Safety and Efficacy Data

Follow the navigation below to learn more about each indication, including recommended dosage and available study information.

Growth hormone (GH) deficiency in children

Humatrope was approved by the FDA in 1987 for the treatment of growth failure in children with GH deficiency.

Humatrope is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of normal endogenous GH. Somatropin therapy should not be used for growth promotion in pediatric patients with closed epiphyses.

Recommended dosage:

0.026 to 0.043 mg/kg/day
(0.18 to 0.30 mg/kg/week).1

Dosage should be individualized within recommended range based on growth response; failure to increase height velocity should prompt close assessment.

Adverse Reactions Observed in Humatrope Clinical Trials
  • During the first 6 months of Humatrope therapy in 314 previously untreated patients, only 1.6% developed specific antibodies to Humatrope (binding capacity =0.02 mg/L). None had antibody concentrations that exceeded 2 mg/L.1
  • Throughout 8 years of this same study, two patients (0.6%) had binding capacity >2 mg/L. Neither patient demonstrated a decrease in height velocity at or near the time of increased antibody production.1

In studies with GH-deficient pediatric patients, injection site pain was reported infrequently. A mild and transient edema, which appeared in 2.5% of patients, was observed early during the course of treatment.1

Reference

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

SELECT SAFETY INFORMATION

  • Acute Critical Illness: Somatropin should not be used to treat patients with acute critical illness from complications after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure.
  • Prader-Willi Syndrome in Children: Somatropin should not be used in 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. Humatrope is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Growth hormone (GH) deficiency in adults

Humatrope was approved by the FDA in 1996 for the treatment of adults with GH deficiency. Humatrope is indicated for the replacement of endogenous GH in adults with GH deficiency who meet either of the following two criteria:

  • Adult-onset (AO) GH deficiency — Patients who have GH deficiency as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma;

OR

  • Childhood-onset (CO) GH deficiency — Patients who were treated for GH deficiency in childhood and whose epiphyses are closed should be reevaluated to determine if they should continue growth hormone.

Recommended dosage: Non-weight-based dosing:
A starting dose of

approximately 0.2 mg/day
(range, 0.15–0.30 mg/day)

may be used without consideration of body weight, and can be increased gradually every 1–2 months by increments of approximately 0.1–0.2 mg/day.1

Weight-based dosing:
The recommended initial daily dose is

not more than 0.006 mg/kg
(6 μg/kg/day)

the dose may be increased to a maximum of 0.0125 mg/kg (12.5 µg/kg/day) daily.1
Dose should be adjusted based on clinical response, side effects, and determination of age- and gender-adjusted serum IGF-1 concentration.

Study Design1

The effects of replacement therapy with Humatrope were assessed in 2 multicenter trials in patients with adult-onset (AO) GH deficiency (n=98) and 2 studies in patients with childhood-onset (CO) GH deficiency (n=67). The 4 studies included a 6-month, randomized, blinded, placebo-controlled phase, during which approximately half of the patients received placebo injections, while the other half received Humatrope injections. Humatrope dosages for all studies included 1 month of treatment at 0.00625 mg/kg/day (6.25 µg/kg/day) followed by 0.0125 mg/kg/day (12.5 µg/kg/day) for the next 5 months. The 6-month, double-blind phase was followed by 12 months of open-label Humatrope treatment for all patients.

Primary efficacy measures were body composition (lean body mass and fat mass), lipid parameters, and quality of life, as measured by the Nottingham Health Profile (a general health-related quality-of-life questionnaire). Lean body mass was determined by bioelectrical impedance analysis (BIA), validated with potassium 40. Body fat was assessed by BIA and sum of skinfold thickness. Lipid subfractions were analyzed by standard assay methods in a central laboratory. Adult-onset patients and childhood-onset patients differed by diagnosis (organic vs. idiopathic pituitary disease), body size (average vs. small [mean height and weight]), and age (mean 44 vs. 29 years).

