050 mg/kg body weight per day (1.4 mg/m² body surface area per day). Insufficient growth rate may require a higher dose. Dose adjustment may be necessary after 6 months of treatment.

Growth retardation in short children born small for gestational age. The usual recommended dose is 0.035 mg/kg body weight per day (1 mg/m² body surface area per day) until final height is reached (see section 5.1).

Treatment should be discontinued after the first year if the standard deviation for growth velocity is less than +1. Treatment should be discontinued if growth velocity is less than 2 cm per year and (if necessary, confirmation) bone age is greater than 14 years for girls or greater than 16 years for boys, which corresponds to the age of closure of the epiphyses of the bones.

Table 1

Dosage recommendations for children

Adult patients with growth hormone deficiency. For patients continuing growth hormone therapy after childhood onset of growth hormone deficiency, the recommended dose is 0.2–0.5 mg daily. The dose should be gradually increased or decreased according to the individual patient's needs, as determined by IGF-1 levels.

For patients with adult-onset growth hormone deficiency, therapy should be initiated at a low dose of 0.15–0.3 mg/day. The dose should be gradually increased according to the patient's individual needs, as determined by IGF-1 levels.

In both cases, the goal of treatment is to achieve an IGF-1 concentration within 2 standard deviations of the age-related mean. Patients with IGF-1 concentrations within the normal range at the start of treatment should receive growth hormone at a dose sufficient to raise IGF-1 concentrations to the upper limit of normal, but not more than 2 standard deviations. Clinical effect and adverse reactions may also be considered when selecting the dose. It is known that some patients with growth hormone deficiency do not normalize IGF-1 levels despite adequate clinical response; such patients do not require an increase in dose. The daily maintenance dose rarely exceeds 1.0 mg per day. Higher doses may be required for women than for men, since men are more sensitive to IGF-1 over time. This means that women, especially those receiving oral estrogen replacement therapy, are at risk of developing insufficient clinical effect, and men - excessive. Therefore, the accuracy of the dose of growth hormone should be monitored every 6 months. Since there is a physiological decrease in growth hormone production with age, the dose of the drug can be reduced. In patients over 60 years of age, therapy should be started with a dose of 0.1-0.2 mg per day; the dose should be increased slowly depending on the individual needs of the patient. The minimum effective dose should be used. The daily maintenance dose for these patients rarely exceeds 0.5 mg per day.

Patient information

Instructions for use of the pre-filled injection pen for 5.3 mg or 12 mg doses

Genotropin® is administered using a disposable (no cartridge change allowed in the pen) multi-dose pre-filled pen (syringe pen) for injection containing 5.3 mg or 12 mg of somatropin. The drug in the pen is mixed only once before starting to use a new pen. After mixing, one pen can be used for up to 28 days. There is no need to change cartridges. After the drug in the pen has been used, the drug is started from a new pen.

The pen has the ability to remember the dose. The dose is set once at the beginning of use. After that, the pen injects the same dose with each injection. The pen can be used with or without an additional needle guard (not included in the pen kit).

Before using the pen, patients should:

- gain practical skills under the guidance of medical staff;

- get information about the prescribed dose; study the components of the pen;

- make sure that the correct dosage pen is used: with a blue injection button (5.3 mg).

Genotropin® in a dosage of 5.3 mg is available in a pre-filled pen with an injection button, logo and inscriptions in blue, and in a dosage of 12 mg - in purple.

Step 9. Finish using the pen: remove the needle; close the pen with the cap and put it in storage. Step 9a. With needle safety device a. Place the outer needle case into the tip of the needle shield. b. Using the needle case, push the needle shield inward until it locks into place. c. Using the needle case, unscrew the needle and place it in the appropriate container for used needles. d. Leave the needle guard on the handle. e. Put the black cap on the needle guard. Store the pen in the refrigerator. Step 9b. Without needle guard a. Do not touch the needle. b. About Specifications Characteristics Active ingredient Somatropin ATC code H HORMONAL PREPARATIONS FOR SYSTEMIC USE (EXCEPT SEX HORMONES AND INSULIN); H01 PITUITARY, HYPOTHALAMIC HORMONES AND THEIR ANALOGUES; H01A ANTERIOR PITUITARY HORMONES AND THEIR ANALOGUES; H01A C Somatropin and its agonists; H01A C01 Somatropin Country of manufacture Germany Dosage 5,3 мг Form Cartridges and syringe pens Method of application Injections Producer Pfizer Pharmaceuticals Quantity per package 1 filled pen Trade name Genotropin Vacation conditions By prescription Reviews There are no reviews for this product. + Add review Write a review Genotropin lyophilized powder for solution for injection 16 IU (5.3 mg) pre-filled pen No. 1 My mark: Continue There are no reviews for this product, be the first to leave your review. Answers & questions Add your question and we will answer as soon as possible. + Ask a question Ask a question Add your question and we will answer as soon as possible. * Your question Continue No questions about this product, be the first and ask your question. You are watched new Hit Neomycin plus ointment 20 g In stock 0 288.62 грн. Add to Cart new Hit Sikaprotect eye drops dropper bottle 10 ml In stock 0 427.43 грн. Add to Cart new Hit Sold out Neemplast bactericidal plaster 19 mm x 72 mm No. 10 Распродано 0 43.00 грн. new Hit Boostrix suspension for injection 1 dose syringe 0.5 ml with 2 needles No. 1 In stock 0 1 052.47 грн. Add to Cart new Hit Xanthase capsules No. 30 In stock 0 680.52 грн. Add to Cart new Hit Fari Verde oral spray 1.5 mg/ml 30 ml In stock 0 411.90 грн. Add to Cart new Hit Spazmolix tablets No. 20 In stock 0 241.00 грн. Add to Cart new Hit Farmazolin with mint and eucalyptus spray nasal solution 1 mg/ml bottle 10 ml In stock 0 275.96 грн. Add to Cart new Hit Methotrexate Rompharm solution for injection 10mg/ml syringe 1 ml No. 1 In stock 0 482.20 грн. Add to Cart new Hit Beloderm ointment for external use 0.05% tube 15 g In stock 0 318.06 грн. Add to Cart