G GENOTROP

Substance: Recombinant Human Growth Hormone for Injection
Strenght:
10 UI/ 3,7mg/ 10ml/ vial
Packaging:
Glass vials, 10vials/pack
Glass vial 10ml of bacteriostatic water

Please read the package insert carefully and administer under the guidance of physicians.
   GENOTROP should not be used for growth promotion in children with closed epiphyses.
   GENOTROP should not be used in patient with severe generalized infections who are in acute shocks.
 

Name of Medical product:
   Generic name: Recombinant Human Growth Hormone for Injection.
   Trade name: GENOTROP.
 

Ingredients:
   Recombinant Human Growth Hormone and excipients.
   Molecular Formula: C990H1528N262O300S7 with 191 amino acid.
   Molecular weight: 22125 D
   Origin of the Active Ingredient: GENOTROP is a recombinant human growth hormone (rhGH) produced by gene recombination E. Coli secretion expression technology. Its precursor synthesized in E. Coli including gene of human growth hormone (hGH) was secreted to periplasmic space of the cell guided under signal peptide. The signal peptide was removed and polypeptide molecule is folded exactly to growth hormone(GH) molecule. GENOTROP has 191 amino acid residues and a molecular weight of 22125 daltons. Its amino acid content, structure and sequence are identical to those of hGH
 

Characters:
   White lyophilized powder.
   One vial/10 ml of  bacteriostatic water for injection.
 

Indications:
   Pediatric growth retardation due to inadequate secretion of endogenous Gh.
   Severe burns.
   Growth hormone deficiency (GHD) due to diseases of hypothalamuspituitary gland or as diagnosed by 2 independent GH stimulation tests.

Strength:
   10 UI /3,7 mg/10 ml/vial.

Dosage and administration:
   Before administration, add 1 ml of bacteriological water to the rhGH vial of lyophilized powder. And make the solvent run slowly down the side of the vial. Swirl the vial with a gentle rotary motion until contents are dissolved completely. Do not shake vigorously.
   The dose of administration should be individual for each patient. For growth promotion purpose in children, the recommended dose is 0,1-0,15IU/kg Alay. Once per day, subcutaneous injection. The period of treatment is from 3 months to 3 years. Or follow your physicians prescription.
   For severe burn patients, a daily dose of 0,2-0,4 UI/kg subcutaneous injections is recommended. The period of treatment is about 2 weeks.
   The dose night require adjustment individually for human replacement therapy. Generally the dose is from small dose, e.g. 0,5 UI (0,17mg)/day or up to 0,02 UI/kg/day. After 1-2 months treatment, the dose might be modulated graduelly to 0,04 UI/kg/day, it is equal to 0,013 mg/kg/day. The daily dose should be modulated according to the determination of Insulin-like Growth Factor-I (IGF-I0 in serum. The dose may decrease with age increasing.
 

Adverse reactions:
   GENOTROP may cause temporary hyperglycemia, which will usually return to normal after continual uses, or stop using.
   In clinical trials in children with short stature, side effects have been noted in approximately 1% of the subjects. The most common effects are temporary local response an injection sites (such as pain, numbness, redness, swelling, etc.) and symptoms of fluid retention (such as periphery edema, arthralgia and myosalgia).These side effects have an early onset after initiation of therapy, but with a reduction in incidence and prevalence over time which rarely influence daily activities.
   During long-term GENOTROP treatment a few patients may develop antibodies to the protein. The affinity of the antibody is usually low, and it has no exact clinical significance, however, if the expected growth effect is not observed there is a possibility that formation of antibody taking place in the body. If the affinity exceeds 2 mg/l. It might interfere with the treatment.

Contraindictions:
   GENOTROP should not be used for growth promotion in children with closed epiphyses.
   GENOTROP should not be used in patients with severs generalized infections who are in acute shocks.
 

Warnings and precautions:
   Diagnosis confirmation is required before initiation of the treatment. Therapy with GENOTROP should be prescribed directly by qualified physicians.
   In diabets mellitus patients, the dose of insulin might require adjustment by physicians before GENOTROP treatment.
   Simultaneous glucocorticoid therapy will inhibit the growth promoting effect of GENOTROP. patient with ACTH deficiency should have their glucocorticoid-replacement dose carefully adjusted to avoid an inhibitory effect on growth (see DRUGINTERACTIONS)
   Hypothyroidism may develop during GENOTROP therapy in very few patient, which should be corrected promptly to avoid the compromised curative effect of GENOTROP therefore, Thyroid function should be monitored periodically during GENOTROP administration, and, thyroid hormone replacement should be initiated if necessary.
   Slipped capital femoral epiphysis may occur in patient with endocrine disorders(including GHD). Evaluation should be made carefully if limp emerges during GENOTROP treatment.
   Sometimes GENOTROP may reduce insulin sensitivity. Patients should be monitored closely for evidence of glucose intolerance.
   Insulin treatment might be needed if BG exceeds 10 mmil/L during treatment, if BG cannot be controlled with a dose of insulin exceeding 150 IU/day. Stop GENOTROP treatment.
   The injection site should be varied to prevent lipoatrophy.
   Athletes should administer with caution.

