Norditropin
somatropin · Injection, Solution · Subcutaneous
Uses
1 INDICATIONS AND USAGE NORDITROPIN is a recombinant human growth hormone indicated for:
• Pediatric : Treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH), short stature associated with Noonan syndrome, short stature associated with Turner syndrome, short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years, Idiopathic Short Stature (ISS), and growth failure due to Prader-Willi Syndrome ( 1.1 )
• Adult : Replacement of endogenous GH in adults with growth hormone deficiency ( 1.2 ) 1.1 Pediatric Patients NORDITROPIN is indicated for the treatment of pediatric patients with:
• growth failure due to inadequate secretion of endogenous growth hormone (GH),
• short stature associated with Noonan syndrome,
• short stature associated with Turner syndrome,
• short stature born small for gestational age (SGA) with no catch-up growth by age 2 years to 4 years of age,
• Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range,
• growth failure due to Prader-Willi syndrome (PWS). 1.2 Adult Patients NORDITROPIN is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)
Dosage and administration
• Administer by subcutaneous injection to the back of upper arm, abdomen, buttock, or thigh with regular rotation of injection sites ( 2.1 )
• Pediatric Dosage - divide the calculated weekly dosage into equal doses given either 6, or 7 days per week o GHD: 0.17 mg/kg/week to 0.24 mg/kg/week( 2.2 ) o Noonan Syndrome: Up to 0.46 mg/kg/week ( 2.2 ) o Turner Syndrome: Up to 0.47 mg/kg/week ( 2.2 ) o SGA: Up to 0.47 mg/kg/week ( 2.2 ) o ISS: Up to 0.47 mg/kg/week ( 2.2 ) o Prader-Willi Syndrome: 0.24 mg/kg/week ( 2.2 ) o Adult Dosage: Either of the following two dosing regimens may be used: o Non-weight based dosing: Initiate with a dose of approximately 0.2 mg/day (range, 0.15 mg/day-0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day-0.2 mg/day, according to individual patient requirements ( 2.3 ) o Weight-based dosing (Not recommended for obese patients): Initiate at 0.004 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.016 mg/kg daily ( 2.3 ) 2.1 Administration and Use Instructions
• Therapy with NORDITROPIN should be supervised by a physician who is experienced in the diagnosis and management of patients with the conditions for which NORDITROPIN is indicated [see Indications and Usage (1) ].
• Fundoscopic examination should be performed routinely before initiating treatment with NORDITROPIN to exclude preexisting papilledema, and periodically thereafter [see Warnings and Precautions (5.5) ].
• Administer NORDITROPIN by subcutaneous injection to the back of the upper arm, abdomen, buttocks, or thigh with regular rotation of injection sites to avoid lipoatrophy.
• Inspect visually for particulate matter and discoloration. NORDITROPIN should be clear and colorless. If the solution is cloudy or contains particulate matter do not use.
• Instructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the NORDITROPIN FlexPro prefilled pen. 2.2 Pediatric Dosage
• Individualize dosage for each patient based on the growth response.
• Divide the calculated weekly NORDITROPIN dosage into equal doses given either 6, or 7 days per week.
• The recommended weekly dose in milligrams (mg) per kilogram (kg) of body weight for pediatric patients is: o Pediatric GH Deficiency: 0.17 mg/kg/week to 0.24 mg/kg/week (0.024 to 0.034 mg/kg/day) o Noonan Syndrome: Up to 0.46 mg/kg/week (up to 0.066 mg/kg/day) o Turner Syndrome: Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day) o Small for Gestational Age (SGA): Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day)
• In very short pediatric patients, HSDS less than -3, and older pubertal pediatric patients consider initiating treatment with a larger dose of NORDITROPIN (up to 0.067 mg/kg/day). Consider a gradual reduction in dosage if substantial catch-up growth is observed during the first few years of therapy. In pediatric patients less than 4 years of age with less severe short stature, baseline HSDS values between -2 and -3, consider initiating treatment at 0.033 mg/kg/day and titrate the dose as needed. o Idiopathic Short Stature: Up to 0.47 mg/kg/week (up to 0.067 mg/kg/day) o Prader-Willi Syndrome: 0.24 mg/kg/week (0.034 mg/kg/day)
• Assess compliance and evaluate other causes of poor growth such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human growth hormone if patients experience failure to increase height velocity, particularly during the first year of treatment.
