Infants, children and adolescents: growth disorders due to insufficient secretion of growth hormone (GH); growth disorders associated with Turner syndrome; growth disorders associated with chronic renal failure; growth disorders (standard deviation (SDS)) of current height <-2.5 and SDS corrected for parental height <-1) in children and adolescents with weight and / or birth body length <-2 standard deviations (SD) that do not supplemented the shortage of growth for 4 years or more (growth rate (HV) during the last year of SDS <0); Prader-Willi syndrome (PWS), to improve growth and body composition. Diagnosis of the PWS syndrome should be confirmed by appropriate genetic tests.Adults: replacement therapy in adults with a significant deficiency of growth hormone. Adult patients with severe growth hormone deficiency are patients diagnosed with hypothalamic pituitary pathology and a deficiency of at least one pituitary hormone that is not prolactin. In such patients, a single dynamic test should be performed to confirm or rule out growth hormone deficiency. In case of patients diagnosed with growth hormone deficiency in childhood (for lack of evidence of hypothalamic-pituitary disease or history of cranial irradiation), two dynamic tests should be recommended, except for people with low IGF-I (SDS <-2), which one test can be considered. The cut-off point for the dynamic test should be precisely defined.
Composition:
1 cartridge (1.5 ml) contains 5 mg or 10 mg somatropin (equivalent to 15 IU or 20 IU). The drug at a dose of 5 mg / 1.5 ml contains benzyl alcohol.
Action:
Human growth hormone produced in cellsE. coli, obtained by recombinant DNA technology. Somatropin is a potent hormone that plays an important role in the metabolism of lipids, carbohydrates and proteins. In children with insufficient endogenous growth hormone, somatropin stimulates body growth to length and increases growth rate. In both adults and children, somatropin maintains normal body structure, increasing nitrogen retention and stimulating skeletal muscle growth as well as activating body fat deposits. Visceral fat tissue is particularly sensitive to somatropin. In addition to enhancing lipolysis, somatropin reduces the uptake of triglycerides by the adipose tissue deposits in the body. Somatropin increases the levels of insulin-like growth factor-I (IGF-I) and the insulin-like growth factor-3 binding protein (IGFBP3) in serum. The bioavailability of somatropin administered subcutaneously is about 80% in both healthy people and patients with growth hormone deficiency. T0,5 somatropin after subcutaneous administration in adult patients with growth hormone deficiency is 3 hours.
Contraindications:
Hypersensitivity to somatropin or to any of the excipients. Somatropin must not be used if there is evidence of tumor activity and for growth support in patients with ossified bone metaphyses. Growth of anti-cancer treatment should be stopped before starting growth hormone treatment, intracranial tumors must be inactive. Treatment should be discontinued in case of evidence of tumor growth. Somatropin patients with acute critical conditions who have had complications after open heart surgery, abdominal surgery, multi-organ trauma, acute respiratory failure or similar conditions are not to be treated.
Precautions:
Somatropin may induce insulin resistance, and in some patients hyperglycaemia - patients should be monitored for signs of Glucose intolerance. In rare cases, patients treated with somatropin may meet the diagnostic criteria for type 2 diabetes, however, in most of these cases, there were risk factors such as obesity (including obese patients with Prader-Willi syndrome), family history diabetes, steroid therapy or pre-existing glucose tolerance disorders.In patients with diagnosed diabetes who have had somatropin, it may be necessary to adjust the hypoglycemic therapy. During treatment with somatropin, an increased T4 to T3 conversion was observed, which may result in a decrease in T4 and an increase in serum T3. Peripheral thyroid hormone levels remained essentially within the range of reference values for healthy people. The effect of somatropin on thyroid hormone levels may be of clinical significance in patients with central hypothyroidism who may theoretically develop symptomatic hypothyroidism. Conversely, patients receiving substitution therapy with thyroxine may experience mild hyperthyroidism. Therefore, monitoring thyroid function is particularly recommended after starting treatment with somatropin and after dose modification. It has been reported that somatropin reduces serum cortisol levels, possibly by affecting transport proteins or by increasing hepatic clearance - however, corticosteroid replacement should be optimized before starting treatment. In the case of secondary growth hormone deficiency in the course of treatment of neoplastic diseases, it is recommended to pay attention to the symptoms of tumor recurrence. In patients with endocrine disorders with growth hormone deficiency, epiphyses of the femoral epiphones are more common than in the general population - patients who are limping during treatment with somatropin should be examined clinically. In the case of severe or recurrent headache, visual disturbances, nausea and / or vomiting, it is recommended to perform a fundus examination to detect the swelling of the optic disc. If the edema