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Medical Information | Non-US Health Care Professionals
Important Safety Information | Patient Site
Prescribing Information
Norditropin® (somatropin) injection 5 mg, 10 mg, 15 mg, 30 mg logo

For pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH) and Prader-Willi Syndrome; short stature associated with Noonan Syndrome, Turner Syndrome, and children born small for gestational age; idiopathic short stature; and for the replacement of endogenous GH in adults with growth hormone deficiency (GHD). Please see full indications.

Prescribing Information
Important Safety Information | Patient Site

Growth data for patients with non-GHD growth-related disorders

The efficacy of Norditropin® was assessed in clinical studies with pediatric patients diagnosed with Noonan syndrome, Turner syndrome, and born small for gestational age. Studies for idiopathic short stature and Prader-Willi syndrome included patients treated with another somatropin product.1

Explore data by indication

Significant increase in HSDS in pre-pubertal children with Idiopathic Short Stature treated to FH vs untreated controls1,a

See study design

Idiopathic Short Stature (ISS) final height graph

HSDS = height standard deviation score; SDS = standard deviation score.
a0.033 mg/kg/day vs untreated (95% CI): +0.53 (0.20, 0.87) P<0.05; 0.067 mg/kg/day vs untreated (95% CI): +0.94 (0.63, 1.26) P<0.05.1

  • Patients were treated to final height with another somatropin product1 
  • 69% of patients achieved a height gain of 1 SDS with a dose of 0.067 mg/kg/day1 
  • A height gain of 1 SDS was also seen in 10% of untreated patients and 50% of patients receiving 0.033 mg/kg/day1
A randomized, open-label, clinical study that evaluated the efficacy and safety of another somatropin product in 105 patients who were retrospectively identified as having ISS. All patients were observed for height progression for 12 months and were subsequently randomized to this other somatropin product or observation only and followed to final height. Two doses of this other somatropin product were evaluated in this trial: 0.23 mg/kg/week (0.033 mg/kg/day) and 0.47 mg/kg/week (0.067 mg/kg/day). Patients were treated for a median duration of 5.7 years.1

Patients with Noonan syndrome obtained a final height (FH) gain from baseline of 1.6 SDS (Noonan reference)1

See study design

Noonan syndrome HV graph

 HV = height velocity.

  • Patients achieved greater HV with a higher dose (0.066 mg/kg/day) vs lower dose (0.033 mg/kg/day) during both Year 1 and Year 21
  • After the initial 2-year study, Norditropin® treatment continued until FH1 
  • Patients obtained a FH gain from baseline of 1.5 and 1.6 standard deviation score (SDS), estimated according to the national and the Noonan reference, respectively1 
  • A height gain of 1.5 SDS (national) corresponds to a mean height gain of 9.9 cm in boys and 9.1 cm in girls at 18 years of age; a height gain of 1.6 SDS (Noonan) corresponds to a mean height gain of 11.5 cm in boys and 11.0 cm in girls at 18 years of age1

A prospective, open-label, randomized, parallel group study with 21 pediatric patients was conducted for 2 years to evaluate the efficacy and safety of Norditropin®. The patients 3 to 14 years of age received either 0.033 mg/kg/day or 0.066 mg/kg/day of Norditropin® subcutaneously which was adjusted based on growth response after the first 2 years. After the initial 2-year study, Norditropin® treatment continued until final height. Retrospective final height was collected from 18 patients in the study and the 6 who had followed the protocol without randomization. Historical reference materials of height velocity and adult height analyses of Noonan patients served as the controls.1

70% of children with Turner syndrome who attained final height (FH) did so within normal range (Study 1)1,c

See study design

Turner syndrome normal height percentage graph

HSDS = height standard deviation score.
cUsing National standard.1

  • Overall mean FH was 161 cm in the 46 children who attained FH1

A randomized, parallel group, open-label, multicenter, study conducted to evaluate the efficacy and safety of Norditropin®. Patients were treated to final height (HV <2 cm/year). 68 euthyroid Caucasian patients stratified based on age and baseline HSDS were randomized in a 1:1:1 ratio to 3 different Norditropin® treatment regimens: 0.045 mg/kg/day (Dose A) for the entire study; 0.045 mg/kg/day for the first year and 0.067 mg/kg/day thereafter (Dose B); or 0.045 mg/kg/day for the first year, 0.067 for the second year, and 0.089 mg/kg/day thereafter (Dose C). Patients also received estrogen therapy after age 12 and the following 4 years of Norditropin® treatment if they did not have spontaneous puberty.1

