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.
The maximum recommended daily dose should not be exceeded (see Dosage & Administration).
Neoplasm: Patients with an intra- or extra-cranial 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.
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.
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 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.
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.
Insulin sensitivity: Because somatropin may reduce insulin sensitivity, patients should be monitored for evidence of glucose intolerance. For patients with diabetes mellitus, the insulin dose may require adjustment after somatropin containing product therapy is instituted. Patients with diabetes or glucose intolerance should be monitored closely during somatropin therapy.
Retinopathy: Stable background retinopathy should not lead to discontinuation of somatropin replacement therapy.
Thyroid function: Growth hormone increases the extra thyroid conversion of T4 to T3 and may, as such, unmask incipient 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.
Benign intracranial hypertension: In cases of severe or recurrent headache, visual problems, nausea and/or vomiting, a funduscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension (or pseudotumor cerebri) should be considered and if appropriate, 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.
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.
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 (SGA): 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.
Fluid retention: Fluid retention is expected during growth hormone replacement therapy in adults.
In case of persistent oedema or severe paraesthesia the dosage should be decreased in order to avoid the development of carpal tunnel syndrome.
Acute critical illness: In all patients developing acute critical illness, the possible benefit of treatment with somatropin must be weighed against the potential risk involved.
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 (see Interactions).
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 (see Interactions).
General: 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.
Powder for injection 3.33 mg vial: Benzyl alcohol as a preservative in bacteriostatic sodium chloride solution may cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old and must not be given to premature babies or neonates. Saizen may be reconstituted with Sodium Chloride Injection BP or Sterile Water for Injections for immediate use when administering to children under 3 years of age.
Effects on ability to drive and use machines: Saizen has no influence on the ability to drive and use machines.