Study Results and Adverse Reactions Observed in Humatrope Clinical Trials

Decreased body fat and increased lean body mass

In patients with AO GH deficiency, those who received Humatrope therapy for 6 months showed a statistically significant reduction of body fat and a statistically significant increase in lean body mass compared with patients who received placebo injections.1

  • Humatrope-treated patients lost an average of 7.2 lbs (3.27 kg) body fat, while placebo-treated patients gained an average of 1.2 lbs (0.56 kg) body fat (p<0.001).1
  • Humatrope-treated patients gained an average of 5.7 lbs (2.59 kg) lean body mass, while placebo-treated patients lost an average of 0.5 lbs (0.22 kg) lean body mass (p<0.001).1

Similar changes were seen in patients with CO GH deficiency. These significant changes in lean body mass persisted throughout the 18-month period for both the AO and CO groups; the changes in fat mass persisted in the CO group.1

  • Humatrope-treated patients lost an average of 7.3 lbs (3.33 kg) body fat, while placebo-treated patients gained an average of 4.9 lbs (2.23 kg) body fat (p<0.001).2

Humatrope-treated patients gained an average of 8.1 lbs (3.68 kg) lean body mass, while placebo-treated patients lost an average of 4.2 lbs (1.91 kg) lean body mass (p<0.001).3

Adverse Reactions Observed in Humatrope Clinical Trials

  • During the placebo-controlled phase (first 6 months) of the study, elevations of serum glutamic oxaloacetic transferase were reported significantly more often for Humatrope-treated (12.5%) than placebo-treated CO GH deficient patients (0.0%, p=0.031).
  • In the first 6 months of controlled blinded trials during which patients received either Humatrope or placebo, adults with AO GH deficiency who received Humatrope experienced a statistically significant increase in edema (Humatrope 17.3% vs. placebo 4.4%, p=0.043) and peripheral edema (11.5% vs. 0%, respectively, p=0.017).1
  • In patients with AO GH deficiency, edema, muscle pain, joint pain, and joint disorder were reported early in therapy and tended to be transient or responsive to dosage titration.1
  • Two of 113 patients with AO GH deficiency developed carpal tunnel syndrome after beginning maintenance therapy without a low dose lead-in phase. Symptoms abated in these patients after dosage reduction.1

References

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

2. Data on file, Lilly Research Laboratories, HG20120305A.

3. Data on file, Lilly Research Laboratories, HG20120305B.

SELECT SAFETY INFORMATION

  • Active Malignancy: Somatropin is contraindicated in patients with any evidence of active malignancy.
  • Hypersensitivity: Humatrope is contraindicated in patients with a known hypersensitivity to somatropin or the supplied diluent.
  • Diabetic Retinopathy or Closed Epiphyses: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. It should not be used for growth promotion in pediatric patients with closed epiphyses.

Idiopathic short stature (ISS)

Humatrope was approved by the FDA in 2003 for the treatment of idiopathic short stature, also called non-GH-deficient short stature, defined by height SDS =- 2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients for whom diagnostic evaluation excludes other causes of short stature that should be observed or treated by other means; SDS = standard deviation scores.

Recommended dosage:

Up to 0.053 mg/kg/day
(0.37 mg/kg/week).1

Dosage should be individualized within recommended range based on growth response; failure to increase height velocity should prompt close assessment.

Study Design

Two randomized, multicenter trials—1 placebo-controlled and 1 dose-response—were conducted in pediatric patients with idiopathic short stature (ISS). The diagnosis of ISS was made after excluding other known causes of short stature, as well as growth hormone (GH) deficiency.1

  • The placebo-controlled, double-blind study enrolled 71 pediatric patients (55 males, 16 females), 9 to 15 years old (mean age 12.4 ± 1.5 years), with short stature, 68 of whom received study drug (placebo, n=31; Humatrope, n=37). Patients were predominantly prepubertal (Tanner I, 45%) or in early puberty (Tanner II, 47%) at baseline.1
  • Patients received subcutaneous injections of either Humatrope 0.222 mg/kg/week or placebo given in divided doses 3 times per week until height velocity decreased to =1.5 cm/year (study definition of "final height").1
  • The dose-response study included 239 pediatric patients (158 males, 81 females), 5 to 15 years old (mean age 9.8 ± 2.3 years). All but 3 patients were prepubertal at baseline. Patients were randomized to 1 of 3 Humatrope treatment regimens: 0.24 mg/kg/week; 0.24 mg/kg/week for 1 year, followed by 0.37 mg/kg/week; and 0.37 mg/kg/week. Humatrope was administered in divided doses 6 times per week.1
Study Results and Adverse Reactions Observed in Humatrope Clinical Trials

Increased final (near-adult) height and height gains: placebo-controlled study

Mean final (or "near adult") height standard deviation score (SDS) after a mean treatment duration of 4.4 years was significantly greater in the Humatrope-treated group (n=22) compared with the placebo-treated group (n=11; p=0.017).1

  • The Humatrope-treated group achieved a mean final height SDS of -1.8 vs. -2.3 for the placebo group (mean treatment difference, 0.51 SDS, p=0.017).
  • The following additional efficacy parameters also demonstrated greater height gains for the Humatrope group compared with the placebo group:
  • Mean height SDS gain across the duration of the study (final height SDS minus baseline height SDS) was significantly greater in the Humatrope group than in the placebo group (p=0.034).
  • Mean final height SDS minus baseline-predicted height SDS (the height the patient was predicted at baseline to achieve if untreated) was significantly greater in the Humatrope group than in the placebo group (p=0.043).
  • Forty-one percent of Humatrope-treated patients achieved final height above the 5th percentile of the general population height standard for age and sex, whereas no patient who received placebo injections attained this height (p<0.05).
  • Fifty percent of Humatrope-treated patients gained at least 1 SDS in height over the duration of the study vs. 0% of patients who received placebo injections (p<0.05).

Increased height velocity and final (near-adult) height: dose-response study

Treatment with Humatrope significantly increased height velocity in a dose-dependent manner (p=0.003).1

  • After 2 years of treatment the group that received the Humatrope dosage of 0.37 mg/kg/week had a significantly greater increase in mean height velocity than patients who received 0.24 mg/kg/week
    (4.04 cm/year vs. 3.27 cm/year, p=0.003).1

Fifty patients were followed to final (near-adult) height. The mean difference between final height and baseline-predicted height was 5.4 cm for patients who received Humatrope 0.24 mg/kg/week and 7.2 cm for patients who received 0.37 mg/kg/week; patients who received Humatrope 0.24 mg/kg/week for the 1st year then increased to 0.37 mg/kg/week for the remainder of treatment had intermediate height gain of 6.7 cm. While no patient had height above the 5th percentile of the general population height standards in any group at baseline, 47% of the patients who received 0.24 mg/kg/week and 82% of the patients who received 0.37 mg/kg/week achieved final heights above the 5th percentile at completion of treatment.1

Adverse Reactions Observed in Humatrope Clinical Trials

  • In the placebo-controlled study, the adverse events reported for Humatrope-treated patients were similar to those observed in other pediatric populations treated with Humatrope. Mean serum glucose concentration did not change during Humatrope treatment. Mean fasting serum insulin concentration increased by 10% at the end of treatment vs. baseline in the Humatrope treatment group, whereas the value decreased by 2% in the placebo group. However, mean values remained within the normal range for both groups, and the occurrence rates of above-normal values for glucose, insulin, and HbA1c were similar in the Humatrope- and placebo-treated groups. No patient developed diabetes mellitus.1
  • Consistent with the known mechanism of GH action, mean increase in serum insulin-like growth factor-1 (IGF-1) vs. baseline was greater for the Humatrope-treated group than the placebo group at each study observation. However, in both treatment groups approximately one-quarter of patients had at least one serum IGF-1 concentration more than 2.0 SD above the age- and gender-appropriate mean (Humatrope: 9 of 35 patients [26%]; placebo: 7 of 28 patients [25%]; p=NS).1
  • The adverse events observed in the 2-year dose-response study did not indicate a pattern suggestive of a dose effect. Mean fasting blood glucose, HbA1c, and the occurrence rates of elevated fasting blood glucose concentrations were similar among Humatrope dose groups. One patient developed glucose intolerance and high serum HbA1c.1

Reference

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

SELECT SAFETY INFORMATION

  • Acute Critical Illness: Increased mortality in patients with acute critical illness from complications after 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.

