Omnitrope
Somatropin · Injection, Solution · Subcutaneous
Uses
1 INDICATIONS AND USAGE OMNITROPE is a recombinant human growth hormone indicated for:
• Pediatric: Treatment of children with growth failure due to growth hormone deficiency (GHD), Prader-Willi Syndrome, Small for Gestational Age, Turner Syndrome, and Idiopathic Short Stature ( 1.1 )
• Adult: Treatment of adults with either adult onset or childhood onset GHD ( 1.2 ) 1.1 Pediatric Patients OMNITROPE is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone (GH). OMNITROPE is indicated for the 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 ( 4 ) and Warnings and Precautions ( 5.2 )] . OMNITROPE is indicated for the treatment of growth failure in children born small for gestational age (SGA) who fail to manifest catch-up growth by age 2 years. OMNITROPE is indicated for the treatment of growth failure associated with Turner Syndrome. OMNITROPE is indicated for the treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (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. 1.2 Adult Patients OMNITROPE is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:
• Adult Onset (AO): 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
• Childhood Onset (CO): Patients who were GH deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for growth hormone deficient adults. Confirmation of the diagnosis of adult growth hormone deficiency in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.
Dosage and administration
The weekly dose should be divided over 6 or 7 days of subcutaneous injections. Therapy with OMNITROPE should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with GHD, Prader-Willi Syndrome (PWS), Turner Syndrome (TS), those who were born small for gestational age (SGA), Idiopathic Short Stature (ISS) and adult patients with either childhood onset or adult onset GHD. OMNITROPE should be administered subcutaneously ( 2 ).
• Pediatric GHD: 0.16 to 0.24 mg/kg/week, divided into 6 to 7 daily injections ( 2.1 )
• Prader-Willi Syndrome: 0.24 mg/kg/week, divided into 6 to 7 daily injections ( 2.1 )
• Small for Gestational Age: Up to 0.48 mg/kg/week, divided into 6 to 7 daily injections ( 2.1 )
• Turner Syndrome: 0.33 mg/kg/week, divided into 6 to 7 daily injections ( 2.1 )
• Idiopathic Short Stature: Up to 0.47 mg/kg/week, divided into 6 to 7 daily injections ( 2.1 )
• Adult GHD: not more than 0.04 mg/kg/week (divided into daily injections) to be increased as tolerated to not more than 0.08 mg/kg/week; to be increased gradually every 1 to 2 months ( 2.2 )
• OMNITROPE Cartridges 5 mg/1.5 mL and 10 mg/1.5 mL must be used with the corresponding OMNITROPE Pen 5 and Pen 10 delivery system, respectively ( 2.3 )
• Injection sites should always be rotated to avoid lipoatrophy ( 2.3 ) 2.1 Dosing of Pediatric Patients General Pediatric Dosing Information The OMNITROPE dosage and administration schedule should be individualized based on the growth response of each patient. Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human GH (rhGH). Treatment with OMNITROPE for short stature should be discontinued when the epiphyses are fused. Pediatric Growth Hormone Deficiency (GHD) Generally, a dosage of 0.16 to 0.24 mg/kg body weight/week is recommended. The weekly dose should be divided over 6 or 7 days of subcutaneous injections. Prader-Willi Syndrome (PWS) Generally, a dosage of 0.24 mg/kg body weight/week is recommended. The weekly dose should be divided over 6 or 7 days of subcutaneous injections. Small for Gestational Age (SGA) Generally, a dosage of up to 0.48 mg/kg body weight/week is recommended. The weekly dose should be divided over 6 or 7 days of subcutaneous injections. Turner Syndrome (TS) Generally, a dose of 0.33 mg/kg body weight/week is recommended. The weekly dose should be divided over 6 or 7 days of subcutaneous injections. Idiopathic Short Stature (ISS) Generally, a dose up to 0.47 mg/kg of body weight/week is recommended. The weekly dose should be divided over 6 or 7 days of subcutaneous injections. 