• Discontinue NORDITROPIN for stimulation of linear growth once epiphyseal fusion has occurred [see Contraindications (4) ]. 2.3 Adult Dosage
• Patients who were treated with somatropin for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin for GH deficient adults.
• Consider using a lower starting dose and smaller dose increment increases for geriatric patients as they may be at increased risk for adverse reactions with NORDITROPIN than younger individuals [see Use in Specific Populations (8.5) ].
• Estrogen-replete women and patients receiving oral estrogen may require higher doses [see Drug Interactions (7) ].
• Administer the prescribed dose daily.
• Either of two NORDITROPIN dosing regimens may be used: o Non-weight based
• Initiate NORDITROPIN with a dose of approximately 0.2 mg/day (range, 0.15 mg/day to 0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day to 0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor 1 (IGF-1) concentrations.
• Decrease the dose as necessary on the basis of adverse reactions and/or serum IGF-1 concentrations above the age- and gender-specific normal range.
• Maintenance dosages will vary considerably from person to person, and between male and female patients. o Weight-based
• Initiate NORDITROPIN at 0.004 mg/kg daily and increase the dose according to individual patient requirements to a maximum of 0.016 mg/kg daily.
• Use the patient’s clinical response, adverse reactions, and determination of age- and gender-adjusted serum IGF-1 concentrations as guidance in dose titration.
• Not recommended for obese patients as they are more likely to experience adverse reactions with this regimen
Dosage forms and strengths
Injection: NORDITROPIN is available as a clear and colorless solution in a
• 5 mg/1.5 mL FlexPro single-patient-use pen (orange)
• 10 mg/1.5 mL FlexPro single-patient-use pen (blue)
• 15 mg/1.5 mL FlexPro single-patient-use pen (green)
• 30 mg/3 mL FlexPro single-patient-use pen (purple) Injection:
• 5 mg/1.5 mL: FlexPro single-patient-use pen ( 3 )
• 10 mg/1.5 mL: FlexPro single-patient-use pen ( 3 )
• 15 mg/1.5 mL: FlexPro single-patient-use pen ( 3 )
• 30 mg/3 mL: FlexPro single-patient-use pen ( 3 )
Contraindications
4 CONTRAINDICATIONS NORDITROPIN is contraindicated in patients with:
• Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5.1) ].
• Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death [see Warnings and Precautions (5.2) ].
• Active Malignancy [see Warnings and Precautions (5.3) ].
• Hypersensitivity to NORDITROPIN or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins [see Warnings and Precautions (5.6) ].
• Active proliferative or severe non-proliferative diabetic retinopathy.
• Pediatric patients with closed epiphyses.
