Protropin hGH Somatropin
Protropin® (Somatrem for Injection)
Protropin growth hormone releasing agent for injection to treat human growth hormone deficiency.
Protropin is a white powder intended for intramuscular or subcutaneous administration by injection after reconstitution with Bacteriostatic Water. With growth hormone therapy in adults, increases in lean body mass and physical performance, and decreases in body fat and waist circumference are seen.
Read more about HGH (Human Growth Hormone)
Replacement Therapy and HGH Injections – Human Growth Hormone Therapy
Protropin (somatrem for injection) is a polypeptide hormone created through recombinant DNA (rDNA) technology. Protropin has 192 amino acid residues with the same sequence of 191 amino acids that constitute human growth hormone of pituitary origin, as well as an additional amino acid (methionine). Protropin is synthesized in a special laboratory strain of E. coli bacteria which has been modified by the addition of the gene for human growth hormone production.
Protropin is a purified preparation with potency determined through cell proliferation bioassay. Protropin is a sterile freeze-dried powder designed for subcutaneous or intramuscular injection after reconstitution.
Every 5mg vial of Protropin contains 5mg of somatrem, lyophilized with 40mg mannitol and 1.7mg sodium phosphates. Every 10mg vial of Protropin contains 10mg of somatrem lyophilized with 80mg mannitol and 3.4mg sodium phosphates. Phosphoric acid may be used for pH adjustment.
Bacteriostatic Water for Injection is a sterile water with 0.9% benzyl alcohol per mL used as an antimicrobial preservative.
In vivo and in vitro clinical and pre-clinical tests have shown that Protropin is equivalent to HGH derived from the pituitary gland. Treatment of pediatric patients lacking sufficient endogenous growth hormone secretion with Protropin resulted in improved growth rate and an increase in insulin-like growth factor-I (IGF-I) levels similar to those observed with pituitary-derived HGH.
The following actions have been demonstrated for Protropin, somatropin and/or natural HGH:
1. Tissue Growth
Protropin prompts skeletal growth in pediatric patients with growth failure caused by insufficient secretion of endogenous growth hormone, which is achieved at the epiphyseal plates at the ends of long bones.
Metabolism and growth of plate cells are stimulated by growth hormone and its mediator, IGF-I. Serum levels of IGF-I are low in pediatric patients with growth hormone deficiency (GHD), although levels increase during Protropin treatment. New bone is formed at the epiphyseal plates in response to GH, resulting in linear growth until plates fuse after puberty. Treatment with HGH also increase the size and number of skeletal muscle cells.
Pituitary-derived HGH influences the size of organs and increases red cell mass. Genetic dwarf rats or rats who have had pituitary glands removed treated with somatropin resulted in organ growth proportional to overall growth of the body.
2. Protein Metabolism
Linear growth is assisted by GH-stimulated protein synthesis. Growth hormone treatment improves nitrogen retention with reduced urinary nitrogen excretion and lower blood urea nitrogen during therapy.
3. Carbohydrate Metabolism
GH modulates the metabolism of carbohydrates. Children with GHD often develop fasting hypoglycemia, which is improved with growth hormone therapy. Protropin treatent may lower glucose tolerance. Administration of Protropin to normal adults and patients who lacked adequate secretion of endogenous growth hormone led to increased mean serum fasting and postprandial insulin levels, although mean glucose and hemoglobin A 1C levels stayed within the normal range.
4. Lipid Metabolism
Acute administration of pituitary-derived human growth hormone to humans resulted in lipid mobilization. Nonesterified fatty acids increased in plasma within two hours of pituitary-derived human growth hormone administration. In growth hormone–deficient patients, long-term growth hormone administration often decreases body fat. Mean cholesterol levels decreased in patients treated with growth hormone.
5. Mineral Metabolism
Growth hormone therapy improves the retention of potassium due to cellular growth. Inorganic phosphorus serum levels may raise slightly in patients with GHD due to metabolic activity associated with bone growth and phosphate reabsorption of the kidneys, although serum calcium does not change dramatically. Sodium retention is also improved with GH treatment.
6. Connective Tissue Metabolism
Growth hormone prompts synthesis of collagen and chondroitin sulfate and increases urinary secretion of hydroxyproline.
INDICATIONS AND USAGE
Protropin® (somatrem for injection) is indicated only for the long-term treatment of pediatric patients who have growth failure caused by insufficient excretion of endogenous growth hormone. Other etiologies of short stature should be excluded.
