Anabolics
Search More Than 6,000,000 Posts
Results 1 to 16 of 16
  1. #1
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812

    Medical journal evidence of reconstited life of several different GH's

    Soooooooo i got tired of arguing and pleading my case w/ everyone and hearing a different time frame from everyone that thinks they know the reconstitued life of Serostim.
    My gf is an MD and i had here look online @ statref; which is an online medical compilation of all medical journals published that is accessable only by physicians.
    below you will find all avaible info and reconstituted lives of different brands of gh. This of course is from statref, which sites Mosbys drug book 2005, 25th edition for it's source for this particular info. Unless you know something the worlds leading researchers and scientists don't know this is what goes. No if's or buts.

    If you scroll down to the bottm of each GH that is reviewed it states the life of it and storage recomendations.


    Somatropin, Biosynthetic

    INTRODUCTION

    Pronounciation: soe-ma-troe'-pin

    Ingredients: Somatropin, Biosynthetic

    FDA Approval Date: 1987-03-01

    HCFA JCODE(S): J2941

    Foreign Brand Availability: Genotropin (US); Genotropin Miniquick (US); Growject BC (JAPAN); Humatrope (US); Norditropin (US); Norditropin Cartridge (US); Norditropin S (JAPAN); Norditropin Simplexx (GERMANY); Nutropin (US); Nutropin AQ (EUROPE; US; CANADA); Nutropin Depot (US); Saizen (US); Scitropin (HONG-KONG; PHILIPPINES; SINGAPORE); Serostim (US); Zorbtive (US)

    Drug Class: Hormones/hormone modifiers; Recombinant DNA Origin

    Pregnancy Categories: B

    Indications: Growth failure, secondary to growth hormone deficiency; Short bowel syndrome; Growth failure, secondary to small for gestational age; Growth failure, secondary to Prader-Willi syndrome; Growth hormone deficiency; Short stature, secondary to Turner syndrome; Short stature, idiopathic; Growth failure, secondary to chronic renal failure; Wasting, secondary to HIV; Cachexia, secondary to HIV

    Off Label Uses: None found

    Cost of Therapy: $1,480.47 (CRF Growth Failure; 5 mg/ml; 2 ml; Nutropin AQ Injection Solution; 7 mg/week (divided; 20 Kg BW); 28 day supply) $528.76 (GHD-Adults (initial therapy); 5 mg/vial; Nutropin Powder for Injection; 2.5 mg/week (divided doses); 28 day supply) $609.12 (GHD-Children; 5 mg/vial; Humatrope; 3 mg/week (divided; 16 KgBW); 28 day supply) $1,057.52 (GHD-Children; 5 mg/vial; Nutropin Powder for Injection; 5 mg/week (divided; 16 KgBW); 28 day supply) $1,079.08 (GHD-Children; 22.5 mg/vial; Nutropin Depot; 22.5 mg/month (16 Kg BW); 28 day supply) $2,114.96 (GHD-Children; 5 mg/ml; 2 ml; Nutropin AQ Injection Solution; 10 mg/week (divided; 32 Kg BW); 28 day supply) $2,114.96 (Turner's Syndrome; 5 mg/ml; 2 ml; Nutropin AQ Injection Solution; 10 mg/week (divided; 27.5 Kg BW); 28 day supply)

    BRAND NAME: GENOTROPIN

    DESCRIPTION

    Genotropin lyophilized powder contains somatropin [rDNA origin], which is a polypeptide hormone of recombinant DNA origin. It has 191 amino acid residues and a molecular weight of 22,124 daltons. The amino acid sequence of the product is identical to that of human growth hormone of pituitary origin (somatropin). Genotropin is synthesized in a strain of Escherichia coli that has been modified by the addition of the gene for human growth hormone. Genotropin is a sterile white lyophilized powder intended for SC injection.

    Genotropin 1.5 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 1.5 mg (approximately 4.5 IU), glycine 27.6 mg, sodium dihydrogen phosphate anhydrous 0.3 mg, and disodium phosphate anhydrous 0.3 mg; the rear chamber contains 1.13 ml water for injection.

    Genotropin 5.8 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 5.8 mg (approximately 17.4 IU), glycine 2.2 mg, mannitol 1.8 mg, sodium dihydrogen phosphate anhydrous 0.32 mg, and disodium phosphate anhydrous 0.31 mg; the rear chamber contains 0.3% m-Cresol (as a preservative) and mannitol 45 mg in 1.14 ml water for injection.

    Genotropin 13.8 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 13.8 mg (approximately 41.4 IU), glycine 2.3 mg, mannitol 14.0 mg, sodium dihydrogen phosphate anhydrous 0.47 mg, and disodium phosphate anhydrous 0.46 mg; the rear chamber contains 0.3% m-Cresol (as a preservative) and mannitol 32 mg in 1.13 ml water for injection.

    Genotropin Miniquick is dispensed as a single-use syringe device containing a two-chamber cartridge. Genotropin Miniquick is available as individual doses of 0.2 to 2.0 mg in 0.2-mg increments. The front chamber contains recombinant somatropin 0.22 to 2.2 mg (approximately 0.66 to 6.6 IU), glycine 0.23 mg, mannitol 1.14 mg, sodium dihydrogen phosphate 0.05 mg, and disodium phosphate anhydrous 0.027 mg; the rear chamber contains mannitol 12.6 mg in water for injection 0.275 ml.

    Genotropin is a highly purified preparation. The reconstituted recombinant somatropin solution has an osmolality of approximately 300 mOsm/kg, and a pH of approximately 6.7. The concentration of the reconstituted solution varies by strength and presentation (see HOW SUPPLIED).

    CLINICAL PHARMACOLOGY

    In vitro, preclinical, and clinical tests have demonstrated that Genotropin lyophilized powder is therapeutically equivalent to human growth hormone of pituitary origin and achieves similar pharmacokinetic profiles in normal adults. In pediatric patients who have growth hormone deficiency (GHD) or Prader-Willi syndrome (PWS), or who were born small for gestational age (SGA), treatment with Genotropin stimulates linear growth. In patients with GHD or PWS, treatment with Genotropin also normalizes concentrations of IGF-I (Insulin -like Growth Factor-I/Somatomedin C). In adults with GHD, treatment with Genotropin results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.

    In addition, the following actions have been demonstrated for Genotropin and/or somatropin. Tissue Growth: Skeletal Growth: Genotropin stimulates skeletal growth in pediatric patients with GHD, PWS, or SGA. The measurable increase in body length after administration of Genotropin results from an effect on the epiphyseal plates of long bones. Concentrations of IGF-I, which may play a role in skeletal growth, are generally low in the serum of pediatric patients with GHD, PWS, or SGA, but tend to increase during treatment with Genotropin. Elevations in mean serum alkaline phosphatase concentration are also seen.
    Cell Growth: It has been shown that there are fewer skeletal muscle cells in short-statured pediatric patients who lack endogenous growth hormone as compared with the normal pediatric population. Treatment with somatropin results in an increase in both the number and size of muscle cells.

    Protein Metabolism: Linear growth is facilitated in part by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, follows the initiation of therapy with Genotropin.
    Carbohydrate Metabolism: Pediatric patients with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with Genotropin. Large doses of growth hormone may impair glucose tolerance.
    Lipid Metabolism: In GHD patients, administration of somatropin has resulted in lipid mobilization, reduction in body fat stores, and increased plasma fatty acids.
    Mineral Metabolism: Somatropin induces retention of sodium, potassium, and phosphorus. Serum concentrations of inorganic phosphate are increased in patients with GHD after therapy with Genotropin. Serum calcium is not significantly altered by Genotropin. Growth hormone could increase calciuria.
    Body Composition: Adult GHD patients treated with Genotropin at the recommended adult dose (see DOSAGE AND ADMINISTRATION) demonstrate a decrease in fat mass and an increase in lean body mass. When these alterations are coupled with the increase in total body water, the overall effect of Genotropin is to modify body composition, an effect that is maintained with continued treatment.

    PHARMACOKINETICS
    Absorption
    Following a 0.03 mg/kg SC injection in the thigh of 1.3 mg/ml Genotropin to adult GHD patients, approximately 80% of the dose was systemically available as compared with that available following IV dosing. Results were comparable in both male and female patients. Similar bioavailability has been observed in healthy adult male subjects.

    In healthy adult males, following an SC injection in the thigh of 0.03 mg/kg, the extent of absorption (AUC) of a concentration of 5.3 mg/ml Genotropin was 35% greater than that for 1.3 mg/ml Genotropin. The mean ( standard deviation) peak (Cmax) serum levels were 23.0 (9.4) ng/ml and 17.4 (9.2) ng/ml, respectively.

    In a similar study involving pediatric GHD patients, 5.3 mg/ml Genotropin yielded a mean AUC that was 17% greater than that for 1.3 mg/ml Genotropin. The mean Cmax levels were 21.0 ng/ml and 16.3 ng/ml, respectively.

    Adult GHD patients received 2 single SC doses of 0.03 mg/kg of Genotropin at a concentration of 1.3 mg/ml, with a 1- to 4-week washout period between injections. Mean Cmax levels were 12.4 ng/ml (first injection) and 12.2 ng/ml (second injection), achieved at approximately 6 hours after dosing.

    There are no data on the bioequivalence between the 12-mg/ml formulation and either the 1.3-mg/ml or the 5.3-mg/ml formulations.

    Distribution
    The mean volume of distribution of Genotropin following administration to GHD adults was estimated to be 1.3 ( 0.8) L/kg.

    Metabolism
    The metabolic fate of Genotropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation. The mean terminal half-life of IV Genotropin in normal adults is 0.4 hours, whereas subcutaneously administered Genotropin has a half-life of 3.0 hours in GHD adults. The observed difference is due to slow absorption from the SC injection site.

    Excretion
    The mean clearance of subcutaneously administered Genotropin in 16 GHD adult patients was 0.3 ( 0.11) L/h/kg.

    Special Populations
    Pediatric: The pharmacokinetics of Genotropin are similar in GHD pediatric and adult patients.
    Gender: No gender studies have been performed in pediatric patients; however, in GHD adults, the absolute bioavailability of Genotropin was similar in males and females.
    Race: No studies have been conducted with Genotropin to assess pharmacokinetic differences among races.
    Renal or Hepatic Insufficiency: No studies have been conducted with Genotropin in these patient populations.

    See TABLE 1 Mean SC Pharmacokinetic Parameters in Adult GHD Patients

    CLINICAL STUDIES

    ADULT PATIENTS WITH GROWTH HORMONE DEFICIENCY (GHD)
    Genotropin lyophilized powder was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received Genotropin and 87 patients received placebo, followed by an open-label treatment period in which participating patients received Genotropin for up to a total of 24 months. Genotropin was administered as a daily SC injection at a dose of 0.04 mg/kg/wk for the first month of treatment and 0.08 mg/kg/wk for subsequent months.

    Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving Genotropin as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.

    PEDIATRIC PATIENTS WITH PRADER-WILLI SYNDROME (PWS)
    The safety and efficacy of Genotropin in the treatment of pediatric patients with Prader-Willi syndrome (PWS) were evaluated in two randomized, open-label, controlled clinical trials. Patients received either Genotropin or no treatment for the first year of the studies, while all patients received Genotropin during the second year. Genotropin was administered as a daily SC injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received Genotropin at a dose of 0.24 mg/kg/wk during the entire study. During the second year, the control group received Genotropin at a dose of 0.48 mg/kg/wk. In Study 2, the treatment group received Genotropin at a dose of 0.36 mg/kg/wk during the entire study. During the second year, the control group received Genotropin at a dose of 0.36 mg/kg/wk.

    Patients who received Genotropin showed significant increases in linear growth during the first year of study, compared with patients who received no treatment (see TABLE 2). Linear growth continued to increase in the second year, when both groups received treatment with Genotropin.

    See TABLE 2 Efficacy of Genotropin in Pediatric Patients With Prader-Willi Syndrome (Mean SD)

    Changes in body composition were also observed in the patients receiving Genotropin (see TABLE 3). These changes included a decrease in the amount of fat mass, and increases in the amount of lean body mass and the ratio of lean-to-fat tissue, while changes in body weight were similar to those seen in patients who received no treatment. Treatment with Genotropin did not accelerate bone age, compared with patients who received no treatment.

    See TABLE 3 Effect of Genotropin on Body Composition in Pediatric Patients With Prader-Willi Syndrome (Mean SD)

    PEDIATRIC PATIENTS BORN SMALL FOR GESTATIONAL AGE (SGA) WHO FAIL TO MANIFEST CATCH-UP GROWTH BY AGE 2
    The safety and efficacy of Genotropin in the treatment of children born small for gestational age (SGA) were evaluated in 4 randomized, open-label, controlled clinical trials. Patients (age range of 2-8 years) were observed for 12 months before being randomized to receive either Genotropin (2 doses per study, most often 0.24 and 0.48 mg/kg/wk) as a daily SC injection or no treatment for the first 24 months of the studies. After 24 months in the studies, all patients received Genotropin.

    Patients who received any dose of Genotropin showed significant increases in growth during the first 24 months of study, compared with patients who received no treatment (see TABLE 4). Children receiving 0.48 mg/kg/wk demonstrated a significant improvement in height standard deviation score (SDS) compared with children treated with 0.24 mg/kg/wk. Both of these doses resulted in a slower but constant increase in growth between months 24-72 (data not shown).

    See TABLE 4 Efficacy of Genotropin in Children Born Small for Gestational Age (Mean SD)

    INDICATIONS AND USAGE

    Genotropin lyophilized powder is indicated for:
    Long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone.
    Long-term treatment of pediatric patients who have growth failure due to Prader-Willi syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing (see CONTRAINDICATIONS).
    Long-term treatment of growth failure in children born small for gestational age (SGA) who fail to manifest catch-up growth by age 2.
    Other causes of short stature in pediatric patients should be excluded.
    Long-term replacement therapy in adults with growth hormone deficiency (GHD) of either childhood- or adult-onset etiology. GHD should be confirmed by an appropriate growth hormone stimulation test.

    CONTRAINDICATIONS

    Genotropin lyophilized powder should not be used when there is any evidence of neoplastic activity. Intracranial lesions must be inactive and antitumor therapy complete prior to the institution of therapy. Genotropin should be discontinued if there is evidence of tumor growth. Growth hormone should not be used for growth promotion in pediatric patients with fused epiphyses.

    Growth hormone 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).

    Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS).

    WARNINGS

    The 5.8- and 13.8-mg presentations of Genotropin lyophilized powder contain m-Cresol as a preservative. These products should not be used by patients with a known sensitivity to this preservative. The Genotropin 1.5-mg and Genotropin Miniquick presentations are preservative-free (see HOW SUPPLIED).

    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.

    There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with growth hormone. If during treatment with growth hormone patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with growth hormone should also have effective weight control and be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively (see CONTRAINDICATIONS).

    PRECAUTIONS

    GENERAL
    Treatment with Genotropin lyophilized powder, as with other growth hormone preparations, should be directed by physicians who are experienced in the diagnosis and management of patients with GHD or Prader-Willi syndrome (PWS), or those who were born small for gestational age (SGA).

    Patients and caregivers who will administer Genotropin in medically unsupervised situations should receive appropriate training and instruction on the proper use of Genotropin from the physician or other suitably qualified health professional.

    Patients with GHD secondary to an intracranial lesion should be examined frequently for progression or recurrence of the underlying disease process. Review of literature reports of pediatric use of somatropin replacement therapy reveals no relationship between this therapy and recurrence of central nervous system (CNS) tumors. In adults, it is unknown whether there is any relationship between somatropin treatment and CNS tumor recurrence.

    Patients should be monitored carefully for any malignant transformation of skin lesions.

    Caution should be used if growth hormone is administered to patients with diabetes mellitus, and insulin dosage may need to be adjusted. Patients with diabetes or glucose intolerance should be monitored closely during treatment with Genotropin. Patients with risk factors for glucose intolerance, such as obesity (including obese patients with PWS) or a family history of Type 2 diabetes, should be monitored closely as well. Because growth hormone may induce a state of insulin resistance, patients should be observed for evidence of glucose intolerance.

    In patients with hypopituitarism (multiple hormonal deficiencies) standard hormonal replacement therapy should be monitored closely when treatment with Genotropin is instituted. Hypothyroidism may develop during treatment with Genotropin, and inadequate treatment of hypothyroidism may prevent optimal response to Genotropin. Therefore, patients should have periodic thyroid function tests and be treated with thyroid hormone when indicated.