2.2 Dosing of Adult Patients Adult Growth Hormone Deficiency (GHD) Weight-Based Dosing Based on the weight-based dosing utilized in clinical studies with another somatropin product, the recommended dosage at the start of therapy is not more than 0.04 mg/kg/week given as a daily subcutaneous injection. The dose may be increased at 4- to 8-week intervals according to individual patient requirements to not more than 0.08 mg/kg/week. Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-1 levels may be used as guidance in dose titration. Non-Weight Dosing Alternatively, taking into account 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 to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum IGF-1 concentrations. During therapy, the dose should be decreased if required by the occurrence of adverse events and/or serum IGF-1 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. 2.3 Preparation and Administration OMNITROPE Cartridge 5 mg/1.5 mL and Cartridge 10 mg/1.5 mL Each cartridge of OMNITROPE must be inserted into its corresponding OMNITROPE Pen 5 or OMNITROPE Pen 10 delivery system. Instructions for delivering the dosage are provided in the OMNITROPE INSTRUCTIONS FOR USE booklet enclosed with the OMNITROPE drug and the OMNITROPE Pens. OMNITROPE for injection 5.8 mg/vial Instructions for delivering the dosage are provided in the INSTRUCTIONS FOR USE leaflets enclosed with the OMNITROPE drug. Once the diluent is added to the lyophilized powder, swirl gently; do not shake. Shaking may cause denaturation of the active ingredient. Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. OMNITROPE MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter. Use it only if it is clear and colorless. OMNITROPE must be refrigerated at 2° to 8°C (36° to 46°F). Patients and caregivers who will administer OMNITROPE in medically unsupervised situations should receive appropriate training and instruction on the proper use of OMNITROPE from the physician or other suitably qualified health professional. The dosage of OMNITROPE must be adjusted for the individual patient.
Dosage forms and strengths
Injection: 5 mg/1.5 mL or 10 mg/1.5 mL clear, colorless solution in a single-patient-use prefilled cartridge. For Injection: 5.8 mg white to off-white lyophilized powder in a single-patient-use vial.
• Injection: 5 mg/1.5 mL or 10 mg/1.5 mL solution in a single-patient-use prefilled cartridge ( 3 )
• For injection: 5.8 mg lyophilized powder in a single-patient-use vial ( 3 )
Contraindications
4 CONTRAINDICATIONS OMNITROPE is contraindicated in patients with:
• Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure [see Warnings and Precautions ( 5.1 )] .
• Prader-Willi Syndrome in Children Somatropin is contraindicated in patients with Prader-Willi Syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients [see Warnings and Precautions ( 5.2 )] .
• Active Malignancy In general, somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since GHD may be an early sign of the presence of a pituitary tumor (or, rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor [see Warnings and Precautions ( 5.3 )] .
• Hypersensitivity OMNITROPE is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins [see Warnings and Precautions ( 5.6 )].
• Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.
• Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.
