Genotropin

Active material: Somatropin
When ATH: H01AC01
CCF: Recombinant growth hormone
ICD-10 codes (testimony): E23.0, N25.0, P05, Q87.1, Q96, R62
When CSF: 15.06.01
Manufacturer: PFIZER MFG. BELGIUM N.V. (Belgium)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for s / c administration white; solvent – transparent colorless liquid.

Excipients: glycine, mannitol, sodium dihydrogen phosphate anhydrous, sodium hydrogen phosphate, anhydrous.

The composition of the solvent: m-cresol, mannitol, water d / and.

Cartridges for two sections injectors Genotropin^® And 5.3 Solvent (1) – packs cardboard.
Cartridges for two sections injectors Genotropin^® And 5.3 Solvent (5) – packs cardboard.

Valium for drug of a solution for s / c administration white; solvent – transparent colorless liquid.

Excipients: glycine, mannitol, sodium dihydrogen phosphate anhydrous, sodium hydrogen phosphate, anhydrous.

The composition of the solvent: m-cresol, mannitol, water d / and.

Cartridges for two sections injectors Genotropin^® And 12 Solvent (1) – packs cardboard.
Cartridges for two sections injectors Genotropin^® And 12 Solvent (5) – packs cardboard.

Pharmacological action

The drug growth hormone. It represents synthesized by recombinant techniques somatropin, identical to human growth hormone.

Children with lack of endogenous growth hormone, and Prader-Willi syndrome somatropin increases and accelerates the linear growth of the skeleton.

As in adults, and children somatropin maintains a normal body structure, stimulating muscle growth and promoting the mobilization of fat. Especially sensitive to somatropin visceral adipose tissue. In addition to stimulation of lipolysis, somatropin decreases the entry of triglycerides in fat depots. Somatropin increases the concentration of insulin-like growth factor (IRF-1) and IGF-binding protein (IRFSB-3) serum.

Besides, drug affects fat, carbohydrate and water-salt metabolism.

Somatropin stimulates LDL receptors in the liver, and acts on lipid and lipoprotein profile in serum. Generally, assignment somatropin patients with growth hormone deficiency reduces the concentration of LDL cholesterol and apolipoprotein B in serum. Also, there may be a reduction in total cholesterol.

Somatropin increases insulin levels, However, fasting glucose levels normally not changed. Children with hypopituitarism may experience fasting hypoglycemia, docked in patients receiving the drug.

Somatropin restores plasma volume and tissue fluid, reduced with a lack of growth hormone; promotes sodium retention, potassium and phosphorus.

Somatropin stimulates the bone metabolism. In patients with growth hormone deficiency and osteoporosis somatropin prolonged treatment leads to a recovery of the mineral composition and bone density.

Somatropin treatment increases muscle strength and physical endurance.

Somatropin also increases cardiac output, but the mechanism of this effect is not yet known. A role it may play in a decrease in peripheral vascular resistance.

In patients with growth hormone deficiency may be a decrease in mental abilities and changes in mental status. Somatropin increases vitality, It improves memory and affects the balance of neurotransmitters in the brain.

Pharmacokinetics

Absorption and distribution

As in healthy persons, and in patients with growth hormone deficiency absorbed approximately 80% n / a entered Genotropin^®. When p / injection dose 0.1 IU / kg body weight C_max is 13-35 ng / ml achieved after 3-6 no.

V_d is 0.5-2.1 l / kg.

Metabolism and excretion

Biotransformiroetsa kidney and liver. Average T_1/2 after the on / in the Genotropin^® in patients with growth hormone deficiency is about 0.4 no. When s / to the introduction of the drug T_1/2 reaches 2-3 no. The observed difference, probably, associated with a slower absorption of the drug in n / a injection. About 0.1% administered drug in unchanged form excreted in the bile.

Pharmacokinetics in special clinical situations

The absolute bioavailability of Genotropin^® when s / to the same in males and females.

Testimony

For children

- Dysplasia with insufficient secretion of growth hormone;

- Dysplasia at Turner's syndrome;

- Dysplasia in chronic renal failure;

- Intrauterine growth;

- Prader-Willi syndrome.

