Nutropin [somatropin (rDNA origin) for injection] is a human growth hormone (hGH) produced by recombinant DNA technology. Nutropin 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 hGH. Nutropin may contain not more than fifteen percent deamidated GH at expiration. The deamidated form of GH has been extensively characterized and has been shown to be safe and fully active.
Whats Nutropin package in market ?
Nutropin is a sterile, white lyophilized powder intended for subcutaneous administration after reconstitution with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). The reconstituted product is nearly isotonic at a concentration of 5 mg/mL GH and has a pH of approximately 7.4.
Each 10 mg Nutropin vial contains 10 mg (approximately 30 IU) somatropin, lyophilized with 90 mg mannitol, 3.4 mg sodium phosphates (0.8 mg sodium phosphate monobasic and 2.6 mg sodium phosphate dibasic), and 3.4 mg glycine.
Bacteriostatic Water for Injection, USP is sterile water containing 0.9 percent benzyl alcohol per mL as an antimicrobial preservative packaged in a multidose vial. The diluent pH is 4.5 – 7.0.
|Pediatric Patients||Growth Hormone Deficiency (GHD)|
Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH).
|Growth Failure Secondary to Chronic Kidney Disease (CKD)||Nutropin is indicated for the treatment of growth failure associated with CKD up to the time of renal transplantation. Nutropintherapy should be used in conjunction with optimal management of CKD.|
|Idiopathic Short Stature (ISS)||Nutropin is indicated for the treatment of ISS, also called non-GHD 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.|
|Short Stature Associated with Turner Syndrome (TS)||Nutropin is indicated for the treatment of short stature associated with TS.|
|Adult Patients||Nutropin is indicated for the replacement of endogenous GH in adults with GHD who meet eitherof the following two criteria:|
|Childhood Onset||Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.|
|Adult Onset||Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma,or idiopathic causes.|
Patients who were treated with somatropin for GHD in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults. According to current standards, confirmation of the diagnosis of adult GHD in both groups involves an appropriate GH provocative test with two exceptions: (1) patients with multiple pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic GHD.
Nutropin AQ DOSAGE AND ADMINISTRATION For subcutaneous injection.
Therapy with Nutropin should be supervised by a physician who is experienced in the diagnosisand management of pediatric patients with short stature associated with growth hormone deficiency(GHD), chronic kidney disease, Turner syndrome, idiopathic short stature, or adult patients with either childhood-onset or adult-onset GHD.
|Dosing for Pediatric Patients||Nutropin dosage and administration schedule should be individualized for each patient. Response to growth hormone (GH) therapy in pediatric patients tends to decrease with time. However, in pediatric patients 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, advanced bone age and antibodies to recombinant human GH (rhGH).|
Treatment with Nutropin for short stature should be discontinued when the epiphyses are fused.
|Pediatric Growth Hormone Deficiency (GHD)||A weekly dosage of up to 0.3 mg/kg of body weight divided into daily subcutaneous injection is recommended. In pubertal patients, a weekly dosage of up to 0.7 mg/kg divided daily may be used.|
|Growth Failure Secondary to Chronic Kidney Disease (CKD)||A weekly dosage of up to 0.35 mg/kg of body weight divided into daily subcutaneous injection is recommended.|
Nutropin 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 least3 to 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.
Idiopathic Short Stature (ISS)
|A weekly dosage of up to 0.3 mg/kg of body weight divided into daily subcutaneous injections is recommended.|
|Short Stature Associated with Turner Syndrome (TS)||A weekly dosage of up to 0.375 mg/kg of body weight divided into equal doses 3 to 7 times per week by subcutaneous injection is recommended.|
|Dosing for Adult Patients|
Adult Growth Hormone Deficiency (GHD)
|Either of two approaches to Nutropin dosing may be followed: a weight-based regimen or a non weight-based regimen.|
|Weight based||Based on the dosing regimen used in the original adult GHD registration trials, the recommended dosage at the start of treatment is not more than 0.006 mg/kg daily. The dose may be increased according to individual patient requirements to a maximum of 0.025 mg/kg daily inpatients ≤35 years and to a maximum of 0.0125 mg/kg daily in patients over 35 years old. Clinical response, side effects, and determination of age- and gender-adjusted serum insulin-like growth factor (IGF-1) concentrations should be used as guidance in dose titration.|
|Non-weight based||Alternatively, taking into account the published literature, a starting dose of approximately 0.2 mg/day (range, 0.15 to 0.30 mg/day) may be used without consideration of bodyweight. This dose can be increased gradually every 1 to 2 months by increments of approximately 0.1 to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum IGF-1 concentrations. The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-1 concentrations above the age- and gender-specific normal range.|
|Maintenance dosages vary considerably from person to person, and between male and female patients.||A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger individuals. In addition, obese individuals are more likely to manifest adverse effects, when treated with a weight-based regimen.|
In order to reach the defined treatment goal, estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.