of the optic disc is confirmed, a diagnosis of benign intracranial hypertension should be considered and, if necessary, discontinuation of growth hormone therapy. There is currently insufficient data to provide specific recommendations regarding the continuation of GH treatment in patients with intracranial hypertension. Clinical experience, however, indicates that it is often possible to restart treatment without recurrent intracranial hypertension. If resumption of GH therapy, patients should be monitored for signs of intracranial hypertension. In patients with Prader-Willi syndrome (PWS), treatment should always be combined with calorie restriction in the diet. There have been reports of deaths associated with the use of growth hormone in children with PWS syndrome, in which there was one or more of the following risk factors: severe obesity, history of respiratory disorders, sleep apnea or respiratory infection with unidentified microbes. Before starting treatment with somatropin, patients with PWS should be screened to detect upper airway obstruction, sleep apnea or respiratory infection (in addition, patients should be monitored during treatment if these conditions are suspected). In the case of upper airway obstruction symptoms, their cause should be removed before starting treatment with somatropin. Sleep apnea should be examined before starting treatment with growth hormone by a recognized method, such as polysomnography or nocturnal oximetry, and monitored if sleep apnea is suspected. If patients exhibit symptoms of airway obstruction during treatment with somatropin (including the onset or worsening of snoring), treatment should be discontinued and a new laryngological examination performed. In all patients with PWS syndrome, body weight should be effectively controlled before and during treatment with somatropin, and monitored for signs of lateral curvature of the spine. However, growth hormone treatment has not been shown to increase the incidence or severity of lateral curvature of the spine. There is limited experience in the long-term treatment of adults and patients with PWS. In the case of young children and adolescents born too small in relation to gestational age, other medical causes or drugs that could cause growth disorders should be ruled out before starting treatment. In children and adolescents with low birth weight, it is recommended that the blood level of fasting insulin and glucose be measured before starting treatment, and then every year. In patients with an increased risk of diabetes (e.g.with family history of diabetes, obesity, increased insulin resistance, dark keratosis) an oral glucose load test should be performed. In the case of symptomatic diabetes, growth hormone should not be administered. In children and adolescents born with low birth weight, it is recommended that IGF-I be measured before starting treatment and then twice a year. If the results of repeated determinations of IGF-I concentration deviate by two standard deviations (+2 SD) from reference values for a given age and maturation phase, the IGF-I / IGFBP-3 ratio may be taken into account to consider dose modification. The experience in starting treatment of patients born with body weight too low in relation to gestational age, immediately before puberty, is limited - it is not recommended to start treatment in the period immediately preceding puberty. There is limited experience with patients with Silver-Russell Syndrome. The increase in growth obtained by treatment with low growth hormone in children and adolescents born with a body weight too low in relation to gestational age may be partially lost if the treatment is stopped before the growing process is completed. The effect of somatropin on the healing process was assessed in two placebo-controlled studies involving 522 adult critically ill patients who had complications after open heart surgery, abdominal surgery, multi-organ trauma or acute respiratory failure. Mortality in patients treated with somatropin 5.3 or 8 mg daily was higher than in patients receiving placebo: 42% and 19%, respectively. Based on the above data, such patients should not be treated with somatropin. Since no information is available on the safety of GH replacement therapy in patients with an acute critical condition, the benefit of continued treatment should be referred to the potential risk associated with it. For all patients experiencing other or similar acute critical conditions, the possible benefits of somatropin treatment should be related to the potential risks associated with such treatment. There is limited experience in the use of the drug in patients over 60 years of age. In the case of chronic renal failure, the growth rate should be monitored for a year to confirm growth disturbances before starting treatment. During this period, conservative treatment of renal failure (including acidosis, hyperparathyroidism and nutrition control) should be implemented and continued during treatment. Treatment should not be continued if the kidneys are transplanted. Currently, no data are available on the final increase in patients with chronic renal failure treated with the product. The drug at a dose of 5 mg / 1.5 ml contains benzyl alcohol - the drug must not be given to premature babies or newborns due to the risk of toxic and anaphylactoid reactions in infants and children up to 3 years of age.
