Somatropin

Registered South African indications: 

• Growth hormone deficiency

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Any evidence of activity of a tumour, including tumour growth
• Children with closed epiphyses (when used for longitudinal growth promotion)
• Acute critical illness with complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions
• In children with chronic renal disease, treatment with somatropin should be discontinued at renal transplantation

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Children
• Prader-Willi syndrome with one or more risk factors of severe obesity, history of upper airway obstruction or sleep apnoea or unidentified respiratory infection (children)
• Onset of puberty
• Silver-Russell syndrome (children)
• Turner syndrome (girls)
• Noonan syndrome (children)
• Children born at small gestational age
• Scoliosis
• Diabetes mellitus or increased risk thereof
  - Familial history of diabetes
  - Obesity
  - Severe insulin resistance
  - Acanthosis nigricans
• Glucose intolerance
• Leukaemia  or presence of predisposition factors
• Benign intracranial hypertension
• Patients >60 years
• >5 years of treatment for adult growth hormone deficiency
• Childhood cancer survivors
• Prior exposure to radiation
• Growth hormone deficiency secondary to an intracranial lesion
• Incipient hypothyroidism
• Hypopituitarism
• Thyroid dysfunction
• Pituitary disease in progression
• Previously undiagnosed central (secondary) hypoadrenalism
• Limp, hip or knee pain

Forms avail. in SA and covered in this monograph: inj

Childhood onset growth hormone deficiency

• SC: Initial: 0.2-0.5mg/day, titrate up according to IGF-1 concentration

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Patients with childhood onset growth hormone deficiency should be re-evaluated for growth hormone secretory capacity after growth completion

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Adult onset growth hormone deficiency 
- One other deficient axis other than prolactin
- Hypothalamic-pituitary disease
- Cranial irradiation
- Traumatic brain injury

• SC: Initial: 0.1-0.3mg/day, titrate up at intervals of 1 month according to IGF-1 concentration, clinical response and adverse effects

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Somatropin should only be prescribed by doctors with special knowledge of the therapeutic indication of use

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The dosage is individual and must always be adjusted in accordance with the individual's clinical and biochemical response to therapy

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Women may require higher doses than men, with men showing an increasing IGF-1 sensitivity over time. This means that there is a risk that women, especially those on oral oestrogen replacement, are undertreated while men are overtreated

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Dose requirements decline with age. Maintenance dosages vary considerably from person to person, but seldom exceed 1.0mg/day

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Generally, daily subcutaneous administration in the evening is recommended

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The injection site should be varied to prevent lipoatrophy

Paed. forms avail. in SA and covered in this monograph: inj

Growth hormone insufficiency 

• SC: 0.025-0.035mg/kg/day or 0.7-1.0mg/m²/day

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The dosage is individual and must always be adjusted in accordance with the individual's clinical and biochemical response to therapy

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When growth hormone deficiency persists after growth completion, growth hormone treatment should be continued to achieve full somatic adult development including lean body mass and bone mineral accrual

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Turner syndrome 

• SC: 0.045-0.067mg/kg/day or 1.3-2.0mg/m²/day

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The dosage is individual and must always be adjusted in accordance with the individual's clinical and biochemical response to therapy

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Growth retardation in prepubertal children due to chronic renal disease 

• SC: 0.050mg/kg/day or 1.4mg/m²/day

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The dosage in children with chronic renal disease is individual and must be adjusted according to the individual response to therapy

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The growth disturbance should be clearly established before somatropin treatment by following growth on optimal treatment for renal disease over one year

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Conservative management of uraemia with customary medicinal product and if needed dialysis should be maintained during somatropin therapy

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See additional prescribing points 

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Small for gestational age
- Growth disturbance (current height SDS <-2.5 and parental adjusted height SDS <-1) in short children born small for gestational age (SGA), with 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

• SC: 0.035mg/kg/day or 1.0mg/m²/day, until final height is reached

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Treatment should be discontinued after the first year of treatment, if the height velocity SDS is below +1

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Treatment should be discontinued if height velocity is <2 cm/year and, if confirmation is required, bone age is >14 years (girls) or > 16 years (boys), corresponding to closure of the epiphyseal growth plates

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Noonan syndrome

• SC: 0.033-0.066mg/kg/day, until time of epiphyseal closure

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The dosage is individual and must always be adjusted in accordance with the individual's clinical and biochemical response to therapy

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Somatropin should only be prescribed by doctors with special knowledge of the therapeutic indication of use

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Generally, daily subcutaneous administration in the evening is recommended

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The injection site should be varied to prevent lipoatrophy

Pregnancy

• Caution; not recommended
• Animal studies are insufficient with regard to effects on pregnancy, embryo-foetal development, parturition or postnatal development. No clinical data on exposed pregnancies are available
• Somatropin containing products are not recommended during pregnancy and in women of childbearing potential not using contraception