GH therapy should not be started on patients with acute critical illness caused by complications of abdominal surgery or open heart surgery, multiple accidental trauma or patients with acute respiratory failure. Clinical studies in non GHD patients with these conditions found an increased mortality rate (41.9% compared to 19.3%) of patients trated with somatropin compared to those receiving a placebo.
Protropin should not be used for patients with closed epiphyses (long bone growth plates).
Protropin should not be used on patients with active neoplasia, and GH treatment should be discontinued if neoplasia develops.
Protropin that is reconstituted with Bacteriostatic Water for Injection should not be used in patients with a known benzyl alcohol sensitivity.
See CONTRAINDICATIONS for information on raised mortality rate among patients with acute critical illnesses in ICUs due to complications after abdominal or open heart surgery, acute respiratory failure or multiple accident trauma.
Benzyl alcohol is used as a preservative in Bacteriostatic Water for Injection and has been linked to toxicity in newborns. Reconstitute with Sterile Water for Injection when administering Protropin to newborns.
General: Protropin should only be prescribed by physicians who are experienced with diagnosing and management patients with growth failure.
Because Protropin may induce a state of insulin resistance, patients should be observed for evidence of glucose intolerance.
Frequently examine patients with a history of intracranial lesion for progression or recurrence.
Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Physicians and parents should be alert for limps or complaints of knee or hip pain in patients treated with Protropin.
Children who experience rapid regrowth may experience progression of scoliosis. As GH increases growth rate, patients who have a history of scoliosis should be monitored.
Intracranial hypertension along with swelling, vision changes, headaches, vomiting and nausea have been reported in a small number of people treated with GH. Symptoms typically begin within the first eight weeks and, in all reported cases, symptoms resolved after growth hormone therapy was terminated or the GH dose was reduced. Patients should be examined for IH signs at the start and periodically during GH therapy.
See WARNINGS regarding Bacteriostatic Water for Injection use in newborns.
Local or systemic allergic reactions may occur in some patients. Parents and patients should be informed that reactions are a possibility and that quick medical attention is necessary if allergic reactions occur.
Laboratory Tests: Inorganic phosphorus serum levels, alkaline phosphatase, and parathyroid hormone (PTH) may raise with Protropin therapy. Changes in thyroid hormone laboratory measurements may develop during Protropin treatment of children who lack adequate endogenous growth hormone secretion. Untreated hypothyroidism prevents optimal response to Protropin. Patients should receive regular thyroid function testing and be treated when necessary.
Drug Interactions: Concomitant glucocorticoid treatment may prevent the growth promoting effects of Protropin. If glucocorticoid replacement is necessary, the dose should be adjusted.
Carcinogenesis, Mutagenesis, Fertility Impairement: These studies have not been conducted on Protropin.
Pregnancy: Animal reproduction studies have not been completed with Protropin and it is unknown if Protropin causes fetal harm when given to a pregnant woman, or if it impacts reproduction capability. Protropin should be avoided in pregnant women unless clearly necessary.
Nursing Mothers: It is unknown if Protropin is excreted in breast milk. Caution should be used when administered Protropin to nursing mothers.
Information for Patients: GH patients and/or parents should be informed of potential risks and benefits associated with growth hormone treatment. If home use is determined to be desirable, instructions should be provided on appropraite use as well as a review of contents of the Patient Information Insert. If home use is prescribed, a puncture resistant container for disposal of syringes and needles is recommended.
A small number of patients may develop antibodies to the protein. GH antibody binding capacities below 2mg/L are not associated with a gradual loss of intensity in growth. In some cases in which binding capacity exceeds 2mg/L, a loss of intensity of growth effects may be seen.
In clinical studies and postmarketing experience of patients treated with Protropin, about 0.4% of patients screened for antibody production developed antibodies with binding capacities exceeding this amount after six months. Out of 26,000 Protropin patients, 5 patients have had growth deceleration associated with binding capacities > 2 mg/L. If growth deceleration is observed that is not attributable to another cause, the patient should be tested for antibodies to growth hormone. Although no evidence exists to indicate that the methionine on the N-terminus of somatrem causes antibodies to growth hormone, the physician should consider transferring the patient to somatropin (rDNA origin) for injection, if a patient has antibody binding capacity > 2 mg/L, and has exhibited growth attenuation.
Along with an evaluation of compliance with the prescribed treatment plan and regular thyroid function tests, testing for antibodies to HGH should be conducted in patients who do not respond to treatment.