• Acute Critical Illness ( 4 )
• Pediatric patients with Prader-Willi syndrome who are severely obese, have history of severe upper airway obstruction, or have severe respiratory impairment due to risk of sudden death ( 4 )
• Active Malignancy ( 4 )
• Hypersensitivity to somatropin or excipients ( 4 )
• Active Proliferative or Severe Non-Proliferative Diabetic Retinopathy ( 4 )
• Pediatric patients with closed epiphyses ( 4 )
Warnings and precautions
• Increased Risk of Neoplasms : Second neoplasms have occurred in childhood cancer survivors. Monitor patients with preexisting tumors for progression or recurrence. ( 5.3 )
• Glucose Intolerance and Diabetes Mellitus : NORDITROPIN may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving NORDITROPIN, especially in patients with existing diabetes mellitus or at risk for development. ( 5.4 )
• Intracranial Hypertension (IH) : Has been reported usually within 8 weeks of initiation. Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema occurs, stop treatment. ( 5.5 )
• Severe Hypersensitivity : Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention. ( 5.6 )
• Fluid Retention : May occur in adults and may be dose dependent. ( 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 : Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of somatropin. ( 5.9 )
• Slipped Capital Femoral Epiphysis in Pediatric Patients : May occur; evaluate patients with onset of a limp or hip/knee pain. ( 5.10 )
• Progression of Preexisting Scoliosis in Pediatric Patients : Monitor patients with scoliosis for progression. ( 5.11 )
• Pancreatitis : Has been reported; consider pancreatitis in patients with abdominal pain, especially pediatric patients. ( 5.12 ) 5.1 Increased Mortality in Patients with 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 NORDITROPIN treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. NORDITROPIN is not indicated for the treatment of non-GH deficient adults. 5.2 Sudden Death in Pediatric Patients with Prader-Willi Syndrome There have been reports of sudden death 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 and sleep apnea before initiation of treatment with somatropin. If, during treatment with NORDITROPIN, 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 NORDITROPIN 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 Increased Risk of Neoplasms Active Malignancy There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [See Contraindications (4) ]. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with NORDITROPIN. Discontinue NORDITROPIN if there is evidence of recurrent activity. Risk of Second Neoplasm in Pediatric Patients There is an increased risk of a second neoplasm in pediatric cancer survivors who were treated with radiation to the brain/head and who developed subsequent GH deficiency and were treated with somatropin. 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. Monitor all patients receiving NORDITROPIN who have a history of GH deficiency secondary to an intracranial neoplasm for progression or recurrence of the tumor. New Malignancy During Treatment Because pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting NORDITROPIN in these patients. If NORDITROPIN is initiated, carefully monitor patients for development of neoplasms. Monitor all patients receiving NORDITROPIN carefully for increased growth, or potential malignant changes, of preexisting nevi. Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances and/or changes in skin pigmentation or changes in the appearance of pre-existing nevi. 5.4 Glucose Intolerance and Diabetes Mellitus Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes mellitus has been reported in patients taking somatropin. Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked. Monitor glucose levels periodically in all patients receiving NORDITROPIN, 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. The doses of antidiabetic agents may require adjustment when NORDITROPIN is initiated.
Side effects
The following important adverse reactions are also described elsewhere in the labeling:
• Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1) ]
• Sudden death 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) ]
• Pancreatitis [see Warnings and Precautions (5.12) ]
• Lipoatrophy [see Warnings and Precautions (5.13) ] Common adverse reactions in adult and pediatric patients include: upper respiratory infection, fever, pharyngitis, headache, otitis media, edema, arthralgia, paresthesia, myalgia, peripheral edema, flu syndrome, and impaired glucose tolerance. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk at 1-888-NOVO-444 (1-888-668-6444) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 product cannot always be directly compared to the rates observed during the clinical trials performed with another somatropin product, and may not reflect the adverse reaction rates observed in practice. Pediatric Patients Growth Failure due to Inadequate Secretion of Endogenous Growth Hormone In one randomized, open label, clinical study the most frequent adverse reactions were headache, pharyngitis, otitis media and fever. There were no clinically significant differences between the three doses assessed in the study (0.025, 0.05 and 0.1 mg/kg/day). Short Stature Associated with Noonan Syndrome NORDITROPIN was studied in 21 pediatric patients, 3 years to 14 years of age at doses of 0.033 mg/kg/day and 0.066 mg/kg/day. After the two-year study, patients continued NORDITROPIN treatment until final height was achieved; randomized dose groups were not maintained. Adverse reactions were later collected retrospectively from 18 pediatric patients; total follow-up was 11 years. An additional 6 pediatric patients were not randomized, but followed the protocol and are included in this assessment of adverse reactions. The most frequent adverse reactions were upper respiratory infection, gastroenteritis, ear infection, and influenza. Cardiac disorders was the system organ class with the second most adverse reactions reported. Scoliosis was reported in 1 and 4 pediatric patients receiving doses of 0.033 mg/kg/day and 0.066 mg/kg/day respectively. The following additional adverse reactions also occurred once: insulin resistance and panic reaction for the 0.033 mg/kg/day dose group; injection site pruritus, bone development abnormal, depression, and self-injurious ideation in the 0.066 mg/kg/day dose group. Headache occurred in 2 cases in the 0.066 mg/kg/day dose group. Short Stature Associated with Turner Syndrome In two clinical studies in pediatric patients that were treated until final height with various doses of NORDITROPIN, the most frequently reported adverse reactions were influenza-like illness, otitis media, upper respiratory tract infection, otitis externa, gastroenteritis, eczema and, impaired fasting glucose. Adverse reactions in study 1 were most frequent in the highest dose groups. Three patients in study 1 had excessive growth of hands and/or feet in the high dose groups. Two patients in study 1 had a serious adverse reaction of exacerbation of preexisting scoliosis in the 0.045 mg/kg/day group. Small for Gestational Age (SGA) with No Catch-up Growth by Age 2-4 Years In a study, 53 pediatric patients were treated with 2 doses of NORDITROPIN (0.033 or 0.067 mg/kg/day) to final height for up to 13 years (mean duration of treatment 7.9 and 9.5 years for girls and boys, respectively). The most frequently reported adverse reactions were influenza-like illness, upper respiratory tract infection, bronchitis, gastroenteritis, abdominal pain, otitis media, pharyngitis, arthralgia, headache, gynecomastia, and increased sweating. One pediatric patient treated with 0.067 mg/kg/day for 4 years was reported with disproportionate growth of the lower jaw, and another patient treated with 0.067 mg/kg/day developed a melanocytic nevus. 4 pediatric patients treated with 0.067 mg/kg/day and 2 pediatric patients treated with 0.033 mg/kg/day of NORDITROPIN had increased fasting blood glucose levels after 1 year of treatment. In addition, small increases in mean fasting blood glucose and insulin levels after 1 and 2 years of NORDITROPIN treatment appeared to be dose-dependent. In a second study, 98 Japanese pediatric patients were treated with 2 doses of NORDITROPIN (0.033 or 0.067 mg/kg/day) for 2 years or were untreated for 1 year. Adverse reactions were otitis media, arthralgia and impaired glucose tolerance. Arthralgia and transiently impaired glucose tolerance were reported in the 0.067 mg/kg/day treatment group. Idiopathic Short Stature In two open-label clinical studies with another somatropin product in pediatric patients, the most common adverse reactions were upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia.
Drug interactions
Table 2 includes a list of drugs with clinically important drug interactions when administered concomitantly with NORDITROPIN and instructions for preventing or managing them. Table 2: Clinically Important Drug Interactions with NORDITROPIN Glucocorticoids Clinical Impact: 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. NORDITROPIN inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of NORDITROPIN may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. Intervention: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of NORDITROPIN [see Warnings and Precautions (5.8) ]. Examples: Cortisone acetate and prednisone may be effected more than others since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1. Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment Clinical Impact: Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of NORDITROPIN in pediatric patients. Intervention: Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth. Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that somatropin treatment increases cytochrome P450 (CP450)-mediated antipyrine clearance. NORDITROPIN may alter the clearance of compounds known to be metabolized by CP450 liver enzymes. Intervention: Careful monitoring is advisable when NORDITROPIN is administered in combination with drugs metabolized by CP450 liver enzymes. Oral Estrogen Clinical Impact: Oral estrogens may reduce the serum IGF-1 response to NORDITROPIN. Intervention: Patients receiving oral estrogen replacement may require greater NORDITROPIN dosages [see Dosage and Administration (2.3) ] . Insulin and/or Other Hypoglycemic Agents Clinical Impact: Treatment with NORDITROPIN may decrease insulin sensitivity, particularly at higher doses. Intervention: Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other hypoglycemic agents [see Warnings and Precautions (5.4) ].
