Scitropin A

Scitropin A

somatropin

Manufacturer:

SciGen

Distributor:

Metro Drug
Full Prescribing Info
Contents
Somatropin (rbe).
Description
Somatropin (SciTropin A) 5 mg/1.5mL (15 IU) Solution for Injection: Each cartridge (1.5 mL) contains 5 mg recombinant somatropin. Other ingredients: 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 ad 1.5 mL.
Somatropin (SciTropin A) 10 mg/1.5mL (30 IU) Solution for Injection: Each cartridge (1.5 mL) contains 10 mg recombinant somatropin. Other ingredients: 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 ad 1.5 mL.
Somatropin (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.
Somatropin (SciTropin A) Solution for Injection is a clear, colourless solution.
This medicinal product contains less than 1 mmol sodium (23 mg) per mL, i.e. essentially 'sodium free.'
Action
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, 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 increase 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-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.
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 hypopituarism 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 osteopenia 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/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 Somatropin (SciTropin A) 1.3 mg/mL Solution for Injection in healthy adults results in plasma Cmax and tmax values of 71±24 g/L and 4 (range 2-8) hours, respectively. A subcutaneous dose of 5 mg of Somatropin (SciTropin A) 5 mg/1.5mL Solution for Injection in healthy adults results in plasma Cmax and tmax values of 72±28 g/L and 4.0±2.0 hours, respectively. A subcutaneous dose of 5 mg of Somatropin (SciTropin A) 10 mg/ 1.5 mL Solution for Injection in healthy adults results in plasma Cmax and tmax values of 74±22 g/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 Somatropin (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.
Special 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.
Indications/Uses
Children: Growth disturbance due to insufficient secretion of growth hormone (Growth Hormone Deficiency GHD).
Growth disturbance associated with Turner syndrome.
Growth disturbance associated with chronic renal insufficiency.
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted height 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.
Prader-Willi syndrome (PWS), for improvement of growth and body composition. The diagnosis of PWS should be confirmed by appropriate genetic testing.
Adults: Replacement therapy in adults with pronounced growth hormone deficiency.
Adult onset: Patients with severe growth hormone associated with multiple hormone deficiencies as a result of hypothalamic pituitary pathology and who have at least one known deficiency of pituitary hormone not being prolactin. These patients should undergo an appropriate dynamic test in order to diagnose or exclude a growth hormone deficiency.
Childhood onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired or idiopathic causes. Patients with childhood onset should be re-evaluated for growth hormone secretory capacity after completion of longitudinal growth. In patients with a high likelihood for persistent GHD, i.e. a congenital cause or GHD secondary to a hypothalamic-pituitary disease or insult, an insulin-like growth factor-I (IGF-I) SDS < -2 off growth hormone treatment for at least 4 weeks should be considered sufficient evidence of profound GHD.
Dosage/Direction for Use
Diagnosis 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/m2 body surface area per day is recommended. Even higher doses have been used.
Where childhood onset GHD persists into adolescence, treatment should be continued to achieve full somatic development (e.g. body composition, bone mass). For monitoring, the attainment of a normal peak bone mass defined as a T score > -1 (i.e. standardized to average adult peak bone mass measured by dual energy X-ray absorptiometry taking into account sex and ethnicity) is one of the therapeutic objectives during the transition period. For guidance on dosing see adult as follows.
Prader-Willi syndrome, for improvement of growth and body composition in children: Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m body surface area per day is recommended. Daily doses of 2.7 mg should not be exceeded.
Growth disturbance due to Turner syndrome: A dose of 0.045-0.050 mg/kg body weight per day or 1.4 mg/ m2 body surface area per day is recommended.
Growth disturbance in chronic renal insufficiency: A dose of 0.045-0.050 mg/kg body weight per day (1.4 mg/m2 body surface area per day) is recommended. Higher doses can be needed if growth velocity is too low. A dose correction can be needed after six months of treatment.
Growth disturbance in short children born small for gestational age (SGA): A dose of 0.035 mg/kg body weight per day (1 mg/m2 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 years (boys), corresponding to closure of the epiphyseal growth plates.