    Pediatric patients with endocrine disorders, including GHD, have a higher incidence of slipped capital femoral epiphyses. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during growth hormone therapy should be evaluated.

    Progression of scoliosis can occur in patients who experience rapid growth. Because growth hormone increases growth rate, patients with a history of scoliosis who are treated with growth hormone should be monitored for progression of scoliosis. However, growth hormone has not been shown to increase the incidence of scoliosis. Scoliosis is commonly seen in untreated patients with PWS. Physicians should be alert to this abnormality, which may manifest during growth hormone therapy.

    Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with growth hormone products. Symptoms usually occurred within the first 8 weeks of the initiation of growth hormone therapy. In all reported cases, IH-associated signs and symptoms resolved after termination of therapy or a reduction of the growth hormone dose. Funduscopic examination of patients is recommended at the initiation, and periodically during the course of, growth hormone therapy. Patients with PWS may be at increased risk for development of IH.

    Before continuing treatment as an adult, a post-pubertal GHD patient who received growth hormone replacement therapy in childhood should be reevaluated with proper testing as described in INDICATIONS AND USAGE. If continued treatment is appropriate, Genotropin should be administered at the reduced dose level recommended for adult GHD patients.

    CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
    Carcinogenicity studies have not been conducted with rhGH. No potential mutagenicity of rhGH was revealed in a battery of tests including induction of gene mutations in bacteria (the Ames test), gene mutations in mammalian cells grown in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats). See Pregnancy Category B for effect on fertility.

    PREGNANCY CATEGORY B
    Reproduction studies carried out with Genotropin at doses of 0.3, 1, and 3.3 mg/kg/day administered SC in the rat and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in the rabbit (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area) resulted in decreased maternal body weight gains but were not teratogenic. In rats receiving SC doses during gametogenesis and up to 7 days of pregnancy, 3.3 mg/kg/day (approximately 24 times human dose) produced anestrus or extended estrus cycles in females and fewer and less motile sperm in males. When given to pregnant female rats (Days 1-7 of gestation) at 3.3 mg/kg/day a very slight increase in fetal deaths was observed. At 1 mg/kg/day (approximately 7 times human dose) rats showed slightly extended estrus cycles, whereas at 0.3 mg/kg/day no effects were noted.

    In perinatal and postnatal studies in rats, Genotropin doses of 0.3, 1, and 3.3 mg/kg/day produced growth-promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed increased weight gain during suckling but the effect was not apparent by 10 weeks of age. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offsprings due to Genotropin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

    NURSING MOTHERS
    There have been no studies conducted with Genotropin in nursing mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Genotropin is administered to a nursing woman.

    GERIATRIC USE
    The safety and effectiveness of Genotropin in patients aged 65 and over has not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of Genotropin and may be more prone to develop adverse reactions.

    DRUG INTERACTIONS

    Concomitant glucocorticoid treatment may inhibit the growth-promoting effect of growth hormone. Pediatric GHD patients with coexisting ACTH deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth (see also PRECAUTIONS, General). Limited published data indicate that growth hormone treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that growth hormone administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids , anticonvulsants, cyclosporine). Careful monitoring is advisable when growth hormone is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.

  2. #2
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    ADVERSE REACTIONS

    As with all protein drugs, a small number of patients may develop antibodies to the protein. Growth hormone antibody with binding lower than 2 mg/L has not been associated with growth attenuation. In some cases when binding capacity is > 2 mg/L, interference with growth response has been observed.

    In 419 pediatric patients evaluated in clinical studies with Genotropin lyophilized powder, 244 had been treated previously with Genotropin or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in 6 previously treated patients at baseline. Three (3) of the 6 became negative for anti-hGH antibodies during 6-12 months of treatment with Genotropin. Of the remaining 413 patients, 8 (1.9%) developed detectable antihGH antibodies during treatment with Genotropin; none had an antibody binding capacity >2 mg/L. There was no evidence that the growth response Genotropin was affected in these antibody-positive patients.

    Preparations of Genotropin contain a small amount of periplasmic Escherichia coli peptides (PECP). Anti-PECP antibodies are found in a small number of patients treated with Genotropin, but these appear to be of no clinical significance.

    In clinical studies with Genotropin in pediatric GHD patients, the following events were reported infrequently: injection site reactions, including pain or burning associated with the injection, fibrosis, nodules, rash, inflammation, pigmentation, or bleeding; lipoatrophy; headache; hematuria; hypothyroidism; and mild hyperglycemia.

    Leukemia has been reported in a small number of pediatric patients who have been treated with growth hormone, including growth hormone of pituitary origin and recombinant somatropin. The relationship, if any, between leukemia and growth hormone therapy is uncertain.

    In two clinical studies with Genotropin in pediatric patients with Prader-Willi syndrome, the following drug-related events were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia.

    In clinical studies of 273 pediatric patients born small for gestational age treated with Genotropin, the following clinically significant events were reported: mild transient hyperglycemia, 1 patient with benign intracranial hypertension, 2 patients with central precocious puberty, 2 patients with jaw prominence, and several patients with aggravation of pre-existing scoliosis, injection site reactions, and self-limited progression of pigmented nevi. Anti-hGH antibodies were not detected in any of the patients treated with Genotropin.

    In clinical trials with Genotropin in 1145 GHD adults, the majority of the adverse events consisted of mild to moderate symptoms of fluid retention, including peripheral swelling, arthralgia, pain and stiffness of the extremities, peripheral edema, myalgia, paresthesia, and hypoesthesia. These events were reported early during therapy, and tended to be transient and/or responsive to dosage reduction.

    TABLE 5 displays the adverse events reported by 5% or more of adult GHD patients in clinical trials after various durations of treatment with Genotropin. Also presented are the corresponding incidence rates of these adverse events in placebo patients during the 6-month double-blind portion of the clinical trials.

    See TABLE 5 Adverse Events Reported by 5% of 1145 Adult GHD Patients During Clinical Trials of Genotropin and Placebo, Grouped by Duration of Treatment

    In expanded post-trial extension studies, diabetes mellitus developed in 12 of 3,031 patients (0.4%) during treatment with Genotropin. All 12 patients had predisposing factors, e.g., elevated glycated hemoglobin levels and/or marked obesity, prior to receiving Genotropin. Of the 3031 patients receiving Genotropin, 61 (2%) developed symptoms of carpal tunnel syndrome, which lessened after dosage reduction or treatment interruption (52) or surgery (9). Other adverse events that have been reported include generalized edema and hypoesthesia.

    OVERDOSAGE

    There is little information on acute or chronic overdosage with Genotropin lyophilized powder. Intravenously administered growth hormone has been shown to result in an acute decrease in plasma glucose. Subsequently, hyperglycemia was seen. It is thought that the same effect might occur on rare occasions with a high dosage of Genotropin administered SC. Long-term overdosage may result in signs and symptoms of acromegaly consistent with overproduction of growth hormone.

    DOSAGE AND ADMINISTRATION

    The dosage of Genotropin lyophilized powder must be adjusted for the individual patient. The weekly dose should be divided into 6 or 7 SC injections. Genotropin may be given in the thigh, buttocks, or abdomen; the site of SC injections should be rotated daily to help prevent lipoatrophy.

    Pediatric GHD Patients: Generally, a dose of 0.16-0.24 mg/kg body weight/wk is recommended.
    Pediatric PWS Patients: Generally, a dose of 0.24 mg/kg body weight/wk is recommended.
    Pediatric SGA Patients: Generally, a dose of 0.48 mg/kg body weight/wk is recommended.
    Adult GHD Patients: The recommended dosage at the start of therapy is not more than 0.04 mg/kg/wk. The dose may be increased at 4- to 8-week intervals according to individual patient requirements to a maximum of 0.08 mg/kg/wk, depending upon patient tolerance of treatment. Clinical response, side effects, and determination of age-adjusted serum IGF-I may be used as guidance in dose titration. This approach will tend to result in weight-adjusted doses that are larger for women compared with men and smaller for older and obese patients.

    Genotropin must not be injected intravenously.

    Genotropin is supplied in a two-chamber cartridge, with the lyophilized powder in the front chamber and a diluent in the rear chamber. A reconstitution device is used to mix the diluent and powder.

    Follow the directions for reconstitution provided with each device. Do not shake; shaking may cause denaturation of the active ingredient.

    All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If the solution is cloudy, the contents MUST NOT be injected.

    Patients and caregivers who will administer Genotropin in medically unsupervised situations should receive appropriate training and instruction on the proper use of Genotropin from the physician or other suitably qualified health professional.

    HOW SUPPLIED

    Genotropin lyophilized powder is available in the following packages:
    1.5-mg two-chamber cartridge (without preservative), concentration of 1.3 mg/ml (approximately 4 IU/ml): Pre-assembled in a Genotropin intra-mix growth hormone reconstitution device and packaged with a pressure release needle.

    5.8-mg two-chamber cartridge (with preservative), concentration of 5 mg/ml (approximately 15 IU/ml): For use with the Genotropin pen 5 growth hormone delivery device and/or the Genotropin mixer growth hormone reconstitution device.
    Pre-assembled in a Genotropin intra-mix growth hormone reconstitution device and packaged with a pressure release needle.

    13.8-mg two-chamber cartridge (with preservative), concentration of 12 mg/ml (approximately 36 IU/ml): For use with the Genotropin pen 12 growth hormone delivery device and/or the Genotropin mixer growth hormone reconstitution device.

    Genotropin Miniquick growth hormone delivery device containing a two-chamber cartridge of Genotropin (without preservative): After reconstitution, each Genotropin miniquick delivers a fixed volume of 0.25 ml, regardless of strength. Available in the following strengths: 0.2, 0.4, 0.6, 0.8, and 1.0 mg.

    Please see directions for use of the reconstitution and/or delivery device that accompany the prescription.

    STABILITY AND STORAGE
    Except as noted below, store Genotropin lyophilized powder under refrigeration at 2-8C (36-46F). Do not freeze. Protect from light.

    The 1.5-mg cartridge of Genotropin contains a diluent with no preservative. After reconstitution, the cartridge may be stored under refrigeration for up to 24 hours. Use only once and discard any remaining solution.

    The 5.8- and 13.8-mg cartridges of Genotropin contain a diluent with a preservative. Thus, after reconstitution, they may be stored under refrigeration for up to 21 days.

    The Genotropin Miniquick Growth Hormone Delivery Device should be refrigerated prior to dispensing, but may be stored at or below 25C (77F) for up to 3 months after dispensing. The diluent has no preservative. After reconstitution, the Genotropin Miniquick may be stored under refrigeration for up to 24 hours before use. The Genotropin Miniquick should be used only once and then discarded.

    BRAND NAME: HUMATROPE

    DESCRIPTION

    Humatrope (somatropin, rDNA origin, for Injection) is a polypeptide hormone of recombinant DNA origin. Humatrope has 191 amino acid residues and a molecular weight of about 22,125 daltons. The amino acid sequence of the product is identical to that of human growth hormone of pituitary origin. Humatrope is synthesized in a strain of Escherichia coli that has been modified by the addition of the gene for human growth hormone.

    Humatrope is a sterile, white, lyophilized powder intended for SC or IM administration after reconstitution. Humatrope is a highly purified preparation. Phosphoric acid and/or sodium hydroxide may have been added to adjust the pH. Reconstituted solutions have a pH of approximately 7.5. This product is oxygen sensitive.

    VIAL
    Each vial of Humatrope contains 5 mg somatropin (15 IU or 225 nanomoles); 25 mg mannitol; 5 mg glycine; and 1.13 mg dibasic sodium phosphate. Each vial is supplied in a combination package with an accompanying 5-ml vial of diluting solution. The diluent contains water for injection with 0.3% Metacresol as a preservative and 1.7% glycerin.

    CARTRIDGE
    The cartridges of somatropin contain either 6 mg (18 IU), 12 mg (36 IU), or 24 mg (72 IU) of somatropin. The 6, 12, and 24 mg cartridges contain respectively: mannitol 18, 36, and 72 mg; glycine 6, 12, and 24 mg; dibasic sodium phosphate 1.36, 2.72, and 5.43 mg. Each cartridge is supplied in a combination package with an accompanying syringe containing approximately 3 ml of diluting solution. The diluent contains water for injection; 0.3% Metacresol as a preservative; and 1.7%, 0.29%, and 0.29% glycerin in the 6, 12, and 24 mg cartridges, respectively.

    CLINICAL PHARMACOLOGY

    GENERAL
    Linear Growth
    Humatrope stimulates linear growth in pediatric patients who lack adequate normal endogenous growth hormone. In vitro, preclinical, and clinical testing have demonstrated that Humatrope is therapeutically equivalent to human growth hormone of pituitary origin and achieves equivalent pharmacokinetic profiles in normal adults. Treatment of growth hormone-deficient pediatric patients and patients with Turner syndrome with Humatrope produces increased growth rate and IGF-I (Insulin -like Growth Factor-I/Somatomedin-C) concentrations similar to those seen after therapy with human growth hormone of pituitary origin.

    In addition, the following actions have been demonstrated for Humatrope and/or human growth hormone of pituitary origin. Tissue Growth: Skeletal Growth: Humatrope stimulates skeletal growth in pediatric patients with growth hormone deficiency. The measurable increase in body length after administration of either Humatrope or human growth hormone of pituitary origin results from an effect on the growth plates of long bones. Concentrations of IGF-I, which may play a role in skeletal growth, are low in the serum of growth hormone-deficient pediatric patients but increase during treatment with Humatrope. Elevations in mean serum alkaline phosphatase concentrations are also seen.
    Cell Growth: It has been shown that there are fewer skeletal muscle cells in short-statured pediatric patients who lack endogenous growth hormone as compared with normal pediatric populations. Treatment with human growth hormone of pituitary origin results in an increase in both the number and size of muscle cells.

    Protein Metabolism: Linear growth is facilitated in part by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, follows the initiation of therapy with human growth hormone of pituitary origin. Treatment with Humatrope results in a similar decrease in serum urea nitrogen.
    Carbohydrate Metabolism: Pediatric patients with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with Humatrope. Large doses of human growth hormone may impair glucose tolerance. Untreated patients with Turner syndrome have an increased incidence of glucose intolerance. Administration of human growth hormone to normal adults or patients with Turner syndrome resulted in increases in mean serum fasting and postprandial insulin levels although mean values remained in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1c levels remained in the normal range.
    Lipid Metabolism: In growth hormone-deficient patients, administration of human growth hormone of pituitary origin has resulted in lipid mobilization, reduction in body fat stores, and increased plasma fatty acids.
    Mineral Metabolism: Retention of sodium, potassium, and phosphorus is induced by human growth hormone of pituitary origin. Serum concentrations of inorganic phosphate increased in patients with growth hormone deficiency after therapy with Humatrope or human growth hormone of pituitary origin. Serum calcium is not significantly altered in patients treated with either human growth hormone of pituitary origin or Humatrope.

    PHARMACOKINETICS
    Absorption
    Humatrope has been studied following IM, SC, and IV administration in adult volunteers. The absolute bioavailability of somatropin is 75% and 63% after SC and IM administration, respectively.

    Distribution
    The volume of distribution of somatropin after IV injection is about 0.07 L/kg.

    Metabolism
    Extensive metabolism studies have not been conducted. The metabolic fate of somatropin involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products of growth hormone is returned to the systemic circulation. In normal volunteers, mean clearance is 0.14 L/h/kg. The mean half-life of IV somatropin is 0.36 hours, whereas subcutaneously and intramuscularly administered somatropin have mean half-lives of 3.8 and 4.9 hours, respectively. The longer half-life observed after SC or IM administration is due to slow absorption from the injection site.

    Excretion
    Urinary excretion of intact Humatrope has not been measured. Small amounts of somatropin have been detected in the urine of pediatric patients following replacement therapy.

    Special Populations
    Geriatric: The pharmacokinetics of Humatrope has not been studied in patients greater than 65 years of age.
    Pediatric: The pharmacokinetics of Humatrope in pediatric patients is similar to adults.
    Gender: No studies have been performed with Humatrope. The available literature indicates that the pharmacokinetics of growth hormone is similar in both men and women.
    Race: No data are available.
    Renal, Hepatic Insufficiency: No studies have been performed with Humatrope.