• Glucocorticoids : Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of NORDITROPIN ( 7 )
• Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment : Adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatment to avoid both hypoadrenalism and an inhibitory effect on growth. ( 7 )
• Cytochrome P450-Metabolized Drugs : NORDITROPIN may alter the clearance. Monitor carefully if used with NORDITROPIN ( 7 )
• Oral Estrogen : Larger doses of NORDITROPIN may be required ( 7 )
• Insulin and/or Other Hypoglycemic Agents : Dose adjustment of insulin or hypoglycemic agent may be required ( 5.4 , 7 )
Use in specific populations
8.1 Pregnancy Risk Summary Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, there was no evidence of fetal or neonatal harm when pregnant rats were administered subcutaneous NORDITROPIN during organogenesis or during lactation at doses approximately 10-times higher than the maximal clinical dose of 0.016 mg/kg, based on body surface area (see Data). The estimated background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, NORDITROPIN was administered via subcutaneous injection to pregnant rats from gestation Day 6 to 17, corresponding with the period of organogenesis. NORDITROPIN did not adversely affect fetal viability or developmental outcomes at maternal doses that were approximately 10-times the clinical dose of 0.016 mg/kg, based on body surface area. In a pre- and post-natal development study in pregnant rats, NORDITROPIN was administered from gestation Day 17 through lactation Day 21 (weaning). No adverse developmental effects were observed in the offspring at doses up to 1.1 mg/kg (approximately 10 times the clinical dose of 0.016 mg/kg, based on body surface area). 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 on the breastfed infant have been reported with somatropin. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NORDITROPIN and any potential adverse effects on the breastfed infant from NORDITROPIN or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of NORDITROPIN in pediatric patients have been established in growth failure due to inadequate secretion of endogenous growth hormone, short stature associated with Noonan syndrome, short stature associated with Turner syndrome, short stature in children born small for gestational age (SGA) with no catch-up growth by age 2 years to 4 years of age, idiopathic short stature (ISS), and growth failure due to Prader-Willi syndrome (PWS). Growth Failure due to Inadequate Secretion of Endogenous Growth Hormone Safety and effectiveness of NORDITROPIN have been established in pediatric patients with growth failure due to growth hormone deficiency in a multi-center, prospective, randomized, open-label, dose-response study in 111 pediatric patients conducted for a two-year period [see Clinical Studies (14.1) ]. Short Stature Associated with Noonan Syndrome Safety and effectiveness of NORDITROPIN have been established in pediatric patients with Noonan syndrome in a prospective, open-label, randomized, parallel group study in 21 pediatric patients conducted for 2 years [see Clinical Studies (14.2) ]. Short Stature Associated with Turner Syndrome Safety and effectiveness of NORDITROPIN have been established in pediatric patients with short stature associated with Turner syndrome in two randomized, parallel group, open-label, multicenter studies in 87 pediatric patients [see Clinical Studies (14.3) ]. Short Stature in Pediatric Patients Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2 Years to 4 Years of Age Safety and effectiveness of NORDITROPIN have been established in pediatric patients with short stature born SGA with no catch-up growth in a multi-center, randomized, double-blind, two-arm study to final height in 53 pediatric patients and in a randomized study of 84 prepubertal, non-GHD, Japanese pediatric patients [see Clinical Studies (14.4) ]. Idiopathic Short Stature (ISS) Safety and effectiveness of NORDITROPIN have been established in pediatric patients with ISS based on data from a randomized, open-label clinical study with another somatropin product in 105 pediatric patients [see Clinical Studies (14.5) ]. Growth Failure Due to Prader-Willi Syndrome (PWS) Safety and effectiveness of NORDITROPIN have been established in pediatric patients with growth failure due to Prader-Willi Syndrome based on data from two randomized, open label, controlled clinical trials with another somatropin product in pediatric patients. There have been reports of sudden death 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 and sleep apnea before initiation of treatment with somatropin. [see Contraindications (4) , Warnings and Precautions (5.2) , Clinical Studies (14.6) ]. 8.5 Geriatric Use The safety and effectiveness of NORDITROPIN in patients aged 65 and over has 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 (2.3) ].