Click on icon to see table/diagram/image

Treatment should not be used in children with a growth velocity less than 1 cm per year and near closure of epiphyses.
Growth hormone deficient adult patients: In patients who continue growth hormone therapy after childhood GHD, the recommended dose to restart is 0.2-0.5 mg per day. The dose should be gradually increased or decreased according to individual patient requirements as determined by the IGF-I concentration.
In adults with adult onset GHD, therapy should start with a low dose, 0.15-0.3 mg per day. The dose should be gradually increased according to individual patient requirements as determined by the IGF-I concentration. In both cases, treatment goal should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean. Patients with normal IGF-I concentrations at the start of the treatment should be administered growth hormone up to an IGF-I level into upper range of normal, not exceeding the 2 SDS. Clinical response and side effects may also be used as guidance for dose titration. It is recognized that there are patients with GHD who do not normalize IGF-I levels despite a good clinical response, and thus do not require dose escalation. The maintenance dose seldom exceeds 1.0 mg per day. Woman may require higher dose than men, with men showing an increasing IGF-I sensitivity over time. This means that there is a risk that women, especially those on oral oestrogen replacement are under-treated while men are over-treated. The accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal physiological growth hormone production decreases with age, dose requirements may be reduced.
Special Population: Elderly: In patients above 60 years, therapy should start with a dose of 0.1-0.2 mg per day and should be slowly increased according to individual patient requirements. The minimum effective dose should be used. The maintenance dose in these patients seldom exceeds 0.5 mg per day.
Renal impairment: 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, hyperparathyroidism 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.
Overdosage
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdose could result in signs and symptoms consistent with the known effects of human growth hormone excess.
Contraindications
Hypersensitivity to somatropin or to any of the excipients.
Somatropin should not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and anti-tumour therapy must be completed prior to starting GH therapy. Treatment should be discontinued if there is evidence of tumour growth.
Somatropin 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. With regards to patients undergoing substitution therapy, see Precautions.
Special Precautions
Insulin sensitivity: Somatropin may induce a state of insulin resistance. For patients with diabetes mellitus, the insulin dose may require adjustment after somatropin therapy is instituted. Patients with an already manifested diabetes, glucose intolerance, or additional risk factors for diabetes should be monitored closely during somatropin therapy.
Growth hormone increases the extrathyroidal conversion of T4 to T3 which may result in a reduction in serum T4 and an increase in serum T3 concentrations. Whereas, the peripheral thyroid hormone levels have remained within the reference ranges for healthy subjects, hypothyroidism theoretically may develop in subjects with subclinical hypothyroidism. Consequently, monitoring of thyroid function should therefore be conducted in all patients. In patients with hypopituitarism on standard replacement therapy, the potential effect of growth hormone treatment on thyroid function must be closely monitored.
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.
Benign intracranial hypertension: 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. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.
Leukaemia: Leukaemia has been reported in a small number of growth hormone deficiency patients, some of whom have been treated with somatropin. However, there is no evidence that leukaemia incidence is increased in growth hormone recipients without predisposition factors.
Antibodies: A small percentage of patients may develop antibodies to somatropin (SciTropin A). Somatropin has given rise to the formation of antibodies in approximately 1% of patients. The binding capacity of these antibodies is low and there is no effect on growth rate. Testing for antibodies to somatropin should be carried out in any patient with otherwise unexplained lack of response.
Acute critical illness: The effects of somatropin on recovery were 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 maximum recommended daily dose should not be exceeded.
Effects on Ability to Drive or Use Machine: Somatropin has no or negligible influence on the ability to drive and use machines
Use in Children: In patients with PWS, treatment should always be in combination with a calorie-restricted diet.
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 (those patients exceeding a weight/height of 200%), 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.
Before initiation of treatment with somatropin, patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory infections should be assessed.
If during the evaluation of upper airway obstruction, pathological findings are observed, the child should be referred to an Ear, nose and throat (ENT) specialist for treatment and resolution of the respiratory disorder prior to initiating growth hormone treatment.