Children born small for gestational age (SGA)

Humatrope was approved by the FDA in 2009 for the treatment of growth failure in children born small for gestational age (SGA) who fail to demonstrate catch- up growth by age 2 to 4 years.

Recommended dosage:

Up to 0.067 mg/kg/day
(0.47 mg/kg/week).1

Dosage should be individualized within recommended range based on growth response; failure to increase height velocity should prompt close assessment.

Study Design

Data from 2 clinical trials demonstrate the effectiveness of Humatrope in promoting linear growth in short children born SGA.1

  • Study 1 was a 2-year, open-label, multicenter study that enrolled 193 prepubertal, non-growth hormone (GH)-deficient children born small for gestational age (defined in this study as birth weight below the 10th percentile and/or birth length below -2 SDS).
  • Study entry criteria included height at least 3 SDS below the mean for age and sex, and absence of syndromal conditions (e.g., Turner syndrome), chronic disease (e.g., diabetes mellitus), and tumor activity.
  • The primary objective of this study was to evaluate whether an individually adjusted dose regimen would promote a 1-year increase in height SDS similar to that seen with a fixed high dose regimen.1
  • Children aged 3.0 to 12.3 years at baseline were randomly assigned to either a fixed dosage group (0.067 mg/kg/day [0.47 mg/kg/week]; n=99) or an individually adjusted dose group (n=94). The initial Humatrope dosage in the individualized group was 0.035 mg/kg/day (0.25 mg/kg/week). After 3 months of treatment, the dosage was increased to 0.067 mg/kg/day (0.47 mg/kg/week) in those patients whose height gain was predicted (using a height gain prediction model) to be less than 0.75 SDS at 1 year (n=40). In addition, those patients whose actual height gain at 1 year was less than 0.75 SDS also underwent the same dosage increase (n=11).
  • Study 2 was an open-label, multicenter, single-arm study of 35 prepubertal, non-GH-deficient children born small for gestational age (defined in this study as birth length below -2 SDS or below 3rd percentile for gestational age).
  • Study entry criteria included height below -2 SDS for chronological age and absence of syndromal conditions (e.g., Turner syndrome), chronic disease (e.g., diabetes mellitus), and any active disease.
  • Children aged 6.7 to 10.8 years at baseline were treated for 2 years with Humatrope 0.067 mg/kg/day (0.47 mg/kg/week).1
Study Results and Adverse Reactions Observed in Humatrope Clinical Trials

Height gains

Study 1 demonstrated that the increase from baseline in height SDS in the individually adjusted dosage group at 1 year was clinically similar to that in the fixed dosage group (mean between-group difference = -0.3 SDS).1

  • The average increases in height SDS at the end of the 2-year study were 1.4 and 1.6 SDS in the individually adjusted and fixed dosage groups, respectively.
  • In Study 2, mean height SDS increased from a baseline value of -2.7 ± 0.5 to -1.5 ± 0.6 after 2 years of Humatrope treatment.1