Additional short-term immunologic and renal function studies were carried out in a group of patients after approximately two years of treatment to detect other potential adverse effects of antibodies to growth hormone. The antibody was determined to be of the lgG class; no antibodies to growth hormone of the IgE class were detected. Testing included immune complex determination, measurement of total hemolytic complement and specific complement components, and immunochemical analyses. No adverse effects of growth hormone antibody formation were observed.
These findings are supported by a toxicity study conducted in a primate model in which a similar antibody response to growth was observed. Protropin, administered to monkeys by intramuscular injection at doses of 125 and 625 ug/kg TIW, was compared to pituitary-human growth hormone at the same doses and with placebo over a period of 90 days. Most monkeys treated with high-dose Protropin developed persistent antibodies at Week 4. There were no biologically significant drug related changes in standard laboratory variables. Histopathologic examination of the kidneys and other selected organs (pituitary, lungs, liver and pancreas) showed no treatment-related toxicity. There was no evidence of immune complexes or immune-complex toxicity when the kidneys were also examined for the presence of immune complexes and possible toxic effects of immune complexes by immunohistochemistry and electron microscopy.
In studies in children treated with Protropin, injection site pain was reported infrequently.
In a small number of GHD patients treated with growth hormone, leukemia was reported. It is unknown if this increased risk is related to the pathology of GHD, growth hormone treatment or other associated treatments like radiation therapy for tumors. Based on current evidence, experts cannot be sure that growth hormone treatment is responsible for these cases of leukemia.
Other adverse drug reactions reported in GH patients: mild and transient peripheral edema; carpal tunnel syndrome; increased growth of pre-existing nevi; gynecomastia.
The recommended dosage of up to 0.30 mg/kg (approximately 0.90 IU/kg) of body weight weekly should not be exceeded due to the potential risk of known effects of excess human growth hormone.
PROTROPIN DOSAGE AND ADMINISTRATION
A weekly dosage of 0.30 mg/kg (approximately 0.90 IU/kg) of body weight administered by daily intramuscular or subcutaneous injection is recommended.
The Protropin dosage and administration schedule should be individualized for each patient. Therapy should not be continued if final height is achieved or epiphyseal fusion occurs.
Patients who fail to respond adequately while on Protropin therapy should be evaluated to determine the cause of unresponsiveness.
After an appropriate dose is determined, Protropin should be reconstituted as follows:
Every 5mg Protropin vial should be reconstituted with 1-5mL of Bacteriostatic Water for Injection. Each 10mg vial should be reconstituted with 1-10mL of Bacteriostatic Water for Injection. For newborns, see WARNINGS.
To prepare Protropin solution, inject Bacteriostatic Water for Injection into the vial, aiming the liquid against the glass. Swirl the vial gently until contents are dissolved. Do not shake. Protropin is a protein, and shaking can cause the solution to become cloudy. Protropin solution should clear immediately upon reconstitution.
In some cases after refrigeration, small colorless particles may be present in the solution. This is not unusual for protein solutions. If the solution is cloudy immediately after refrigeration or reconstitution, do not inject the contents.
Before inserting the needle wipe the septum of the diluent and Protropin vials with antiseptic solution to prevent contamination. Protropin should be administered with disposable, sterile needles and syringes, which should have a small enough volume that the prescribed dose can be drawn accurately.
STABILITY AND STORAGE
Before reconstitution: Protropin and Bacteriostatic Water for Injection should be stored at 2-8 degrees Celsius or 36-46 degrees Fahrenheit under refrigeration. Avoid freezing vials. Expiration dates are printed on vial labels.
After reconstitution: Protropin vial contents will be stable for 14 days when reconstituted with Bacteriostatic Water for Injection. Stored unused portion of Bacteriostatic Water for Injection under refrigeration as described above. Avoid freezing vials.
Protropin® (somatrem for injection) is supplied as 5 mg (approximately 15 IU) or 10 mg (approximately 30 IU) of lyophilized, sterile, somatrem per vial.
Each 5 mg carton contains two vials of Protropin® (somatrem for injection) (5 mg per vial) and one 10 mL multiple dose vial of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). NDC 50242-015-02
Each 10 mg carton contains two vials of Protropin® (somatrem for injection) (10 mg per vial) and two 10 mL multiple dose vials of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). NDC 50242-016-20
(Above information has been provided by PDR.)
HGH Therapy for Hormone Replacement Therapy
HGH Therapy & HGH Injections
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