For adults

- Confirmation of growth hormone deficiency.

Dosage regimen

The dose should be selected individually. The drug is administered s / c, to prevent lipoatrophy should change the injection site.

The recommended dose for children are presented in Table

The initial dose for Adult from growth hormone deficiency is 0.15-0.3 mg (0.45-0.9 ME)/d. The maintenance dose is selected individually according to age and sex. It rarely exceeds 1.3 mg (4 ME)/d. Women may need a higher dose, than men. Since the age normal physiological growth hormone production decreases, age-appropriate dose can be reduced.

Clinical and side effects, as well as determining the level of IGF-1 in the blood serum can be used as guidance for dose selection.

Genotropin^® 5.3 mg (16 ME) and 12 mg (36 ME) administered s / c via injectors Genotropin^® And 5.3 and Genotropin^® And 12 respectively. Once the cartridge is inserted into the injector drug dilution occurs automatically. Dilution of the drug solution can not be shaken.

Side effect

Side effects, caused by fluid retention: adult (>1% and <10%) – peripheral edema, pastoznost lower extremities, artralgii, myalgia and paraesthesia. These effects usually are mild or moderate, It occurs during the first months of treatment and decrease spontaneously or after dose reduction. The frequency of these side effects was dose-dependent Genotropin^®, the age of patients and, perhaps, inversely proportional to the age, in which an insufficiency of growth hormone. In children, these side effects are rare (>0.1% and <1%).

CNS: rarely (>0.01% and <0.1%) – benign intracranial hypertension, may develop swelling of the optic nerve.

On the part of the endocrine system: rarely (>0.01% and <0.1%) – development of diabetes mellitus type 2. Also revealed a decrease in serum cortisol. The clinical significance of this phenomenon appears to be limited.

On the part of the musculoskeletal system: dislocation and subluxation of the femoral head, soprovozhdaющiesя prihramыvaniem, pain in the hip and knee; in patients with Prader-Willi syndrome may develop scoliosis (tk. Genotropin^® It enhances the growth rate); rarely – myositis, which may be caused by the action of m-cresol preservative, which is part of Genotropin^®.

Allergic reactions: skin rash and itching.

Local reactions: at the injection site (>1% and <10%) – rash, itch, soreness, numbness, hyperemia, swelling, lipoatrophy.

Other: in a few cases (<0.01%) – The development of leukemia in children, however, the incidence of leukemia is not different from that in children without growth hormone deficiency.

Contraindications

- Symptoms of tumor growth, including the uncontrolled growth of benign intracranial tumor (antitumor therapy should be completed prior to initiation of treatment Genotropin^®);

- Critical condition, urgently develop in patients as a result of open-heart surgery or abdominal, multiple trauma and acute respiratory distress;

- Severe obesity (the ratio of body weight / height exceeds 200%) or severe respiratory disorders in patients with Prader-Willi syndrome;

- The closure of epiphyseal growth zones of long bones;

- Hypersensitivity to any component of the drug.

FROM caution should be prescribed for patients with diabetes, intracranial hypertension, gipotireoze.

Pregnancy and lactation

Clinical experience with Genotropin^® during pregnancy is limited. Therefore, during pregnancy should clearly assess the need for the appointment of the drug and the potential risk, associated with this. During normal pregnancy levels of pituitary growth hormone significantly reduced after 20 of the week, being replaced almost entirely by placental 30 week, and therefore the need for continued replacement therapy Genotropin^® in the III trimester of pregnancy is unlikely.

Experimental studies animals did not reveal any adverse effects on the fetus, from which however should not be, that similar results will be obtained when applying Genotropin^® human.

Reliable information about the excretion of growth hormone in breast milk are absent, but in any case, absorption of intact protein from the gastrointestinal tract of the child is extremely unlikely.

Cautions

If during substitution therapy Genotropin^® for some reason, there is a critical state, to continue treatment should assess the risk / benefit ratio for a particular patient.