Pregnancy
8.1 Pregnancy Risk Summary Limited available data with somatropin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, there was no evidence of fetal or neonatal harm when pregnant rats were administered subcutaneous NORDITROPIN during organogenesis or during lactation at doses approximately 10-times higher than the maximal clinical dose of 0.016 mg/kg, based on body surface area (see Data). The estimated background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, NORDITROPIN was administered via subcutaneous injection to pregnant rats from gestation Day 6 to 17, corresponding with the period of organogenesis. NORDITROPIN did not adversely affect fetal viability or developmental outcomes at maternal doses that were approximately 10-times the clinical dose of 0.016 mg/kg, based on body surface area. In a pre- and post-natal development study in pregnant rats, NORDITROPIN was administered from gestation Day 17 through lactation Day 21 (weaning). No adverse developmental effects were observed in the offspring at doses up to 1.1 mg/kg (approximately 10 times the clinical dose of 0.016 mg/kg, based on body surface area).
Pediatric use
8.4 Pediatric Use Safety and effectiveness of NORDITROPIN in pediatric patients have been established in growth failure due to inadequate secretion of endogenous growth hormone, short stature associated with Noonan syndrome, short stature associated with Turner syndrome, short stature in children born small for gestational age (SGA) with no catch-up growth by age 2 years to 4 years of age, idiopathic short stature (ISS), and growth failure due to Prader-Willi syndrome (PWS). Growth Failure due to Inadequate Secretion of Endogenous Growth Hormone Safety and effectiveness of NORDITROPIN have been established in pediatric patients with growth failure due to growth hormone deficiency in a multi-center, prospective, randomized, open-label, dose-response study in 111 pediatric patients conducted for a two-year period [see Clinical Studies (14.1) ]. Short Stature Associated with Noonan Syndrome Safety and effectiveness of NORDITROPIN have been established in pediatric patients with Noonan syndrome in a prospective, open-label, randomized, parallel group study in 21 pediatric patients conducted for 2 years [see Clinical Studies (14.2) ]. Short Stature Associated with Turner Syndrome Safety and effectiveness of NORDITROPIN have been established in pediatric patients with short stature associated with Turner syndrome in two randomized, parallel group, open-label, multicenter studies in 87 pediatric patients [see Clinical Studies (14.3) ]. Short Stature in Pediatric Patients Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2 Years to 4 Years of Age Safety and effectiveness of NORDITROPIN have been established in pediatric patients with short stature born SGA with no catch-up growth in a multi-center, randomized, double-blind, two-arm study to final height in 53 pediatric patients and in a randomized study of 84 prepubertal, non-GHD, Japanese pediatric patients [see Clinical Studies (14.4) ]. Idiopathic Short Stature (ISS) Safety and effectiveness of NORDITROPIN have been established in pediatric patients with ISS based on data from a randomized, open-label clinical study with another somatropin product in 105 pediatric patients [see Clinical Studies (14.5) ]. Growth Failure Due to Prader-Willi Syndrome (PWS) Safety and effectiveness of NORDITROPIN have been established in pediatric patients with growth failure due to Prader-Willi Syndrome based on data from two randomized, open label, controlled clinical trials with another somatropin product in pediatric patients. There have been reports of sudden death 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 and sleep apnea before initiation of treatment with somatropin. [see Contraindications (4) , Warnings and Precautions (5.2) , Clinical Studies (14.6) ].