Medication for woman in pregnancy and lactation:
   It should not be used for women in pregnancy and lactation.

Medication for children:
   There is no significant difference in GENOTROP’s pharmacology and pharmacokinetics between children and adults. Administer GENOTROP safely according to weights..

Medication for children.
   There is no clinical report in senior population.

Drug interations.
   Simultaneous glucocorticoid therapy might inhibit the effect of hGH. Generally, the dose of glucocorticoid can not exceed 10-15 mg CORT/m2 of surface areas. Growth rate can be increased by the combination with other non-androgen steroids.

Overdose.
   There is no report on acute overdose. Overdose could lea to initially hypoglycemia and subsequently gyperglycemia. Long-term overdose could result in symptoms of acromegaly, consistent with the known effects of excessive GH.

Pharmacology.
   HGH was secreted by anterior lob of the pituitary, it is a peptide hormone with 191 amino acids, GENOTROP is a rhGH produced by recombinant DNA technology in E.coli with secretion expression. The content and sequence of GENOTROP are completely identical with thoseof Hgh GENOTROP is synthesized in E.coli as a prehormone. The prehormone is composed of GH with a signal peptide derived originally from the bacterium. The prehormone splits in the cytosol of bacterium, and then the finished product, similar to the native GH, is released to periplasmic space. The product is then collected thought lysis of the outer membrane, which leaves inner membrane intact, and thus guarantees almost no contamination from other bacteria proteins..
   The effect of the secretion expression rhGH is the same at that of the endogenous GH in human body, GENOTROP stimulates cartilage cells of osteoepiphysis to differentiate and propagate; it stimulates stroma cells of the cartilage to grow; it stimulatesosteoblast to differentiate and regenerate; it causes acceleration of linear growth and ossature widening, GENOTROP promotes whole-body synthesis of proteins; it corrects the condition of negative nitrogen balance after operation and other wounds; it corrects hypoproteinemia initiated by severe infections and hepatic cirrhosis. GENOTROP stimulates the synthesis of immune globulin; it stimulates the generation of lymphoid tissue, macrophage and homeocyte; it increases the ability of anti-infections, GENOTROP stimulates the synthesis from collagen cells to fibrocytes in burn wounding and operative incisions, it stimulates differentiation and generation of macrophage; it accelerates wound healing. GENOTROP promotes the synthesis of protein; of cardiac muscle; it increase the contraction force of cardiac muscle; it decrease myocardial consumption of oxygen; it regulates fat metabolism; it decrease levels of cholesterol and low density lipoprotein in serum. GENOTROP complements the insufficient and deficiency of GH, in adjusts fat metabolism, bone metabolism, cardiac and renal function.

Pharmacokinetics.
   It has been reported in literature that the therapeutic effects are the same for both subcutaneously and intramuscularly administrations. Usually subcutaneously administration cause higher concentration of GH than intramuscularly administration, but the concentration of IGF-I are the same with these two approaches of administration. Generally. The absorption of GH is slow. The concentration of GH in plasma reaches the peak after 3-hours, GH is eliminated through liver and kidney, and the process in adults is faster than in children. Non-metabolized GH eliminated directly through urine is very little.
   Almost all GH in the blood circulation is bound to the high affinity GH binding protein (Hghbp), which increases the half life of GH in serum. Different injection time does not influence the concentration of GH in serum.

Storage.
   Store and transport at 2-8 0C. protect from light.

Packaging.
   Glass vials, 10 vials/pack.
   Glass vial 10 ml of bacteriostatic water.

Shelf life:
   24 months.

Safety.
   Each box of GENOTROP has original code, which could check at the web site.
 

Manufacturer:
   Manufacturer name: GEN PHARMACEUTICALS Co., Ltd..
   Manufacturer address:NO.16, Jiefang Road, Shangcheng District, Hangzhou, Zhejiang, China.
   Post code: 130012
   Phone: 86-420-83192872
   Fax: 86-420-83100650