• Acute Critical Illness ( 4 )
• Children with Prader-Willi Syndrome who are severely obese or have severe respiratory impairment - reports of sudden death ( 4 )
• Active Malignancy ( 4 )
• Hypersensitivity to somatropin or its excipients ( 4 )
• Active Proliferative or Severe Non-Proliferative Diabetic Retinopathy ( 4 )
• Children with closed epiphyses ( 4 )
Warnings and precautions
• Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk ( 5.1 )
• Prader-Willi Syndrome in children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment. Discontinue treatment if these signs occur ( 5.2 )
• Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin - in particular meningiomas in patients treated with radiation to the head for their first neoplasm ( 5.3 )
• Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment ( 5.4 )
• Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction ( 5.5 )
• Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention ( 5.6 )
• Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome - especially in adults): May occur frequently. Reduce dose as necessary ( 5.7 )
• Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism ( 5.8 )
• Hypothyroidism: May first become evident or worsen ( 5.9 )
• Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain ( 5.10 )
• Progression of Preexisting Scoliosis: May develop ( 5.11 )
• Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain (5.15) 5.1 Acute Critical Illness Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications ( 4 )] . Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo. The safety of continuing somatropin 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 somatropin in patients experiencing acute critical illnesses should be weighed against the potential risk. 5.2 Prader-Willi Syndrome in Children There have been reports of fatalities after initiating therapy with somatropin 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 (including onset of or increased snoring) and sleep apnea before initiation of treatment with somatropin. If, during treatment with somatropin, 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 somatropin 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 ( 4 )] . 5.3 Neoplasms In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Intracranial tumors, in particular meningiomas, 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 [see Contraindications ( 4 )] . Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor [see Contraindications ( 4 )] . Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, practitioners should thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, these patients should be carefully monitored for development of neoplasms. Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi. 5.4 Impaired Glucose Tolerance and Diabetes Mellitus 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, and new onset type 2 diabetes mellitus has been reported in patients taking somatropin. 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, 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 [see Drug Interactions ( 7.5 )].
Side effects
Other common somatropin-related adverse reactions include injection site reactions/rashes and lipoatrophy ( 6.1 ) and headaches ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch The following important adverse reactions are also described elsewhere in labeling:
• Increased mortality in patients with acute critical illness [see Warnings and Precautions ( 5.1 )]
• Fatalities in children with Prader-Willi Syndrome [see Warnings and Precautions ( 5.2 )]
• Neoplasms [see Warnings and Precautions ( 5.3 )]
• Glucose intolerance and diabetes mellitus [see Warnings and Precautions ( 5.4 )]
• Intracranial hypertension [see Warnings and Precautions ( 5.5 )]
• Severe hypersensitivity [see Warnings and Precautions ( 5.6 )]
• Fluid retention [see Warnings and Precautions ( 5.7 )]
• Hypoadrenalism [see Warnings and Precautions ( 5.8 )]
• Hypothyroidism [see Warnings and Precautions ( 5.9 )]
• Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions ( 5.10 )]
• Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions ( 5.11 )]
• Otitis media and cardiovascular disorders in patients with Turner Syndrome [see Warnings and Precautions ( 5.12 )]
• Lipoatrophy [see Warnings and Precautions ( 5.13 )]
• Pancreatitis [see Warnings and Precautions ( 5.15 )]
• Benzyl Alcohol [see Warnings and Precautions ( 5.16 )] 6.1 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. Clinical Trials in Pediatric GHD Patients The following events were observed during clinical studies with OMNITROPE Cartridge conducted in children with GHD: Table 1. Incidence of Adverse Reactions Reported in ≥ 5% Pediatric Patients with GHD During Treatment with OMNITROPE Cartridge (N=86) Adverse Event n (%) N=number of patients receiving treatment n=number of patients who reported the event during study period %=percentage of patients who reported the event during study period Elevated HbA1c 12 (14%) Eosinophilia 10 (12%) Hematoma 8 (9%) The following events were observed during clinical studies with OMNITROPE for injection conducted in children with GHD: Table 2. Incidence of Adverse Reactions Reported in ≥ 5% Pediatric Patients with GHD During Treatment with OMNITROPE for Injection (N=44) Adverse Event n (%) N=number of patients receiving treatment n=number of patients who reported the event during study period %= percentage of patients who reported