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Drug Details

Saizen 5.83 mg/ml and 8 mg/ml solution for injection

• Drug Class Description
  Growth Hormones
• Generic Name
  Somatropin
• Presentation
  Solution for injection. Clear to slightly opalescent solution with pH of 5.6-6.6 and osmolality 250-450 mOsm/kg
• Description
  Saizen 5.83 mg/ml solution for injection. Each cartridge contains 1.03 ml solution (6 mg somatropin*) Saizen 8 mg/ml solution for injection. Each cartridge contains 1.50 ml solution (12 mg somatroprin*) or 2.50 ml solution (20 mg somatropin*). *recombinant human growth hormone, produced by recombinant DNA technology in mammalian cells
• Indications
  Saizen is indicated in the treatment of: Children and adolescents: - Growth failure in children caused by decreased or absent secretion of endogenous growth hormone. - Growth failure in girls with gonadal dysgenesis (Turner Syndrome), confirmed by chromosomal analysis. - Growth failure in prepubertal children due to chronic renal failure (CRF). - Growth disturbance (current height SDS <-2.5 and parental adjusted height SDS <-1) in short children born small for gestational age (SGA) with a birth weight and/or length below -2 SD, who failed to show catch-up growth (HV SDS <0 during the last year) by 4 years of age or later. Adults: - Replacement therapy in adults with pronounced growth hormone deficiency as diagnosed by a single dynamic test for growth hormone deficiency. Patients must also fulfil the following criteria: - Childhood Onset: Patients who were diagnosed as growth hormone deficient during childhood, must be retested and their growth hormone deficiency confirmed before replacement therapy with Saizen is started. - Adult Onset: Patients must have growth hormone deficiency as a result of hypothalamic or pituitary disease and at least one other hormone deficiency diagnosed (except for prolactin) and adequate replacement therapy instituted, before replacement therapy using growth hormone may begin.
• Adult Dosage
  

  Saizen 5.83 mg/ml and Saizen 8 mg/ml are intended for multiple dose use in an individual patient.

  It is recommended that Saizen be administered at bedtime according to the following dosage:

   

  Children and adolescents:

  Saizen dosage should be individualised for each patient based on body surface area (BSA) or on body weight (BW).

  - Growth failure due to inadequate endogenous growth hormone secretion: 0.7-1.0 mg/m2 body surface area (BSA) per day or 0.025-0.035 mg/kg body weight (BW) per day by subcutaneous administration. - Growth failure in girls due to gonadal dysgenesis (Turner Syndrome): 1.4 mg/m2 body surface area (BSA) per day or 0.045-0.050 mg/kg body weight (BW) per day by subcutaneous administration. Concomitant therapy with non-androgenic anabolic steroids in patients with Turner Syndrome can enhance the growth response. - Growth failure in prepubertal children due to chronic renal failure (CRF): 1.4 mg/m2 body surface area (BSA), approximately equal to 0.045-0.050 mg/kg body weight (BW), per day by subcutaneous administration. - Growth failure in short children born small for gestational age (SGA): The recommended daily dose is 0.035 mg/kg body weight (or 1 mg/m2/day) by subcutaneous administration. Treatment should be discontinued when the patient has reached a satisfactory adult height, or the epiphyses are fused. For growth disturbance in short children born SGA, treatment is usually recommended until final height is reached. Treatment should be discontinued after the first year if height velocity SDS is below +1. Treatment should be discontinued when final height is reached (defined as height velocity <2 cm/year), and if confirmation is required if bone age is >14 years (girls) or >16 years (boys), corresponding to closure of the epiphyseal growth plates.

  Adults:

  - Growth Hormone Deficiency in adults At the start of somatropin therapy, low doses of 0.15-0.3 mg are recommended, given as a daily subcutaneous injection. The dose should be adjusted stepwise, controlled by Insulin-like Growth Factor 1 (IGF-1) values. The recommended final GH dose seldom exceeds 1.0 mg/day. In general the lowest efficacious dose should be administered. In older or overweight patients, lower doses may be necessary.

  For administration of the solution for injection of Saizen follow the instructions given in the package leaflet and in the instruction manual provided with the selected auto-injector: cool.click needle-free auto-injectors or easypod auto-injector.

  Intended users of easypod are primarily children starting from the age of 7 up to adults. Use of the devices by children should always be made under adult's supervision.

• Contra Indications
  

  Hypersensitivity to the active substance or to any of the excipients.

  Somatropin should not be used for growth promotion in children with closed epiphyses.

  Any evidence of active malignant tumours. Intracranial neoplasm must be inactive and antitumor therapy should be completed prior to institution of therapy.

  Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions should not be treated with somatropin.

  In children with chronic renal disease, treatment with somatropin should be discontinued at renal transplantation.

• Special Precautions
  

  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.

  Prader-Willi Syndrome

  Somatropin 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.

  Insuline 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.

  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

  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 case of severe or recurrent headache, visual problems, nausea and/or vomiting, funduscopy for papille oedema is recommended. If papille oedema 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 treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.

   

  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 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.

  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.

  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 SilverRussel 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 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.

  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.

  In all patients developing acute critical illness, the possible benefit of treatment with somatropin must be weighed against the potential risk involved.

• Interactions
  

  Concomitant treatment with glucocorticoids inhibits the growth-promoting effects of somatropin containing products. Patients with ACTH deficiency should have their glucocorticoid replacement therapy carefully adjusted to avoid any inhibitory effect on growth hormone.

  Data from an interaction study performed in growth hormone deficient adults, suggests that somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsivants and cyclosporine) may be especially increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.

• Adverse Drug Reactions
  

  Up to 10 % of patients may experience redness and itching at the site of injection, particularly when the subcutaneous route is used.

  Fluid retention is expected during growth hormone replacement therapy in adults. Oedema, joint swelling, arthralgias, myalgias and paresthesias may be clinical manifestations of fluid retention. However, these symptoms / signs are usually transient and dose dependent.

  Adult patients with growth hormone deficiency, following diagnosis of growth hormone deficiency in childhood, reported side-effects less frequently than those with adult onset growth hormone deficiency.

  Antibodies to somatropin can form in some patients; the clinical significance of these antibodies is unknown, though to date the antibodies have been of low binding capacity and have not been associated with growth attenuation except in patients with gene deletions. In very rare instances, where short stature is due to deletion of the growth hormone gene complex, treatment with growth hormone may induce growth attenuating antibodies.

  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 predisposing factors.

  Within each frequency grouping, undesirable effects are presented in order of decreasing seriuousness.

   

  System Organ Class	Common (1/100, <1/10)	Uncommon (1/1,000, <1/100)	Very rare (<1/10,000)	Frequency unknown
  Nervous system disorders	Headache (isolated)	Idiopathic intracranial hypertension (benign intracranial hypertension) Carpal tunnel syndrome
  Musculoskeletal and connective tissue disorders			Slipped capital femoral epiphysis (Epiphysiolysis capitis femoris), or avascular necrosis of the femoral head
  Endocrine disorders			Hypothyroidism
  Metabolism and nutrition disorders	In adults: Fluid retention: peripheral oedema, stiffness, arthralgia, myalgia, paresthesia.	In children: Fluid retention: peripheral oedema, stiffness, arthralgia, myalgia, paresthesia.		Insulin resistance can result in hyperinsulinism and in rare cases in hyperglycemia.
  General disorders and administration site conditions	Injection site reactions: Localized lipoatrophy, which can be avoided by varying the site of injection