Breastfeeding

• Caution
• There have been no clinical studies conducted with somatropin containing products in breastfeeding women. It is not known whether somatropin is excreted in human milk. Therefore caution should be exercised when somatropin containing products are administered to breastfeeding women

Fertility

• Fertility studies with somatropin have not been performed

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no dose adjustment recommended
  Consider initiating at a lower dose and up-titrating with smaller dose increments

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Paresthesia
• Benign intracranial hypertension

Cardiovascular Disorders

• Fluid retention with peripheral oedema

Hepatobiliary Disorders

• Increase in blood alkaline phosphatase

Endocrine and Metabolic Disorders

• Hypothyroidism
• Hyperglycaemia
• Diabetes mellitus
• Decreased serum thyroxin levels
• Increased growth of hands and feet (Turner syndrome)

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Joint stiffness
• Muscle stiffness
• Carpal tunnel syndrome
• Legg-Calvé-Perthes disease
• Scoliosis

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash (children)
• Benign and malignant neoplasms (including cysts and polyps)
• Injection site pain
• Injection site reaction (children)

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Antibody formation
• Leukaemia

Sensory Disorders

• Otitis media (Turner syndrome)

• Glucocorticoids
• Cortisone
• Gonadotropin
• Oestrogen
• Anabolic steroids
• Thyroid hormone
• CYP3A4 substrates
• Sex steroids
• Anticonvulsants  
• Cyclosporine
• Insulin

• Thyroid function
• IGF-1 concentration

None routine. Specific cases may require

• Blood glucose
• HbA1c
• Growth hormone secretory capacity
• Funduscopy
• Otological evaluation (Turner syndrome)
• Adrenal function
• Lipid profile
• Body Mass Index
• Blood pressure
• Heart rate
• Bone mineral density
• Renal function

Additional observations

• Signs of relapse of malignant disease
• Symptoms of intracranial hypertension
• Progression or recurrence underlying intracranial lesion
• Antibody development
• Growth
  - Children
  - Hands and feet (Turner syndrome)
• Progression of scoliosis (children)
• Pubertal development (children)

Considerations when treating children

• Children treated with somatropin should be regularly assessed by a specialist in child growth. Somatropin treatment should always be instigated by a doctor with special knowledge of growth hormone insufficiency and its treatment. This is true also for the management of Turner syndrome, chronic renal disease, small gestational weight and Noonan syndrome
• Data of final adult height following use are limited for children with Noonan syndrome and are not available for children with chronic renal disease
• The stimulation of longitudinal growth in children can only be expected until epiphyseal closure

Growth retardation in prepubertal children due to chronic renal disease 

• 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 somatropin treatment, renal function should be monitored for an excessive decline or increase in the glomerular filtration rate (which could imply hyperfiltration)

Women on oral oestrogen therapy

• When 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

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Precautions for handling 

• To ensure proper dosing and avoid injection of air, check the growth hormone flow before the first injection. Do not use if a drop of growth hormone does not appear at the needle tip
• A dose is to be selected by turning the dose selector until the desired dose appears at the window of the housing. The push button is then pressed to inject the dose
• Somatropin should not be shaken vigorously at any time
• Do not use if the solution for injection is cloudy or discoloured. Check this by turning the pen upside down once or twice

Precautions for storage

• Store in a refrigerator (2°C–8°C) and protect from light. Do not freeze
• When in use, always replace the pen cap on the pre-filled pen after each injection
• Always use a new needle for each injection. The needle must not be screwed onto the pre-filled pen when it is not in use

Somatropin, a human growth hormone produced by recombinant DNA-technology, stimulates skeletal and somatic growth with pronounced influence on the body's metabolic processes. Somatropin exerts most of its actions through insulin-like growth factor 1 (IGF-1), which is produced in tissues throughout the body but predominantly by the liver. A lipolytic and protein sparing effect of the hormone becomes of particular importance during stress. Somatropin also increases bone turnover indicated by an increase in plasma levels of biochemical bone markers.

Injection (per 1.5ml) 5mg

• Norditropin Nordiflex 5mg (Novo Nordisk) originator

Injection (per cartridge) 6mg

• Humatrope (Eli Lilly) originator

Injection (per 1.5ml) 10mg

• Norditropin Nordiflex 10mg (Novo Nordisk) originator
• Omnitrope (Sandoz)

Injection (per cartridge) 12mg

• Humatrope (Eli Lilly) originator

Injection (per 1.5ml) 15mg

• Omnitrope (Sandoz)

Injection (per ml) 16iu (5.3mg)

• Genotroptin (Pfizer) originator