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Treatment should be carried out under the regular guidance of a physician who is experienced in the diagnosis and management of patients with growth hormone deficiency.
Patients with an intra or extracranial neoplasia in remission who are receiving treatment with growth hormone should be examined carefully and at regular intervals by the physician.
Patients with growth hormone deficiency secondary to an intracranial tumour should be examined frequently for progression or recurrence of the underlying disease process.
There is limited data on the risk of malignancies with somatotropin, patients on treatment with Saizen should be carefully monitored.
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 neoplasms.
Leukemia: Some cases of leukaemia have been reported in growth hormone deficient children, untreated as well as treated with growth hormone, and might possibly represent a slightly increased incidence compared with non-growth hormone deficient children. A causal relationship to growth hormone therapy has not been established.
Insulin sensitivity: Growth Hormone administration is followed by a transient phase of hypoglycemia of approximately 2 hours, then from 2-4 hours onward by an increase in blood glucose levels despite high insulin concentrations. Somatropin may induce a state of insulin resistance which can result in hyperinsulinism and in some patients in hyperglycemia. To detect insulin resistance, patients should be monitored for evidence of glucose intolerance.
Saizen should be used with caution in patients with diabetes mellitus or with a family history of diabetes mellitus. Patients with diabetes mellitus may require adjustment of their antidiabetic therapy.
Stable background retinopathy should not lead to discontinuation of Somatropin replacement therapy. In case of development of preproliferative changes and the presence of proliferative retinopathy Somatropin replacement therapy should be discontinued.
Thyroid function: 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 overt hypothyroidism theoretically may develop. If hypothyroidism is diagnosed in the course of Saizen therapy, it should be corrected.
Conversely, in patients receiving replacement therapy with thyroxine mild hyperthyroidism may occur. It is therefore particularly advisable to test thyroid function after starting treatment with Somatropin and after dose adjustments.
Fluid retention is expected during growth hormone replacement therapy in adults. However, these symptoms/signs are usually transient and dose dependent.
In case of persistent oedema or severe paraesthesia the dosage should be decreased in order to avoid the development of carpal tunnel syndrome.
Benign intracranial hypertension: In case of severe or recurrent headache, visual problems, nausea and/or vomiting, fundoscopy for papilloedema is recommended. If papilloedema is confirmed a diagnosis of benign intracranial hypertension (or pseudotumor cerebri) should be considered and Saizen treatment should be discontinued. At present there is insufficient evidence to guide clinical decision-making in patients with resolved intracranial hypertension. If growth hormone is restarted, careful monitoring for symptoms of intracranial hypertension is necessary and treatment should be discontinued if intracranial hypertension recurs.
Fundoscopic examination should be performed routinely before initiating treatment with Saizen to exclude pre-existent papilloedema and repeated if there is any clinical suspicion. If papilloedema is confirmed by fundoscopy, Saizen treatment should be stopped. It can be restarted at a lower dose after idiopathic intracranial hypertension has resolved which occurs rapidly when treatment is withdrawn.
Pancreatitis: Although rare, pancreatitis should be considered in somatropin-treated patients, especially children who develop abdominal pain.
Scoliosis: Scoliosis is known to be more frequent in some of the patient groups treated with somatropin, for example Turner syndrome. In addition, rapid growth in any child can cause progression of scoliosis. Somatropin has not been shown to increase the incidence or severity of scoliosis. Signs of scoliosis should be monitored during treatment.
Special populations: Patients with renal impairment: Somatropin clearance is known to be reduced in patients with renal impairment.
Patients with hepatic impairment: Somatropin clearance is known to be reduced in patients with hepatic impairment. However, as Saizen has not been studied in patients with hepatic impairment, the clinical significance of this finding is unknown.
Antibodies: 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.
Slipped capital femoral epiphysis: Slipped capital femoral epiphysis is often associated with endocrine disorders such as growth hormone deficiency and hypothyroidism, and with growth spurts. In children treated with growth hormone, slipped capital femoral epiphysis may either be due to underlying endocrine disorders or to the increased growth velocity caused by the treatment. Growth spurts may increase the risk of joint-related problems, the hip joint being under particular strain during the prepubertal growth spurt.
Physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in children treated with Saizen.
Growth failure due to chronic renal failure: Patients with growth failure due to chronic renal failure should be examined periodically for evidence of progression of renal osteodystrophy. Slipped capital femoral epiphysis or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy and it is uncertain whether these problems are affected by growth hormone therapy. X-rays of the hip should be obtained prior to initiating therapy.
In children with chronic renal failure, renal function should have decreased to below 50% of normal before therapy is instituted. To verify the growth disturbance, growth should have been followed for a year before institution of therapy. Conservative treatment for renal insufficiency (which includes control of acidosis, hyperparathyroidism and nutritional status for one year prior to the treatment) should have been established and should be maintained during treatment. Treatment should be discontinued at the time of renal transplantation.
Children born 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.
For SGA patients 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, increased body mass index, severe insulin resistance, acanthosis nigricans) oral glucose tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not be administered.
For SGA patients it is recommended to measure 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 with SGA patients with Silver-Russel syndrome is limited.
Some of the height gain obtained with treating short children born SGA with Somatropin may be lost if treatment is stopped before final height is reached.
The injection site should be varied to prevent lipoatrophy.
Growth Hormone Deficiency in the Adult is a lifelong condition and should be treated accordingly, however experience with patients over sixty years and experience with prolonged treatment is limited.
Acute critical illness: As there is no information available on the safety of growth hormone substitution therapy in patients with acute critical illness, the benefits of continued treatment in this situation should be weighed against the potential risks involved.
Prader-Willi Syndrome: Saizen 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 growth hormone deficiency. There have been reports of sleep apnoea and sudden death in patients 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.
Interaction with glucocorticoids: Initiation of growth hormone replacement may unmask secondary adrenal insufficiency in some patients by reducing the activity of 11β-hydroxysteroid dehydrogenase, type 1 (11β-HSD1), an enzyme converting inactive cortisone to cortisol and glucocorticoid replacement may be required. Initiation of somatropin in patients receiving glucocorticoid replacement therapy may lead to manifestation of cortisol deficiency. Adjustment of glucocorticoid dose may be required.
Use with oral oestrogen therapy: If a woman taking somatropin begins oral oestrogen therapy, the dose of somatropin may need to be increased to maintain the serum IGF-1 levels within the normal age-appropriate range. Conversely, if a woman on somatropin discontinues oral oestrogen therapy, the dose of somatropin may need to be reduced to avoid excess of growth hormone and/or side effects.
Effects on ability to drive and use machines: Saizen does not interfere with the patient's ability to drive or use machinery.
