Scitropin A is produced using recombinant DNA technology. The active substance somatropin (biosynthetic human growth hormone, rDNA-derived human growth hormone [r-hGH]) is produced in cell culture by Escherichia coli cells bearing the gene For human growth hormone.
Scitropin A solution for injection is a clear, colourless solution.
Excipients/Inactive Ingredients: Scitropin A 5 mg/1.5 mL (15U) Solution for Injection: Sodium phosphate dibasic heptahydrate 1.33 mg, sodium phosphate monobasic dihydrate 1.57 mg, poloxamer 188 3.0 mg, benzyl alcohol 13.50 mg, mannitol 52.51 mg and water for injection and 1.5 mL.
Scitropin 10 mg/1.5 mL (30 IU) Solution for Injection: Sodium phosphate dibasic heptahydrate 1.70 mg, sodium phosphate monobasic dihydrate 1.35 mg, poloxamer 188 3.0 mg, phenol 4.50 mg, glycine 27.75 mg and water for injection and 1.5 mL.
Pharmacotherapeutic Group: Anterior pituitary lobe hormones and analogues.
ATC Code: H01AC01.
Pharmacology: Pharmacodynamics: 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 mobilization 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-1 (lnsulin-like Growth Factor-I) and IGFBP3 (lnsulin-like Growth Factor Binding Protein 3) are increased by somatropin. In addition, the following actions have been demonstrated.
Lipid metabolism: 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.
Carbohydrate metabolism: Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with hypopituitarism may experience fasting hypoglycaemia. This condition is reversed by somatropin.
Water and mineral metabolism: 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 phosphorous.
Bone metabolism: Somatropin stimulates the turnover of skeletal bone. Long-term administration of somatropin to growth hormone deficient patients with osteopoenia results in an increase in bone mineral content and density at weight-bearing sites.
Physical capacity: 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 born SGA doses of 0.033 and 0.067 mg somatropin/kg body weight per day have been used for treatment until final height. In 56 patients who are 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 without early spontaneous catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.
Pharmacokinetics: Absorption: 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 Scitropin A 5 mg/1.5 mL solution for injection in healthy adults results in plasma Cmax and tmax values of 74±22μg/L and 3.9±1.2 hours respectively.
Elimination: 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 Scitropin A, a half- life of 3 hours is achieved. The observed difference is likely due to slow absorption from the injection site following subcutaneous administration.
Sub populations: 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.
Children: Growth disturbance due to insufficient secretion of secretion of growth hormone (GH).
Growth disturbance associated with Turner syndrome.
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted SDS < -1) in short children born small for gestational age (SGA), with a birth weight and/or length below -2 standard deviation (SD), who fail to show catch-up growth (height velocity (HV) SDS <0 during the last year) by 4 years of age or later.
Dignosis and therapy with somatropin should be initiated and monitored by physicians who are appropriately qualified and experienced in the diagnosis and management of patients with the therapeutic indication of use.
The dosage and administration schedule should be individualized.
The injection should be given subcutaneously and the site varied to prevent lipoatrophy.
Instruction for use and handling: Growth disturbance due to insufficient secretion of growth hormone in children: Generally a dose of 0.025-0.035 mg/kg body weight per day or 0.7-1.0 mg/m
2 body surface area per day is recommended. Even higher doses have been used.
Growth disturbance due to Turner syndrome: A dose of 0.045-0.050 mg/kg body weight per day or 1.4 mg/m
2 body surface area per day is recommended.
Growth disturbance in short children born small for gestational age (SGA): A dose of 0.035 mg/kg body weight per day (1 mg/m
2 body surface area per day) is usually recommended until final height is reached. Treatment should be discontinued after the first year of treatment if the height velocity SDS is below +1. Treatment should be discontinued if height velocity is <2 cm/year and, if confirmation is required, bone age is >14 years (girls) or >16 (boys), corresponding to epiphyseal closure. See Table.
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Treatment should not be used in children with a growth velocity less than 1 cm per year and near closure of epiphyses.
No case of overdose or intoxication has been reported.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdosage could result in signs and symptoms consistent with the known effects of human growth hormone excess.
