Nutropin

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.

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. [See HOW SUPPLIED/Storage and Handling].

Pediatric Patients

Nutropin® is indicated for the treatment of pediatric patients who have growth failure due to inadequate secretion of endogenous growth hormone (GH).

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.

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.

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:

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

Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, 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.

Dosage Forms And Strengths

Nutropin 10 mg vial and 10 mL diluent.

10 mg per vial and one 10 mL multiple dose vial of NDC 50242-018-21

Bacteriostatic Water for Injection, USP (benzyl alcohol preserved)

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.

Manufactured by: Genentech, Inc., A Member of the Roche Group 1 DNA Way, South San Francisco, CA 94080-4990. Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), Manufactured for: Genentech, Inc. A Member of the Roche Group

Before you receive somatropin, tell your doctor about all your past and present medical conditions, especially allergies, trauma, surgery, diabetes, cancer, breathing problems, liver or kidney disease, scoliosis, high blood pressure, pancreas disorder, underactive thyroid, or a brain tumor.

Also tell your doctor about all other medications you use, especially steroids or diabetes medications. Your dosages of these medicines may need to be changed when you start using somatropin. Do not stop using a steroid suddenly or change any of your medication doses without your doctor's advice.

If you have Prader-Willi syndrome and are using somatropin, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring.

Call your doctor at once if you have sudden and severe pain in your upper stomach with nausea and vomiting, fast heartbeat, increased thirst or urination, weight loss, or vision changes and sudden, severe pain behind your eyes.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Call your doctor if you miss more than 3 doses in a row.

Most Serious and/or Most Frequently Observed Adverse Reactions

This list presents the most seriousa and/or most frequently observedb adverse reactions during treatment with somatropin:

• aSudden 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].
• aIntracranial 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].
• a [see WARNINGS AND PRECAUTIONS]
• a,bGlucose intolerance including impaired glucose tolerance/impaired fasting glucose as well asovert diabetes mellitus [see WARNINGS AND PRECAUTIONS].
• aIntracranial hypertension [see WARNINGS AND PRECAUTIONS].
• aSignificant diabetic retinopathy [see CONTRAINDICATIONS].
• aSlipped capital femoral epiphysis in pediatric patients [see WARNINGS AND PRECAUTIONS].
• aProgression of preexisting scoliosis in pediatric patients [see WARNINGS AND PRECAUTIONS].
• bFluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias [see WARNINGS AND PRECAUTIONS].
• aUnmasking of latent central hypothyroidism [see WARNINGS AND PRECAUTIONS].
• aInjection site reactions/rashes and lipoatrophy (as well as rare generalized hypersensitivity reactions) [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

Pediatric Patients

Injection site discomfort has been reported. This is more commonly observed in childrens witched from another somatropin product to Nutropin.

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 somatropin.

In a post-marketing surveillance study, the National Cooperative Growth Study (NCGS), the pattern of adverse events in over 8,000 patients with ISS was consistent with the known safety profile of growth hormone (GH), and no new safety signals attributable to GH were identified. The frequency of protocol-defined targeted adverse events is described in the table, below.

Table 1: 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.

Adult Patients

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.

Post-Marketing Experience

Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The adverse events reported during post-marketing surveillance do not differ from those listed/discussed above in Sections 6.1 and 6.2 in children and adults.

Leukemia has been reported in a small number of GHD children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, CKD, or TS, if any, remains to be established [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

The following additional adverse reactions have been reported in GH-treated patients: gynecomastia (children), and pancreatitis [(Children and adults, see WARNINGS AND PRECAUTIONS].

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Nutropin with the incidence of antibodies to other products may be misleading. In the case of GH, antibodies with binding capacities lower than 2 mg/L have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/L, interference with the growth response was observed.

In clinical studies of pediatric patients that were treated with Nutropin for the first time, 0/107 GHD patients, 0/125 CKD patients, 0/112 TS, and 0/117 ISS patients screened for antibody production developed antibodies with binding capacities ≥ 2 mg/L at six 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 pediatric patients with CKD after approximately one 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 blood urea nitrogen (BUN). No adverse effects of GH antibodies were noted.