    See TABLE 6 Summary of Somatropin Parameters in the Normal Population

    CLINICAL STUDIES

    EFFECTS OF HUMATROPE TREATMENT IN ADULTS WITH GROWTH HORMONE DEFICIENCY
    Two multicenter trials in adult-onset growth hormone deficiency (n=98) and two studies in childhood-onset growth hormone deficiency (n=67) were designed to assess the effects of replacement therapy with Humatrope. The primary efficacy measures were body composition (lean body mass and fat mass), lipid parameters, and the Nottingham Health Profile. The Nottingham Health Profile is a general health-related quality of life questionnaire. These four studies each included a 6-month randomized, blinded, placebo-controlled phase followed by 12 months of open-label therapy for all patients. The Humatrope dosages for all studies were identical: 1 month of therapy at 0.00625 mg/kg/day followed by the proposed maintenance dose of 0.0125 mg/kg/day. Adult-onset patients and childhood-onset patients differed by diagnosis (organic versus idiopathic pituitary disease), body size (normal versus small for mean height and weight), and age (mean = 44 vs 29 years). Lean body mass was determined by bioelectrical impedance analysis (BIA), validated with potassium 40. Body fat was assessed by BIA and sum of skinfold thickness. Lipid subfractions were analyzed by standard assay methods in a central laboratory.

    Humatrope-treated adult-onset patients, as compared to placebo, experienced an increase in lean body mass (2.59 vs -0.22 kg, p <0.001) and a decrease in body fat (-3.27 vs 0.56 kg, p <0.001). Similar changes were seen in childhood-onset growth hormone-deficient patients. These significant changes in lean body mass persisted throughout the 18-month period as compared to baseline for both groups, and for fat mass in the childhood-onset group. Total cholesterol decreased short-term (first 3 months) although the changes did not persist. However, the low HDL cholesterol levels observed at baseline (mean=30.1 mg/ml and 33.9 mg/ml in adult-onset and childhood-onset patients) normalized by the end of 18 months of therapy (a change of 13.7 and 11.1 mg/dl for the adult-onset and childhood-onset groups, p <0.001). Adult-onset patients reported significant improvements as compared to placebo in the following two of six possible health-related domains: physical mobility and social isolation (TABLE 7). Patients with childhood-onset disease failed to demonstrate improvements in Nottingham Health Profile outcomes.

    Two additional studies on the effect of Humatrope on exercise capacity were also conducted. Improved physical function was documented by increased exercise capacity (VO2 max, p <0.005) and work performance (Watts, p <0.01) (J Clin Endocrinol Metab 1995; 80:552-557).

    See TABLE 7 Changes* in Nottingham Health Profile Scores1 in Adult-Onset Growth Hormone-Deficient Patients

    EFFECTS OF GROWTH HORMONE TREATMENT IN PATIENTS WITH TURNER SYNDROME
    One long-term, randomized, open-label multicenter concurrently controlled study, two long-term, open-label multicenter, historically controlled studies and one long-term, randomized, dose-response study were conducted to evaluate the efficacy of growth hormone for the treatment of patients with short stature due to Turner syndrome.

    In the randomized study, GDCT, comparing growth hormone-treated patients to a concurrent control group who received no growth hormone, the growth hormone-treated patients who received a dose of 0.3 mg/kg/wk given 6 times per week from a mean age of 11.7 years for a mean duration of 4.7 years attained a mean near final height of 146.0 6.2 cm (n=27, mean SD) as compared to the control group who attained a near final height of 142.1 4.8 cm (n=19). By analysis of covarianceasdfWhatIsThis4, the effect of growth hormone therapy was a mean height increase of 5.4 cm (p=0.001).

    In two of the studies (85-023 and 85-044), the effect of long-term growth hormone treatment (0.375 mg/kg/wk given either 3 times per week or daily) on adult height was determined by comparing adult heights in the treated patients with those of age-matched historical controls with Turner syndrome who never received any growth-promoting therapy. The greatest improvement in adult height was observed in patients who received early growth hormone treatment and estrogen after age 14 years. In Study 85-023, this resulted in a mean adult height gain of 7.4 cm (mean duration of GH therapy of 7.6 years) vs matched historical controls by analysis of covariance.

    In Study 85-044, patients treated with early growth hormone therapy were randomized to receive estrogen replacement therapy (conjugated estrogens, 0.3 mg escalating to 0.625 mg daily) at either age 12 or 15 years. Compared with matched historical controls, early GH therapy (mean duration of GH therapy 5.6 years) combined with estrogen replacement at age 12 years resulted in an adult height gain of 5.9 cm (n=26), whereas patients who initiated estrogen at age 15 years (mean duration of GH therapy 6.1 years) had a mean adult height gain of 8.3 cm (n=29). Patients who initiated GH therapy after age 11 (mean age 12.7 years; mean duration of GH therapy 3.8 years) had a mean adult height gain of 5.0 cm (n=51).

    In a randomized blinded dose-response study, GDCI, patients were treated from a mean age of 11.1 years for a mean duration of 5.3 years with a weekly dose of either 0.27 mg/kg or 0.36 mg/kg administered 3 or 6 times weekly. The mean near final height of patients receiving growth hormone was 148.7 6.5 cm (n=31). When compared to historical control data, the mean gain in adult height was approximately 5 cm.

    In some studies, Turner syndrome patients (n=181) treated to final adult height achieved statistically significant average height gains ranging from 5.0-8.3 cm.

    See TABLE 8 Summary Table of Efficacy Results

    *Analysis of covariance includes adjustments for baseline height relative to age and for mid-parental height.

    EFFECT OF HUMATROPE TREATMENT IN PEDIATRIC PATIENTS WITH IDIOPATHIC SHORT STATURE
    Two randomized, multicenter trials, 1 placebo-controlled and 1 dose-response, were conducted in pediatric patients with idiopathic short stature, also called non-growth hormone-deficient short stature. The diagnosis of idiopathic short stature was made after excluding other known causes of short stature, as well as growth hormone deficiency. Limited safety and efficacy data are available below the age of 7 years. No specific studies have been conducted in pediatric patients with familial short stature or who were born small for gestational age (SGA).

    The placebo-controlled study enrolled 71 pediatric patients (55 males, 16 females) 9-15 years old (mean age 12.38 1.51 years), with short stature, 68 of whom received study drug. Patients were predominately Tanner I (45.1%) and Tanner II (46.5%) at baseline.

    In this double-blind trial, patients received SC injections of either Humatrope 0.222 mg/kg/wk or placebo. Study drug was given in divided doses 3 times per week until height velocity decreased to 1.5 cm/year ("final height"). Thirty-three subjects (22 Humatrope, 11 placebo) had final height measurements after a mean treatment duration of 4.4 years (range 0.11-9.08 years).

    The Humatrope group achieved a mean final height Standard Deviation Score (SDS) of -1.8 (TABLE 9). Placebo-treated patients had a mean final height SDS of -2.3 (mean treatment difference = 0.51, p=0.017). Height gain across the duration of the study and final height SDS minus baseline predicted height SDS were also significantly greater in Humatrope-treated patients than in placebo-treated patients (TABLE 9 and TABLE 10). In addition, the number of patients who achieved a final height above the 5th percentile of the general population for age and sex was significantly greater in the Humatrope group than the placebo group (41% vs 0%, p <0.05), as was the number of patients who gained at least 1 SDS unit in height across the duration of the study (50% vs 0%, p <0.05).

    See TABLE 9 Baseline Height Characteristics and Effect of Humatrope on Final Height*

    The dose-response study included 239 pediatric patients (158 males, 81 females), 5-15 years old, (mean age 9.8 2.3 years). Mean baseline characteristics included: a height SDS of -3.21 (0.70), a predicted adult height SDS of -2.63 (1.08), and a height velocity SDS of -1.09 (1.15). All but 3 patients were Tanner I. Patients were randomized to one of three Humatrope treatment groups: 0.24 mg/kg/wk; 0.24 mg/kg/wk for 1 year, followed by 0.37 mg/kg/wk; and 0.37 mg/kg/wk.

    The primary hypothesis of this study was that treatment with Humatrope would increase height velocity during the first 2 years of therapy in a dose-dependent manner. Additionally, after completing the initial 2-year dose-response phase of the study, 50 patients were followed to final height.

    Patients receiving 0.37 mg/kg/wk had a significantly greater increase in mean height velocity after 2 years of treatment than patients receiving 0.24 mg/kg/wk (4.04 vs 3.27 cm/year, p=0.003). The mean difference between final height and baseline predicted height was 7.2 cm for patients receiving 0.37 mg/kg/wk and 5.4 cm for patients receiving 0.24 mg/kg/wk (TABLE 10). While no patient had height above the 5th percentile in any dose group at baseline, 82% of the patients receiving 0.37 mg/kg/wk and 47% of the patients receiving 0.24 mg/kg/wk achieved a final height above the 5th percentile of the general population height standards (p=NS).

    See TABLE 10 Final Height Minus Baseline Predicted Height: Idiopathic Short Stature Trials

    INDICATIONS AND USAGE

    PEDIATRIC PATIENTS
    Humatrope is indicated for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of normal endogenous growth hormone.

    Humatrope is indicated for the treatment of short stature associated with Turner syndrome in patients whose epiphyses are not closed.

    Humatrope is indicated for the long-term treatment of idiopathic short stature, also called non-growth hormone-deficient short stature, defined by height SDS -2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.

    ADULT PATIENTS
    Humatrope is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria: Adult Onset: Patients who have growth hormone 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 growth hormone-deficient during childhood who have growth hormone deficiency confirmed as an adult before replacement therapy with Humatrope is started.

  3. #3
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    CONTRAINDICATIONS

    Humatrope should not be used for growth promotion in pediatric patients with closed epiphyses.

    Humatrope should not be used or should be discontinued when there is any evidence of active malignancy. Anti-malignancy treatment must be complete with evidence of remission prior to the institution of therapy.

    Humatrope should not be reconstituted with the supplied diluent for Humatrope for use by patients with a known sensitivity to either Metacresol or glycerin.

    Growth hormone 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).

    Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Humatrope is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

    WARNINGS

    If sensitivity to the diluent should occur, the vials may be reconstituted with bacteriostatic water for injection or sterile water for injection. When Humatrope is used with bacteriostatic water (benzyl alcohol preserved), the solution should be kept refrigerated at 2-8C (36-46F) and used within 14 days. Benzyl alcohol as a preservative in bacteriostatic water for injection has been associated with toxicity in newborns. When administering Humatrope to newborns, use the Humatrope diluent provided or if the patient is sensitive to the diluent, use sterile water for injection. When Humatrope is reconstituted with sterile water for injection in this manner, use only one dose per Humatrope vial and discard the unused portion. If the solution is not used immediately, it must be refrigerated (2- 8C [36-46F]) and used within 24 hours.

    Cartridges should be reconstituted only with the supplied diluent. Cartridges should not be reconstituted with the dluent for Humatrope provided with Humatrope vials, or with any other solution. Cartridges should not be used if the patient is allergic to Metacresol or glycerin.

    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.

    There have been reports of fatalities after initiating therapy with growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with growth hormone. If, during treatment with growth hormone, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with growth hormone should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively (see CONTRAINDICATIONS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Humatrope is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

    PRECAUTIONS

    GENERAL
    Therapy with Humatrope should be directed by physicians who are experienced in the diagnosis and management of patients with growth hormone deficiency, Turner syndrome, idiopathic short stature, or adult patients with either childhood-onset or adult-onset growth hormone deficiency.

    Patients with preexisting tumors or with growth hormone deficiency secondary to an intracranial lesion should be examined routinely for progression or recurrence of the underlying disease process. In pediatric patients, clinical literature has demonstrated no relationship between somatropin replacement therapy and CNS tumor recurrence. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence.

    Patients should be monitored carefully for any malignant transformation of skin lesions.

    For patients with diabetes mellitus, the insulin dose may require adjustment when somatropin therapy is instituted. Because human growth hormone may induce a state of insulin resistance, patients should be observed for evidence of glucose intolerance. Patients with diabetes or glucose intolerance should be monitored closely during somatropin therapy.

    In patients with hypopituitarism (multiple hormonal deficiencies) standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered. Hypothyroidism may develop during treatment with somatropin and inadequate treatment of hypothyroidism may prevent optimal response to somatropin.

    PEDIATRIC PATIENTS
    See General.

    Pediatric patients with endocrine disorders, including growth hormone deficiency, may develop slipped capital epiphyses more frequently. Any pediatric patient with the onset of a limp during growth hormone therapy should be evaluated.

    Growth hormone has not been shown to increase the incidence of scoliosis. Progression of scoliosis can occur in children who experience rapid growth. Because growth hormone increases growth rate, patients with a history of scoliosis who are treated with growth hormone should be monitored for progression of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients.

    Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear or hearing disorders (see ADVERSE REACTIONS). Patients with Turner syndrome are at risk for cardiovascular disorders (e.g., stroke, aortic aneurysm, hypertension) and these conditions should be monitored closely.

    Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease. Therefore, patients should have periodic thyroid function tests and be treated as indicated (see General).

    Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of pediatric patients treated with growth hormone products. Symptoms usually occurred within the first 8 weeks of the initiation of growth hormone therapy. In all reported cases, IH-associated signs and symptoms resolved after termination of therapy or a reduction of the growth hormone dose. Funduscopic examination of patients is recommended at the initiation and periodically during the course of growth hormone therapy. Patients with Turner syndrome may be at increased risk for development of IH.

    ADULT PATIENTS
    See General.

    Patients with epiphyseal closure who were treated with growth hormone replacement therapy in childhood should be re-evaluated according to the criteria in INDICATIONS AND USAGE before continuation of somatropin therapy at the reduced dose level recommended for growth hormone-deficient adults.

    Experience with prolonged treatment in adults is limited.

    GERIATRIC USE
    The safety and effectiveness of Humatrope in patients aged 65 and over has not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of Humatrope and may be more prone to develop adverse reactions.

    CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
    Long-term animal studies for carcinogenicity and impairment of fertility with this human growth hormone (Humatrope) have not been performed. There has been no evidence to date of Humatrope-induced mutagenicity.

    PREGNANCY CATEGORY C
    Animal reproduction studies have not been conducted with Humatrope. It is not known whether Humatrope can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Humatrope should be given to a pregnant woman only if clearly needed.

    NURSING MOTHERS
    There have been no studies conducted with Humatrope in nursing mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Humatrope is administered to a nursing woman.

    INFORMATION FOR THE PATIENT
    Patients being treated with growth hormone and/or their parents should be informed of the potential risks and benefits associated with treatment. Instructions on appropriate use should be given, including a review of the contents of the patient information insert. This information is intended to aid in the safe and effective administration of the medication. It is not a disclosure of all possible adverse or intended effects.

    Patients and/or parents should be thoroughly instructed in the importance of proper needle disposal. A puncture resistant container should be used for the disposal of used needles and/or syringes (consistent with applicable state requirements). Needles and syringes must not be reused (see the Information for the Patient insert that is provided with the prescription).

    DRUG INTERACTIONS

    Excessive glucocorticoid therapy may prevent optimal response to somatropin. If glucocorticoid replacement therapy is required, the glucocorticoid dosage and compliance should be monitored carefully to avoid either adrenal insufficiency or inhibition of growth promoting effects.

    Limited published data indicate that growth hormone (GH) treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that GH administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids , anticonvulsants, cyclosporin). Careful monitoring is advisable when GH is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.

    ADVERSE REACTIONS

    GROWTH HORMONE-DEFICIENT PEDIATRIC PATIENTS
    As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. During the first 6 months of Humatrope therapy in 314 naive patients, only 1.6% developed specific antibodies to Humatrope (binding capacity 0.02 mg/L). None had antibody concentrations which exceeded 2 mg/L. Throughout 8 years of this same study, two patients (0.6%) had binding capacity >2 mg/L. Neither patient demonstrated a decrease in growth velocity at or near the time of increased antibody production. It has been reported that growth attenuation from pituitary-derived growth hormone may occur when antibody concentrations are >1.5 mg/L.

    In addition to an evaluation of compliance with the treatment program and of thyroid status, testing for antibodies to human growth hormone should be carried out in any patient who fails to respond to therapy.

    In studies with growth hormone-deficient pediatric patients, injection site pain was reported infrequently. A mild and transient edema, which appeared in 2.5% of patients, was observed early during the course of treatment.

    Leukemia has been reported in a small number of pediatric patients who have been treated with growth hormone, including growth hormone of pituitary origin as well as of recombinant DNA origin (somatrem and somatropin). The relationship, if any, between leukemia and growth hormone therapy is uncertain.