the event during study period Hypothyroidism 7 (16%) Eosinophilia 5 (11%) Elevated HbA1c 4 (9%) Hematoma 4 (9%) Headache 3 (7%) Hypertriglyceridemia 2 (5%) Leg Pain 2 (5%) Clinical Trials in PWS In two clinical studies in pediatric patients with Prader-Willi Syndrome carried out with another somatropin product, the following drug-related events were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia. Clinical Trials in Children with SGA In clinical studies of 273 pediatric patients born small for gestational age treated with another somatropin product, the following clinically significant events were reported: mild transient hyperglycemia, one patient with benign intracranial hypertension, two patients with central precocious puberty, two patients with jaw prominence, and several patients with aggravation of preexisting scoliosis, injection site reactions, and self-limited progression of pigmented nevi. Clinical Trials in Children with Idiopathic Short Stature In two open-label clinical studies conducted with another somatropin product in pediatric patients with ISS, the most commonly encountered adverse events were upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia. In one of the two studies during treatment with this other somatropin product, the mean IGF-1 standard deviation (SD) scores were maintained in the normal range. IGF-1 SD scores above +2 SD were observed as follows: 1 subject (3%), 10 subjects (30%) and 16 subjects (38%) in the untreated control, 0.23 and the 0.47 mg/kg/week groups respectively, had at least one measurement; while 0 subjects (0%), 2 subjects (7%) and 6 subjects (14%) had two or more consecutive IGF-1 measurements above +2 SD. Clinical Trials in Children with Turner Syndrome In two clinical studies with another somatropin product in pediatric patients with Turner Syndrome, the most frequently reported adverse events were respiratory illnesses (influenza, tonsillitis, otitis, sinusitis), joint pain, and urinary tract infection. The only treatment-related adverse event that occurred in more than 1 patient was joint pain. Clinical Trials in Adults with GHD In clinical trials with another somatropin product in 1,145 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 3 displays the adverse events reported by 5% or more of adult GHD patients in clinical trials after various durations of treatment with another somatropin product. 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. Table 3.
Drug interactions
• 11β-Hydroxysteroid Dehydrogenase Type 1: May require the initiation of glucocorticoid replacement therapy. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance doses ( 7.1 , 7.2 )
• Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Should be carefully adjusted ( 7.2 )
• Cytochrome P450-Metabolized Drugs: Monitor carefully if used with somatropin ( 7.3 )
• Oral Estrogen: Larger doses of somatropin may be required in women ( 7.4 )
• Insulin and/or Oral Hypoglycemic Agents: May require adjustment ( 7.5 ) 7.1 11β-Hydroxysteroid Dehydrogenase Type 1 (11βHSD-1) The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH and somatropin inhibit 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment; 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 11βHSD-1 [see Warnings and Precautions ( 5.8 )]. 7.2 Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of somatropin in children. Therefore, glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth. 7.3 Cytochrome P450-Metabolized Drugs Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes. However, formal drug interaction studies have not been conducted. 7.4 Oral Estrogen 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 ( 2.2 )] . 7.5 Insulin and/or Oral Hypoglycemic Agents 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 Warnings and Precautions ( 5.4 )] .
Use in specific populations
8.1 Pregnancy Risk Summary OMNITROPE contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.16)] . Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies (rats and rabbits), there was no evidence of embryo‑fetal or neonatal harm following somatropin administration during organogenesis at doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area ( see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies with somatropin during the period of organogenesis at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously in pregnant rats and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in pregnant rabbits were not teratogenic (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area). In perinatal and postnatal studies in rats, doses of 0.3, 1, and 3.3 mg/kg/day somatropin 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 offspring due to somatropin. 8.2 Lactation Risk Summary There is no information regarding the presence of somatropin in human milk. Limited published data indicate that exogenous somatropin does not increase normal breastmilk concentrations of growth hormone. No adverse effects related to somatropin in the breastfed infant have been reported. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OMNITROPE and any potential adverse effects on the breastfed infant from OMNITROPE or from the underlying maternal condition. 8.5 Geriatric Use The safety and effectiveness of OMNITROPE in patients aged 65 and over have not been evaluated in clinical studies. 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 Dosage and Administration ( 2.2 )] .