Geriatric use
8.5 Geriatric Use The safety and effectiveness of NORDITROPIN in patients aged 65 and over has 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 (2.3) ].
Overdosage
Short-term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with somatropin is likely to cause fluid retention. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone .
Description
Somatropin is a human growth hormone (GH) produced by recombinant DNA technology using Escherichia Coli. The protein is comprised of 191 amino acids and has a molecular weight of about 22,000 daltons. The amino acid sequence is identical to that of human growth hormone of pituitary origin. NORDITROPIN (somatropin) injection is a sterile, clear and colorless solution for subcutaneous use in ready-to-administer prefilled single-patient-use pens with a volume of 1.5 mL or 3 mL with a pH of 6.13–6.20. Each NORDITROPIN contains the following (see Table 3 ): Table 3. Contents of NORDITROPIN Pen Component 5 mg/1.5 mL 10 mg/1.5 mL 15 mg/1.5 mL 30 mg/3 mL Somatropin 5 mg 10 mg 15 mg 30 mg Histidine 1 mg 1 mg 1.7 mg 3.3 mg Mannitol 60 mg 60 mg 58 mg 117 mg Phenol 4.5 mg 4.5 mg 4.5 mg 9 mg Poloxamer 188 4.5 mg 4.5 mg 4.5 mg 9 mg Hydrochloric acid/sodium hydroxide to adjust pH as needed as needed as needed as needed Water for Injection, USP up to 1.5 mL up to 1.5 mL up to 1.5 mL up to 3 mL
Mechanism of action
12.1 Mechanism of Action Somatropin binds to dimeric GH receptors located within the cell membranes of target tissue cells. This interaction results in intracellular signal transduction and subsequent induction of transcription and translation of GH-dependent proteins including IGF-1, IGF BP-3 and acid-labile subunit. Somatropin has direct tissue and metabolic effects or mediated indirectly by IGF-1, including stimulation of chondrocyte differentiation, and proliferation, stimulation hepatic glucose output, protein synthesis and lipolysis. Somatropin stimulates skeletal growth in pediatric patients with GHD as a result of effects on the growth plates (epiphyses) of long bones. The stimulation of skeletal growth increases linear growth rate (height velocity) in most somatropin-treated pediatric patients. Linear growth is facilitated in part by increased cellular protein synthesis.
How supplied
(somatropin) injection is a clear and colorless solution available as FlexPro single-patient-use prefilled pens:
• NORDITROPIN FlexPro 5 mg/1.5 mL (orange) NDC 0169-7704-21
• NORDITROPIN FlexPro 10 mg/1.5 mL (blue) NDC 0169-7705-21
• NORDITROPIN FlexPro 15 mg/1.5 mL (green) NDC 0169-7708-21
• NORDITROPIN FlexPro 30 mg/3 mL (purple) NDC 0169-7703-21 NORDITROPIN 5 mg/1.5 mL, 10 mg/1.5 mL, and 15 mg/1.5 mL FlexPro pens are compatible with FlexPro PenMate. The FlexPro PenMate is an accessory device that is dispensed separately with its enclosed Instructions for Use. NORDITROPIN 30 mg/3 mL FlexPro pen is not compatible with FlexPro PenMate. Each NORDITROPIN FlexPro pen is for use by a single patient. A NORDITROPIN FlexPro pen must never be shared between patients, even if the needle is changed. Unused NORDITROPIN FlexPro prefilled pens must be stored refrigerated at 2°C to 8°C (36°F to 46°F). Do not store directly adjacent to the refrigerator cooling element. Do not freeze. Avoid direct light. Table 14 – Storage Conditions and Expiration Before Use In-use (After 1 st injection) Storage requirement Storage Option 1 (Refrigeration) Storage Option 2 (Room temperature) 2ºC to 8ºC (36ºF to 46ºF) Until exp. date 2ºC to 8ºC (36ºF to 46ºF) 4 weeks Up to 25ºC (77ºF) 3 weeks
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
• Neoplasms – Advise childhood cancer survivors/caregivers that individuals treated with brain/head radiation are at increased risk of secondary neoplasms and as a precaution need to be monitored for recurrence. Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances and/or changes in skin pigmentation or changes in the appearance of pre-existing nevi.