    TURNER SYNDROME PATIENTS
    In a randomized, concurrent controlled trial, there was a statistically significant increase in the occurrence of otitis media (43% vs 26%), ear disorders (18% vs 5%) and surgical procedures (45% vs 27%) in patients receiving Humatrope compared with untreated control patients (TABLE 11). Other adverse events of special interest to Turner syndrome patients were not significantly different between treatment groups (TABLE 11). A similar increase in otitis media was observed in an 18-month placebo-controlled trial.

    See TABLE 11 Treatment-Emergent Events of Special Interest by Treatment Group in Turner Syndrome

    PATIENTS WITH IDIOPATHIC SHORT STATURE
    In the placebo-controlled study, the adverse events associated with Humatrope therapy were similar to those observed in other pediatric populations treated with Humatrope (TABLE 12). Mean serum glucose level did not change during Humatrope treatment. Mean fasting serum insulin levels increased 10% in the Humatrope treatment group at the end of treatment relative to baseline values but remained within the normal reference range. For the same duration of treatment the mean fasting serum insulin levels decreased by 2% in the placebo group. The incidence of above-range values for glucose, insulin, and HbA1c were similar in the growth hormone and placebo-treated groups. No patient developed diabetes mellitus. Consistent with the known mechanism of growth hormone action, Humatrope-treated patients had greater mean increases, relative to baseline, in serum insulin-like growth factor-I (IGF-I) than placebo-treated patients at each study observation. However, there was no significant difference between the Humatrope and placebo treatment groups in the proportion of patients who had at least one serum IGF-I concentration more than 2.0 SD above the age- and gender-appropriate mean (Humatrope: 9 of 35 patients [26%]; placebo: 7 of 28 patients [25%]).

    See TABLE 12 Nonserious Clinically Significant Treatment-Emergent Adverse Events by Treatment Group in Idiopathic Short Stature

    The adverse events observed in the dose-response study (239 patients treated for 2 years) did not indicate a pattern suggestive of a growth hormone dose effect. Among Humatrope dose groups, mean fasting blood glucose, mean glycosylated hemoglobin, and the incidence of elevated fasting blood glucose concentrations were similar. One patient developed abnormalities of carbohydrate metabolism (glucose intolerance and high serum HbA1c) on treatment.

    Adult Patients
    In clinical studies in which high doses of Humatrope were administered to healthy adult volunteers, the following events occurred infrequently: headache, localized muscle pain, weakness, mild hyperglycemia, and glucosuria.

    In the first 6 months of controlled blinded trials during which patients received either Humatrope or placebo, adult-onset growth hormone-deficient adults who received Humatrope experienced a statistically significant increase in edema (Humatrope 17.3% vs placebo 4.4%, p=0.043) and peripheral edema (11.5% vs 0%, respectively, p=0.017). In patients with adult-onset growth hormone deficiency, edema, muscle pain, joint pain, and joint disorder were reported early in therapy and tended to be transient or responsive to dosage titration.

    Two (2) of 113 adult-onset patients developed carpal tunnel syndrome after beginning maintenance therapy without a low dose (0.00625 mg/kg/day) lead-in phase. Symptoms abated in these patients after dosage reduction.

    All treatment-emergent adverse events with 5% overall incidence during 12 or 18 months of replacement therapy with Humatrope are shown in TABLE 13 (adult-onset patients) and in TABLE 14 (childhood-onset patients).

    Adult patients treated with Humatrope who had been diagnosed with growth hormone deficiency in childhood reported side effects less frequently than those with adult-onset growth hormone deficiency.

    See TABLE 13 Treatment-Emergent Adverse Events With 5% Overall Incidence in Adult-Onset Growth Hormone-Deficient Patients Treated With Humatrope for 18 Months as Compared With 6-Month Placebo and 12-Month Humatrope Exposure

    See TABLE 14 Treatment-Emergent Adverse Events With 5% Overall Incidence in Childhood-Onset Growth Hormone-Deficient Patients Treated With Humatrope for 18 Months as Compared With 6-Month Placebo and 12-Month Humatrope Exposure

    Other adverse drug events that have been reported in growth hormone-treated patients include the following:
    Metabolic: Infrequent, mild and transient peripheral or generalized edema.
    Musculoskeletal: Rare carpal tunnel syndrome.
    Skin: Rare increased growth of pre-existing nevi. Patients should be monitored carefully for malignant transformation.
    Endocrine: Rare gynecomastia . Rare pancreatitis.

    OVERDOSAGE

    Acute overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Long-term overdosage could result in signs and symptoms of gigantism/acromegaly consistent with the known effects of excess human growth hormone. (See recommended and maximal dosage instructions in DOSAGE AND ADMINISTRATION.)

    DOSAGE AND ADMINISTRATION

    PEDIATRIC PATIENTS
    The Humatrope dosage and administration schedule should be individualized for each patient. Therapy should not be continued if epiphyseal fusion has occurred. Response to growth hormone therapy tends to decrease with time. However, failure to increase growth rate, particularly during the first year of therapy, should prompt close assessment of compliance and evaluation of other causes of growth failure such as hypothyroidism, under-nutrition and advanced bone age.

    Growth Hormone-Deficient Pediatric Patients
    The recommended weekly dosage is 0.18 mg/kg (0.54 IU/kg) of body weight. The maximal replacement weekly dosage is 0.3 mg/kg (0.90 IU/kg) of body weight. It should be divided into equal doses given either on 3 alternate days, 6 times per week or daily. The SC route of administration is preferable; IM injection is also acceptable. The dosage and administration schedule for Humatrope should be individualized for each patient.

    Turner Syndrome
    A weekly dosage of up to 0.375 mg/kg (1.125 IU/kg) of body weight administered by SC injection is recommended. It should be divided into equal doses given either daily or on 3 alternate days.

    Patients With Idiopathic Short Stature
    A weekly dosage of up to 0.37 mg/kg of body weight administered by SC injection is recommended. It should be divided into equal doses given 6-7 times per week.

    ADULT PATIENTS
    Growth Hormone-Deficient Adult Patients
    The recommended dosage at the start of therapy is not more than 0.006 mg/kg/day (0.018 IU/kg/day) given as a daily SC injection. The dose may be increased according to individual patient requirements to a maximum of 0.0125 mg/kg/day (0.0375 IU/kg/day).

    During therapy, dosage should be titrated if required by the occurrence of side effects or to maintain the IGF-I response below the upper limit of normal IGF-I levels, matched for age and sex. To minimize the occurrence of adverse events in patients with increasing age or excessive body weight, dose reductions may be necessary.

    RECONSTITUTION
    Vial
    Each 5-mg vial of Humatrope should be reconstituted with 1.5-5 ml of diluent for Humatrope. The diluent should be injected into the vial of Humatrope by aiming the stream of liquid against the glass wall. Following reconstitution, the vial should be swirled with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE. The resulting solution should be inspected for clarity. It should be clear. If the solution is cloudy or contains particulate matter, the contents MUST NOT be injected.

    Before and after injection, the septum of the vial should be wiped with rubbing alcohol or an alcoholic antiseptic solution to prevent contamination of the contents by repeated needle insertions. Sterile disposable syringes and needles should be used for administration of Humatrope. The volume of the syringe should be small enough so that the prescribed dose can be withdrawn from the vial with reasonable accuracy.

  4. #4
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    Cartridge
    Each cartridge of Humatrope should only be reconstituted using the diluent syringe and the diluent connector which accompany the cartridge and should not be reconstituted with the diluent for Humatrope provided with Humatrope vials. (See WARNINGS .) See the HumatroPen User Guide that is provided with the prescription for comprehensive directions on Humatrope cartridge reconstitution.

    The reconstituted solution should be inspected for clarity. It should be clear. If the solution is cloudy or contains particulate matter, the contents MUST NOT be injected.

    The HumatroPen allows the somatropin dosage volume to be dialed in increments of 0.048 ml per click of dosage knob, and the maximum dosage volume that can be injected is 0.576 ml (based on a 12-click maximum). (See TABLE 15 for additional information.)

    See TABLE 15 Concentration of Reconstituted Humatrope Solutions, Incremental Dosage and Maximum Injectable Dose for Each Cartridge

    This cartridge has been designed for use only with the HumatroPen. A sterile disposable needle should be used for each administration of Humatrope.

    HOW SUPPLIED

    Vials:
    5 mg and 5-ml vials of diluent for Humatrope.

    Cartridges:
    6-mg cartridge and prefilled syringe of diluent for Humatrope.
    12-mg cartridge and prefilled syringe of diluent for Humatrope.
    24-mg cartridge and prefilled syringe of diluent for Humatrope.

    STABILITY AND STORAGE
    Vials
    Before Reconstitution: Vials of Humatrope and diluent for Humatrope are stable when refrigerated (2-8C [36-46F]). Avoid freezing diluent for Humatrope. Expiration dates are stated on the labels.
    After Reconstitution: Vials of Humatrope are stable for up to 14 days when reconstituted with diluent for Humatrope or bacteriostatic water for injection and stored in a refrigerator at 2-8C (36-46F). Avoid freezing the reconstituted vial of Humatrope.
    After Reconstitution With Sterile Water: Use only one dose per Humatrope vial and discard the unused portion. If the solution is not used immediately, it must be refrigerated (2-8C [36-46F]) and used within 24 hours.

    Cartridges
    Before Reconstitution: Cartridges of Humatrope and diluent for Humatrope are stable when refrigerated (2-8C [36-46F]). Avoid freezing diluent for Humatrope. Expiration dates are stated on the labels.
    After Reconstitution: Cartridges of Humatrope are stable for up to 28 days when reconstituted with diluent for Humatrope and stored in a refrigerator at 2-8C (36-46F). Store the HumatroPen without the needle attached. Avoid freezing the reconstituted cartridge of Humatrope.

    BRAND NAME: NUTROPIN AQ

    DESCRIPTION

    Nutropin AQ is a human growth hormone (hGH) produced by recombinant DNA technology. Nutropin AQ has 191 amino acid residues and a molecular weight of 22,125 daltons. The amino acid sequence of the product 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.

    Nutropin AQ is a highly purified preparation. Biological potency is determined using a cell proliferation bioassay. Nutropin AQ 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.

    Nutropin AQ is a sterile liquid intended for SC administration. The product is nearly isotonic at a concentration of 5 mg of GH per ml and has a pH of approximately 6.0.

    The Nutropin AQ 2 ml vial contains 10 mg (approximately 30 IU) somatropin, formulated in 17.4 mg sodium chloride, 5 mg phenol, 4 mg polysorbate 20, and 10 mm sodium citrate.

    The Nutropin AQ 2 ml pen cartridge contains 10 mg (approximately 30 IU) somatropin, formulated in 17.4 mg sodium chloride, 5 mg phenol, 4 mg polysorbate 20, and 10 mM sodium citrate.

    CLINICAL PHARMACOLOGY

    GENERAL
    In vitro and in vivo preclinical and clinical testing have demonstrated that Nutropin AQ 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 Nutropin AQ or Nutropin resulted in an increase in growth rate and an increase in insulin -like growth factor-I (IG F-I) levels similar to that seen with pituitary-derived hGH.

    Actions that have been demonstrated for Nutropin AQ, somatropin, somatrem, and/or pituitary-derived hGH include:
    Tissue Growth: 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.
    Cell Growth: Treatment with hGH results in an increase in both the number and the size of skeletal muscle cells.
    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.

    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.
    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 A1c levels remained in the normal range.
    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.
    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). GH therapy results in increases in serum alkaline phosphatase. (See PRECAUTIONS, Laboratory Tests.)
    Connective Tissue Metabolism: GH stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.

    PHARMACOKINETICS
    Subcutaneous Absorption
    The absolute bioavailability of recombinant human growth hormone (rhGH) after SC administration in healthy adult males has been determined to be 81 20%. The mean terminal T 1/2 after SC administration is significantly longer than that seen after IV administration (2.1 0.43 h vs 19.5 3.1 min) indicating that the SC 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 or 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 IV administration of rhGH in healthy adult males is estimated to be 19.5 3.1 minutes. Clearance of rhGH after IV administration in healthy adults and children is reported to be in the range of 116-174 ml/h/kg.

    Bioequivalence of Formulations
    Nutropin AQ has been determined to be bioequivalent to Nutropin based on the statistical evaluation of AUC and Cmax.

    SPECIAL POPULATIONS
    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.

    Growth Hormone Deficiency (GHD)
    Reported values for clearance of rhGH in adults and children with GHD range 138-245 ml/h/kg and are similar to those observed in healthy adults and children. Mean terminal T 1/2 values following IV and SC 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 normal individuals. 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.

    See TABLE 16 Summary of Nutropin AQ Pharmacokinetic Parameters in Healthy Adult Males 0.1 mg (approximately 0.3 IU*)/kg SC

    CLINICAL STUDIES

    GROWTH HORMONE DEFICIENCY (GHD) IN PUBERTAL PATIENTS
    One open label, multicenter, randomized clinical trial of 2 dosages of Nutropin was performed in pubertal patients with GHD. Ninety-seven (97) patients (mean age 13.9 years, 83 male, 14 female) currently being treated with approximately 0.3 mg/kg/wk of GH were randomized to 0.3 mg/kg/wk or 0.7 mg/kg/wk Nutropin doses. All patients were already in puberty (Tanner stage 2) and had bone ages 14 years in males or 12 years in females. Mean baseline height standard deviation (SD) score was -1.3.

    The mean last measured height in all 97 patients after a mean duration of 2.7 1.2 years, by analysis of covariance (ANCOVA) adjusting for baseline height, is shown in TABLE 17.

    See TABLE 17 Last Measured Height* by Sex and Nutropin Dose

    The mean height SD score at last measured height (n=97) was -0.7 1.0 in the 0.3 mg/kg/wk group and -0.1 1.2 in the 0.7 mg/kg/wk group. For patients completing 3.5 or more years (mean 4.1 years) of Nutropin treatment (15/49 patients in the 0.3 mg/kg/wk group and 16/48 patients in the 0.7 mg/kg/wk group), the mean last measured height was 166.1 8.0 cm in the 0.3 mg/kg/wk group and 171.8 7.1 cm in the 0.7 mg/kg/wk group, adjusting for baseline height and sex.

    The mean change in bone age was approximately 1 year for each year in the study in both dose groups. Patients with baseline height SD scores above -1.0 were able to attain normal adult heights with the 0.3 mg/kg/wk dose of Nutropin (mean height SD score at near-adult height = -0.1, n=15).

    Thirty-one (31) patients had bone mineral density (BMD) determined by dual energy x-ray absorptiometry (DEXA) scans at study conclusion. The 2 dose groups did not differ significantly in mean SD score for total body BMD (-0.9 1.9 in the 0.3 mg/kg/wk group vs -0.8 1.2 in the 0.7 mg/kg/wk group, n=20) or lumbar spine BMD (-1.0 1.0 in the 0.3 mg/kg/wk group vs -0.2 1.7 in the 0.7 mg/kg/wk group, n=21).

    Over a mean duration of 2.7 years, patients in the 0.7 mg/kg/wk group were more likely to have IGF-I values above the normal range than patients in the 0.3 mg/kg/wk group (27.7% vs 9.0% of IGF-I measurements for individual patients). The clinical significance of elevated IGF-I values is unknown.

    EFFECTS OF NUTROPIN ON GROWTH FAILURE DUE TO CHRONIC RENAL INSUFFICIENCY (CRI)
    Two multicenter, randomized, controlled clinical trials were conducted to determine whether treatment with Nutropin prior to renal transplantation in patients with chronic renal insufficiency could improve their growth rates and height deficits. One study was a double-blind, placebo-controlled trial and the other was an open-label, randomized trial. The dose of Nutropin in both controlled studies was 0.05 mg/kg/day (0.35 mg/kg/wk) administered daily by SC injection. Combining the data from those patients completing 2 years in the two controlled studies results in 62 patients treated with Nutropin and 28 patients in the control groups (either placebo-treated or untreated). The mean first year growth rate was 10.8 cm/yr for Nutropin-treated patients, compared with a mean growth rate of 6.5 cm/yr for placebo/untreated controls (p <0.00005). The mean second year growth rate was 7.8 cm/yr for the Nutropin-treated group, compared with 5.5 cm/yr for controls (p <0.00005). There was a significant increase in mean height standard deviation (SD) score in the Nutropin group (-2.9 at baseline to -1.5 at Month 24, n=62) but no significant change in the controls (-2.8 at baseline to -2.9 at Month 24, n=28). The mean third year growth rate of 7.6 cm/yr in the Nutropin-treated patients (n=27) suggests that Nutropin stimulates growth beyond 2 years. However, there are no control data for the third year because control patients crossed over to Nutropin treatment after 2 years of participation. The gains in height were accompanied by appropriate advancement of skeletal age. These data demonstrate that Nutropin therapy improves growth rate and corrects the acquired height deficit associated with chronic renal insufficiency. Currently there are insufficient data regarding the benefit of treatment beyond 3 years. Although predicted final height was improved during Nutropin therapy, the effect of Nutropin on final adult height remains to bedetermined.

