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 )
1.1Pediatric 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).
1.2Adult Patients
NORDITROPIN is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)
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) ].
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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 )
5.1Increased 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.
5.2Sudden 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) ] .
5.3Increased 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.
5.4Glucose 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.
5.5Intracranial Hypertension
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropins. 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 NORDITROPIN to exclude preexisting papilledema, and periodically thereafter.
If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with NORDITROPIN can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome may be at increased risk for the development of IH.
5.6Severe Hypersensitivity
Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4) ].
5.7Fluid Retention
Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) are usually transient and dose dependent.
5.8Hypoadrenalism
Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation
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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 )
Pregnancy and breastfeeding
8.1Pregnancy 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).
Adverse reactions
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.
6.1Clinical 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. Growth Failure Due to Prader-Willi Syndrome In two clinical studies in pediatric patients with PWS carried out with another somatropin product, the following adverse reactions were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia.
Adult Patients Adults with Growth Hormone Deficiency Adverse reactions with an incidence of ≥5% occurring in patients with AO GHD during the 6 month placebo-controlled portion of a clinical trial for NORDITROPIN are presented in Table 1 . Table 1 – Adverse Reactions with ≥5% Overall Incidence in Adult Onset Growth Hormone Deficient Patients Treated with NORDITROPIN During a Six Month Placebo-Controlled Clinical Trial Placebo (N=52) NORDITROPIN (N=53) Adverse Reactions % % Peripheral Edema 8 42 Edema 0 25 Arthralgia 15 19 Leg Edema 4 15 Myalgia 8 15 Infection (non-viral) 8 13 Paraesthesia 6 11 Skeletal Pain 2 11 Headache 6 9 Bronchitis 0 9 Flu-like symptoms 4 8 Hypertension 2 8 Gastroenteritis 8 8 Other Non-Classifiable Disorders (excludes accidental injury) 6 8 Increased sweating 2 8 Glucose tolerance abnormal 2 6 Laryngitis 6 6 Type 2 diabetes mellitus 0 5
6.2Postmarketing Experience
The following adverse reactions have been identified during post-approval use of somatropin or NORDITROPIN. Because these adverse reactions 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 . Immune system disorders — Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema Skin — Increase in size or number of cutaneous nevi Endocrine disorders — Hypothyroidism - Gynecomastia Metabolism and nutrition disorders — Hyperglycemia Musculoskeletal and connective tissue disorders — Slipped capital femoral epiphysis and osteonecrosis (including Legg-Calvé-Perthes disease) have been reported in pediatric patients treated with growth hormone [see Warnings and Precautions (5.10)].
Cases have been reported with NORDITROPIN. Investigations — Increase in blood alkaline phosphatase level — Decrease in serum thyroxin (T4) levels Gastrointes
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Composition
Active ingredients
SOMATROPIN 30MG/3ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
