Human growth hormone (somatropin) for the treatment of growth failure in children

In the UK, seven preparations of somatropin are available: Genotropin, Pfizer; Humatrope, Lilly; Norditropin, Novo Nordisk; NutropinAq, Ipsen; Omnitrope, Sandoz; Saizen, Merck Serono; Zomacton, Ferring. Each product is produced by recombinant DNA technology and has a sequence identical to that of human growth hormone produced by the pituitary gland. The licensed indications are as follows (for the different products the wording may differ):

• growth disturbance in children due to insufficient secretion of growth hormone (growth hormone deficiency).

• growth failure in girls associated with gonadal dysgenesis (Turner syndrome).

• growth retardation in prepubertal children associated with chronic renal insufficiency (CRI).

• improvement of growth and body composition in children with Prader–Willi syndrome. The diagnosis of Prader–Willi syndrome should be confirmed by appropriate genetic testing.

• growth disturbance (current height standard deviation score [SDS] less than -2.5 and parental adjusted height SDS less than -1) in short children born small for gestational age, with a birth weight and/or length below -2 SD, who failed to show catch‑up growth (height velocity SDS less than 0 during the past year) by 4 years of age or later.

• growth failure associated with SHOX deficiency, as confirmed by DNA analysis.

The seven manufacturers have UK marketing authorisations for somatropin for the following indications:

• Lilly (Humatrope): growth hormone deficiency; Turner syndrome; CRI; short children born small for gestational age and SHOX deficiency.

• Ferring (Zomacton): growth hormone deficiency and Turner syndrome.

• Ipsen (NutropinAq): growth hormone deficiency; Turner syndrome and CRI.

• Novo Nordisk (Norditropin SimpleXx): growth hormone deficiency; Turner syndrome; CRI and short children born small for gestational age.

• