Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Sandoz GmbH, Biochemiestr. 10, A-6250 Kundl, Austria
Pharmacotherapeutic group: Anterior pituitary lobe hormones and analogues
ATC code: H01AC01
Somatropin is a potent metabolic hormone of importance for the metabolism of lipids, carbohydrates and proteins. In children with inadequate endogenous growth hormone, somatropin stimulates linear growth and increases growth rate. In adults as well as in children, somatropin maintains a normal body composition by increasing nitrogen retention and stimulation of skeletal muscle growth, and by mobilisation of body fat. Visceral adipose tissue is particularly responsive to somatropin. In addition to enhanced lipolysis, somatropin decreases the uptake of triglycerides into body fat stores. Serum concentrations of IGF-I (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor Binding Protein 3) are increased by somatropin. In addition, the following actions have been demonstrated.
Somatropin induces hepatic LDL cholesterol receptors, and affects the profile of serum lipids and lipoproteins. In general, administration of somatropin to growth hormone deficient patients results in reduction in serum LDL and apolipoprotein B. A reduction in serum total cholesterol may also be observed.
Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with hypopituitarism may experience fasting hypoglycaemia. This condition is reversed by somatropin.
Growth hormone deficiency is associated with decreased plasma and extracellular volumes. Both are rapidly increased after treatment with somatropin. Somatropin induces the retention of sodium, potassium and phosphorus.
Somatropin stimulates the turnover of skeletal bone. Long-term administration of somatropin to growth hormone deficient patients with osteopenia results in an increase in bone mineral content and density at weight-bearing sites.
Muscle strength and physical exercise capacity are improved after long-term treatment with somatropin. Somatropin also increases cardiac output, but the mechanism has yet to be clarified. A decrease in peripheral vascular resistance may contribute to this effect.
In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg/kg body weight per day have been used for treatment until final height is reached. In 56 patients who were continuously treated and have reached (near) final height, the mean change from height at start of treatment was +1.90 SDS (0.033 mg/kg body weight per day) and +2.19 SDS (0.067 mg/kg body weight per day). Literature data from untreated SGA children/adolescents without early spontaneous catch-up suggest a late growth of 0.5 SDS.
An international, non-interventional, non-controlled, longitudinal, open and multicenter, voluntary category 3 PASS designed to record the safety and effectiveness data of 7359 pediatric patients treated with Omnitrope in various indications was conducted by Sandoz between 2006 and 2020 in 11 European countries, in North America, Canada, Australia and Taiwan.
The main pediatric indications were: GHD (57.9%), SGA (26.6%), TS (4.9%), ISS (3.3%), PWS (3.2%) and CRI (1.0%). Most patients were naïve of previous rhGH treatment (86.0%). Across all indications, the most frequent AEs with a suspected causal relationship to Omnitrope treatment in patients were headache (1.6%), injection site pain (1.1%), injection site hematoma (1.1%) and arthralgia (0.6%), assessed in 7359 pediatric patients (SAF). The majority of AEs assessed as related to Omnitrope treatment were expected based on the SmPC and as known for this type of class of molecule (GH). The intensity of most AEs was mild or moderate.
The effectiveness results, assessed in 6589 pediatric patients (EFF consisting of 5671 naïve, 915 rhGH pretreated and 3 patients with missing pre-treatment information), show that Omnitrope treatment was effective and resulted in a substantial catch-up growth which are consistent with those reported in observational studies of other approved rhGH medicines: the median H SDS increased effectively from -2.64 at baseline to -1.97 after 1 year and to -0.98 after 5 years of treatment in naïve patients, and a median H SDS increased from -1.49 to -1.21 after 1 year and to -0.98 after 5 years of Omnitrope treatment in pre-treated patients. 1628/6589 (24.7%) patients of the EFF reached final height according to physician's opinion (naïve: 1289/5671, 22.7%); rhGH pretreated: 338/915, 36.9%). Median (range) final H SDS in naïve patients -1.51 (-9.3 to 2.7) and -1.43 (-8.7 to 2.1) in pre-treated patients.
The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy subjects and growth hormone deficient patients.
A subcutaneous dose of 5 mg of Omnitrope 5 mg/1.5 ml solution for injection in healthy adults results in plasma Cmax and tmax values of 72 ± 28 μg/l and 4.0 ± 2.0 hours, respectively.
A subcutaneous dose of 5 mg of Omnitrope 10 mg/1.5 ml solution for injection in healthy adults results in plasma Cmax and tmax values of 74 ± 22 μg/l and 3.9 ± 1.2 hours, respectively.
The mean terminal half-life of somatropin after intravenous administration in growth hormone deficient adults is about 0.4 hours. However, after subcutaneous administration of Omnitrope 5 mg/1.5 ml, Omnitrope 10 mg/1.5 ml solution for injection, a half-life of 3 hours is achieved. The observed difference is likely due to slow absorption from the injection site following subcutaneous administration.
The absolute bioavailability of somatropin seems to be similar in males and females following subcutaneous administration.
Information about the pharmacokinetics of somatropin in geriatric and paediatric populations, in different races and in patients with renal, hepatic or cardiac insufficiency is either lacking or incomplete.
In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant effects have been observed.
In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity no clinically relevant effects have been observed.
With somatropins, in vitro and in vivo genotoxicity studies on gene mutations and induction of chromosome aberrations have been negative.
An increased chromosome fragility has been observed in one in vitro study on lymphocytes taken from patients after long term treatment with somatropin and following the addition of the radiomimetic drug bleomycin. The clinical significance of this finding is unclear.
In another study with somatropin, no increase in chromosomal abnormalities was found in the lymphocytes of patients who had received long-term somatropin therapy.
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