Cases of fatalities on the background use of growth hormone in children with Prader-Willi syndrome with one or more of the following risk factors: severe form of obesity, respiratory disorders, sleep apnea, or unidentified respiratory infection. Another possible risk factor could be male patient. Patients with Prader-Willi syndrome should be evaluated for upper airway obstruction. If symptoms occur during the treatment of upper airway obstruction (including the emergence and / or worsening of snoring, apnea or similar clinical symptoms), treatment should be discontinued. All patients with Prader-Willi syndrome should be evaluated for sleep apnea and be monitored carefully in case of suspicion. These patients also need to control body weight and symptoms of respiratory infections, the development of which should be as soon as possible to begin the most active treatment.

As a result, the treatment of Genotropin^® activated T transition hormone₄ in T₃, that reduces the concentration of T₄ and an increase in the concentration of T₃ serum. Typically, levels of these hormones in the peripheral blood remained within the normal range. However, the effect of Genotropin^® It can cause hypothyroidism in patients with latent subclinical hypothyroidism Central. It is recommended to investigate the thyroid function after starting treatment with Genotropin^® and after changing its dose.

In secondary growth hormone deficiency, due to the treatment of cancer, recommended closer monitoring for symptoms of tumor recurrence.

Genotropin Treatment^® appoint only those patients with chronic renal failure, whose renal function is reduced by more than 50%. To confirm this figure growth disorders should be monitored throughout the year. During treatment with Genotropin^® should continue to pursue conservative treatment of kidney failure. Treatment should be discontinued at renal transplantation.

Genotropin^® may reduce the sensitivity of peripheral receptors and insulin, Consequently, Patients, before use Genotropin^® You should be evaluated for impairment of glucose tolerance. The risk of developing diabetes mellitus type 2 during treatment with Genotropin^® It is greatest in patients with other risk factors, such as overweight, cases of diabetes among relatives, SCS therapy or formerly known impaired glucose tolerance. In patients with diabetes mellitus during treatment with Genotropin^® It may need to change the dose of hypoglycemic drugs.

In the case of myalgia or increased pain at the injection site Genotropin^® should assume the development of myositis. In the case of confirmation of the diagnosis is necessary to use a form of somatropin without m-cresol.

Dislocation and subluxation of the femoral head (lameness, pain in the hip and knee) are more frequently observed in patients with endocrine disorders, including growth hormone deficiency. Children, receiving growth hormone, which marked lameness, They must be carefully examined.

In the case of the intake of Genotropin^® severe or recurring headaches, visual impairment, nausea and / or vomiting, It recommended a study of the fundus to identify papilledema. In the case of confirmation of papilledema should assume the presence of benign intracranial hypertension. If necessary, treatment Genotropin^® should be suspended. With the resumption of treatment requires careful monitoring of the patient's condition.

Formation of antibodies to the drug, Study titer antibodies to somatropin should be carried out in cases of lack of therapeutic response.

The drug is not effective, if the body is not synthesized growth factors or lack receptors for growth factors.

Patient preparation before breeding can be stored for 1 month at room temperature (above 25 ° C).

Effects on ability to drive vehicles and management mechanisms

Genotropin^® It does not influence the ability to drive the truck and to the mechanisms.

Overdose

Cases of overdose Genotropin^® unknown.

Symptoms: in acute overdose possible hypoglycemia, and then hyperglycemia. Long-term overdose could occur known symptoms of excess human growth hormone (akromegalija, gigantizm).

Treatment: removal of the drug, simptomaticheskaya therapy.

Drug Interactions

GCS at joint application reduces the stimulating effect of Genotropin^® on the growth process.

With simultaneous use of Genotropin^® with thyroxin mild hyperthyroidism may develop.

Genotropin^® while the application may increase the clearance of compounds, metabolized by the CYP3A4 isoenzyme (hormones, corticosteroids, anticonvulsants, cyclosporine). The clinical relevance of this effect has not been studied.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 °C. Shelf life – 3 year.

The finished solution can be stored in the refrigerator (at a temperature of from 2 ° to 8 °C) during 4 weeks. Avoid freezing or cartridge, no ready solution.