NORDITROPIN Special Precautions
NORDITROPIN Special Precautions
Children treated with Norditropin SimpleXx should be regularly assessed by a specialist in child growth. Norditropin SimpleXx treatment should always be instigated by a physician with special knowledge of growth hormone insufficiency and its treatment. This is true also for the management of Turner's syndrome and chronic renal disease and SGA. Data of final adult height following the use of Norditropin for children with chronic renal disease are not available.
The stimulation of skeletal growth in children can only be expected until the epiphyseal discs are closed.
The dosage in children with chronic renal disease is individual and must be adjusted according to the individual response to therapy. The growth disturbance should be clearly established before Norditropin SimpleXx treatment by following growth on optimal treatment for renal disease over one year. Conservative management of uraemia with customary medication and if needed dialysis should be maintained during Norditropin SimpleXx therapy.
Patients with chronic renal disease normally experience a decline in renal function as part of the natural course of their illness. However, as a precautionary measure during Norditropin SimpleXx treatment renal function should be monitored for an excessive decline, or increase in the glomerular filtration rate (which could imply hyperfiltration).
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 with 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.
Somatropin has been found to influence carbohydrate metabolism, therefore, patients should be observed for evidence of glucose intolerance.
Serum thyroxine levels may fall during treatment with Norditropin SimpleXx due to the increased peripheral deiodination of T4 to T3.
In patients with a pituitary disease in progression, hypothyroidism may develop.
Patients with Turner's syndrome have an increased risk of developing primary hypothyroidism associated with anti-thyroid antibodies.
As hypothyroidism interferes with the response to Norditropin SimpleXx therapy patients should have their thyroid function tested regularly, and should receive replacement therapy with thyroid hormone when indicated.
In insulin treated patients adjustment of insulin dose may be needed after initiation of Norditropin SimpleXx treatment.
Patients with growth hormone deficiency secondary to an intracranial lesion should be examined frequently for progression or recurrence of the underlying disease process.
Leukaemia has been reported in a small number of growth hormone deficient patients some of whom have been treated with somatropin. Based on 10 years global assessment there is no increased risk of development of leukaemia during somatropin treatment. In patients in complete remission from tumours or malignant disease, growth hormone therapy has not been associated with an increased relapse rate. Nevertheless, patients who have achieved complete remission of malignant disease should be followed closely for relapse after commencement of Norditropin SimpleXx therapy.
Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders and Legg-Calvé-Perthes disease may occur more frequently in patients with short stature. These diseases may present as the development of a limp or complaints of hip or knee pain and physicians and parents should be alerted to this possibility.
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.
In the event 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 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.
Growth hormone deficiency in adults is a lifelong disease and needs to be treated accordingly, however, experience in patients older than 60 years and in patients with more than five years of treatment in adult growth hormone deficiency is still limited.
Two placebo-controlled clinical trials of patients in intensive care units have demonstrated an increased mortality among patients suffering from acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure, who were treated with somatropin in high doses (5.3 – 8 mg/day). The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with growth hormone in patients having acute critical illness should be weighed against the potential risk.
NORDITROPIN Adverse Reactions
NORDITROPIN Adverse Reactions
Growth hormone deficient patients are characterised by extracellular volume deficit. When treatment with somatropin is initiated, this deficit is corrected. Fluid retention with peripheral oedema may occur especially in adults. Carpal tunnel syndrome is uncommon, but may be seen in adults. The symptoms are usually transient dose dependent and may require dose reduction. Mild arthralgia, muscle pain and paresthesia may also occur, but is usually self-limiting.
Adverse reactions in children are uncommon or rare.
Clinical trial experience:
Nervous system disorders
Common (>1/100, <1/10): In adults headache and paraesthesia.
Uncommon (>1/1000, <1/100): In adults carpal tunnel syndrome. In children headache.
Musculoskeletal, connective tissue and bone disorders
Common (>1/100, <1/10): In adults arthralgia, joint stiffness and myalgia.
Uncommon (>1/1000, <1/100): In adults muscle stiffness.
Rare (>1/10000, <1/1000): In children arthralgia and myalgia.
General disorders and administration site conditions
Very common (>1/10): In adults peripheral oedema
Uncommon (>1/1000, <1/100): In adults and children injection site pain. In children injection site reaction NOS.
Rare (>1/10000, <1/1000): In children peripheral oedema.
Skin and subcutaneous tissue disorders
Uncommon (>1/1000, <1/100): In adults pruritus.
Rare (>1/10000, <1/1000): In children rash NOS.
Metabolism and nutrition disorders
Uncommon (>1/1000, <1/100): In adults Diabetes mellitus type 2 (See Post marketing experience)
Post marketing experience:
Very rare cases of hypersensitivity reactions have been reported.
Formation of antibodies directed against somatropin has rarely been observed during Norditropin therapy. The titres and binding capacities of these antibodies have been very low and have not interfered with the growth response to Norditropin administration.
Very rare cases of decrease in serum thyroxin levels have been reported during treatment with Norditropin. Increase in blood alkaline phosphatase level may be seen during the treatment with Norditropin.
Very rare cases of benign intracranial hypertension have been reported.
Very rare cases of diabetes mellitus type 2 have been reported, but most of the available literature does not demonstrate an increased incidence of diabetes associated with somatropin treatment.