Pregnancy
8.1 Pregnancy Risk Summary OMNITROPE contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.16)] . Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal studies (rats and rabbits), there was no evidence of embryo‑fetal or neonatal harm following somatropin administration during organogenesis at doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area ( see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies with somatropin during the period of organogenesis at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously in pregnant rats and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in pregnant rabbits were not teratogenic (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area). In perinatal and postnatal studies in rats, doses of 0.3, 1, and 3.3 mg/kg/day somatropin 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 offspring due to somatropin.
Geriatric use
8.5 Geriatric Use The safety and effectiveness of OMNITROPE in patients aged 65 and over have not been evaluated in clinical studies. 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 Dosage and Administration ( 2.2 )] .
Overdosage
Short-Term Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Furthermore, overdose with somatropin is likely to cause fluid retention. Long-Term Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone [see Dosage and Administration ( 2 )] .
Description
Somatropin is a human growth hormone (GH) produced by recombinant DNA technology using Escherichia coli. The protein is comprised of 191 amino acid residues and a molecular weight of approximately 22,125 daltons. The amino acid sequence is identical to that of human GH of pituitary origin. OMNITROPE (somatropin) injection is a clear, colorless, sterile solution for subcutaneous injection supplied in a cartridge for use with OMNITROPE Pen delivery system. Sodium hydroxide and/or phosphoric acid may be added during manufacture to adjust pH. OMNITROPE (somatropin) for injection is a white to off-white lyophilized powder supplied in a vial for subcutaneous injection after reconstitution. Sodium hydroxide and/or hydrochloric acid may be added during manufacture to adjust pH. Vials are co-packaged with accompanying 1.14 mL vials of a diluent containing Bacteriostatic Water for Injection with 1.5% benzyl alcohol as a preservative. After reconstitution, the concentration is 5 mg/mL. Each OMNITROPE cartridge or vial contains the following (see Table 4 ): Table 4. Contents of OMNITROPE Cartridges and Vial Product Cartridge 5 mg/ 1.5 mL Cartridge 10 mg/ 1.5 mL For Injection 5.8 mg/ vial Component Somatropin 5 mg 10 mg 5.8 mg Dibasic sodium phosphate 0.609 mg 0.71 mg 0.996 mg Monobasic sodium phosphate 1.28 mg 1.2 mg 0.52 mg Poloxamer 3 mg 3 mg - Mannitol 52.5 mg - - Glycine - 27.75 mg 27.6 mg Benzyl alcohol 13.5 mg - - Phenol - 4.5 mg - Water for Injection to make 1.5 mL to make 1.5 mL - Diluent (vials only) Bacteriostatic Water for Injection Water for injection to make 1.14 mL Benzyl alcohol 17 mg
Mechanism of action
12.1 Mechanism of Action Somatropin (as well as endogenous GH) binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by IGF-1 produced in the liver and also locally (e.g., skeletal growth, protein synthesis), while others are primarily a consequence of the direct effects of somatropin (e.g., lipolysis) [see Pharmacodynamics ( 12.2 )] .