    POSTTRANSPLANT GROWTH
    The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has reported data for growth posttransplant in children who did not receive GH. The average change in height SD score during the initial 2 years posttransplant was 0.18 (n=300, J Pediatr. 1993;122:397-402).

    Controlled studies of GH treatment for the short stature associated with CRI were not designed to compare the growth of treated or untreated patients after they received renal transplants. However, growth data are available from a small number of patients who have been followed for at least 11 months. Of the 7 control patients, 4 increased their height SD score and 3 had either no significant change or a decrease in height SD score. The 13 patients treated with Nutropin prior to transplant had either no significant change or an increase in height SD score after transplantation, indicating that the individual gains achieved with GH therapy prior to transplant were maintained after transplantation. The differences in the height deficit narrowed between the treated and untreated groups in the post-transplant period.

    TURNER SYNDROME
    One long-term, randomized, open-label, multicenter, concurrently controlled study, two long-term, open-label, multicenter, historically controlled studies, and one long-term, randomized, dose-response study were conducted to evaluate the efficacy of GH for the treatment of girls with short stature due to Turner syndrome.

    In the randomized study GDCT, comparing GH-treated patients to a concurrent control group who received no GH, the GH-treated patients who received a dose of 0.3 mg/kg/wk given 6 times per week from a mean age of 11.7 years for a mean duration of 4.7 years attained a mean near final height of 146.0 cm (n=27) as compared to the control group who attained a near final height of 142.1 cm (n=19). By analysis of covariance, the effect of GH therapy was a mean height increase of 5.4 cm (p=0.001).

    In two of the studies (85-023 and 85-044), the effect of long-term GH treatment (0.375 mg/kg/wk given either 3 times per week or daily) on adult height was determined by comparing adult heights in the treated patients with those of age-matched historical controls with Turner syndrome who never received any growth-promoting therapy. In Study 85-023, estrogen treatment was delayed until patients were at least age 14. GH therapy resulted in a mean adult height gain of 7.4 cm (mean duration of GH therapy of 7.6 years) versus matched historical controls by analysis of covariance.

    In Study 85-044, patients treated with early GH therapy were randomized to receive estrogen-replacement therapy (conjugated estrogens, 0.3 mg escalating to 0.625 mg daily) at either age 12 or 15 years. Compared with matched historical controls, early GH therapy (mean duration of GH therapy 5.6 years) combined with estrogen replacement at age 12 years resulted in an adult height gain of 5.9 cm (n=26), whereas girls who initiated estrogen at age 15 years (mean duration of GH therapy 6.1 years) had a mean adult height gain of 8.3 cm (n=29). Patients who initiated GH therapy after age 11 (mean age 12.7 years; mean duration of GH therapy 3.8 years) had a mean adult height gain of 5.0 cm (n=51).

    Thus, in both studies, 85-023 and 85-044, the greatest improvement in adult height was observed in patients who received early GH treatment and estrogen after age 14 years.

    In a randomized, blinded, dose-response study, GDCI, patients were treated from a mean age of 11.1 years for a mean duration of 5.3 years with a weekly dose of either 0.27 mg/kg or 0.36 mg/kg administered 3 or 6 times weekly. The mean near final height of patients receiving growth hormone was 148.7 cm (n=31). This represents a mean gain in adult height of approximately 5 cm compared with previous observations of untreated Turner syndrome girls.

    In these studies, Turner syndrome patients (n=181) treated to final adult height achieved statistically significant average estimated adult height gains ranging from 5.0-8.3 cm.

    See TABLE 18

    ADULT GROWTH HORMONE DEFICIENCY (GHD)
    Two multicenter, double-blind, placebo-controlled clinical trials were conducted using Nutropin in GH-deficient adults. One study was conducted in subjects with adult-onset GHD, mean age 48.3 years, n=166, at doses of 0.0125 or 0.00625 mg/kg/day; doses of 0.025 mg/kg/day were not tolerated in these subjects. A second study was conducted in previously treated subjects with childhood-onset GHD, mean age 23.8 years, n=64, at randomly assigned doses of 0.025 or 0.0125 mg/kg/day. The studies were designed to assess the effects of replacement therapy with GH on body composition.

    Significant changes from baseline to Month 12 of treatment in body composition (i.e., total body % fat mass, trunk % fat mass, and total body % lean mass by DEXA scan) were seen in all Nutropin groups in both studies (p <0.0001 for change from baseline and vs placebo), whereas no statistically significant changes were seen in either of the placebo groups. In the adult-onset study, the Nutropin group improved mean total body fat from 35.0% to 31.5%, mean trunk fat from 33.9% to 29.5%, and mean lean body mass from 62.2% to 65.7%, whereas the placebo group had mean changes of 0.2% or less (p = not significant). Due to the possible effect of GH-induced fluid retention on DEXA measurements of lean body mass, DEXA scans were repeated approximately 3 weeks after completion of therapy; mean % lean body mass in the Nutropin group was 65.0%, a change of 2.8% from baseline, compared with a change of 0.4% in the placebo group (p <0.0001 between groups).

    In the childhood-onset study, the high-dose Nutropin group improved mean total body fat from 38.4% to 32.1%, mean trunk fat from 36.7% to 29.0%, and mean lean body mass from 59.1% to 65.5%; the low-dose Nutropin group improved mean total body fat from 37.1% to 31.3%, mean trunk fat from 37.9% to 30.6%, and mean lean body mass from 60.0% to 66.0%; the placebo group had mean changes of 0.6% or less (p = not significant).

    See TABLE 19A Mean Changes From Baseline to Month 12 in Proportion of Fat and Lean by DEXA for Study M0431g (Adult-Onset GHD)

    See TABLE 19B Mean Changes From Baseline to Month 12 in Proportion of Fat and Lean by DEXA for Study M0381g (Childhood-Onset GHD)

    In the adult-onset study, significant decreases from baseline to Month 12 in LDL cholesterol and LDL:HDL ratio were seen in the Nutropin group compared to the placebo group, p <0.02; there were no statistically significant between-group differences in change from baseline to Month 12 in total cholesterol, HDL cholesterol, or triglycerides. In the childhood-onset study, significant decreases from baseline to Month 12 in total cholesterol, LDL cholesterol, and LDL:HDL ratio were seen in the high-dose Nutropin group only, compared to the placebo group, p <0.05. There were no statistically significant between-group differences in HDL cholesterol or triglycerides from baseline to Month 12.

    In the childhood-onset study, 55% of the patients had decreased spine bone mineral density (BMD) (z-score < -1) at baseline. The administration of Nutropin (n=16) (0.025 mg/kg/day) for 2 years resulted in increased spine BMD from baseline when compared to placebo (n=13) (4.6% vs 1.0%, respectively, p <0.03); a transient decrease in spine BMD was seen at 6 months in the Nutropin-treated patients. Thirty-five percent (35%) of subjects treated with this dose had supraphysiological levels of IGF-I at some point during the study, which may carry unknown risks. No significant improvement in total body BMD was found when compared to placebo. A lower GH dose (0.0125 mg/kg/day) did not show significant increments in either of these bone parameters when compared to placebo. No statistically significant effects on BMD were seen in the adult-onset study where patients received GH (0.0125 mg/kg/day) for 1 year.

    Muscle strength, physical endurance, and quality of life measurements were not markedly abnormal at baseline, and no statistically significant effects of Nutropin therapy were observed in the two studies.

    INDICATIONS AND USAGE

    PEDIATRIC PATIENTS
    Nutropin AQ is indicated for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion.

    Nutropin AQ is also indicated for the treatment of growth failure associated with chronic renal insufficiency up to the time of renal transplantation. Nutropin AQ therapy should be used in conjunction with optimal management of chronic renal insufficiency.

    Nutropin AQ is also indicated for the long-term treatment of short stature associated with Turner syndrome.

    ADULT PATIENTS
    Nutropin AQ is indicated for the replacement of endogenous GH in patients with adult GH deficiency who meet both of the following two criteria: Biochemical diagnosis of adult GH deficiency by means of a subnormal response to a standard GH stimulation test (peak GH 5 ug/L), and
    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 Nutropin AQ is started.

    CONTRAINDICATIONS

    Growth hormone 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).

    Nutropin AQ should not be used for growth promotion in pediatric patients with closed epiphyses.

    Nutropin AQ should not be used in patients with active neoplasia. GH therapy should be discontinued if evidence of neoplasia develops.

    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.

    PRECAUTIONS

    GENERAL
    Nutropin AQ should be prescribed by physicians experienced in the diagnosis and management of patients with GH deficiency, Turner syndrome, or chronic renal insufficiency (CRI). No studies have been completed of Nutropin AQ 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.

  5. #5
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    GERIATRIC USE
    Clinical studies of Nutropin AQ did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    Patients with epiphyseal closure who were treated with GH-replacement therapy in childhood should be re-evaluated according to the criteria in INDICATIONS AND USAGE before continuation of GH therapy at the reduced dose level recommended for GH-deficient adults.

    Because Nutropin AQ may reduce insulin sensitivity, patients should be monitored for evidence of glucose intolerance.

    For patients with diabetes mellitus, the insulin dose may require adjustment when GH therapy is instituted. Because GH may reduce insulin sensitivity, particularly in obese individuals, patients should be observed for evidence of glucose intolerance. Patients with diabetes or glucose intolerance should be monitored closely during GH therapy.

    Nutropin therapy in adults with GH deficiency of adult onset was associated with an increase of median fasting insulin in the Nutropin 0.0125 mg/kg/day group from 9.0 uU/ml at baseline to 13.0 uU/ml at Month 12 with a return to the baseline median after a 3-week post-washout period of GH therapy. In the placebo group there was no change from 8.0 uU/ml at baseline to Month 12, and after the post-washout the median was 9.0 uU/ml. The between-treatment-groups difference in change from baseline to Month 12 was significant, p <0.0001. In childhood-onset subjects there was a change of median fasting insulin in the Nutropin 0.025 mg/kg/day group from 11.0 uU/ml at baseline to 20.0 uU/ml at Month 12, in the Nutropin 0.0125 mg/kg/day group from 8.5 uU/ml to 11.0 uU/ml, and in the placebo group from 7.0 uU/ml to 8.0 uU/ml. The between-treatment-groups difference for these changes was significant, p=0.0007.

    In subjects with adult-onset GH deficiency, there was no between-treatment-group difference in changes from baseline to Month 12 in mean HbA1c, p=0.08. In childhood-onset mean HbA1c increased in the Nutropin 0.025 mg/kg/day group from 5.2% at baseline to 5.5% at Month 12, and did not change in the Nutropin 0.0125 mg/kg/day group from 5.1% at baseline or in the placebo group from 5.3% at baseline. The between-treatment-groups difference was significant, p=0.009.

    Patients with a history of an intracranial lesion should be examined frequently for progression or recurrence of the lesion. In pediatric patients, clinical literature has demonstrated no relationship between GH-replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors. In adults, it is unknown whether there is any relationship between GH-replacement therapy and CNS tumor recurrence.

    Patients with growth failure secondary to CRI should be examined periodically for evidence of progression of renal osteodystrophy. Slipped capital femoral epiphysis or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy, and it is uncertain whether these problems are affected by GH therapy. x-rays of the hip should be obtained prior to initiating GH therapy for CRI patients. Physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in patients treated with Nutropin AQ.

    Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth.

    Progression of scoliosis can occur in patients who experience rapid growth. Because GH increases growth rate, patients with a history of scoliosis who are treated with GH should be monitored for progression of scoliosis. GH has not been shown to increase the incidence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Physicians should be alert to these abnormalities, which may manifest during GH therapy.

    Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear or hearing disorders. In a randomized, controlled trial, there was a statistically significant increase, as compared to untreated controls, in otitis media (43% vs 26%) and ear disorders (18% vs 5%) in patients receiving GH. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm, hypertension) as these patients are also at risk for these conditions.

    Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with GH products. Symptoms usually occurred within the first 8 weeks of the initiation of GH therapy. In all reported cases, IH-associated signs and symptoms resolved after termination of therapy or a reduction of the GH dose. Funduscopic examination of patients is recommended at the initiation and periodically during the course of GH therapy. Patients with CRI and Turner syndrome may be at increased risk for development of IH.

    As with any protein, local or systemic allergic reactions may occur. Parents/Patient should be informed that such reactions are possible and that prompt medical attention should be sought if allergic reactions occur.

    LABORATORY TESTS
    Serum levels of inorganic phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) may increase with Nutropin AQ therapy.

    Untreated hypothyroidism prevents optimal response to Nutropin AQ. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease. Changes in thyroid hormone laboratory measurements may develop during Nutropin AQ treatment. Therefore, patients should have periodic thyroid function tests and should be treated with thyroid hormone when indicated.

    CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
    Carcinogenicity, mutagenicity, and reproduction studies have not been conducted with Nutropin AQ.

    PREGNANCY CATEGORY C
    Animal reproduction studies have not been conducted with Nutropin AQ. It is also not known whether Nutropin AQ can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nutropin AQ should be given to a pregnant woman only if clearly needed.

    NURSING MOTHERS
    It is not known whether Nutropin AQ is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nutropin AQ is administered to a nursing mother.

    INFORMATION FOR THE PATIENT
    Patients being treated with GH and/or their parents should be informed of the potential benefits and risks associated with treatment. If home use is determined to be desirable by the physician, instructions on appropriate use should be given, including a review of the contents of the Patient Information Insert. This information is intended to aid in the safe and effective administration of the medication. It is not a disclosure of all possible adverse or intended effects.

    If home use is prescribed, a puncture-resistant container for the disposal of used syringes and needles should be recommended to the patient. Patients and/or parents should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes (see the Patient Information Insert that is provided with the prescription).

    DRUG INTERACTIONS

    Excessive glucocorticoid therapy will inhibit the growth-promoting effect of human GH. Patients with ACTH deficiency should have their glucocorticoid-replacement dose carefully adjusted to avoid an inhibitory effect on growth.

    The use of Nutropin AQ in patients with CRI receiving glucocorticoid therapy has not been evaluated. Concomitant glucocorticoid therapy may inhibit the growth-promoting effect of Nutropin AQ. If glucocorticoid replacement is required, the glucocorticoid dose should be carefully adjusted.

    There was no evidence in the controlled studies of GH's interaction with drugs commonly used in chronic renal insufficiency patients. Limited published data indicate that GH treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that GH administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids , anticonvulsants, cyclosporin). Careful monitoring is advisable when GH is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.

    ADVERSE REACTIONS

    As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. GH antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. In clinical studies of pediatric patients that were treated with Nutropin for the first time, 0/107 growth hormone -deficient (GHD) patients, 0/125 CRI patients, and 0/112 Turner syndrome patients screened for antibody production developed antibodies with binding capacities 2 mg/L at 6 months. In a clinical study of patients that were treated with Nutropin AQ for the first time, 0/38 GHD patients screened for antibody production, for up to 15 months, developed antibodies with binding capacities 2 mg/L.

    Additional short-term immunologic and renal function studies were carried out in a group of CRI patients after approximately 1 year of treatment to detect other potential adverse effects of antibodies to GH. Testing included measurements of C1q, C3, C4, rheumatoid factor, creatinine, creatinine clearance, and BUN. No adverse effects of GH antibodies were noted.

    In addition to an evaluation of compliance with the prescribed treatment program and thyroid status, testing for antibodies to GH should be carried out in any patient who fails to respond to therapy.

    Injection site discomfort has been reported. This is more commonly observed in children switched from another GH product to Nutropin AQ. Experience with Nutropin AQ in adults is limited.

    Leukemia has been reported in a small number of GHD patients treated with GH. It is uncertain whether this increased risk is related to the pathology of GH deficiency itself, GH therapy, or other associated treatments such as radiation therapy for intracranial tumors. On the basis of current evidence, experts cannot conclude that GH therapy is responsible for these occurrences. The risk to GHD, CRI, or Turner syndrome patients, if any, remains to be established.