Read the entire FDA prescribing information for Nutropin (Somatropin (rDNA origin) for Inj)

• Genotropin
• Humatrope
• Norditropin
• NutreStore

• Nutropin AQ
• Nutropin Depot
• Omnitrope
• Saizen

© Nutropin Patient Information is supplied by Cerner Multum, Inc. and Nutropin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Pediatric Patients

Nutropin® [somatropin (rDNA origin) for injection] is indicated for the long‑term treatment of growth failure due to a lack of adequate endogenous GH secretion.

Nutropin® [somatropin (rDNA origin) for injection] is also indicated for the treatment of growth failure associated with chronic renal insufficiency up to the time of renal transplantation. Nutropin therapy should be used in conjunction with optimal management of chronic renal insufficiency.

Nutropin® [somatropin (rDNA origin) for injection] is also indicated for the long‑term treatment of short stature associated with Turner syndrome.

Nutropin® [somatropin (rDNA origin) for injection] is also 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

Nutropin® [somatropin (rDNA origin) for injection] is indicated for the replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:

Adult Onset: Patients who have adult growth hormone deficiency either alone or associated 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 as a result of congenital, genetic, acquired, or idiopathic causes.

In general, confirmation of the diagnosis of adult growth hormone deficiency in both groups usually requires an appropriate growth hormone stimulation test. However, confirmatory growth hormone stimulation testing may not be required in patients with congenital/genetic growth hormone deficiency or multiple pituitary hormone deficiencies due to organic disease.

General

Nutropin should be prescribed by physicians experienced in the diagnosis and management of patients with GH deficiency, idiopathic short stature, Turner syndrome, or chronic renal insufficiency. No studies have been completed evaluating Nutropin therapy in patients who have received renal transplants. Currently, treatment of patients with functioning renal allografts is not indicated.

Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity (including obese patients with Prader-Willi syndrome), Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients.

In subjects treated in a long‑term study of Nutropin for idiopathic short stature, mean fasting and postprandial insulin levels increased, while mean fasting and postprandial glucose levels remained unchanged. Mean hemoglobin A1c levels rose slightly from baseline as expected during adolescence; sporadic values outside normal limits occurred transiently.

Nutropin therapy in adults with GH deficiency 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 groups difference on 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 groups differences for these changes were significant, p=0.0007.

In subjects with adult-onset GH deficiency , there were no between-treatment group differences on changes from baseline to Month 12 in mean HbA1c level, p = 0.08. In childhood-onset GH deficiency, the mean HbA1c 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.

Patients with preexisting tumors or 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 revealed no relationship between somatropin replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors. However, in childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm. Intracranial tumors, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome, CRI, and Prader-Willi syndrome may be at increased risk for the development of IH.

In patients with hypopituitarism (multiple hormone deficiencies), standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered.

Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with growth hormone deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

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

When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site.

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

Pediatric Patients

(see PRECAUTIONS, General)

Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GH deficiency and Turner syndrome) or in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.

Children 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 somatropin therapy. X-rays of the hip should be obtained prior to initiating somatropin therapy in CRI patients. Physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in CRI patients treated with Nutropin.

Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Scoliosis is also commonly seen in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin 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 and 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 somatropin. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

Adult Patients

(see PRECAUTIONS, General)

Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated according to the criteria in INDICATIONS AND USAGE before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults. Fluid retention during somatropin replacement therapy in adults may occur. Clinical manifestations of fluid retention are usually transient and dose dependent (see ADVERSE REACTIONS).

Experience with prolonged somatropin treatment in adults is limited.

Information for Patients

Patients being treated with Nutropin (and/or their parents) should be informed about the potential benefits and risks associated with Nutropin treatment, including a review of the contents of the Patient Information Insert. This information is intended to better educate patients (and caregivers); it is not a disclosure of all possible adverse or intended effects.

Patients and caregivers who will administer Nutropin should receive appropriate training and instruction on the proper use of Nutropin from the physician or other suitably qualified health care professional. A puncture-resistant container for the disposal of used syringes and needles should be strongly recommended. Patients and/or parents should be thoroughly instructed in the importance of proper disposal, and cautioned against any reuse of needles and syringes. This information is intended to aid in the safe and effective administration of the medication (see Patient Information Insert).