Turner syndrome change in HSDS graph
  • Data from all patients in this study were pooled. Overall mean FH was 155 cm in the 17 children who attained FH1

A randomized, parallel group, open-label, multicenter, study conducted to evaluate the efficacy and safety of Norditropin®. Patients were treated to final height (HV <2 cm/year). 19 euthyroid Caucasian patients (with bone age ≤13.9 years) were randomized to treatment with 0.067 mg/kg/day of Norditropin® as a single subcutaneous dose in the evening, or divided into 2 doses (1/3 morning and 2/3 evening). All subjects were treated with concomitant ethinyl estradiol.1

Significantly greater final height SDS and increase in HSDS from baseline to FH with 0.067 mg/kg/day vs 0.033 mg/kg/day1

See study design

Small for gestational age (SGA) final height graph
  • In a pivotal trial, 72% of patients reached final height (FH), and 63% of them were within the normal range of their healthy peers (Dutch national reference)1 
  • The treatment difference between 0.033 mg/kg/day and 0.067 mg/kg/day in final height SDS and change in HSDS from baseline to final height (0.5) was statistically significant (95% CI; 0.0-0.9), P<0.051 
  • Height velocity was significantly greater after treatment with 0.067 mg/kg/day vs 0.033 mg/kg/day1,e

SDS = standard deviation score; HSDS = height standard deviation score; GHD = growth hormone deficiency.

dValues are adjusted (least-squares) means +/- standard error based on an analysis of covariance model including terms for treatment, gender, age at baseline, bone age at baseline, height SDS at baseline, duration of treatment, peak GH after stimulation and baseline IGF-1.1
eOverall mean height velocity at baseline was 5.4 cm/y (SD 1.2; n=29). Height velocity was greatest during the first year of Norditropin® treatment and was significantly greater after treatment with 0.067 mg/kg/day (mean 11.1 cm/y [SD 1.9; n=19]) compared with 0.033 mg/kg/day (mean 9.7 cm/y [SD 1.3; n=10])1

A multicenter, randomized, double-blind, 2-arm study to final height conducted to assess the efficacy and safety of Norditropin®. The study included 53 (38 male, 15 female) non-GHD, Dutch pre-pubertal pediatric patients 3 to 11 years of age with short stature born SGA with no catch-up growth. Norditropin® was administered subcutaneously daily at bedtime at a dose of approximately 0.033 (Dose A) or 0.067 mg/kg/day (Dose B) for the entire treatment period. Final height was defined as a height velocity below 2 cm/year.1

Pediatric patients with Prader-Willi syndrome showed a significant increase in growth through Year 1, which continued to increase through Year 21

See study design

Prader-Willi syndrome (PWS) growth graph

fP<0.05.

  • Patients were treated with another somatropin product (0.24 mg/kg/week in Study 1 and 0.36 mg/kg/week in Study 2) vs untreated controls1
  • During Year 2, the control group received treatment with this other somatropin product1 
  • On average, the growth in cm from baseline to 12 months was statistically significant compared to untreated controls in both studies with this other somatropin product (P<0.05)1

The safety and efficacy of another somatropin product were evaluated in 2 randomized, open-label, controlled clinical studies. Patients received either this other somatropin product or no treatment for the first year of the studies, while all patients received this other somatropin product during the second year. In Study 1, the treatment group received this other somatropin product at a dose of 0.24 mg/kg/week during the entire study, while the control group received this other somatropin product at a dose of 0.48 mg/kg/week during Year 2. In Study 2, the treatment group received this other somatropin product at a dose of 0.36 mg/kg/week during the entire study, while the control group received this other somatropin product at a dose of 0.36 mg/kg/week during Year 2.1

Treating patients with GHD?

Safety and efficacy studies for Norditropin® have included pediatric and adult patients with growth hormone deficiency (GHD).1

How did Norditropin® perform in a real-world-setting?

View safety and efficacy results from an observational study of pediatric patients in the U.S. (ANSWER—originally a post-marketing registry).2,a

aThe ANSWER Program was originally a post-marketing registry of adults and pediatric patients treated with Norditropin® as prescribed by their physician and according to routine clinical practice. Since it did not investigate treatment specifics, it was developed into a non-interventional, observational study that allowed evaluation of the safety and effectiveness of Norditropin® in a real-world setting in the United States.2

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Individualized treatment

Norditropin® FlexPro® pens allow you to personalize your patients’ dosing regimens from childhood through adolescence.1

Study designs

Clinical Study: Idiopathic Short Stature (ISS):