    Other adverse drug reactions that have been reported in GH-treated patients include the following:
    Metabolic: Mild, transient peripheral edema. In GHD adults, edema or peripheral edema was reported in 41% of GH-treated patients and 25% of placebo-treated patients.
    Musculoskeletal: Arthralgias; carpal tunnel syndrome. In GHD adults, arthralgias and other joint disorders were reported in 27% of GH-treated patients and 15% of placebo-treated patients.
    Skin: Rare increased growth of pre-existing nevi; patients should be monitored for malignant transformation.
    Endocrine: Gynecomastia . Rare pancreatitis.

    OVERDOSAGE

    Acute overdosage could lead to hyperglycemia. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess GH. (See recommended and maximal dosage instructions given in DOSAGE AND ADMINISTRATION.)

    DOSAGE AND ADMINISTRATION

    The Nutropin AQ dosage and administration schedule should be individualized for each patient. Response to GH therapy in pediatric patients tends to decrease with time. However, in pediatric patients whose failure to increase growth rate, particularly during the first year of therapy, suggests the need for close assessment of compliance and evaluation of other causes of growth failure, such as hypothyroidism, under-nutrition, and advanced bone age.

    DOSAGE
    Pediatric Growth Hormone Deficiency (GHD)
    A weekly dosage of up to 0.30 mg/kg of body weight divided into daily SC injection is recommended. In pubertal patients, a weekly dosage of up to 0.7 mg/kg divided daily may be used.

    Adult Growth Hormone Deficiency (GHD)
    The recommended dosage at the start of therapy is not more than 0.006 mg/kg given as a daily SC injection. The dose may be increased according to individual patient requirements to a maximum of 0.025 mg/kg daily in patients under 35 years and to a maximum of 0.0125 mg/kg daily in patients over 35 years.

    To minimize the occurrence of adverse events in older or overweight patients, lower doses may be necessary. During therapy, dosage should be decreased if required by the occurrence of side effects or excessive IGF-I levels.

    Chronic Renal Insufficiency (CRI)
    A weekly dosage of up to 0.35 mg/kg of body weight divided into daily SC injection is recommended.

    Nutropin AQ therapy may be continued up to the time of renal transplantation.

    In order to optimize therapy for patients who require dialysis, the following guidelines for injection schedule are recommended: Hemodialysis patients should receive their injection at night just prior to going to sleep or at least 3-4 hours after their hemodialysis to prevent hematoma formation due to the heparin.
    Chronic Cycling Peritoneal Dialysis (CCPD) patients should receive their injection in the morning after they have completed dialysis.
    Chronic Ambulatory Peritoneal Dialysis (CAPD) patients should receive their injection in the evening at the time of the overnight exchange.

    Turner Syndrome
    A weekly dosage of up to 0.375 mg/kg of body weight divided into equal doses 3-7 times per week by SC injection is recommended.

    ADMINISTRATION
    The solution should be clear immediately after removal from the refrigerator. Occasionally, after refrigeration, you may notice that small colorless particles of protein are present in the solution. This is not unusual for solutions containing proteins. Allow the vial or pen cartridge to come to room temperature and gently swirl. If the solution is cloudy, the contents MUST NOT be injected.

    For Nutropin AQ Vial
    Before needle insertion, wipe the septum of the Nutropin AQ vial with rubbing alcohol or an antiseptic solution to prevent contamination of the contents by microorganisms that may be introduced by repeated needle insertions. It is recommended that Nutropin AQ be administered using sterile, disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be drawn from the vial with reasonable accuracy.

    For Nutropin AQ Pen Cartridge
    The Nutropin AQ pen cartridge is intended for use only with the Nutropin AQ Pen. Wipe the septum of the Nutropin AQ pen cartridge with rubbing alcohol or an antiseptic solution to prevent contamination of the contents by microorganisms that may be introduced by repeated needle insertions. It is recommended that Nutropin AQ be administered using sterile, disposable needles. Follow the directions provided in the Nutropin AQ Pen Instructions for Use.

    The Nutropin AQ pen allows for administration of a minimum dose of 0.1 mg to a maximum dose of 4.0 mg, in 0.1 mg increments.

    HOW SUPPLIED

    Nutropin AQ is supplied as either 10 mg (approximately 30 IU) of sterile liquid somatropin per vial, or as 10 mg (approximately 30 IU) of sterile liquid somatropin per pen cartridge.

    Each vial carton contains 1 single vial containing 2 ml of Nutropin AQ (5 mg/ml).

    Each pen cartridge carton contains 1 single pen cartridge containing 2 ml of Nutropin AQ (5 mg/ml).

    STABILITY AND STORAGE
    Vial and cartridge contents are stable for 28 days after initial use when stored at 2-8C/36-46F (under refrigeration). Avoid Freezing the vial or the cartridge of Nutropin AQ. The vials and cartridges of Nutropin AQ are light sensitive and they should be protected from light. Store the vial and cartridge refrigerated in a dark place when they are not in use.

    BRAND NAME: SEROSTIM

    DESCRIPTION

    Serostim is a human growth hormone (hGH) produced by recombinant DNA technology. Serostim has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary GH. Serostim is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. Serostim is secreted directly through the cell membrane into the cell-culture medium for collection and purification.

    Serostim is a highly purified preparation. Biological potency is determined by measuring the increase in the body weight induced in hypophysectomized rats.

    Serostim is available in 4, 5 and 6 mg vials for single dose administration. Each 4 mg vial contains 4.0 mg (approximately 12 IU) somatropin, 27.3 mg sucrose, 0.9 mg phosphoric acid. Each 5 mg vial contains 5.0 mg (approximately 15 IU) somatropin, 34.2 mg sucrose and 1.2 mg phosphoric acid. Each 6 mg vial contains 6.0 mg (approximately 18 IU) somatropin, 41.0 mg sucrose and 1.4 mg phosphoric acid. The pH is adjusted with sodium hydroxide or phosphoric acid to give a pH of 7.4-8.5 after reconstitution.

    CLINICAL PHARMACOLOGY

    Serostim is an anabolic and anticatabolic agent which exerts its influence by interacting with specific receptors on a variety of cell types including myocytes, hepatocytes, adipocytes, lymphocytes, and hematopoietic cells. Some, but not all of its effects, are mediated by insulin-like growth factor-I (IGF-I).

    HIV-associated wasting or cachexia, which commonly involves involuntary loss of lean body mass or body weight, is a metabolic disorder characterized by abnormalities of intermediary metabolism resulting in weight loss, inappropriate depletion of lean body mass (LBM), and paradoxical preservation of body fat. LBM includes primarily skeletal muscle, organ tissue, blood and blood constituents, and both intracellular and extracellular water. Depletion of LBM results in muscle weakness, organ failure, and death. Unlike nutritional intervention for HIV-associated wasting, in which supplemental calories are converted predominantly to body fat, Serostim treatment resulted in a significant increase in LBM and a decrease in fat mass with a significant increase in body weight due to the dominant effect of LBM gain.

    EFFECTS ON PROTEIN, LIPID, AND CARBOHYDRATE METABOLISM
    A 1-week study in 6 patients with HIV-associated wasting has shown that treatment with Serostim 0.1 mg/kg/day improved nitrogen balance, increased protein-sparing lipid oxidation, and had little effect on overall carbohydrate metabolism.

    EFFECTS ON NITROGEN AND MINERAL RETENTION
    In the 1-week study in 6 patients with HIV-associated wasting, treatment with Serostim resulted in the retention of phosphorous, potassium, nitrogen, and sodium. The ratio of retained potassium and nitrogen during Serostim therapy was consistent with retention of these elements in lean tissue.

  6. #6
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    PHARMACOKINETICS
    Subcutaneous Absorption
    The absolute bioavailability of Serostim after SC administration of a formulation not equivalent to the marketed formulation was determined to be 70-90%. The T 1/2 (Mean SD) after SC administration is significantly longer than that seen after IV administration in normal male volunteers down-regulated with somatostatin (3.94 3.44 h vs 0.58 0.08 h), indicating that the SC absorption of the clinically tested formulation of the compound is slow and rate-limiting.

    Distribution
    The steady-state volume of distribution (Mean SD) following IV administration of Serostim in healthy volunteers is 12.0 1.08 L.

    Metabolism
    Although the liver plays a role in the metabolism of GH, GH is primarily cleaved in the kidney. GH undergoes glomerular filtration and, after cleavage within the renal cells, the peptides and amino acids are returned to the systemic circulation.

    Elimination
    The T 1/2 (Mean SD) in 9 patients with HIV-associated wasting with an average weight of 56.7 6.8 kg, given a fixed dose of 6.0 mg recombinant hGH (r-hGH) subcutaneously was 4.28 2.15 h The renal clearance of r-hGH after SC administration in 9 patients with HIV-associated wasting was 0.0015 0.0037 L/h. No significant accumulation of r-hGH appears to occur after 6 weeks of dosing as indicated.

    SPECIAL POPULATIONS
    Pediatric
    Available evidence suggests that r-hGH clearances are similar in adults and children, but no pharmacokinetic studies have been conducted in children with HIV.

    Gender
    Biomedical literature indicates that a gender- related difference in the mean clearance of r-hGH could exist (clearance of r-hGH in males > clearance of r-hGH in females). However, no gender-based analysis is available in normal volunteers or patients infected with HIV.

    Race
    No data are available.

    Renal Insufficiency
    It has been reported that individuals with chronic renal failure tend to have decreased r-hGH clearance compared to normals, but there are no data on Serostim use in the presence of renal insufficiency.

    Hepatic Insufficiency
    A reduction in r-hGH clearance has been noted in patients with severe liver dysfunction. However, the clinical significance of this in HIV+ patients is unknown.

    CLINICAL STUDIES

    The clinical efficacy of Serostim was assessed in two placebo-controlled trials. All study subjects received concomitant antiretroviral therapy.

    CLINICAL TRIAL 1
    A 12-week, randomized, double-blind, placebo-controlled study followed by an open-label extension phase enrolled 178 patients with severe AIDS wasting taking nucleoside analogue therapy (pre-HAART era). The primary endpoint was body weight. Body composition was assessed using dual energy x-ray absorptiometry (DXA) and physical function was assessed by treadmill exercise testing. Patients meeting the inclusion/exclusion criteria were treated with either placebo or Serostim 0.1 mg/kg daily. Ninety-six percent (96%) were male. The average baseline CD4 count/ul was 85. The results from one hundred forty (140) evaluable patients were analyzed (those completing the 12-week course of treatment and who were at least 80% compliant with study drug). After 12 weeks of therapy, the mean difference in weight increase between the Serostim-treated group and the placebo-treated group was 1.6 kg (3.5 lb). Mean difference in lean body mass (LBM) change between the Serostim-treated group and the placebo-treated group was 3.1 kg (6.8 lb) as measured by DXA. Mean increase in weight and LBM, and mean decrease in body fat, were significantly greater in the Serostim-treated group than in the placebo group (p=0.011, p <0.001, p <0.001, respectively) after 12 weeks of treatment. There were no significant changes with continued treatment beyond 12 weeks suggesting that the original gains of weight and LBM were maintained.

    Treatment with Serostim resulted in a significant increase in physical function as assessed by treadmill exercise testing. The median treadmill work output increased by 13% (p=0.039) at 12 weeks in the group receiving Serostim. There was no improvement in the placebo-treated group at 12 weeks. Changes in treadmill performance were significantly correlated with changes in LBM.

    CLINICAL TRIAL 2
    A 12-week, randomized, double-blind, placebo-controlled study enrolled 757 patients with HIV-associated wasting, or cachexia. The primary efficacy endpoint was physical function as measured by cycle ergometry work output. Body composition was assessed using bioelectrical impedance absorptiometry (BIA) and also by dual energy x-ray absorptiometry (DXA) at a subset of centers. Patients meeting the inclusion/exclusion criteria were treated with either placebo, approximately 0.1 mg/kg every other day (qod) of Serostim, or approximately 0.1 mg/kg daily (qhs) of Serostim. All results were analyzed in intent-to-treat populations (for cycle ergometry work output, n=670). Ninety-one percent (91%) were male and 88% were on HAART anti-retroviral therapy. The average baseline CD4 count/uL was 446. Six hundred forty-six patients (646) completed the 12-week study and continued in the Serostim treatment extension phase of the trial.

    Clinical Trial 2 results are summarized in TABLE 20 and TABLE 21.

    See TABLE 20 Mean (Median) of Cycle Work Output (kJ) Response After 12 Weeks of Treatment ITT Population

    See TABLE 21 Mean (Median) Change From Baseline for Lean Body Mass, Fat Mass and Body Weight

    The mean maximum cycle work output until exhaustion increased after 12 weeks by 2.57 kilojoules (kJ) in the Serostim 0.1 mg/kg daily group (p <0.0001) and by 2.53 kJ in the Serostim 0.1 mg/kg every other day group (p <0.0001) compared with placebo (TABLE 20). Cycle work output improved approximately 9% in both active treatment arms and decreased <1% in the placebo group. Lean body mass (LBM) and body weight (BW) increased, and fat mass decreased, in a dose-related fashion after treatment with Serostim and placebo (TABLE 21). The LBM results obtained by BIA were confirmed with DXA.

    Patients' perceptions of the impact of 12 weeks of treatment on their wasting symptoms as assessed by the Bristol-Meyers Anorexia/Cachexia Recovery Instrument improved with both doses of Serostim in Clinical Trial 2.

    Extension Phase
    All patients (n=646) completing the 12-week placebo-controlled phase of Clinical Trial 2 continued Serostim treatment into an extension phase. Five hundred and forty eight (548) of these patients completed an additional 12 weeks of active treatment. In these patients, changes in cycle ergometry work output, LBM, BW, and fat mass either improved further or were maintained with continued Serostim treatment.

    INDICATIONS AND USAGE

    Serostim is indicated for the treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance. Concomitant antiretroviral therapy is necessary (see PRECAUTIONS).

    CONTRAINDICATIONS

    Growth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or 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).

    Serostim is contraindicated in patients with active neoplasia (either newly diagnosed or recurrent). Any anti-tumor therapy should be completed prior to starting therapy with Serostim.

    Serostim is contraindicated in patients with a known hypersensitivity to growth hormone.

    WARNINGS

    See CONTRAINDICATIONS for information regarding increased mortality in growth hormone-treated patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or 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 developing acute critical illnesses should be weighed against the potential risk.

    PRECAUTIONS

    GENERAL
    Serostim therapy should be carried out under the regular guidance of a physician who is experienced in the diagnosis and management of HIV infection. Inadequate nutritional intake, malabsorption and hypogonadism, which are common in individuals with HIV infection and which may contribute to catabolism and weight loss, should be diagnosed and treated.

    HIV AND GROWTH HORMONE CONSIDERATIONS
    In some experimental systems, recombinant human growth hormone (r-hGH) has been shown to potentiate HIV replication in vitro at concentrations ranging from 50-250 ng/ml. There was no increase in virus production when the antiretroviral agents, zidovudine, didanosine or lamivudine were added to the culture medium. Additional in vitro studies have shown that r-hGH does not interfere with the antiviral activity of zalcitabine or stavudine. In the controlled clinical trials, no significant growth hormone-associated increase in viral burden was observed. However, the protocol required all participants to be on concomitant antiretroviral therapy for the duration of the study. In view of the potential for acceleration of virus replication, it is recommended that HIV patients be maintained on antiretroviral therapy for the duration of Serostim treatment.

    Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Serostim, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing (see DOSAGE AND ADMINISTRATION).

    Carpal tunnel syndrome may occur during treatment with Serostim. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the weekly number of doses of Serostim, it is recommended that treatment be discontinued.

    Patients should be informed that allergic reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs. None of the 651 study participants with HIV-associated wasting treated with Serostim for the first time developed detectable antibodies to growth hormone (>4 pg binding). Patients were not rechallenged.

    Recombinant human growth hormone (r-hGH) has been associated with acute pancreatitis.

    Hyperglycemia may occur in HIV infected individuals due to a variety of reasons. Treatment with Serostim 0.1 mg/kg daily and 0.1 mg/kg every other day for 12 weeks were associated with approximately 10 mg/dl and 6 mg/dl increases of mean blood glucose concentration, respectively. The increases occurred early in treatment. Patients with other risk factors for glucose intolerance should be monitored closely during Serostim therapy.

    During postmarketing surveillance, cases of new onset impaired glucose intolerance, new onset Type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving Serostim. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when Serostim was discontinued, while in others the glucose intolerance persisted. Some patients necessitated initiation or adjustment of antidiabetic treatment while on Serostim.

