DESCRIPTION- HGH (hGH Somatropin Human Growth Hormone)
HGH [somatropin (rDNA origin) injection] is a human growth hormone (hGH) produced by recombinant DNA technology. HGH has 191 amino acid residues and a molecular weight of 22,125 daltons.
The amino acid sequence of SOMATROPIN HGH is identical to that of pituitary-derived human growth hormone. The protein is synthesized by a specific laboratory strain of E. coli as a precursor consisting of the rhGH molecule preceded by the secretion signal from an E. coli protein. This precursor is directed to the plasma membrane of the cell. The signal sequence is removed and the native protein is secreted into the periplasm so that the protein is folded appropriately as it is synthesized.
HGH growth hormone used for injection is a highly purified preparation. Biological potency is determined using a cell proliferation bioassay. HGH may contain not more than fifteen percent deamidated growth hormone (GH) at expiration. The deamidated form of GH has been extensively characterized and has been shown to be safe and fully active.
HGH is a sterile liquid intended for subcutaneous administration. The product is nearly isotonic at a concentration of 6 mg or 9 mg of GH per mL and has a pH of approximately 6.0.
Each 6 mg vial contains 18 IU Somatropin
Each 9 mg vial contains 27 IU Somatropin
HGH CLINICAL PHARMACOLOGY
Somatropin HGH General
In vitro and in vivo preclinical and clinical testing have demonstrated that HGH is therapeutically equivalent to pituitary-derived human GH (hGH). Pediatric patients who lack adequate endogenous GH secretion, patients with chronic renal insufficiency, and patients with Turner syndrome that were treated with HGH or Nutropin® [somatropin (rDNA origin) for injection] resulted in an increase in growth rate and an increase in insulin-like growth factor-I (IGF-I) levels similar to that seen with pituitary-derived HGH.
Actions that have been demonstrated for HGH, somatropin, somatrem, and/or pituitary-derived HGH include:
A. Tissue Growth --1) Skeletal Growth: GH stimulates skeletal growth in pediatric patients with growth failure due to a lack of adequate secretion of endogenous GH or secondary to chronic renal insufficiency and in patients with Turner syndrome. Skeletal growth is accomplished at the epiphyseal plates at the ends of a growing bone. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and one of its mediators, IGF-I. Serum levels of IGF-I are low in children and adolescents who are GH deficient, but increase during treatment with GH. In pediatric patients, new bone is formed at the epiphyses in response to GH and IGF-I. This results in linear growth until these growth plates fuse at the end of puberty. 2) Cell Growth: Treatment with hGH results in an increase in both the number and the size of skeletal muscle cells. 3) Organ Growth: GH influences the size of internal organs, including kidneys, and increases red cell mass. Treatment of hypophysectomized or genetic dwarf rats with GH results in organ growth that is proportional to the overall body growth. In normal rats subjected to nephrectomy-induced uremia, GH promoted skeletal and body growth.
B. Protein Metabolism --Linear growth is facilitated in part by GH-stimulated protein synthesis. This is reflected by nitrogen retention as demonstrated by a decline in urinary nitrogen excretion and blood urea nitrogen during GH therapy.
C. Carbohydrate Metabolism --GH is a modulator of carbohydrate metabolism. For example, patients with inadequate secretion of GH sometimes experience fasting hypoglycemia that is improved by treatment with GH. GH therapy may decrease insulin sensitivity. Untreated patients with chronic renal insufficiency and Turner syndrome have an increased incidence of glucose intolerance. Administration of hGH to adults or children resulted in increases in serum fasting and postprandial insulin levels, more commonly in overweight or obese individuals. In addition, mean fasting and postprandial glucose and hemoglobin A 1c levels remained in the normal range.
D. Lipid Metabolism --In GH-deficient patients, administration of GH resulted in lipid mobilization, reduction in body fat stores, increased plasma fatty acids, and decreased plasma cholesterol levels.
E. Mineral Metabolism --The retention of total body potassium in response to GH administration apparently results from cellular growth. Serum levels of inorganic phosphorus may increase slightly in patients with inadequate secretion of endogenous GH, chronic renal insufficiency, or patients with Turner syndrome during GH therapy due to metabolic activity associated with bone growth as well as increased tubular reabsorption of phosphate by the kidney. Serum calcium is not significantly altered in these patients. Sodium retention also occurs. Adults with childhood-onset GH deficiency show low bone mineral density (BMD).
F. Connective Tissue Metabolism --GH stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.
Pharmacokinetics of Somatropin HGH (How the body influences absorption and delivery)
Subcutaneous Absorption--The absolute bioavailability of recombinant human growth hormone (rhGH) after subcutaneous administration in healthy adult males has been determined to be 81±20%. The mean terminal t 1/2 after subcutaneous administration is significantly longer than that seen after intravenous administration (2.1±0.43 hr vs. 19.5±3.1 min) indicating that the subcutaneous absorption of the compound is slow and rate-limiting.
