In vitro, preclinical, and clinical tests have demonstrated that GENOTROPIN lyophilized powder 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.
In addition, the following actions have been demonstrated for GENOTROPIN and/or somatropin.
Tissue Growth
Protein Metabolism
Linear growth is facilitated in part by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, follows the initiation of therapy with GENOTROPIN.
Carbohydrate Metabolism
Pediatric patients with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with GENOTROPIN. Large doses of growth hormone may impair glucose tolerance.
Lipid Metabolism
In GHD patients, administration of somatropin has resulted in lipid mobilization, reduction in body fat stores, and increased plasma fatty acids.
Mineral Metabolism
Somatropin induces retention of sodium, potassium, and phosphorus. Serum concentrations of inorganic phosphate are increased in patients with GHD after therapy with GENOTROPIN. Serum calcium is not significantly altered by GENOTROPIN. Growth hormone could increase calciuria.
Body Composition
Adult GHD patients treated with GENOTROPIN at the recommended adult dose [see Dosage and Administration (2)] demonstrate a decrease in fat mass and an increase in lean body mass. When these alterations are coupled with the increase in total body water, the overall effect of GENOTROPIN is to modify body composition, an effect that is maintained with continued treatment.
Absorption
Following a 0.03 mg/kg subcutaneous (SC) injection in the thigh of 1.3 mg/mL GENOTROPIN to adult GHD patients, approximately 80% of the dose was systemically available as compared with that available following intravenous dosing. Results were comparable in both male and female patients. Similar bioavailability has been observed in healthy adult male subjects.
In healthy adult males, following an SC injection in the thigh of 0.03 mg/kg, the extent of absorption (AUC) of a concentration of 5.3 mg/mL GENOTROPIN was 35% greater than that for 1.3 mg/mL GENOTROPIN. The mean (± standard deviation) peak (Cmax) serum levels were 23.0 (± 9.4) ng/mL and 17.4 (± 9.2) ng/mL, respectively.
In a similar study involving pediatric GHD patients, 5.3 mg/mL GENOTROPIN yielded a mean AUC that was 17% greater than that for 1.3 mg/mL GENOTROPIN. The mean Cmax levels were 21.0 ng/mL and 16.3 ng/mL, respectively.
Adult GHD patients received two single SC doses of 0.03 mg/kg of GENOTROPIN at a concentration of 1.3 mg/mL, with a one- to four-week washout period between injections. Mean Cmax levels were 12.4 ng/mL (first injection) and 12.2 ng/mL (second injection), achieved at approximately six hours after dosing.
There are no data on the bioequivalence between the 12 mg/mL formulation and either the 1.3 mg/mL or the 5.3 mg/mL formulations.
Distribution
The mean volume of distribution of GENOTROPIN following administration to GHD adults was estimated to be 1.3 (± 0.8) L/kg.
Metabolism
The metabolic fate of GENOTROPIN involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation. The mean terminal half-life of intravenous GENOTROPIN in normal adults is 0.4 hours, whereas subcutaneously administered GENOTROPIN has a half-life of 3.0 hours in GHD adults. The observed difference is due to slow absorption from the subcutaneous injection site.
Excretion
The mean clearance of subcutaneously administered GENOTROPIN in 16 GHD adult patients was 0.3 (± 0.11) L/hrs/kg.
Special Populations
Gender: No gender studies have been performed in pediatric patients; however, in GHD adults, the absolute bioavailability of GENOTROPIN was similar in males and females.
Race: No studies have been conducted with GENOTROPIN to assess pharmacokinetic differences among races.
Renal or hepatic insufficiency: No studies have been conducted with GENOTROPIN in these patient populations.
| Bioavailability (%) (N=15) | Tmax (hours) (N=16) | CL/F (L/hr × kg) (N=16) | Vss/F (L/kg) (N=16) | T1/2 (hours) (N=16) | |
|---|---|---|---|---|---|
| Tmax = time of maximum plasma concentration CL/F = plasma clearance Vss/F = volume of distribution | |||||
| T 1/2 = terminal half-life SD = standard deviation CI = confidence interval | |||||
| |||||
Mean | 80.5 | 5.9 | 0.3 | 1.3 | 3.0 |
(± SD) | (± 1.65) | (± 0.11) | (± 0.80) | (± 1.44) | |
95% CI | 70.5 – 92.1 | 5.0 – 6.7 | 0.2 – 0.4 | 0.9 – 1.8 | 2.2 – 3.7 |
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of GENOTROPIN or other somatropins.
In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.
In 419 pediatric patients evaluated in clinical studies with GENOTROPIN lyophilized powder, 244 had been treated previously with GENOTROPIN or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in six previously treated patients at baseline. Three of the six became negative for anti-hGH antibodies during 6 to 12 months of treatment with GENOTROPIN. Of the remaining 413 patients, eight (1.9%) developed detectable anti-hGH antibodies during treatment with GENOTROPIN; none had an antibody binding capacity >2 mg/L. There was no evidence that the growth response to GENOTROPIN was affected in these antibody-positive patients.
In vitro, preclinical, and clinical tests have demonstrated that GENOTROPIN lyophilized powder 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.
In addition, the following actions have been demonstrated for GENOTROPIN and/or somatropin.
Tissue Growth
Protein Metabolism
Linear growth is facilitated in part by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, follows the initiation of therapy with GENOTROPIN.
Carbohydrate Metabolism
Pediatric patients with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with GENOTROPIN. Large doses of growth hormone may impair glucose tolerance.
