GENOTROPIN Special Precautions
GENOTROPIN Special Precautions
Diagnosis and therapy with Genotropin 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.
Myositis is a very rare adverse event that may be related to the preservative metacresol. In the case of myalgia or disproportionate pain at the injection site, myositis should be considered and, if confirmed, a Genotropin presentation without metacresol should be used.
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 has 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.
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 funduscopy 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 is often possible without recurrence of the intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.
Experience in patients above 80 years is limited. Elderly patients may be more sensitive to the action of Genotropin, and therefore may be more prone to develop adverse reactions.
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 Prader-Willi syndrome 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. Patients with one or more of these factors may be at increased risk.
Before initiation of treatment with somatropin in patients with Prader-Willi syndrome, signs 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 ENT specialist for treatment and resolution of the respiratory disorder prior to initiating growth hormone treatment.
Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.
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 Prader-Willi syndrome should be 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 Prader-Willi syndrome should also 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. However, growth hormone treatment has not been shown to increase the incidence or severity of scoliosis.
Experience with prolonged treatment in adults and 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 of 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.
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 Genotropin are available.
The effects of Genotropin 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 Genotropin daily compared to patients receiving placebo, 42% vs. 19%. Based on this information, these types of patients should not be treated with Genotropin. 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 Genotropin must be weighed against the potential risk involved.
GENOTROPIN Adverse Reactions
GENOTROPIN Adverse Reactions
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Patients with growth hormone deficiency are characterised by extracellular volume deficit. When treatment with somatropin is started, this deficit is rapidly corrected. In adult patients, adverse effects related to fluid retention such as peripheral oedema, stiffness in the extremities, arthralgia, myalgia and paraesthesia are common. In general, these adverse effects are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose reduction.
The incidence of these adverse 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.
Transient local skin reactions at the injection site in children are common.
Rare cases of diabetes mellitus type II have been reported.
Rare cases of benign intracranial hypertension have been reported.
Carpal tunnel syndrome is an uncommon event among adults.
Somatropin has given rise to the formation of antibodies in approximately 1% of patients. The binding capacity of these antibodies has been low and no clinical changes have been associated with their formation.
||Common >1/100, <1/10
||Rare>1/10,000, < 1/1000
||Very rare <1/10,000
|Neoplasms, benign and malignant
|Immune system disorders
||Formation of antibodies
||Diabetes mellitus type II
|Nervous system disorders
||In adults paraesthesia
||In adults carpal tunnel syndrome. In children paraesthesia
||Benign intracranial hypertension
|Skin and subcutaneous tissue disorders
||In children transient local skin reactions
|Musculoskeletal, connective tissue and bone disorders
||In adults stiffness in the extremities, arthralgia, myalgia
||In children stiffness in the extremities, arthralgia, myalgia
|General disorders and administration site disorders
||In adults peripheral oedema
||In children peripheral oedema
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, corticosteroid replacement therapy should be optimised before initiation of Genotropin therapy.
Very rare cases of leukaemia have been reported in growth hormone deficient children treated with somatropin, but the incidence appears to be similar to that in children without growth hormone deficiency.
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.