A randomized, open-label, clinical study that evaluated the efficacy and safety of another somatropin product in 105 patients who were retrospectively identified as having ISS. Patients were enrolled on the basis of short stature, stimulated GH secretion >10 ng/mL, and pre-pubertal status. All patients were observed for height progression for 12 months and were subsequently randomized to this other somatropin product or observation only and followed to final height. Two doses of this other somatropin product were evaluated in this trial: 0.23 mg/kg/week (0.033 mg/kg/day) and 0.47 mg/kg/week (0.067 mg/kg/day). Baseline patient characteristics for the ISS patients who remained pre-pubertal at randomization (n=105) were: mean (± SD): chronological age 11.4 (1.3) years, height SDS -2.4 (0.4), height velocity SDS -1.1 (0.8), and height velocity 4.4 (0.9) cm/yr, IGF-1 SDS –0.8 (1.4). Patients were treated for a median duration of 5.7 years.1

Norditropin® Clinical Study: Short Stature Associated With Noonan Syndrome:

A prospective, open-label, randomized, parallel group study with 21 pediatric patients was conducted for 2 years to evaluate the efficacy and safety of Norditropin®. Additional 6 children were not randomized, but did follow the protocol. Inclusion criteria included bone age determination showing no significant acceleration, pre-pubertal status, height SDS <–2, and HV SDS <1 during the 12 months pre-treatment. Exclusion criteria were previous or ongoing treatment with growth hormone, anabolic steroids or corticosteroids, congenital heart disease or other serious disease perceived to possibly have major impact on growth, FPG >6.7 mmol/L (>120 mg/dL), or growth hormone deficiency (peak GH levels <10ng/mL). The twenty-four, 12 female and 12 male, patients 3-14 years of age received either 0.033 mg/kg/day or 0.066 mg/kg/day of Norditropin® subcutaneously which was adjusted based on growth response after the first 2 years.1 After the initial 2-year study, Norditropin® treatment continued until final height. Retrospective final height was collected from 18 patients in the study and the 6 who had followed the protocol without randomization. Historical reference materials of height velocity and adult height analyses of Noonan patients served as the controls.1

Norditropin® Clinical Studies: Short Stature Associated With Turner Syndrome:

Study 1:

A randomized, parallel group, open-label study conducted in the Netherlands to evaluate the efficacy and safety of Norditropin®. Patients were treated to final height (HV <2 cm/year).1 In Study 1, 68 euthyroid Caucasian patients stratified based on age and baseline HSDS were randomized in a 1:1:1 ratio to 3 different Norditropin® treatment regimens: 0.045 mg/kg/day (Dose A) for the entire study; 0.045 mg/kg/day for the first year and 0.067 mg/kg/day thereafter (Dose B); or 0.045 mg/kg/day for the first year, 0.067 for the second year, and 0.089 mg/kg/day thereafter (Dose C). At baseline, mean age was 6.5 years, mean HSDS (National standard) was -2.7, and mean HV during the previous year was 6.5 cm/year. Patients also received estrogen therapy after age 12 and following 4 years of Norditropin® treatment if they did not have spontaneous puberty.1 Patients were treated for a mean of 8.4 years.1

Study 2:

A randomized, parallel group, open-label study conducted in the Netherlands to evaluate the efficacy and safety of Norditropin®. Patients were treated to final height (HV <2 cm/year).1 In Study 2, 19 euthyroid Caucasian patients (with bone age ≤13.9 years) were randomized to treatment with 0.067 mg/kg/day of Norditropin® as a single subcutaneous dose in the evening, or divided into 2 doses (1/3 morning and 2/3 evening). All subjects were treated with concomitant ethinyl estradiol. Overall, at baseline, mean age was 13.6 years, mean height SDS (National standard) was -3.5 and mean HV during the previous year was 4.3 cm/year. Patients were treated for a mean of 3.6 years.1

Norditropin® Clinical Study: Short Stature in Children Born Small for Gestational Age (SGA) With No Catch-up Growth by Age 2-4 Years:

A multicenter, randomized, double-blind, 2-arm study to final height conducted to assess the efficacy and safety of Norditropin®. Changes in height and height velocity were compared to a national reference population.1 The study included 53 (38 male, 15 female,) non-GHD, Dutch pre-pubertal pediatric patients 3-11 years of age with short stature born SGA with no catchup growth. Catch-up growth was defined as obtaining a height of ≥3rd percentile within the first 2 years of life or at a later stage. Inclusion criteria included: birth length <3rd percentile for gestational age, and height velocity (cm/year) for chronological age <50th percentile. Exclusion criteria included chromosomal abnormalities, signs of a syndrome (except for Silver-Russell syndrome), serious/chronic co-morbid disease, malignancy, and previous rhGH therapy. Norditropin® was administered subcutaneously daily at bedtime at a dose of approximately 0.033 (Dose A) or 0.067 mg/kg/day (Dose B) for the entire treatment period. Final height was defined as a height velocity below 2 cm/year. Treatment with Norditropin® was continued to final height for up to 13 years. Mean duration of treatment was 9.5 years (boys) and 7.9 years (girls).1