Hypersensitivity to somatropin or to any of the excipients (benzyl alcohol).
Somatropin should not be used when there is any evidence of tumour activity and anti tumour therapy must be completed prior to starting therapy.
Somatrapin should not be used for growth promotion in children with closed epiphyses.
Somatropin should not be used in children with PWS and a corresponding severe respiratory disorder or severe obesity.
Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions should not be treated with somatropin.
In newborns, Scitropin A 5 mg/1.5 mL solution for injection should not be used because of the presence of the preservative, benzyl alcohol.
Because of the presence of benzyl alcohol in the 15 IU solution for injection, the product must not be given to premature babies or neonates. This may cause toxic reactions and anaphylactoid reactions in infants and children up to 2 years old.
Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired glucose tolerance have been present in most cases where this occurred. In patients with an already manifest diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is instituted.
During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving replacement therapy with thyroxin, mild hyperthyroidism may occur. It is therefore particularly advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increased hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, cortisol replacement therapy shall be optimized before initiation of Scitropin A therapy.
In growth hormone deficiency secondary to treatment of malignant disease, it is recommended to pay attention to signs of relapse of the malignancy.
In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the hip may occur more frequently than in the general population. Children limping during treatment with somatropin, should be examined clinically.
In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension should be considered and, if appropriate, the growth hormone treatment should be discontinued. At present there is insufficient evidence to give specific advice on the continuation of growth hormone treatment in patients with resolved intracranial hypertension. However, clinical experience has shown that reinstitution of the therapy if often possible without recurrence of the intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.
There have been reports of fatalities associated with the use of growth hormone in paediatric patients with PWS who had one or more of the following risk factors: Severe obesity, history of respiratory impairment or sleep apnoea or unidentified respiratory infection. Male patients with PWS and one or more of these risk factors may be at greater risk than females.
Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory infections before initiation of treatment with somatropin.
In case of signs of upper airway obstruction this problem should be solved by a specialist before starting treatment with somatropin.
Sleep apnoea should be examined by representative methods like polysomnographia or oxymetry during the night before initiation of growth hormone therapy and patients should be monitored if necessary.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is suspected.
All patients with PWS should be monitored for signs of respiratory infections which should be diagnosed as early as possible and treated aggresively.
In patients with severe respiratory disorder treatment with somatropin is contraindicated.
If during treatment with somatropin patients show signs of upper airway obstruction (including onset of or increased snoring), treatment should be interrupted, and a new assessment for upper airway obstruction performed.
All patients with PWS should have effective weight control before and during treatment with somatropin.
Scoliosis is common in patients with PWS. Scoliosis may progres in any child during rapid growth. Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not been shown to increase the incidence or severity of scoliosis.
Experience with long term treatment in patients with PWS is limited.
In short children born SGA other medical reasons or treatments that could explain growth disturbance should be ruled out before starting treatment.
In SGA children it is recommended to measure fasting insulin and blood glucose before start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g. familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not be administered.
In SGA children it is recommended to measure the IGF-I level before start of treatment and twice a year thereafter. If on repeated measurements IGF-I levels exceed +2 SD compared to references for age and pubertal status, the IGF-I/IGFBP-3 ratio could be taken into account to consider dose adjustment.
Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not recommended to initiate treatment near onset of puberty. Experience in patients Silver-Russell syndrome is limited.
Some of the height gain obtained with treating short children born SGA with growth hormone may be lost if treatment is stopped before final height is reached.
In chronic renal insufficiency, renal function should be below 50 percent of normal before institution of therapy. To verify growth disturbance, growth should be followed for a year preceding institution of therapy. During this period, conservative treatment for renal insufficiency (which includes control of acidosis, hyperthyroidism and nutritional status) should have been established and should be maintained during treatment.
The treatment should be discontinued at renal transplantation.
To date, no data on final height in patients with chronic renal insufficiency treated with Scitropin A are available.
The effects of somatropin on recovery are studied in two placebo controlled trials involving 522 critically ill adult patients suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. Mortality was higher in patients treated with 5.3 or 8 mg somatropin daily compared to patients receiving placebo, 42% vs. 19%. Based on this information, these types of patients should not be treated with somatropin. As there is no information available on the safety of growth hormone substitution therapy in acutely critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved. In all patients developing other or similar acute critical illness, the possible benefit of treatment with somatropin must be weighed against the potential risk involved.