• Fluid Retention - Advise patients that fluid retention during NORDITROPIN replacement therapy in adults may frequently occur. Inform patients of the clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) and to report to their healthcare provider any of these signs or symptoms occur during treatment with NORDITROPIN .
• Pancreatitis - Advise patients/caregivers that pancreatitis may develop and to report to their healthcare provider any new onset abdominal pain.
• Hypoadrenalism - Advise patients/caregivers who have or who are at risk for pituitary hormone deficiency(s) that hypoadrenalism may develop and to report to their healthcare provider if they experience hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss.
• Hypothyroidism - Advise patients/caregivers that undiagnosed/untreated hypothyroidism may prevent an optimal response to NORDITROPIN. Advise patients/caregivers they may require periodic thyroid function tests.
• Intracranial Hypertension - Advise patients/caregivers to report to their healthcare provider any visual changes, headache, and nausea and/or vomiting.
• Hypersensitivity Reactions – Advise patients/caregivers that serious systemic hypersensitivity reactions (anaphylaxis and angioedema) are possible and that prompt medical attention should be sought if an allergic reaction occurs.
• Glucose Intolerance/ Diabetes Mellitus – Advise patients/caregivers that new onset impaired glucose intolerance/diabetes mellitus or exacerbation of preexisting diabetes mellitus can occur and monitoring of blood glucose during treatment with NORDITROPIN may be needed. NORDITROPIN ® and FlexPro ® are registered trademarks of Novo Nordisk Health Care AG . Novo Nordisk is a registered trademark of Novo Nordisk A/S . PATENT Information: http://novonordisk-us.com/products/product-patents.html Manufactured by: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536 USA U.S. License No. 1261 For information about NORDITROPIN call: 1 (888) 668-6444 © 2025 Novo Nordisk A/S
Label text from the FDA structured product label by Novo Nordisk (revised Jul 7, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Somatropin in 4 products
Norditropin NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0169-7703 | Somatropin 30 mg/3mL Injection, Solution | Novo Nordisk | BLA |
| 0169-7704 | Somatropin 5 mg/1.5mL Injection, Solution | Novo Nordisk | BLA |
| 0169-7705 | Somatropin 10 mg/1.5mL Injection, Solution | Novo Nordisk | BLA |
| 0169-7708 | Somatropin 15 mg/1.5mL Injection, Solution | Novo Nordisk | BLA |
Norditropin recalls
- D-0956-2016 Jun 15, 2016 · Class II · Terminated
Defective Delivery System; may have a low frequency assembly fault which may result in pens block during the so-called "air shot" step
Frequently asked questions
What is Norditropin used for?
1 INDICATIONS AND USAGE NORDITROPIN is a recombinant human growth hormone indicated for: • Pediatric : Treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH), short stature associated with Noonan syndrome, short stature associated with Turner syndrome, short stature born small for gestational age (SGA) with no catch-up growth by age 2 to…
What are the side effects of Norditropin?
The following important adverse reactions are also described elsewhere in the labeling: • Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1) ] • Sudden death 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… See the full label for the complete list.
Who makes Norditropin?
Norditropin is listed by 1 labeler in the FDA NDC directory, including Novo Nordisk.
Has Norditropin been recalled?
The FDA enforcement database lists 1 recall for Norditropin, most recently D-0956-2016 (class ii): Defective Delivery System; may have a low frequency assembly fault which may result in pens block during the so-called "air shot" step