Clinical Studies: Growth Failure Due to Prader-Willi Syndrome:

The safety and efficacy of another somatropin product were evaluated in 2 randomized, open-label, controlled clinical studies. Patients received either this other somatropin product or no treatment for the first year of the studies, while all patients received this other somatropin product during the second year. This other somatropin product was administered as a daily subcutaneous injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received this other somatropin product at a dose of 0.24 mg/kg/week during the entire study. During the second year, the control group received this other somatropin product at a dose of 0.48 mg/kg/week. In Study 2, the treatment group received this other somatropin product at a dose of 0.36 mg/kg/week during the entire study. During the second year, the control group received this other somatropin product at a dose of 0.36 mg/kg/week.1

Selected Important Safety Information for Norditropin®

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
  • 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
  • Active Malignancy
  • Hypersensitivity to Norditropin® or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products
  • Active proliferative or severe non-proliferative diabetic retinopathy
  • Pediatric patients with closed epiphyses

Indications and Usage

Norditropin® (somatropin) injection 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 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) 

Norditropin® is also indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)

Important Safety Information

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
  • 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
  • Active Malignancy
  • Hypersensitivity to Norditropin® or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropin products
  • Active proliferative or severe non-proliferative diabetic retinopathy
  • Pediatric patients with closed epiphyses

Warnings and Precautions

  • Increased mortality in patients with acute critical illness due to complications following open heart or abdominal surgery or multiple accidental trauma, or those with respiratory failure has been reported.
  • Sudden death in pediatric patients with Prader-Willi Syndrome has been reported after initiating treatment with somatropin with one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Evaluate patients for signs of upper airway obstruction and sleep apnea before initiation of treatment.
  • Increased risk of neoplasms: Monitor patients with preexisting tumors for progression or recurrence. 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, in particular meningiomas, has been reported. Pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients carefully for increased growth, or potential malignant changes, of preexisting nevi.
  • 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. Monitor glucose levels in all patients. Doses of concurrent antidiabetic drugs may require adjustment.
  • Intracranial hypertension has been reported in a small number of patients, usually within the first 8 weeks of somatropin treatment. Funduscopic examination should be performed before initiating treatment and periodically thereafter.
  • Severe hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products.
  • Fluid retention in adults (clinically manifesting as edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) may frequently occur and is usually transient and dose-dependent.
  • Hypoadrenalism: Patients 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 of Norditropin® treatment.
  • Hypothyroidism if undiagnosed/untreated, may prevent an optimal response to Norditropin®, in particular, the growth response in pediatric patients. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted when indicated.
  • Slipped capital femoral epiphysis in pediatric patients may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Pediatric patients with the onset of a limp or complaints of hip or knee pain should be evaluated.
  • Progression of preexisting scoliosis in pediatric patients can occur in patients who experience rapid growth. Patients with a history of scoliosis should be monitored for progression.
  • Pancreatitis: Cases of pancreatitis have been reported. Pancreatitis should be considered in any patient who develops persistent severe abdominal pain.
  • Lipoatrophy: Tissue atrophy may result when somatropin is administrated subcutaneously at the same site over a long period of time. Rotate injection sites when administering Norditropin® to reduce this risk.

Adverse Reactions

  • Other common adverse reactions in adults and pediatric patients include: upper respiratory infection, fever, pharyngitis, headache, otitis media, edema, arthralgia, paresthesia, myalgia, peripheral edema, flu syndrome, and impaired glucose tolerance

Drug Interactions

  • Glucocorticoids: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Norditropin®
  • 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
  • Cytochrome P450-Metabolized Drugs: Norditropin® may alter the clearance. Monitor carefully if used with Norditropin®
  • Oral Estrogen: Larger doses of Norditropin® may be required
  • Insulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required

Use in Specific Populations

  • Pregnancy and Nursing Mothers: There are limited data with somatropin use in pregnant women and nursing mothers to inform a drug-associated risk for adverse developmental outcomes.
  • Geriatric Use: The safety and effectiveness in patients aged 65 and over has not been evaluated in clinical studies.

Please click here for Norditropin® Prescribing Information.

References:

  1. Norditropin [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc.
  2. Data on file. Novo Nordisk Inc; Plainsboro, NJ