Adverse Reactions Observed in Humatrope Clinical Trials

  • The most frequently reported adverse events in Study 1 were common childhood infectious diseases. Adverse events possibly/probably related to Humatrope were otitis media and headaches (where there was a suggestion of a modest dose response), and slipped capital femoral epiphysis (1 child).1
  • There were no clear-cut cases of new-onset diabetes mellitus, no children treated for hyperglycemia, and no children whose fasting blood glucose exceeded 126 mg/dL at any time during the study.1
  • However, 4 children in the fixed dosage group and 2 children in the individually adjusted dosage group (whose dose was increased from 0.035 mg/kg/day [0.25 mg/kg/week] to 0.067 mg/kg/day
    [0.47 mg/kg/week]) had impaired fasting glucose after 2 years of treatment. One child was required to discontinue Humatrope after 15 months of treatment as a consequence.
  • A modestly dose-dependent increase in mean serum IGF-1 concentrations within the reference range was observed; of note, at study completion, 20-25% of patients had serum IGF-1 values more than 2 standard deviation scores above the mean for age and sex.
  • Study 2 did not reveal further safety data of note.1
  • In both Study 1 and Study 2 bone maturation did not accelerate excessively with Humatrope treatment, and the timing of puberty was age-appropriate.1
  • Additional safety information was obtained from an observational study of 340 children born SGA who received Humatrope (average dose 0.041 mg/kg/day, maximum dose 0.084 mg/kg/day) for an average of 3 years. Type 2 diabetes was reported in 1 patient, but appeared to resolve after discontinuation of Humatrope. One patient experienced carpal tunnel syndrome, and another developed an exacerbation of preexisting scoliosis.1

Reference

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

SELECT SAFETY INFORMATION

  • Prader-Willi Syndrome in Children: There have been reports of fatalities after starting 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. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin.

SHOX deficiency

Humatrope was approved by the FDA in 2006 for the treatment of short stature or growth failure in children with SHOX deficiency (SHOX-D).

Recommended dosage:

0.050 mg/kg/day
(0.35 mg/kg/week).1

Dosage should be individualized within recommended range based on growth response; failure to increase height velocity should prompt close assessment.

Study Design

A randomized, controlled, 3-arm, open-label, 2-year study was conducted to evaluate the efficacy of Humatrope treatment of short stature in pediatric patients with SHOX deficiency (SHOX-D) who were not growth hormone (GH) deficient.1

  • Fifty-two prepubertal patients (24 male, 28 female) with genetically confirmed SHOX-D, 3.0 to 12.3 years of age, were randomly assigned to either 2 years of Humatrope treatment at a dose of 0.050 mg/kg/day (0.35 mg/kg/week; 27 patients) or non-treatment (no injection) control (25 patients).
  • To evaluate the comparability of treatment effect between patients with SHOX-D and patients with Turner syndrome (who have SHOX-D due to absence of all or part of the second sex chromosome), 26 girls with Turner syndrome, 4.5 to 11.8 years of age, received Humatrope treatment at a dose of 0.050 mg/kg/day (0.35 mg/kg/week).
Study Results and Adverse Reactions Observed in Humatrope Clinical Trials

Increased Height Velocity

  • Humatrope-treated patients with SHOX-D had significantly greater first-year height velocity than untreated patients (8.7 cm/year vs. 5.2 cm/year, p <0.001) and similar first-year height velocity to Humatrope-treated patients with Turner syndrome (8.7 cm/year vs. 8.9 cm/year).1
  • In addition, patients who received Humatrope had significantly greater second-year height velocity, and first- and second-year height gain (both cm and SDS) than untreated patients (p < 0.001). Over the 2-year study period, Humatrope-treated patients gained an average of 5.8 cm more in height than untreated patients.1

Adverse Reactions Observed in Humatrope Clinical Trials

  • Adverse events reported for a greater number of Humatrope-treated patients with SHOX-D than untreated patients during the 2-year study included arthralgia (11.1% vs. 8.0%), gynecomastia (8.3% vs. 0.0%), excessive number of cutaneous nevi (7.4% vs. 0.0%), and scoliosis (3.7% vs. 0.0%).1
  • In both the treated and non-treated SHOX-D groups, the mean fasting plasma glucose concentration at the end of the first year was similar to the baseline value and remained in the normal range. No patient developed diabetes mellitus or had an above normal value for fasting plasma glucose at the end of 1 year of treatment.1
  • Insulin-like growth factor-1 (IGF-1) concentration was greater than 2.0 SD above the age- and gender-appropriate mean at least once during the 2-year study in 37% (10/27) of the Humatrope group vs. no patient in the untreated group. Fifty-nine percent (16/27) of the Humatrope group and 29% (7/24) of the untreated group had at least one IGF-binding protein-3 concentration greater than 2.0 SD above the age- and gender-appropriate mean.1

Reference

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

SELECT SAFETY INFORMATION

  • Neoplasms: An increased risk of a second neoplasm has been reported for childhood cancer survivors treated with somatropin for GH deficiency that developed following radiation to the brain/head. 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 for progression or recurrence in all patients receiving somatropin therapy who have a history of GH deficiency secondary to an intracranial neoplasm.