Distribution--Animal studies with rhGH showed that GH localizes to highly perfused organs, particularly the liver and kidney. The volume of distribution at steady state for rhGH in healthy adult males is about 50 mL/kg body weight, approximating the serum volume.
Metabolism--Both the liver and kidney have been shown to be important metabolizing organs for GH. Animal studies suggest that the kidney is the dominant organ of clearance. GH is filtered at the glomerulus and reabsorbed in the proximal tubules. It is then cleaved within renal cells into its constituent amino acids, which return to the systemic circulation.
Elimination--The mean terminal t 1/2 after intravenous administration of rhGH in healthy adult males is estimated to be 19.5±3.1 minutes. Clearance of rhGH after intravenous administration in healthy adults and children is reported to be in the range of 116-174 mL/hr/kg.
Bioequivalence of Formulations-- HGH® [somatropin (rDNA origin) injection] has been determined to be bioequivalent to Nutropin® [somatropin (rDNA origin) for injection] based on the statistical evaluation of AUC and C max .
Special Populations that use Somatropin rhHGH
Pediatric--Available literature data suggest that rhGH clearances are similar in adults and children.
Gender--No data are available for exogenously administered rhGH. Available data for methionyl recombinant GH, pituitary-derived GH, and endogenous GH suggest no consistent gender-based differences in GH clearance.
Geriatrics--Limited published data suggest that the plasma clearance and average steady-state plasma concentration of rhGH may not be different between young and elderly patients.
Race--Reported values for half-lives for endogenous GH in normal adult black males are not different from observed values for normal adult white males. No data for other races are available.
Human Growth Hormone Deficiency
Growth Hormone Deficiency (GHD)--Reported values for clearance of rhGH in adults and children with GHD range 138-245 mL/hr/kg and are similar to those observed in healthy adults and children. Mean terminal t 1/2 values following intravenous and subcutaneous administration in adult and pediatric GHD patients are also similar to those observed in healthy adult males.
Renal Insufficiency--Children and adults with chronic renal failure (CRF) and end-stage renal disease (ESRD) tend to have decreased clearance compared to normals. Endogenous GH production may also increase in some individuals with ESRD. However, no rhGH accumulation has been reported in children with CRF or ESRD dosed with current regimens.
Turner Syndrome--No pharmacokinetic data are available for exogenously administered rhGH. However, reported half-lives, absorption, and elimination rates for endogenous GH in this population are similar to the ranges observed for normal subjects and GHD populations.
Hepatic Insufficiency--A reduction in rhGH clearance has been noted in patients with severe liver dysfunction. The clinical significance of this decrease is unknown.
INDICATIONS AND USAGE- HGH (Somatropin Injection)
Adult Patients
HGH [somatropin (rDNA origin) injection] is indicated for the replacement of endogenous GH in patients with adult GH deficiency (AGHD) who meet both of the following two criteria:
Biochemical diagnosis of adult GH deficiency by means of a subnormal response to a standard growth hormone stimulation test (peak GH)
Adult-onset: Patients who have adult GH deficiency either alone or with multiple hormone deficiencies (hypopituitarism) as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
Childhood-onset: Patients who were GH deficient during childhood, confirmed as an adult before replacement therapy with HGH is started.
CONTRAINDICATIONS- HGH Somatropin Injecton
Growth Hormone Somatropin should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or to patients having acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone-deficient adult patients (n=522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS and always consult a human growth hormone doctor before administration of injectable HGH ).
HGH should not be used for growth promotion in pediatric patients with closed epiphyses.
HGH should not be used in patients with active neoplasia. GH therapy should be discontinued if evidence of neoplasia develops.
HGH Somatropin WARNINGS
See CONTRAINDICATIONS for information on increased mortality in patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or with acute respiratory failure. The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with growth hormone in patients having acute critical illnesses should be weighed against the potential risk.
HGH Somatropin PRECAUTIONS
General: HGH should be prescribed by physicians experienced in the diagnosis and management of patients with GH deficiency, Turner syndrome, or chronic renal insufficiency. No studies have been completed of HGH therapy in patients who have received renal transplants. Currently, treatment of patients with functioning renal allografts is not indicated.
Experience with prolonged rhGH treatment in adults is limited.
STABILITY AND STORAGE of Somatropin GH
Vial contents are stable for 14 days after mixing when stored at 2-8°C/36-46°F (under refrigeration). Avoid freezing the vial of HGH.
HOW SOMATROPIN GH IS SUPPLIED
Sompatropin HGH is supplied as 6mg and 9mg of sterile liquid somatropin per vial.
HGH Injections and Human Growth Hormone Therapy
HGH® [somatropin (rDNA origin) injection]
SOMATROPIN HGH Injection Defined
HGH Therapy for Hormone Replacement Therapy
HGH Therapy & HGH Injections
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