Currently Enrolling Trials
Genotropin (somatropin) - 5 indications
Scroll down for information on each indication:
- growth hormone deficiency; approved November 1997
- pediatric patients who have growth failure due to Prader-Willi Syndrome; approved June of 2000
- growth failure in children who were born small for gestational age (SGA); approved July 2001
- the long-term treatment of growth failure associated with Turner Syndrome in patients who have open epiphyses; approved April 2006
- idiopathic short stature (non-growth hormone-deficient short stature); approved June 2008
Genotropin (somatropin) is a recombinant human growth hormone.
Genotropin is specifically indicated for the following therapeutic conditions:
- for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone.
- for the treatment of pediatric patients who have growth failure due to Prader-Willi Syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing
- for the treatment of growth failure in children born small for gestational age (SGA) who fail to manifest catch-up growth by age 2 years.
- for the treatment of growth failure associated with Turner syndrome.
- for the treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) ≤-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.
for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:
- Adult Onset (AO): Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or
- Childhood Onset (CO): Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.
Genotropin is supplied as a solution for subcutaneous injection. The weekly dose should be divided into 6 or 7 subcutaneous injections. Genotropin must not be injected intravenously.
In pediatrics the Genotropin dosage and administration schedule should be individualized based on the growth response of each patient. Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human GH (rhGH). Treatment with Genotropin for short stature should be discontinued when the epiphyses are fused.
Scroll down for dosing/administration recommendations for each therapeutic condition.
Mechanism of Action
Genotropin (somatropin) is a polypeptide hormone of recombinant DNA origin. In vitro, preclinical, and clinical tests have demonstrated that Genotropin is therapeutically equivalent to human growth hormone of pituitary origin and achieves similar pharmacokinetic profiles in normal adults. In pediatric patients who have growth hormone deficiency (GHD), have Prader-Willi syndrome (PWS), were born small for gestational age (SGA), have Turner syndrome (TS), or have Idiopathic short stature (ISS), treatment with Genotropin stimulates linear growth. In patients with GHD or PWS, treatment with Genotropin also normalizes concentrations of IGF-I (Insulin-like Growth Factor-I/Somatomedin C). In adults with GHD, treatment with Genotropin results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.
Adverse effects associated with the use of Genotropin may include, but are not limited to, the following:
- injection site reactions/rashes
Indication 1 - growth hormone deficiency in pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone and in adults with adult onset or childhood onset growth hormone deficiency
approved November 1997
Pediatrics: a dose of 0.16 to 0.24 mg/kg body weight/week is recommended.
Adults: Either of two approaches to Genotropin dosing may be followed: a non-weight based regimen or a weight based regimen.
- Non-weight based — based on published consensus guidelines, a starting dose of approximately 0.2 mg/day (range, 0.15–0.30 mg/day) may be used without consideration of body weight. This dose can be increased gradually every 1–2 months by increments of approximately 0.1–0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor I (IGF-I) concentrations. The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-I concentrations above the age- and gender-specific normal range. Maintenance dosages vary considerably from person to person, and between male and female patients.
- Weight based — based on the dosing regimen used in the original adult GHD registration trials, the recommended dosage at the start of treatment is not more than 0.04 mg/kg/week. The dose may be increased according to individual patient requirements to not more than 0.08 mg/kg/week at 4–8 week intervals. Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-I concentrations should be used as guidance in dose titration.
A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger individuals. In addition, obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. In order to reach the defined treatment goal, estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.
Clinical Trial Results
Genotropin was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received Genotropin and 87 patients received placebo, followed by an open-label treatment period in which participating patients received Genotropin for up to a total of 24 months. Genotropin was administered as a daily SC injection at a dose of 0.04 mg/kg/week for the first month of treatment and 0.08 mg/kg/week for subsequent months.
Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving Genotropin as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.