Short stature associated with Turner syndrome

Humatrope was approved by the FDA in 1997 for the treatment of short stature associated with Turner syndrome.

Recommended dosage:

Up to 0.054 mg/kg/day
(0.375 mg/kg/week).1

Dosage should be individualized within recommended range based on growth response; failure to increase height velocity should prompt close assessment.

Study Design

The efficacy of somatropin treatment of short stature associated with Turner syndrome was evaluated in 4 clinical studies: 1 long-term, randomized, controlled, open-label, multicenter, single-dose Canadian study; 1 long-term, randomized U.S. dose-response study; and 2 long-term, open-label, multicenter, historically controlled U.S. studies.1

  • The Canadian study compared near-adult height for Humatrope-treated patients to those of a concurrent control group who received no injections. The Humatrope-treated patients received a dosage of 0.3 mg/kg/week given in divided doses 6 times per week from a mean age of 11.7 years for a mean duration of 4.7 years. Puberty was induced with a standardized estrogen regimen initiated at 13 years of age for both treatment groups.1
  • In the U.S. dose-response study, patients were treated from a mean age of 11.1 years for a mean duration of 5.3 years with a weekly Humatrope dosage of either 0.27 mg/kg or 0.36 mg/kg administered in divided doses 3 or 6 times weekly.1
  • In 2 of the U.S. studies, the effect of long-term somatropin treatment (0.375 mg/kg/week given in divided doses either 3 times per week or daily) on adult height was determined by comparing adult heights in the treated patients with those of age-matched historical controls with Turner syndrome who received no growth-promoting therapy. Puberty was induced with a standardized estrogen regimen initiated after 14 years of age in one study; in the second study, patients treated with somatropin early (before 11 years of age) were randomized to begin pubertal induction at either age 12 (n=26) or 15 (n=29) years, and patients treated with somatropin after 11 years of age began estrogen replacement after 1 year of treatment.1
Study Results and Adverse Reactions Observed in Humatrope Clinical Trials

Height outcomes

Patients with Turner syndrome (total n=181 from 4 studies) treated to adult height achieved statistically significant average height gains ranging from 5.0 to 8.3 cm (by analysis of covariance vs. controls).1

  • In the Canadian study the effect of Humatrope treatment was a mean height increase of 5.4 cm (p=0.001).1
  • In the U.S. dose-response study, the mean gain in adult height was approximately 5 cm when compared to historical control data.1
  • In the 2 historically controlled U.S. studies, mean height gains from baseline to adult (or near-adult) height ranged from 5.0 to 8.3 cm, depending on age at initiation of somatropin treatment and estrogen replacement.1

Adverse Reactions Observed in Humatrope Clinical Trials

  • In the Canadian randomized, controlled trial there was a statistically significant increase in the occurrence of otitis media (43% vs. 26%), ear disorders (18% vs. 5%), and surgical procedures (45% vs. 27%) in patients receiving Humatrope compared with untreated control patients.1
  • Other adverse events of special interest to patients who have Turner syndrome were not significantly different among treatment groups. A similar increase in otitis media was observed in an 18-month placebo-controlled trial.1