Pregnancy and lactation:
Treatment should be discontinued in the event of pregnancy. During normal pregnancy levels of the pituitary growth hormone decreases significantly after the 20th week of pregnancy and is replaced almost completely by the placental growth hormone up to the 30th week. Therefore, it may turn out that further substitution treatment with somatropin in women with growth hormone deficiency will not be necessary in the third trimester of pregnancy. There are no clinical data available on the effect of the drug on pregnancy. There is no experimental animal data on reproductive toxicity. It is not known whether somatropin is excreted in human milk, but it is unlikely that the baby's intestinal tract will be absorbed intact. Caution should be exercised when using the drug in breast-feeding women. Fertility effects have not been studied.
Side effects:
Common: antibody production; in adults: paresthesia, stiffness of limbs, pain in the joints and muscles, peripheral edema; in children: transient local skin reactions. Uncommon: in adults: carpal tunnel syndrome; in children: paresthesia, stiffness of limbs, pain in the joints and muscles, peripheral edema. Rare: type 2 diabetes; benign intracranial hypertension.Very rare cases of leukemia have been reported in growth hormone deficient children treated with the preparation, but the incidence seems to be similar to that found in children without growth hormone deficiency.
Dosage:
Subcutaneously.Children and youth. Growth disorders due to insufficient secretion of growth hormone in children and adolescents: a dose of 0.025-0.035 mg / kg / day or 0.7-1.0 mg / m is usually recommended2 pc./dobę. Even higher doses were used.Prader-Willi syndrome (PWS), to improve the growth and body structure in children and adolescentsA dose of 0.035 mg / kg / day or 1.0 mg / m is usually recommended2 pc./dobę. Do not exceed the daily dose of 2.7 mg. The treatment should not be carried out in children and adolescents, whose growth rate is less than 1 cm per year and in which soon the bone metaphysises should become ossified.Growth disorders due to Turner syndromeA dose of 0.045-0.050 mg / kg / day or 1.4 mg / m is recommended2 pc./dobę.Growth disorders associated with chronic renal failure: a dose of 1.4 mg / m is recommended2 pc. daily (0.045-0.050 mg / kg / day). It may be necessary to use higher doses if the growth rate is too slow. After 6 months of treatment, a dose adjustment may be necessary.Growth disorders in low children and adolescents who were born too small in relation to gestational ageA dose of 0.035 mg / kg / day (1 mg / m) is usually recommended2 pc / day) to achieve the final height. Treatment should be discontinued after one year if SDS has a growth rate below +1. Treatment should be discontinued if the growth rate is <2 cm / year and if required by confirmation, bone age is> 14 years (girls) or> 16 years (boys), which corresponds to ossification of the bone metaphyses. Adults. Growth hormone deficiency in adult patients. Treatment should be started at a low dose of 0.15-0.3 mg per day, then the dose should be gradually increased depending on the individual needs of the patient, which is determined by the IGF-I concentration. The goal of treatment is to achieve an IGF-I concentration in the range of 2 SDS from an age-corrected mean for healthy adults. Patients with normal IGF-I concentrations at the beginning of treatment should be given Growth Hormone to achieve IGF-I levels in the upper range of normal values, not exceeding 2 SDS. Clinical response and side effects may also be a guide for setting the dose. The daily maintenance dose rarely exceeds 1.0 mg daily. Women may require higher doses than men because men show increased sensitivity to IGF-I over time. This means that women, especially those who receive oral estrogen hormone replacement therapy, run the risk of not achieving the required dose, while men are at risk of exceeding the required dose. Therefore, every 6 months should be checked if the dose of growth hormone is adequate. As the normal physiological production of growth hormone diminishes with age, a dose reduction may be necessary. The minimum effective dose should be used. In the case of chronic renal failure, treatment should be started with worsening of renal function by more than 50% in relation to the norm. The sites of injection should be changed to avoid fat loss (lipoatrophy).
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