POM: Prescription only medicine
This information is intended for use by health professionals
Growth Hormone DeficiencyGenerally a dose of 0.17 0.23 mg/kg bodyweight (approximating to 4.9 mg/m2 6.9 mg/m2 body surface area) per week divided into 6 - 7 s.c. injections is recommended (corresponding to a daily injection of 0.02 0.03 mg/kg bodyweight or 0.7 1.0 mg/m2 body surface area).The total weekly dose of 0.27 mg/kg or 8 mg/m2 body surface area should not be exceeded (corresponding to daily injections of up to about 0.04 mg/kg).
Turner's SyndromeGenerally a dose of 0.33 mg/kg/bodyweight (approximating to 9.86 mg/m2/body surface area) per week divided into 6 - 7 s.c. injections are recommended (corresponding to daily injection of 0.05 mg/kg/bodyweight or 1.40-1.63 mg/m2/body surface area).Instructions for preparation, see section 6.6.
AdministrationThe required dose of ZOMACTON 10 mg/ml is administered with a ZOMAJET VISION X needle-free device or with an ordinary syringe.Specific instructions for the use of the ZOMAJET VISION X device are given in a booklet supplied with the device.
The maximum recommended daily dose should not be exceeded (see section 4.2).Very rare cases of myositis have been observed and may be due to the metacresol used as preservative. In the case of myalgia or disproportionate pain at the injection site, myositis should be considered and, if confirmed, a Zomacton presentation without metacresol should be used.Zomacton is not indicated for the long term treatment of paediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome, unless they also have a diagnosis of GH deficiency. There have been reports of sleep apnoea and sudden death after initiating therapy with growth hormone in paediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnoea or unidentified respiratory infection.Rare cases of benign intra-cranial hypertension have been reported. In the event of severe or recurring headache, visual problems, and nausea/vomiting, a funduscopy for papilla edema is recommended. If papilla edema is confirmed, diagnosis of benign intra-cranial hypertension should be considered and if appropriate growth hormone treatment should be discontinued (see also section 4.8). At present, there is insufficient evidence to guide clinical decision making in patients with resolved intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.Leukaemia has been reported in a small number of growth hormone deficient patients treated with somatropin as well as in untreated patients. However, there is no evidence that leukaemia incidence is increased in growth hormone recipients without predisposition factors.As with all somatropin containing products, a small percentage of patients may develop antibodies to somatropin. 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 who fails to respond to therapy.Growth hormone increases the extrathyroidal conversion of T4 to T3 and may, as such, unmask insipiens hypothyroidism. Monitoring of thyroid function should therefore be conducted in all patients. In patients with hypopituitarism, standard replacement therapy must be closely monitored when somatropin therapy is administered.Because somatropin may reduce insulin sensitivity, patients should be monitored for evidence of glucose intolerance. For patients with diabetes mellitus, the insuline dose may require adjustment after somatropin containing product therapy is initiated. Patients with diabetes or glucose intolerance should be monitored closely during somatropin therapy. Zomacton should also be used with caution in patients with a family history predisposing for the disease.In patients with growth hormone deficiency secondary to an intra-cranial lesion, frequent monitoring for progression or recurrence of the underlying disease process is advised. In childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm. Intracranial tumours, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasmsDiscontinue Zomacton therapy if progression or recurrence of the lesion occurs.In patients with previous malignant diseases special attention should be given to signs and symptoms of relapse.Scoliosis may progress in any child during rapid growth. Signs of scoliosis should be monitored during somatropin treatment.Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders. A patient treated with Zomacton who develops a limp or complains of hip or knee pain should be evaluated by a physician.The effects of treatment with growth hormone 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 (42 % vs. 19 %) among patients treated with growth hormones (doses 5.3 to 8 mg/day) compared to those receiving placebo. Based on this information, such patients should not be treated with growth hormones. 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.Experience of local tolerability to administration of ZOMACTON 10 mg/ml with Zomajet Vision X needle-free device has been studied before marketing authorisation in a 12 week study including only Caucasian children.Although rare, pancreatitis should be considered in somatropin-treated patients, especially children who develop abdominal pain.
|System Organ Class||Very Common (≥ 1/10)||Common (≥1/100, <1/10)||Uncommon (≥1/1000, <1/100)||Rare (≥1/10,000, <1/1,000)||Very rare (<1/10,000)|
|Blood and lymphatic system disorders||anemia|
|Cardiac disorders||tachycardia, (adult) hypertension||(children) hypertension|
|Ear and labyrinth disorders||vertigo|
|Eye disorders||papilloedema, diplopia|
|Gastroinyestinal disorders||vomiting, abdominal pain, flatulence, nausea||diarrhoea|
|General disorders and administration site conditions||(adults) oedema, (adults) peripheral oedema||(children) oedema, (children) peripheral oedema, injection site reactions, asthenia||weakness, injection site atrophy, injection site haemorrhage, injection site mass, hypertrophy|
|Immune system disorders||antibody building|
|Investigations||renal function test abnormal|
|Metabolism and nutrition disorders||(adult) mild hyperglycaemia||(children) glucose tolerance impaired||hypoglycaemia, hyperphosphatemia||diabetes mellitus type II|
|Musculoskeletal and connective tissue disorders||(adults) arthralgia; (adults) myalgia||(children) arthralgia (children) myalgia (Adults) Stiffness in the extremities||muscle atrophy, bone pain, carpal tunnel syndrome (Children) Stiffness in the extremities|
|Neoplasms benign, malignant and unspecified||neoplasm malignant, neoplasm||(children) leukaemia|
|Nervous system disorders||(adult) headache, (adult) paresthesia||headache, hypertonia, (adult) insomnia||somnolence, nystagmus||neuropathy, intracranial pressure increased, (children) insomnia, (children) paresthesia|
|Psychiatric disorders||personality disorders|
|Renal and urinary disorders||urinary incontinence, haematuria, polyuria, urine frequency/pollakiuria, urine abnormality|
|Reproductive system and breast disorders||genital discharge, (adult) gynecomastia||(children) Gynecomastia|
|Skin and subcutaneous tissue disorders||lipodystrophy, skin atrophy, dermatitis exfoliative, urticaria, hirsutism, skin hypertrophy|
Reporting of suspected adverse reactionsReporting 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 via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.