Indication 2 - pediatric patients who have growth failure due to Prader-Willi Syndrome
approved June of 2000
A dose of 0.24 mg/kg body weight/week is recommended
Clinical Trial Results
In two randomized, open-label, controlled clinical trials patients received either Genotropin or no treatment for the first year of the studies, while all patients received Genotropin during the second year. Genotropin was administered as a daily SC injection, and the dose was calculated for each patient every 3 months. In Study 1, the treatment group received Genotropin at a dose of 0.24 mg/kg/week during the entire study. During the second year, the control group received Genotropin at a dose of 0.48 mg/kg/week. In Study 2, the treatment group received Genotropin at a dose of 0.36 mg/kg/week during the entire study. During the second year, the control group received Genotropin at a dose of 0.36 mg/kg/week.
Patients who received Genotropin showed significant increases in linear growth during the first year of study, compared with patients who received no treatment. Linear growth continued to increase in the second year, when both groups received treatment with Genotropin. Changes in body composition were also observed in the patients receiving Genotropin. These changes included a decrease in the amount of fat mass, and increases in the amount of lean body mass and the ratio of lean-to-fat tissue, while changes in body weight were similar to those seen in patients who received no treatment. Treatment with Genotropin did not accelerate bone age, compared with patients who received no treatment.
Indication 3 - growth failure in children who were born small for gestational age (SGA)
approved July 2001
A dose of up to 0.48 mg/kg body weight/week is recommended
Clinical Trial Results
The safety and efficacy of Genotropin in the treatment of children born SGA were evaluated in 4 randomized, open-label, controlled clinical trials. Patients (age range of 2 to 8 years) were observed for 12 months before being randomized to receive either Genotropin (two doses per study, most often 0.24 and 0.48 mg/kg/week) as a daily SC injection or no treatment for the first 24 months of the studies. After 24 months in the studies, all patients received Genotropin.
Patients who received any dose of Genotropin showed significant increases in growth during the first 24 months of study, compared with patients who received no treatment. Children receiving 0.48 mg/kg/week demonstrated a significant improvement in height standard deviation score (SDS) compared with children treated with 0.24 mg/kg/week. Both of these doses resulted in a slower but constant increase in growth between months 24 to 72.
Indication 4 - growth failure associated with Turner Syndrome
approved April 2006
A dose of 0.33 mg/kg body weight/week is recommended.
Clinical Trial Results
Two randomized, open-label, clinical trials were conducted that evaluated the efficacy and safety of Genotropin in Turner syndrome patients with short stature. Turner syndrome patients were treated with Genotropin alone or Genotropin plus adjunctive hormonal therapy (ethinylestradiol or oxandrolone). A total of 38 patients were treated with Genotropin alone in the two studies. In Study 055, 22 patients were treated for 12 months, and in Study 092, 16 patients were treated for 12 months. Patients received Genotropin at a dose between 0.13 to 0.33 mg/kg/week.
SDS for height velocity and height are expressed using either the Tanner (Study 055) or Sempé (Study 092) standards for age-matched normal children as well as the Ranke standard (both studies) for age-matched, untreated Turner syndrome patients. Height velocity SDS and height SDS values were smaller at baseline and after treatment with Genotropin when the normative standards were utilized as opposed to the Turner syndrome standard.
Both studies demonstrated statistically significant increases from baseline in all of the linear growth variables (i.e., mean height velocity, height velocity SDS, and height SDS) after treatment with Genotropin. The linear growth response was greater in Study 055 wherein patients were treated with a larger dose of Genotropin.
Indication 5 - idiopathic short stature (non-growth hormone-deficient short stature)
approved June 2008
A dose up to 0.47 mg/kg body weight/week is recommended.
Clinical Trial Results
One randomized, open-label, clinical trial enrolled 177 children with idiopathic short stature (ISS). Patients were enrolled on the basis of short stature, stimulated GH secretion > 10 ng/mL, and prepubertal status (criteria for idiopathic short stature were retrospectively applied and included 126 patients). All patients were observed for height progression for 12 months and were subsequently randomized to Genotropin or observation only and followed to final height. Two Genotropin doses 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 prepubertal 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. Genotropin therapy improved final height in ISS children relative to untreated controls. The observed mean gain in final height was 9.8 cm for females and 5.0 cm for males for both doses combined compared to untreated control subjects. A height gain of 1 SDS was observed in 10 % of untreated subjects, 50% of subjects receiving 0.23 mg/kg/week and 69% of subjects receiving 0.47 mg/kg/week.