Lipid Metabolism
In GHD patients, administration of somatropin has resulted in lipid mobilization, reduction in body fat stores, and increased plasma fatty acids.
Mineral Metabolism
Somatropin induces retention of sodium, potassium, and phosphorus. Serum concentrations of inorganic phosphate are increased in patients with GHD after therapy with GENOTROPIN. Serum calcium is not significantly altered by GENOTROPIN. Growth hormone could increase calciuria.
Body Composition
Adult GHD patients treated with GENOTROPIN at the recommended adult dose [see Dosage and Administration (2)] demonstrate a decrease in fat mass and an increase in lean body mass. When these alterations are coupled with the increase in total body water, the overall effect of GENOTROPIN is to modify body composition, an effect that is maintained with continued treatment.
Absorption
Following a 0.03 mg/kg subcutaneous (SC) injection in the thigh of 1.3 mg/mL GENOTROPIN to adult GHD patients, approximately 80% of the dose was systemically available as compared with that available following intravenous dosing. Results were comparable in both male and female patients. Similar bioavailability has been observed in healthy adult male subjects.
In healthy adult males, following an SC injection in the thigh of 0.03 mg/kg, the extent of absorption (AUC) of a concentration of 5.3 mg/mL GENOTROPIN was 35% greater than that for 1.3 mg/mL GENOTROPIN. The mean (± standard deviation) peak (Cmax) serum levels were 23.0 (± 9.4) ng/mL and 17.4 (± 9.2) ng/mL, respectively.
In a similar study involving pediatric GHD patients, 5.3 mg/mL GENOTROPIN yielded a mean AUC that was 17% greater than that for 1.3 mg/mL GENOTROPIN. The mean Cmax levels were 21.0 ng/mL and 16.3 ng/mL, respectively.
Adult GHD patients received two single SC doses of 0.03 mg/kg of GENOTROPIN at a concentration of 1.3 mg/mL, with a one- to four-week washout period between injections. Mean Cmax levels were 12.4 ng/mL (first injection) and 12.2 ng/mL (second injection), achieved at approximately six hours after dosing.
There are no data on the bioequivalence between the 12 mg/mL formulation and either the 1.3 mg/mL or the 5.3 mg/mL formulations.
Distribution
The mean volume of distribution of GENOTROPIN following administration to GHD adults was estimated to be 1.3 (± 0.8) L/kg.
Metabolism
The metabolic fate of GENOTROPIN involves classical protein catabolism in both the liver and kidneys. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation. The mean terminal half-life of intravenous GENOTROPIN in normal adults is 0.4 hours, whereas subcutaneously administered GENOTROPIN has a half-life of 3.0 hours in GHD adults. The observed difference is due to slow absorption from the subcutaneous injection site.
Excretion
The mean clearance of subcutaneously administered GENOTROPIN in 16 GHD adult patients was 0.3 (± 0.11) L/hrs/kg.
Special Populations
Gender: No gender studies have been performed in pediatric patients; however, in GHD adults, the absolute bioavailability of GENOTROPIN was similar in males and females.
Race: No studies have been conducted with GENOTROPIN to assess pharmacokinetic differences among races.
Renal or hepatic insufficiency: No studies have been conducted with GENOTROPIN in these patient populations.
| Bioavailability (%) (N=15) | Tmax (hours) (N=16) | CL/F (L/hr × kg) (N=16) | Vss/F (L/kg) (N=16) | T1/2 (hours) (N=16) | |
|---|---|---|---|---|---|
| Tmax = time of maximum plasma concentration CL/F = plasma clearance Vss/F = volume of distribution | |||||
| T 1/2 = terminal half-life SD = standard deviation CI = confidence interval | |||||
| |||||
Mean | 80.5 | 5.9 | 0.3 | 1.3 | 3.0 |
(± SD) | (± 1.65) | (± 0.11) | (± 0.80) | (± 1.44) | |
95% CI | 70.5 – 92.1 | 5.0 – 6.7 | 0.2 – 0.4 | 0.9 – 1.8 | 2.2 – 3.7 |
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of GENOTROPIN or other somatropins.
In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was observed.
In 419 pediatric patients evaluated in clinical studies with GENOTROPIN lyophilized powder, 244 had been treated previously with GENOTROPIN or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in six previously treated patients at baseline. Three of the six became negative for anti-hGH antibodies during 6 to 12 months of treatment with GENOTROPIN. Of the remaining 413 patients, eight (1.9%) developed detectable anti-hGH antibodies during treatment with GENOTROPIN; none had an antibody binding capacity >2 mg/L. There was no evidence that the growth response to GENOTROPIN was affected in these antibody-positive patients.
{{section_body_html_patient}}
Chat online with Pfizer Medical Information regarding your inquiry on a Pfizer medicine.
*Speak with a Pfizer Medical Information Professional regarding your medical inquiry. Available 9AM-5PM ET Monday to Friday; excluding holidays.
Submit a medical question for Pfizer prescription products.
Pfizer Safety
To report an adverse event related to the Pfizer-BioNTech COVID-19 Vaccine, and you are not part of a clinical trial* for this product, click the link below to submit your information:
Pfizer Safety Reporting Site*If you are involved in a clinical trial for this product, adverse events should be reported to your coordinating study site.
If you cannot use the above website, or would like to report an adverse event related to a different Pfizer product, please call Pfizer Safety at (800) 438-1985.
FDA Medwatch
You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns either online at www.fda.gov/medwatch or call (800) 822-7967.