Pharmacodynamic properties:Identical to pituitary-derived human growth hormone (pit-hGH) in amino acid sequence, chain length (191 amino acids) and pharmacokinetic profile. Zomacton can be expected to produce the same pharmacological effects as the endogenous hormone.
Skeletal system:Growth hormone produces a generally proportional growth of the skeletal bone in man. Increased linear growth in children with confirmed deficiency of pit-hGH has been demonstrated after exogenous administration of Zomacton. The measurable increase in height after administration of Zomacton results from an effect on the epiphyseal plates of long bones. In children who lack adequate amounts of pit-hGH, Zomacton produces increased growth rates and increased IGF-1 (Insulin-like Growth Factor/Somatomedin-C) concentrations that are similar to those seen after therapy with pit- hGH. Elevations in mean serum alkaline phosphatase concentrations are also involved.
Other organs and tissues:An increase in size, proportional to total increase in body weight, occurs in other tissues in response to growth hormone, as well. Changes include: increased growth of connective tissues, skin and appendages; enlargement of skeletal muscle with increase in number and size of cells; growth of the thymus; liver enlargement with increased cellular proliferation; and a slight enlargement of the gonads, adrenals, and thyroid.Disproportionate growth of the skin and flat bones, and accelerated sexual maturation have not been reported in association with the growth hormone replacement therapy.
Protein, carbohydrate and lipid metabolism:Growth hormone exerts a nitrogen-retaining effect and increases the transport of amino acids into tissue. Both processes augment the synthesis of protein. Carbohydrate use and lipogenesis are depressed by growth hormone. With large doses or in the absence of insulin, growth hormone acts as a diabetogenic agent, producing effects seen typically during fasting (i.e. intolerance to carbohydrate, inhibition of lipogenesis, mobilisation of fat and ketosis).
Mineral metabolism:Conservation of sodium, potassium, and phosphorous occurs after treatment with growth hormone. Increased calcium loss by the kidney is offset by increased absorption in the gut. Serum calcium concentrations are not significantly altered in patients treated with Zomacton or with pit-hGH. Increased serum concentrations of inorganic phosphates have been shown to occur both after Zomacton and pit-hGH. Accumulation of these minerals signals an increased demand during tissue synthesis.
PowderMannitolDisodium phosphate dodecahydrateSodium dihydrogen phosphate dihydrate
SolventMetacresolWater for injections
ReconstitutionThe powder should be reconstituted only by introducing the provided solvent contained in the syringe into the vial.See the package leaflet for detailed instructions for reconstitution.The following is a general description of the reconstitution and administration process. Reconstitution should be performed in accordance with good practice rules, particularly in the respect of asepsis.1. Hands should be washed.2. Flip off the yellow plastic protective caps from the vial.3. The top of the vial should be wiped with an antiseptic solution to prevent contamination of the content.4. Place the vial adaptor or the solvent transfer connector over the centre of the vial with the spike facing downwards then push down firmly until it clicks into place. Remove the adaptor cap.5. Take the syringe. Remove the grey cap. Place the syringe into the adaptor / connector of the vial and inject the solvent slowly into the vial aiming the stream of liquid against the glass wall in order to avoid foam.6. Place the adaptor cap / connector cap back on the adaptor / connector.7. Gently swirl the vial a few times until the content is completely dissolved. Do not shake; this may cause denaturation of the active substance.8. If the solution is cloudy or contains particulate matter, it should not be used. In the case of cloudiness after refrigeration, the product should be allowed to warm to room temperature. If cloudiness persists, discard the vial and its contents. The content must be clear and colourless after reconstitution.Any unused product or waste material should be disposed of in accordance with local requirements.
Reconstitution with vial adaptor for use with ZomaJet Vision X device
|Step 1 Remove the yellow cap from the ZOMACTON vial.||Step 2 Place the vial adaptor over the centre of the vial with the spike facing downwards. Push down firmly until it clicks into place.||Step 3 and 4 Remove the grey syringe cap and also remove the white vial adaptor cap.||Step 5 Place the vial on a flat surface and hold the vial adaptor. Place the syringe into the vial adaptor and push down. firmly.|
|Step 6 Press the syringe plunger slowly. Ensure that all the solution goes into the vial.||Step 7 Hold the vial and firmly pull the syringe away. The syringe adaptor will remain in place.||Step 8 Place the white vial adaptor cap back on the adaptor by pushing firmly until it clicks into place.|
|Step 1 Remove the yellow cap from the ZOMACTON vial. Place the solvent transfer connector over the centre of the vial with the spike facing downwards. Push down firmly until it clicks into place.||Step 2 Remove the grey syringe cap.||Step 3 Place the vial on a flat surface and hold the solvent transfer connector. Place the syringe into the solvent transfer connector and push down firmly. Press the syringe plunger slowly. Ensure that all the solution goes into the vial.|
|Step 4 Hold the vial and firmly pull the syringe away. The solvent transfer connector will remain in place. Place the cap on the solvent transfer connector.||Step 5 The vial must then be swirled gently until the powder has dissolved completely to form a clear, colourless solution. Place the reconstituted vial of ZOMACTON in an upright position in the refrigerator at 2°C to 8°C.|