The solutions for injection (15 IU and 30 IU) contain less than 1 mmol sodium (23 mg) per mL, i.e essentially 'sodium free'.
For Scitropin A no clinical data on exposed pregnancies are available. Animal experimental data on reproductive toxicity are not available. Treatment with should be interrupted if pregnancy occurs.
During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks, being replaced almost entirely by placental growth hormone by 30 weeks. ln view of this, it is unlikely that continued replacement therapy with somatropin would be necessary in growth hormone deficient women in the third trimester of pregnancy.
It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the gastrointestinal tract of the infant is extremely unlikely.
Caution should be exercised when is administered to nursing women.
Within the organ system classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/1000); rare (>1/10,000, <1/1000); very rare (<1/10,000).
Patients with growth hormone deficiency are characterised by extracellular volume deficit. When treatment with somatropin is started this deficit is rapidly corrected. In adults patients adverse reactions related to fluid retention, such as peripheral oedema, stiffness in the extremities, arthralgia, myalgia and paraesthesia are common. In general these adverse reactions are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose-reduction. The incidence of these undesirable effects is related to the administered dose, the age of patients, and possibly inversely related to the age of patients at the onset of growth hormone deficiency. In children such adverse effects are uncommon.
Neoplasms, Benign and Malignant (including cysts and polyps): Very rare:
Leukemia. Very rare cases of leukemia have been reported in growth hormone deficient paediatric patients treated with somatropin, but the incidence appears to be similar to that in the paediatric subjects without growth hormone deficiency.
Immune System Disorders: Common: Formation of antibodies. Somatropin has given rise to the formation of antibodies in approximately 1% of the patients. The binding capacity of these antibodies has been low and no clinical changes have been associated with their formation.
Endocrine Disorders: Rare: Diabetes mellitus type II.
Nervous System Disorders: Common: In adults paraesthesia.
Uncommon: In adults carpal tunnel syndrome; In paediatric patients paraesthesia.
Rare: Benign intracranial hypertension.
Musculoskeletal, Connective Tissue and Bone Disorders: Common: In adults stiffnes in the extremities; arthralgia, myalgia.
Uncommon: In paediatric patients stiffness in the extremities, arthralgia, myalgia.
General Disorders and Administration Site Disorders: Common: In aults peripheral oedema; In paediatric patients transient local skin reactions at the injection site.
Uncommon: In paediatric patients peripheral oedema.
Data from an interaction study performed in growth hormone deficient adults suggests that somatropin administration may increase the clearance of compounds known to be metabolized by cytochrome P450 isoenzymes. The clearance of compounds metabolized by cytochrome P450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporin) may be especially increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.
Also see Precautions for statements regarding diabetes mellitus and thyroid disorders and Dosage & Administration for statement on oral estrogen replacement therapy.
Concomitant glucocorticoid treatment may inhibit the growth-promoting effects of somatropin. Pediatric GHD patients, with coexisting adrenocorticotropic hormone deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth.
Incompatibilities: In the absence of compatibility studies, this medical product must not be mixed with other medicine products.
SciTropin A 5 mg/1.5 mL (15 IU) and 10 mg/1.5 mL (30 IU) Solution for Injection: Both solutions for injection (5 mg/1.5 mL and 10 mg/1.5 mL) should be stored at 2°C to 8°C in a refrigerator. Do not freeze. If unopened, the contents should be stored in the original package in order to protect from light. The 5 mg/1.5 mL is stable for 24 months whereas the 10 mg/1.5 mL is stable for 18 months.
After the first injection, the contents of the cartridge must be used within 28 days and the cartridge should remain in the pen, and kept at 2°C to 8°C (in a refrigerator) protected from light.
H01AC01 - somatropin ; Belongs to the class of somatropin and somatropin agonists. Used in anterior pituitary lobe hormone and analogue preparations.
Inj soln (cartridge) 5 mg/1.5 mL (15 IU) x 1's. 10 mg/1.5 mL (30 IU) x 1's.
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