    No cases of intracranial hypertension (IH) have been observed among patients with AIDS wasting treated with Serostim. The syndrome of IH, with papilledema, visual changes, headache, and nausea and/or vomiting has been reported in a small number of children with growth failure treated with growth hormone products. Nevertheless, funduscopic evaluation of patients is recommended at the initiation and periodically during the course of Serostim therapy.

    Kaposi's sarcoma, lymphoma, and other malignancies are common in HIV+ individuals. There was no increase in the incidence of Kaposi's sarcoma, lymphoma, or in the progression of cutaneous Kaposi's sarcoma in clinical studies of Serostim. Patients with internal KS lesions were excluded from the studies. Potential effects on other malignancies are unknown.

    INFORMATION FOR THE PATIENT
    Patients being treated with Serostim should be informed of the potential benefits and risks associated with treatment. Patients should be instructed to contact their physician should they experience any side effects or discomfort during treatment with Serostim.

    It is recommended that Serostim be administered using sterile, disposable syringes and needles. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes. An appropriate container for the disposal of used syringes and needles should be employed.

    Patients should be instructed to rotate injection sites to avoid localized tissue atrophy.

    CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
    Long-term animal studies for carcinogenicity have not been performed with Serostim. There is no evidence from animal studies to date of Serostim-induced mutagenicity or impairment of fertility.

    PREGNANCY CATEGORY B
    Reproduction studies have been performed in rats and rabbits. Doses up to 5-10 times the human dose, based on body surface area, have revealed no evidence of impaired fertility or harm to the fetus due to Serostim. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

    NURSING WOMEN
    It is not known whether Serostim is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Serostim is administered to a nursing woman.

    PEDIATRIC USE
    In two small studies, 11 children with HIV-associated failure to thrive were treated subcutaneously with human growth hormone. In one study, 5 children (age range, 6-17 years) were treated with 0.04 mg/kg/day for 26 weeks. In a second study, 6 children (age range, 8-14 years) were treated with 0.07 mg/kg/day for 4 weeks. Treatment appeared to be well tolerated in both studies. The preliminary data collected on a limited number of patients with HIV-associated failure to thrive appear to be consistent with safety observations in growth hormone-treated adults with AIDS wasting.

    GERIATRIC USE
    Clinical studies with Serostim did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may be more sensitive to growth hormone action, and may be more prone to develop adverse reactions. Thus, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.

    DRUG INTERACTIONS

    Formal in vitro drug interaction studies have not been conducted. No data are available on drug interactions between Serostim and HIV protease inhibitors or the non-nucleoside reverse transcriptase inhibitors.

    ADVERSE REACTIONS

    In the 12-week, placebo-controlled Clinical Trial 2, 510 patients were treated with Serostim. The most common adverse reactions judged to be associated with Serostim were musculoskeletal discomfort and increased tissue turgor (swelling, particularly of the hands or feet), and were more frequently observed when Serostim 0.1 mg/kg was administered on a daily basis (TABLE 22 and PRECAUTIONS). These symptoms were generally rated by investigators as mild to moderate in severity and often subsided with continued treatment or dose reduction. Approximately 23% of patients receiving Serostim 0.1 mg/kg daily and 11% of patients receiving 0.1 mg/kg every other day required dose reductions. Discontinuations as a result of adverse events occurred in 10.3% of patients receiving Serostim 0.1 mg/kg daily and 6.6% of patients receiving 0.1 mg/kg every other day. The most common reasons for dose reduction and/or drug discontinuation were arthralgia, myalgia, edema, carpal tunnel syndrome, elevated glucose levels, and elevated triglyceride levels.

    Clinical adverse events which occurred during the first 12 weeks of study in at least 5% of the patients in any 1 of the 3 treatment groups are listed in TABLE 22 by treatment group, without regard to causality assessment.

    See TABLE 22 Controlled Clinical Trial 2 Adverse Events

    Adverse events that occurred in 1% to less than 5% of study participants receiving Serostim during the 12-week, placebo-controlled Clinical Trial 2 are listed below by body system. The list of adverse events has been compiled regardless of causal relationship to Serostim.

    Body as a Whole: Rigors, fever, carpal tunnel syndrome (see PRECAUTIONS), night sweats, edema/face edema (see PRECAUTIONS), pain, flu-like symptoms, leg pain, chest pain, asthenia.
    Gastrointestinal System: Vomiting, abdominal pain, dyspepsia, gastroenteritis, and constipation.
    Musculoskeletal System: Back pain, musculoskeletal pain (see PRECAUTIONS), and arthropathy.
    Central and Peripheral Nervous System: Peripheral neuropathy, dizziness, and hypertonia.
    Respiratory System: Coughing, sinusitis, pharyngitis, and pneumonia.
    White Blood Cell and Reticuloendothelial System Disorders: Lymphadenopathy.
    Skin and Appendages: Folliculitis, rash, verruca, and maculopapular rash.
    Psychiatric: Anorexia, depression, anxiety, and somnolence.
    Metabolic and Nutritional: Hypertriglyceridemia, hyperglycemia (see PRECAUTIONS), and periorbital edema (see PRECAUTIONS).
    Immune System Dysfunction: Moniliasis, viral infection, and herpes simplex.
    Urinary System: Urinary tract infection, renal calculus.
    Vision: Conjunctivitis.
    Cardiovascular, General: Dependent edema (see PRECAUTIONS), hypertension, tachycardia.
    Secondary Terms: Accident not otherwise specified.
    Neoplasms: Male breast neoplasm.

    During the 12-week, placebo-controlled portion of Clinical Trial 2, the incidence of hyperglycemia reported as an adverse event was 3.6% for the placebo group, 1.9% for the 0.1 mg/kg qod group and 3.2% for the 0.1 mg/kg daily group. One case of diabetes mellitus was noted in the 0.1 mg/kg daily group during the first 12-weeks of therapy. In addition, during the extension phase of Clinical Trial 2, 2 patients converted from placebo to full dose Serostim, and 1 patient converted from placebo to half-dose Serostim, were discontinued because of the development of diabetes mellitus.

    The types and incidences of adverse events reported during the Clinical Trial 2 extension phase were not different from, or greater in frequency than those observed during the 12-week, placebo-controlled portion of Clinical Trial 2.

    During postmarketing surveillance, cases of new onset impaired glucose intolerance, new onset Type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving Serostim. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when Serostim was discontinued, while in others the glucose intolerance persisted. Some patients necessitated initiation or adjustment of antidiabetic treatment while on Serostim.

    OVERDOSAGE

    Glucose intolerance can occur with overdosage. Long-term overdosage with growth hormone could result in signs and symptoms of acromegaly.

    DOSAGE AND ADMINISTRATION

    The usual starting dose of Serostim is 0.1 mg/kg subcutaneously daily (up to 6 mg). It should be administered SC daily at bedtime according to the dosage recommendations in TABLE 23.

    See TABLE 23

    Serostim 4, 5 or 6 mg with sterile water for injection single use vials, should be administered to patients requiring 4, 5 or 6 mg daily, respectively, as per the above weight-based dosing table (TABLE 23).

    Treatment with Serostim 0.1 mg/kg every other day was associated with fewer side effects, and resulted in a similar improvement in work output, as compared with Serostim 0.1 mg/kg daily. Therefore, a starting dose of Serostim 0.1 mg/kg every other day should be considered in patients at increased risk for adverse effects related to recombinant human growth hormone therapy (i.e., glucose intolerance). In general, dose reductions (i.e., reducing the total daily dose or the number of doses per week) should be considered for side effects potentially related to recombinant human growth hormone therapy, which are unresponsive to symptom-directed treatment.

    Most of the effect of Serostim on work output and lean body mass was apparent after 12 weeks of treatment. The effect was maintained during an additional 12 weeks of therapy. There are no safety or efficacy data available from controlled studies in which patients were treated with Serostim continuously for more than 48 weeks. There are no safety or efficacy data available from controlled trials in which patients were treated intermittently with Serostim.

    Injection sites should be rotated.

    Safety and effectiveness in pediatric patients with HIV have not been established.

    Each vial of Serostim 4, 5 or 6 mg is reconstituted with 0.5-1 ml sterile water for injection.

    To reconstitute Serostim, inject the diluent into the vial of Serostim aiming the liquid against the glass vial wall. Swirl the vial with a gentle rotary motion until contents are dissolved completely. The Serostim solution should be clear immediately after reconstitution. DO NOT INJECT Serostim if the reconstituted product is cloudy immediately after reconstitution or after refrigeration (2-8C/36-46F) for up to 14 days. Occasionally, after refrigeration, small colorless particles may be present in the Serostim solution. This is not unusual for proteins like Serostim.

  7. #7
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    HOW SUPPLIED

    Serostim is available in the following forms:
    Serostim vials containing 4 mg (approximately 12 IU) somatropin (mammalian-cell) with sterile water for injection.
    Serostim vials containing 5 mg (approximately 15 IU) somatropin (mammalian-cell) with sterile water for injection.
    Serostim vials containing 6 mg (approximately 18 IU) somatropin (mammalian-cell) with sterile water for injection.

    STABILITY AND STORAGE
    Before Reconstitution: Vials of Serostim and diluent should be stored at room temperature, (15-30C/59-86F). Expiration dates are stated on product labels.
    After Reconstitution With Sterile Water for Injection: The reconstituted solution should be used immediately and any unused portion should be discarded.

    BRAND NAME: ZORBTIVE

    DESCRIPTION

    Zorbtive (somatropin [rDNA origin] for injection) is a human growth hormone (hGH) produced by recombinant DNA technology. Zorbtive has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary GH. Zorbtive is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. Zorbtive is secreted directly through the cell membrane into the cell-culture medium for collection and purification.

    Zorbtive is a highly purified preparation. Biological potency is determined by measuring the increase in the body weight induced in hypophysectomized rats.

    Zorbtive is available in 4, 5 and 6 mg vials for single dose administration. Zorbtive is also available in 8.8 mg vials for multi-dose administration. Each 4 mg vial contains 4.0 mg (approximately 12 IU) somatropin, 27.3 mg sucrose, 0.9 mg phosphoric acid. Each 5 mg vial contains 5.0 mg (approximately 15 IU) somatropin, 34.2 mg sucrose and 1.2 mg phosphoric acid. Each 6 mg vial contains 6.0 mg (approximately 18 IU) somatropin, 41.0 mg sucrose and 1.4 mg phosphoric acid. Each 8.8 mg vial contains 8.8 mg (approximately 26.4 IU) somatropin, 60.19 mg sucrose and 2.05 mg phosphoric acid. The pH is adjusted with sodium hydroxide or phosphoric acid to give a pH of 7.4-8.5 after reconstitution.

    CLINICAL PHARMACOLOGY

    Zorbtive is an anabolic and anticatabolic agent which exerts its influence by interacting with specific receptors on a variety of cell types including myocytes, hepatocytes, adipocytes, lymphocytes, and hematopoietic cells. Some, but not all of its effects, are mediated by insulin -like growth factor-I (IGF-I).

    MECHANISM OF ACTION IN SHORT BOWEL SYNDROME (SBS) PATIENTS
    Intestinal mucosa contains receptors for growth hormone and for insulin-like growth factor-I (IGF-I), which is known to mediate many of the cellular actions of growth hormone. Thus, the actions of growth hormone on the gut may be direct or mediated via the local or systemic production of IGF.

    In human clinical studies the administration of growth hormone has been shown to enhance the transmucosal transport of water, electrolytes, and nutrients.

    PHARMACOKINETICS
    Subcutaneous Absorption
    The absolute bioavailability of Zorbtive [somatropin (rDNA origin) for injection] after SC administration of a formulation not equivalent to the marketed formulation was determined to be 70-90%. The T 1/2 (Mean SD) after SC administration is significantly longer than that seen after IV administration in normal male volunteers down-regulated with somatostatin (3.94 3.44 h vs 0.58 0.08 h), indicating that the SC absorption of the clinically tested formulation of the compound is slow and rate-limiting.

    Distribution
    The steady-state volume of distribution (Mean SD) following IV administration of Zorbtive in healthy volunteers is 12.0 1.08 L.

    Metabolism
    Although the liver plays a role in the metabolism of GH, GH is primarily cleaved in the kidney. GH undergoes glomerular filtration and, after cleavage within the renal cells, the peptides and amino acids are returned to the systemic circulation.

    Elimination
    The T 1/2 (Mean SD) in nine patients with HIV-associated wasting with an average weight of 56.7 6.8 kg, given a fixed dose of 6.0 mg recombinant hGH (r-hGH) subcutaneously was 4.28 2.15 h The renal clearance of r-hGH after SC administration in 9 patients with HIV-associated wasting was 0.0015 0.0037 L/h. No significant accumulation of r-hGH appears to occur after 6 weeks of dosing as indicated.

    Special Populations
    Pediatric
    Available evidence suggests that r-hGH clearances are similar in adults and children, but no pharmacokinetic studies have been conducted in children with short bowel syndrome.

    Gender
    Biomedical literature indicates that a gender-related difference in the mean clearance of r-hGH could exist (clearance of r-hGH in males > clearance of r-hGH in females). However, no gender-based analysis is available in normal volunteers or patients with short bowel syndrome.

    Race
    No data are available.

    Renal Insufficiency
    It has been reported that individuals with chronic renal failure tend to have decreased r-hGH clearance compared to normals, but there are no data on Zorbtive use in the presence of renal insufficiency.

    Hepatic Insufficiency
    A reduction in r-hGH clearance has been noted in patients with severe liver dysfunction. However, the clinical significance of this in short bowel syndrome patients is unknown.

    CLINICAL STUDIES

    A randomized, double blind, controlled, parallel-group Phase 3 clinical study evaluated the efficacy and safety of the administration of Zorbtive in subjects with Short Bowel Syndrome (SBS) who were dependent on intravenous parenteral nutrition (IPN) for nutritional support. The primary endpoint was the change in weekly total IPN volume defined as the sum of the volumes of IPN, supplemental lipid emulsion (SLE), and intravenous hydration fluid. The secondary endpoints were the change in weekly IPN caloric content and the change in the frequency of IPN administration per week. Subjects received either Zorbtive placebo with the nutritional supplement, glutamine (n=9), Zorbtive without glutamine (n=16) or Zorbtive with glutamine (n=16). All 3 groups received a specialized diet. Following a 2-week equilibration period, treatment was administered in a double blind manner over a further period of four weeks. The dosing of Zorbtive was approximately 0.1 mg/kg/day for 4 weeks. During the double-blind treatment portion of the trial, the glutamine was given at a daily dose of 30 g. The mean baseline IPN volume, mean IPN caloric content, and mean frequency of IPN administration are provided in TABLE 24. Mean reductions in IPN volume, IPN caloric content and the frequency of IPN administration in each patient group were significantly greater in both Zorbtive-treated groups than in group treated with Zorbtive placebo. These changes are tabulated in TABLE 24.

    See TABLE 24 Results for Endpoints After 4 Weeks of Treatment

    INDICATIONS AND USAGE

    Zorbtive is indicated for the treatment of short bowel syndrome in patients receiving specialized nutritional support. Zorbtive therapy should be used in conjunction with optimal management of short bowel syndrome.

    Specialized nutritional support may consist of a high carbohydrate, low-fat diet, adjusted for individual patient requirements and preferences. Nutritional supplements may be added according to the discretion of the treating physician. Optimal management of Short Bowel Syndrome may include dietary adjustments, enteral feedings, parenteral nutrition, fluid and micronutrient supplements, as needed.

    CONTRAINDICATIONS

    Growth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or 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).

    Zorbtive is contraindicated in patients with active neoplasia (either newly diagnosed or recurrent). Any anti-tumor therapy should be completed prior to starting therapy with Zorbtive. Zorbtive reconstituted with bacteriostatic water for injection (0.9% benzyl alcohol) should not be administered to patients with a known sensitivity to benzyl alcohol. (See WARNINGS.)

    Zorbtive is contraindicated in patients with a known hypersensitivity to growth hormone.

    WARNINGS

    Benzyl alcohol as a preservative in bacteriostatic water for injection has been associated with toxicity in newborns. If sensitivity to the diluent occurs, Zorbtive may be reconstituted with sterile water for injection. When Zorbtive is reconstituted in this manner, the reconstituted solution should be used immediately and any unused portion should be discarded.

    See CONTRAINDICATIONS for information regarding increased mortality in growth hormone-treated patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or 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 developing acute critical illnesses should be weighed against the potential risk.

    PRECAUTIONS

    GENERAL
    Zorbtive therapy should be carried out under the regular guidance of a physician who is experienced in the diagnosis and management of short bowel syndrome.