Reference

1. Humatrope [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2017.

SELECT SAFETY INFORMATION

  • Glucose Intolerance and Diabetes Mellitus: Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New-onset type 2 diabetes mellitus has been reported. Blood glucose concentrations should be monitored periodically in all patients taking somatropin, especially in those with risk factors for diabetes mellitus and those with pre-existing type 1 or type 2 diabetes mellitus or impaired glucose tolerance. The dose of antihyperglycemic drugs may require adjustment when somatropin treatment is instituted.
Indications and Important Safety Information for Humatrope
Humatrope® (somatropin for injection) is indicated for the treatment of pediatric patients who have short stature or growth failure as a result of:
  • Growth hormone (GH) deficiency.
  • Turner syndrome.
  • Idiopathic short stature, defined by height standard deviation score =-2.25, associated with growth rates unlikely to result in normal adult height, in whom other causes of short stature have been excluded.
  • SHOX Deficiency.
  • Small for gestational age birth, with failure to show catch-up growth by 2 to 4 years of age.
Humatrope is indicated for the replacement of endogenous GH in adults with GH deficiency, either:
  • Adult-onset, as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
  • Childhood-onset. Patients treated for GH deficiency in childhood who have closed epiphyses should be reevaluated to determine if they should continue growth hormone.
Important Safety Information for Humatrope
CONTRAINDICATIONS
  • Acute Critical Illness: Somatropin should not be used to treat patients with acute critical illness from complications after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure.
  • Prader-Willi Syndrome in Children: Somatropin should not be used in 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. Humatrope is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.
  • Active Malignancy: Somatropin is contraindicated in patients with any evidence of active malignancy.
  • Hypersensitivity: Humatrope is contraindicated in patients with a known hypersensitivity to somatropin or the supplied diluent.
  • Diabetic Retinopathy or Closed Epiphyses: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy. It should not be used for growth promotion in pediatric patients with closed epiphyses.
WARNINGS AND PRECAUTIONS
  • Acute Critical Illness: Increased mortality in patients with acute critical illness from complications after 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.
  • Prader-Willi Syndrome in Children: There have been reports of fatalities after starting 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. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin.
  • Neoplasms: An increased risk of a second neoplasm has been reported for childhood cancer survivors treated with somatropin for GH deficiency that developed following radiation to the brain/head. 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 for progression or recurrence in all patients receiving somatropin therapy who have a history of GH deficiency secondary to an intracranial neoplasm.
  • Glucose Intolerance and Diabetes Mellitus: Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. New-onset type 2 diabetes mellitus has been reported. Blood glucose concentrations should be monitored periodically in all patients taking somatropin, especially in those with risk factors for diabetes mellitus and those with pre-existing type 1 or type 2 diabetes mellitus or impaired glucose tolerance. The dose of antihyperglycemic drugs may require adjustment when somatropin treatment is instituted.
  • Intracranial Hypertension: Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting have been reported in a small number of patients treated with somatropin. If papilledema is observed by funduscopy during treatment with somatropin, treatment should be stopped and the patient’s condition should be reassessed before treatment is resumed.
  • Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with use of somatropin products.
  • Fluid Retention: Transient and dose-dependent fluid retention during somatropin replacement in adults may occur frequently.
  • Hypoadrenalism: Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiencies may be at risk for reduced serum cortisol levels and/or unmasking of central hypoadrenalism. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment.
  • Hypothyroidism: Patients treated with somatropin should have periodic thyroid function tests, and thyroid hormone replacement therapy should be initiated or adjusted in cases of unmasked or worsening hypothyroidism.
  • Slipped Capital Femoral Epiphysis in Pediatric Patients: Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders and in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.
  • Progression of Scoliosis in Pediatric Patients: Progression of scoliosis can occur in patients who experience rapid growth. Patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. Somatropin has not been shown to increase the occurrence of scoliosis.
  • Pancreatitis: Cases of pancreatitis have been reported rarely in children and adults receiving somatropin. Pancreatitis should be considered in any somatropin-treated patient, especially a child, who develops abdominal pain.
  • Lipoatrophy: Tissue atrophy may result when somatropin is administrated subcutaneously at the same site over a long period of time. This can be avoided by rotating the injection site.
ADVERSE REACTIONS
  • Common adverse reactions reported in adult and pediatric patients taking somatropin include injection site reactions, hypersensitivity to the diluent, and hypothyroidism. Additional common adverse reactions in adults include edema, arthralgia, myalgia, carpal tunnel syndrome, paresthesias, and hyperglycemia.
See Full Pen User Manual that accompanies the HumatroPen® 6 mg, 12 mg, and 24 mg.
HG HCP ISI 13JAN2017