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 ENT assessment performed.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is suspected.
Patients should be monitored for signs of respiratory infections which should be diagnosed as early as possible and treated aggressively.
All patients with PWS should have effective weight control before and during growth hormone treatment.
Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth. Signs of scoliosis should be monitored during treatment.
Experience with prolonged treatment in adults and in patients with PWS is limited.
Small for gestational age: 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 with 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.
Pancreatitis in children: Children treated with somatropin have an increased risk of developing pancreatitis compared to adults treated with somatropin. Although rare, pancreatitis should be considered in somatropin-treated children who develop abdominal pain.
Use in Elderly: Experience in patients above 80 years is limited. Elderly patients may be more sensitive to the action of somatropin, and therefore may be more prone to develop adverse reactions.
Use In Pregnancy & Lactation
Use in Pregnancy: Animal studies are insufficient with respect to reproductive toxicity. Somatropin is not recommended during pregnancy and in women of childbearing potential not using contraception.
Use in Lactation: There have been no clinical studies conducted with somatropin containing products in breast-feeding women. 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 therefore caution should be exercised when is administered to nursing women.
Fertility: Fertility studies with SciTropin A have not been performed.
Adverse Reactions
Summary of the safety profile: 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, musculoskeletal stiffness, 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 adverse reactions 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 reactions are uncommon.
SciTropin A 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 (see Precautions).
Tabulated list of adverse reactions: The following undesirable effects have been observed and reported during treatment with Omnitrope with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Neoplasms, benign and malignant (including cysts and polyps): Very rare: Leukemia*.
Immune system disorders: Common: Formation of antibodies.
Endocrine disorders: Rare: Diabetes mellitus type II.
Nervous system disorders: Common: In adults: paraesthesia.
Uncommon: In adults: carpal tunnel syndrome; In children: paraesthesia.
Rare: Benign intracranial hypertension.
Skin and subcutaneous tissue disorders: Common: In children: transient local skin reactions.
Musculoskeletal, connective tissue and bone disorders: Common: In adults stiffness in the extremities, arthralgia, myalgia.
Uncommon: In children: stiffness in the extremities, arthralgia, myalgia.
General disorders and administration site disorders: Common: In adults: peripheral oedema.
Uncommon: In children: peripheral oedema.
Description of selected adverse reactions: Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of therapy.
In the post-marketing experience rare cases of sudden death have been reported in patients affected by Prader-Willi syndrome treated with somatropin, although no causal relationship has been demonstrated.
*Very rare cases of leukaemia have been reported in growth hormone deficient children treated with Omnitrope, but the incidence appears to be similar to that in children without growth hormone deficiency.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions according to national reporting system.
Drug Interactions
Concomitant treatment with glucocorticoids may inhibit the growth-promoting effects of somatropin containing products. Therefore, patients treated with glucocorticoids should have their growth monitored carefully to assess the potential impact of glucocorticoid treatment on growth.
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 on Dosage & Administration for statement on oral estrogen replacement therapy.
Caution For Usage
Incompatibilities: In the absence of compatibility studies, this medical product must not be mixed with other medicinal products.
Storage
Somatropin (SciTropin AT) 5mg/1.5mL (15 IU) and 10mg/1.5 mL (30 IU) Solution for Injection: Unopened cartridge: Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original package in order to protect from light.
Somatropin (SciTropin A ) 5mg/1.5 mL (15 IU) Solution for Injection: The 5 mg/1.5 mL is stable for 24 months.
After the first injection, the contents of the cartridge must be used within 21 days and the cartridge should remain in the pen, and kept at 2°C to 8°C (in a refrigerator) protected from light. For microbiological reasons, any remaining solution should be discarded after 21 days.
Somatropin (SciTropin A) 10mg/1.5 mL (30 IU) Solution for Injection: 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. For microbiological reasons, any remaining solution should be discarded after 28 days.
ATC Classification
H01AC01 - somatropin ; Belongs to the class of somatropin and somatropin agonists. Used in anterior pituitary lobe hormone and analogue preparations.
Presentation/Packing
Soln for inj (cartridge) 5 mg/1.5 mL x 1's, 2's. 10 mg/1.5 mL x 1's.
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