How supplied
16.1 How Supplied OMNITROPE (somatropin) injection is a clear, colorless, sterile solution for subcutaneous injection supplied in a cartridge for use with OMNITROPE Pen delivery system. OMNITROPE (somatropin) for injection is a white to off-white lyophilized powder supplied in a vial for subcutaneous injection after reconstitution with co-packaged diluent. Carton Contents Strength NDC 1 single-patient-use cartridge 5 mg/1.5 mL a NDC 0781-3001-07 5 single-patient-use cartridges 5 mg/1.5 mL a NDC 0781-3001-26 1 single-patient-use cartridge 10 mg/1.5 mL b NDC 0781-3004-07 5 single-patient-use cartridges 10 mg/1.5 mL b NDC 0781-3004-26 8 single-patient-use vials 8 single-dose vials of diluent (Bacteriostatic Water for Injection containing 1.5% benzyl alcohol as a preservative) 5.8 mg per vial NDC 0781-4004-36 a For use only with the OMNITROPE Pen 5 delivery system, which is sold separately. b For use only with the OMNITROPE Pen 10 delivery system, which is sold separately. 16.2 Storage and Handling Before use, store OMNITROPE vials and cartridges refrigerated at 2° to 8°C (36° to 46°F) in the original carton to protect from light. Do not freeze. After first use, the OMNITROPE cartridge should remain in the pen and kept the original carton in a refrigerator at 2° to 8°C (36° to 46°F) for a maximum of 28 days (see Table 11 ). Discard unused portions in the cartridge after 28 days. After reconstitution of the lyophilized powder, the contents of the OMNITROPE vial must be used within 21 days. After the first injection, store the vial in the original carton in a refrigerator at 2° to 8°C (36° to 46°F) (see Table 11 ). Discard unused portions after 21 days. Table 11. Storage Options OMNITROPE Product Formulation Storage Requirement Before Use In-use (after 1st injection) 5 mg/1.5 mL cartridge Refrigerate at 2° to 8°C (36° to 46°F) Until exp date Refrigerate at 2° to 8°C (36° to 46°F) up to 28 days 10 mg/1.5 mL cartridge Refrigerate at 2° to 8°C (36° to 46°F) up to 28 days 5.8 mg per vial Refrigerate at 2° to 8°C (36° to 46°F) Until exp date Refrigerate at 2° to 8°C (36° to 46°F) up to 21 days
Patient information
See FDA-approved patient labeling (Instructions For Use: OMNITROPE Pen 5 Instructions For Use, OMNITROPE Pen 10 Instructions For Use, Instructions For OMNITROPE 5.8 mg/Vial). Patients being treated with OMNITROPE (and/or their parents) should be informed about the potential risks and benefits associated with somatropin treatment. 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 OMNITROPE should receive appropriate training and instruction on the proper use of OMNITROPE 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. Counsel patients and parents that they should never share an OMNITROPE Pen with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection. If patients are prescribed OMNITROPE Cartridge 5 mg/1.5 mL or 10 mg/1.5 mL (to be inserted into OMNITROPE Pen 5 or Pen 10 delivery systems), physicians should instruct patients to read the corresponding Instructions For Use provided with the OMNITROPE Pens delivery systems and the OMNITROPE Cartridges. If patients are prescribed OMNITROPE for injection, physicians should instruct patients to read the Instructions For Use leaflets provided with the OMNITROPE for injection 5.8 mg/vial. Manufactured by: Sandoz Inc., Princeton, NJ 08540 US License No. 2003
Label text from the FDA structured product label by Sandoz Inc (revised Jul 10, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Somatropin in 2 products
Omnitrope NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0781-3001 | Somatropin 5 mg/1.5mL Injection, Solution | Sandoz Inc | BLA |
| 0781-3004 | Somatropin 10 mg/1.5mL Injection, Solution | Sandoz Inc | BLA |
| 0781-4004 | Kit | Sandoz Inc | BLA |
Frequently asked questions
What is Omnitrope used for?
1 INDICATIONS AND USAGE OMNITROPE is a recombinant human growth hormone indicated for: • Pediatric: Treatment of children with growth failure due to growth hormone deficiency (GHD), Prader-Willi Syndrome, Small for Gestational Age, Turner Syndrome, and Idiopathic Short Stature ( 1.1 ) • Adult: Treatment of adults with either adult onset or childhood onset GHD ( 1.2 ) 1.1 Pediatric Patients…
What are the side effects of Omnitrope?
Other common somatropin-related adverse reactions include injection site reactions/rashes and lipoatrophy ( 6.1 ) and headaches ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch The following important adverse reactions are also described elsewhere in labeling: • Increased mortality in patients with acute… See the full label for the complete list.
Who makes Omnitrope?
Omnitrope is listed by 1 labeler in the FDA NDC directory, including Sandoz Inc.