See WARNINGS for use of Bacteriostatic Water for Injection, USP, (benzyl alcohol preserved), in newborns.

Laboratory Tests

Serum levels of inorganic phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) may increase during somatropin therapy.

Drug Interactions

Somatropin inhibits 11β‑hydroxysteroid dehydrogenase type 1 (11βHSD‑1) in adipose/hepatic tissue and may significantly impact the metabolism of cortisol and cortisone. As a consequence, in patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of the 11βHSD‑1 enzyme.

Excessive glucocorticoid therapy may attenuate the growth-promoting effects of somatropin in children. Therefore, glucocorticoid replacement therapy should be carefully adjusted in children with concomitant GH and glucocorticoid deficiency to avoid both hypoadrenalism and an inhibitory effect on growth.

The use of Nutropin in patients with CRI requiring glucocorticoid therapy has not been evaluated. Concomitant glucocorticoid therapy may inhibit the growth promoting effect of Nutropin. Therefore, if glucocorticoid replacement is required for CRI, the glucocorticoid dose should be carefully adjusted to avoid an inhibitory effect on growth.

There was no evidence in the controlled studies of Nutropin’s interaction with drugs commonly used in chronic renal insufficiency patients. Limited published data indicate that somatropin treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that somatropin 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 somatropin is administered in combination with other drugs known to be metabolized by CP450 liver enzymes. However, formal drug interaction studies have not been conducted.

In adult women on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal (see DOSAGE AND ADMINISTRATION).

In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral agent may require adjustment when somatropin therapy is initiated (see PRECAUTIONS, General).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and reproduction studies have not been conducted with Nutropin.

Pregnancy

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

Nursing Mothers

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

Geriatric Usage

Clinical studies of Nutropin 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 the action of somatropin, and therefore may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments should be considered for older patients (see DOSING AND ADMINISTRATION).

The Nutropin® [somatropin (rDNA origin) for injection] dosage and administration schedule should be individualized for each patient. Response to growth hormone 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, and advanced bone age.

Dosage

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.

Based on the weight-based dosing utilized in the original pivotal studies described herein, the recommended dosage at the start of therapy is not more than 0.006 mg/kg given as a daily subcutaneous 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 old 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 IGF-I levels may be used as guidance in dose titration.

Alternatively, taking into account more recent literature, a starting dose of approximately 0.2 mg/day (range, 0.15‑0.30 mg/day) may be used without consideration of body weight. This dose can be increased gradually every 1-2 months by increments of approximately 0.1-0.2 mg/day, according to individual patient requirements based on the clinical response and serum IGF-I concentrations. During therapy, the dose should be decreased if required by the occurrence of adverse events and/or serum IGF-I levels above the age- and gender-specific normal range. Maintenance dosages vary considerably from person to person.

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.

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:

1. 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.
2. Chronic Cycling Peritoneal Dialysis (CCPD) patients should receive their injection in the morning after they have completed dialysis.
3. Chronic Ambulatory Peritoneal Dialysis (CAPD) patients should receive their injection in the evening at the time of the overnight exchange.

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.

A weekly dosage of up to 0.3 mg/kg of body weight divided into daily subcutaneous injection has been shown to be safe and efficacious, and is recommended.

Administration

After the dose has been determined, reconstitute as follows: each 5 mg vial should be reconstituted with 1–5 mL of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved); or each 10 mg vial should be reconstituted with 1–10 mL of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), only. For use in newborns, see WARNINGS. The pH of Nutropin after reconstitution with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved), is approximately 7.4.

To prepare the Nutropin solution, inject the Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) into the Nutropin vial, aiming the stream of liquid against the glass wall. Then swirl the product vial with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE . Because Nutropin is a protein, shaking can result in a cloudy solution. The Nutropin solution should be clear immediately after reconstitution. Occasionally, after refrigeration, you may notice that small colorless particles of protein are present in the Nutropin solution. This is not unusual for solutions containing proteins. If the solution is cloudy immediately after reconstitution or refrigeration, the contents MUST NOT be injected.

Before needle insertion, wipe the septum of both the Nutropin and diluent vials 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 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.