Nutropin AQ SIDE EFFECTS
|the most seriousa SIDE EFFECTS||most frequently observedb adverse reactions during treatment with somatropin|
|Sudden death in pediatric patients with Prader-Willi syndrome (PWS) with risk factors includingsevere obesity, history of upper airway obstruction or sleep apnea and unidentified respiratoryinfection [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].||Intracranial hypertension [see WARNINGS AND PRECAUTIONS].|
|Intracranial tumors, in particular meningiomas, in teenagers/young adults treated with radiationto the head as children for a first neoplasm and somatropin [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].||Significant diabetic retinopathy [see CONTRAINDICATIONS].|
|[see WARNINGS AND PRECAUTIONS]||Slipped capital femoral epiphysis in pediatric patients [see WARNINGS AND PRECAUTIONS].|
|Glucose intolerance including impaired glucose tolerance/impaired fasting glucose as well asovert diabetes mellitus [see WARNINGS AND PRECAUTIONS].||Progression of preexisting scoliosis in pediatric patients [see WARNINGS AND PRECAUTIONS].|
|Fluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias [see WARNINGS AND PRECAUTIONS].|
|Unmasking of latent central hypothyroidism [see WARNINGS AND PRECAUTIONS].|
|Injection site reactions/rashes and lipoatrophy (as well as rare generalized hypersensitivity reactions) [see WARNINGS AND PRECAUTIONS].|
Protocol-Defined Targeted Adverse Events in the ISS NCGS Cohort
In subjects treated in a long-term study of Nutropin for ISS, mean fasting and postprandial insulin levels increased, while mean fasting and postprandial glucose levels remained unchanged. Mean hemoglobin A1c (A1C) levels rose slightly from baseline as expected during adolescence; sporadic values outside normal limits occurred transiently.
Growth Hormone Deficiency
In clinical studies with Nutropin in GHD adults, edema or peripheral edema was reported in 41% of GH-treated patients and 25% of placebo-treated patients. In GHD adults, arthralgias and other joint disorders were reported in 27% of GH-treated patients and 15% of placebo-treated patients.
Nutropin therapy in adults with GHD of adult-onset was associated with an increase of median fasting insulin level in the Nutropin 0.0125 mg/kg/day group from 9.0 μU/mL at baseline to 13.0 μU/mL at Month 12 with a return to the baseline median level after a 3-week post-washout period of GH therapy. In the placebo group there was no change from 8.0 μU/mL at baseline to Month 12, and after the post-washout period, the median level was 9.0 μU/mL. The between-treatment group difference on the change from baseline to Month 12 in median fasting insulin level was significant, p < 0.0001. In childhood-onset subjects, there was an increase of median fasting insulin level in the Nutropin 0.025 mg/kg/day group from 11.0 μU/mL at baseline to 20.0 μU/mL at Month 12, in the Nutropin 0.0125 mg/kg/day group from 8.5 μU/mL to 11.0 μU/mL, and in the placebo group from 7.0 μU/mL to 8.0 μU/mL. The between-treatment group differences for these changes were significant, p = 0.0007.
In subjects with adult-onset GHD, there were no between-treatment group differences on change from baseline to Month 12 in mean A1C level, p = 0.08. In childhood-onset GHD, the mean A1C level 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 group differences were significant, p = 0.009.
Storage and Handling
Before Reconstitution – Nutropin and Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), must be stored at 2-8°C/36-46°F (under refrigeration). Avoid freezing the vials of Nutropin and Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). Expiration dates are stated on the labels.
After Reconstitution – Vial contents are stable for 14 days when reconstituted with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), and stored at 2-8°C/36-46°F (under refrigeration). Avoid freezing the reconstituted vial of Nutropin and Bacteriostatic Water for Injection, USP (benzyl alcohol preserved).
When reconstituting with Sterile Water for Injection, USP, use only one dose per Nutropin vial and discard the unused portion.