    Patients should be informed that allergic reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs.

    Recombinant human growth hormone (r-hGH) has been associated with acute pancreatitis.

    The use of somatropin has been associated with cases of new onset impaired glucose intolerance, new onset Type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving somatropin. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when somatropin was discontinued, while in others the glucose intolerance persisted. Some patients necessitated initiation or adjustment of antidiabetic treatment while on somatropin. Patients with other risk factors for glucose intolerance should be monitored closely during Zorbtive therapy.

    No cases of intracranial hypertension (IH) have been observed among patients with short bowel syndrome treated with Zorbtive. The syndrome of IH, with papilledema, visual changes, headache, and nausea and/or vomiting has been reported in a small number of children with growth failure treated with growth hormone products. Nevertheless, funduscopic evaluation of patients is recommended at the initiation and periodically during the course of Zorbtive therapy.

    Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Zorbtive, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing (see DOSAGE AND ADMINISTRATION).

    Carpal tunnel syndrome may occur during treatment with somatropin. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the dose or frequency of somatropin, it is recommended that treatment be discontinued.

    INFORMATION FOR THE PATIENT
    Patients being treated with Zorbtive should be informed of the potential benefits and risks associated with treatment. Patients should be instructed to contact their physician should they experience any side effects or discomfort during treatment with Zorbtive.

    It is recommended that Zorbtive be administered using sterile, disposable syringes and needles. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes. An appropriate container for the disposal of used syringes and needles should be employed.

    Patients should be instructed to rotate injection sites to avoid localized tissue atrophy.

    CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
    Long-term animal studies for carcinogenicity have not been performed with Zorbtive. There is no evidence from animal studies to date of Zorbtive-induced mutagenicity or impairment of fertility.

    PREGNANCY CATEGORY B
    Reproduction studies have been performed in rats and rabbits. Doses up to 5-10 times the human dose, based on body surface area, have revealed no evidence of impaired fertility or harm to the fetus due to Zorbtive. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

    NURSING WOMEN
    It is not known whether Zorbtive is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zorbtive is administered to a nursing woman.

    PEDIATRIC USE
    There are no formal studies in pediatric patients with short bowel syndrome.

    GERIATRIC USE
    Clinical studies with Zorbtive did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may be more sensitive to growth hormone action, and may be more prone to develop adverse reactions. Thus, dose selection for an elderly patient should be cautious, usually starting at a lower dose.

    DRUG INTERACTIONS

    Formal drug interaction studies have not been conducted.

    ADVERSE REACTIONS

    TABLE 25 summarizes the number of subjects by system-organ class who experienced an adverse event during the 4-week treatment period of the Phase 3 SBS study. To be listed in TABLE 25, an adverse event must have occurred in more than 10% of subjects in any treatment group.

    See TABLE 25 Controlled Trial Adverse Events 4-Week Treatment Period

    TABLE 26 summarizes the number of subjects by system-organ class who experienced an adverse event during the 12-week follow-up period of the Phase 3 SBS study. To be listed in TABLE 26, an adverse event must have occurred in more than 10% of subjects in any treatment group.

    See TABLE 26 Controlled Trial Adverse Events - 12-Week Follow-Up Period

    Adverse events that occurred in 1% to less than 10% of study participants receiving Zorbtive in the placebo-controlled clinical efficacy trial are listed below by body system. The list of adverse events has been compiled regardless of casual relationship to Zorbtive.

    Body as a Whole, General: Edema, periorbital edema.
    Gastrointestinal System: Melena, rectal hemorrhage, mouth disorder, steatorrhea.
    Musculoskeletal System: Arthritis, arthropathy, bursitis, cramps.
    Resistance Mechanism Disorders: Fungal infection.
    Application Site Disorders: Reaction pain, inflammation at injection sites.
    Central and Peripheral Nervous System: Parasthesia, phantom pain, visual field defect.
    Respiratory System: Bronchospasm, dyspnea, pharyngitis, respiratory disorder, respiratory infection.
    Platelet Bleeding and Clotting Disorders: Purpura, prothrombin decrease.
    Skin and Appendages: Skin disorder, increased sweating, alopecia, bullous eruption.
    Psychiatric: Insomnia.
    Metabolic and Nutritional: Hypomagnesemia.
    Urinary System Disorders: Dysuria, urinary tract infection, abnormal urine.
    Reproduction Disorders Female: Breast enlargement, vaginal fungal infection.
    Heart Rate and Rhythm Disorders: Tachycardia.
    Vascular (Extra Cardiac) Disorders: Vasodilatation.

    The safety profile of patients receiving Zorbtive with glutamine was similar to the safety profile of patients receiving Zorbtive without glutamine. During the baseline period, 88% of patients receiving Zorbtive with glutamine, 88% of patients receiving Zorbtive without glutamine, and 78% of patients receiving Zorbtive placebo with glutamine reported baseline signs and symptoms (BSS). During the treatment period, 100% of patients receiving Zorbtive with and without glutamine reported at least one adverse event (AE), whereas 89% of patients receiving Zorbtive placebo with glutamine reported at least one AE. During the follow-up period 81% of patients receiving Zorbtive with glutamine, 80% of patients receiving Zorbtive without glutamine and 78% of patients receiving Zorbtive placebo with glutamine experienced at least one AE. Comparison of the number of serious adverse events (SAEs) before and during treatment demonstrates that this subject population experiences numerous BSSs and AEs due to their underlying conditions and parenteral nutrition complications. Four subjects (25%) receiving Zorbtive without glutamine and one subject (11%) in receiving Zorbtive placebo with glutamine experienced at least one SAE during the treatment period (Zorbtive without glutamine: chest pain, purpura, fungal infection, pharyngitis; Zorbtive placebo with glutamine: hemorrhoids). None of the subjects receiving Zorbtive with glutamine experienced SAEs during the treatment period. During the follow-up period, 3 subjects (19%) receiving Zorbtive with glutamine, 5 subjects (33%) receiving Zorbtive without glutamine and 3 subjects (33%) receiving Zorbtive placebo with glutamine experienced at least one SAE. There were no deaths in this study.

    OVERDOSAGE

    Glucose intolerance can occur with overdosage. Long-term overdosage with growth hormone could result in signs and symptoms of acromegaly.

    DOSAGE AND ADMINISTRATION

    Zorbtive should be administered to patients with short bowel syndrome (SBS) at a dose of approximately 0.1 mg/kg subcutaneously daily to a maximum of 8 mg daily. Administration for more than 4 weeks has not been adequately studied.

    Injections should be administered daily for 4 weeks. Changes to concomitant medications should be avoided. Patients and physicians should monitor for adverse events. Treat moderate fluid retention and arthralgias symptomatically or dose reduce by 50%. Discontinue Zorbtive for up to 5 days for severe toxicities. Upon resolution of symptoms, resume at 50% of original dose. Permanently discontinue treatment if severe toxicity recurs or does not disappear within 5 days.

    Injection sites should be rotated.

    Safety and effectiveness in pediatric patients with short bowel syndrome have not been established.

    Each vial of Zorbtive 4 mg, 5 mg or 6 mg is reconstituted with 0.5-1 ml sterile water for injection. Each vial of Zorbtive 8.8 mg is reconstituted in 1-2 ml of bacteriostatic water for injection (0.9% benzyl alcohol preserved). See TABLE 27 for expected concentration after reconstitution. Approximately 10% mechanical loss can be associated with reconstitution and administration from multi-dose vials. For patients sensitive to benzyl alcohol, see WARNINGS.

    See TABLE 27 Expected Concentration After Reconstitution (mg/ml)

    To reconstitute Zorbtive, inject the diluent into the vial of Zorbtive aiming the liquid against the glass vial wall. Swirl the vial with a gentle rotary motion until contents are dissolved completely. The Zorbtive solution should be clear immediately after reconstitution. DO NOT INJECT Zorbtive if the reconstituted product is cloudy immediately after reconstitution (Zorbtive 4, 5, 6 or 8.8 mg) or after refrigeration (only Zorbtive 8.8 mg). The reconstituted Zorbtive 8.8 mg can be refrigerated (2-8C/36-46F) for up to 14 days. Occasionally, after refrigeration, small colorless particles may be present in the Zorbtive 8.8 mg solution. This is not unusual for proteins like Zorbtive. Allow refrigerated solution to come to room temperature prior to administration. A standard insulin-type SC syringe is recommended for administration.

    HOW SUPPLIED

    Zorbtive is available in the following forms:
    Zorbtive vials containing 4 mg (approximately 12 IU) somatropin (mammalian-cell) with sterile water for injection, 1 ml.
    Zorbtive vials containing 5 mg (approximately 15 IU) somatropin (mammalian-cell) with sterile water for injection, 1 ml.
    Zorbtive vials containing 6 mg (approximately 18 IU) somatropin (mammalian-cell) with sterile water for injection, 1 ml.
    Zorbtive vial containing 8.8 mg (approximately 26.4 IU) somatropin (mammalian-cell) with bacteriostatic water for injection (0.9% benzyl alcohol), 10 ml.

    STABILITY AND STORAGE
    Before Reconstitution: Vials of Zorbtive and diluent should be stored at room temperature, (15-30C/59-86F). Expiration dates are stated on product labels.
    After Reconstitution With Sterile Water for Injection: The reconstituted solution should be used immediately and any unused portion should be discarded.
    After Reconstitution With Bacteriostatic Water for Injection (0.9% benzyl alcohol): The reconstituted solution should be stored under refrigeration (2-8C/36-46F) for up to 14 days. Avoid freezing reconstituted vials of Zorbtive.


    Copyright 2005 Mosby, Inc. All rights reserved.
    (+/-) Show / Hide Bibliography
    Date Accessed:
    9/17/2005 11:24:20 AM PST (GMT -08:00)
    Electronic Address:
    http://online.statref.com/document.a...=26&docid=7501
    Location In Book:
    MOSBY'S DRUG CONSULT - 15th Ed. (2005)
    DRUG INFORMATION
    "S" Monographs
    Somatropin, Biosynthetic
    INTRODUCTION

    Date Posted:
    9/9/2005 2:52:14 PM PST (GMT -08:00)
    Book Title:
    Mosby's Drug Consult - 15th Ed. (2005)
    Send Feedback
    Customer Service
    800.901.5494
    Title Updates
    User Responsibilities
    Training Center
    What's New
    Teton Server (4.0.8) - 2005 Teton Data Systems
    Send Us Your Comments

  8. #8
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    serostim...worthless after 24 hours........bad news huh

  9. #9
    JAMIE720 is offline Junior Member
    Join Date
    Sep 2005
    Posts
    53
    Serostim is prescibed specifically for HIV patients and the daily recommended dose is one 18iu vial per day,thats why any unused gh is to be disgarded.What you printed does not show Serostim is worhless after 24 hours.It says the same thing on the insert inside the box.Thats why it comes with sterile water because its to be used at that dose in one shot for HIV patients and not stored.

  10. #10
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    Quote Originally Posted by JAMIE720
    Serostim is prescibed specifically for HIV patients and the daily recommended dose is one 18iu vial per day,thats why any unused gh is to be disgarded.What you printed does not show Serostim is worhless after 24 hours.It says the same thing on the insert inside the box.Thats why it comes with sterile water because its to be used at that dose in one shot for HIV patients and not stored.
    did you even read anything???.anyways. Say what you will

    Can't argue w/ ignorance.

  11. #11
    liftergirl is offline Female Member
    Join Date
    Feb 2004
    Posts
    177
    hmmmm...I know i havent posted a lot, but i've been reading quite a bit on AR since i joined.... basically b/c my bf is a HUGE believer in this site.

    I'm in the medical field and know quite a bit about the "legal" prescribed uses of alot of this stuff. Anyways.... The insulin /igf/gh thread caught my interest and i've read a lot of what's been said about these meds.

    First of all...a lot of the studies that have been done about gh/igf were done on people who are GH deficient; either they are panhypopit (meaning that they do not have a functional Anterior Pituitary), have had radiation therapy at some point in their life and their Ant Pit has been damaged, .... and then have to have replacements of ALL hormones produced by the Ant. Pit; and GH is one of them. Or, people have chromosomal abnormalities like Prader Wili syndrome, Turners syndrome, etc and they naturally are smaller than the "normal" person, and then, Drs will give them GH to help them appear more normal. ..... For diseases like AIDS and chronic wasting syndromes---- the medical field basically tries anything to help them keep from losing muscle mass .

    So, there arent really studies that have been done on people who have normal functioning Ant. Pit's; for example.... a "normal" GH level in a 30 yr old guy is basically zero. So, no one really knows how a "normal" Ant. Pit would react to exogenous growth hormone .

    As far as the funtioning of Serostim after 24 hrs..... I'd have to agree with MT--> there are other medical sources that explain how it's to be used and tell one to "use immediately after reconstitution".... realize that Serostim is basically a fragile protein that's made by doing rDna technology..... recombinant DNA is REALLY FRAGILE; whereas most proteins actually need to be denatured using specific chemicals; rDNA is a different story.

    So.... J720-- i think you need to redo some of your research.

  12. #12
    JAMIE720 is offline Junior Member
    Join Date
    Sep 2005
    Posts
    53
    I respect your opinion lifter girl however if this were the case everyone using Serostim would basically be wasting there money which is not the case.Everyone that Ive spoken to in my area NYC including a bodybuilder who just turned pro at the USA all use Serostim by refriderating the vial and everyone has seen definate results aside from the anabolics they are using.I believe they advise to disgard the unused portion because its prescribed specifically for HIV patients with comprimised immune function where bacteria might be an issue not because the gh is no longer good

  13. #13
    JAMIE720 is offline Junior Member
    Join Date
    Sep 2005
    Posts
    53
    And btw the way Mealticket just wanted to know how many people you know who use Serostim how they use it and what their results are not a reprinting of whats in the boxs insert

  14. #14
    Mealticket's Avatar
    Mealticket is offline Senior Member
    Join Date
    Jan 2004
    Posts
    1,812
    i know 0 people.
    I understand your point. Everyone has heard of placebo effect. Yolu can'y argue w/ the New England Journal of medicine. Period. So i'll just agree to disagree w/ you

  15. #15
    liftergirl is offline Female Member
    Join Date
    Feb 2004
    Posts
    177
    Quote Originally Posted by JAMIE720
    I respect your opinion lifter girl however if this were the case everyone using Serostim would basically be wasting there money which is not the case.Everyone that Ive spoken to in my area NYC including a bodybuilder who just turned pro at the USA all use Serostim by refriderating the vial and everyone has seen definate results aside from the anabolics they are using.I believe they advise to disgard the unused portion because its prescribed specifically for HIV patients with comprimised immune function where bacteria might be an issue not because the gh is no longer good
    .....I agree that it's possible that it's not recommended simply b.c it's not perfectly safe to reuse an already "contaminated" vial; b/c that's the way it is when one uses any type of vial in the hospital....be it lidocaine, bicarb, etc. However, combination of statements that makes me truly believe it's not any "good" after more than 24 hrs is that the directions not only say to discard after first time use, but it also says to "use immediately after reconstitution". ..... And as far as the statement about not using it twice just b/c they are AIDS patients....J720--> doctors were using it for patients with the other diseases i spoke of a LONG time b/4 we tried it in our HIV patients. And those patients' immune systems were fine.

    As for the results that someone sees after using serostim......it's possible that it's placebo, as MT stated, but to be honest, no one really knows how an otherwise normal anterior pituitary would react to exogenous GH. Would just exposing the Ant Pit to extra GH several years after it hasnt made it trigger it to start making it on its own??? Maybe.

    Or, if you go with the no-good-after-24hrs thought.....you're still getting a "good" dose at least twice a month....would that be enough to trigger the Ant Pit to excrete it's own GH as well....so your body is actually being exposed to more than you actually inject....? Maybe.

    Or, realizing that your body's cells haven't been exposed to GH in a LONG time b/4 you start taking it.....would they just react so much that you're able to see gains even if some of what you inject is non-functional??? Maybe.

    If I were taking it....I'd still believe the NEJM. But, do as you will.....

  16. #16
    oswaldosalcedo's Avatar
    oswaldosalcedo is offline Senior Member
    Join Date
    Jul 2004
    Posts
    1,102
    Quote Originally Posted by Mealticket
    serostim...worthless after 24 hours........bad news huh
    no, if you use bw.

Thread Information

Users Browsing this Thread

There are currently 1 users browsing this thread. (0 members and 1 guests)

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •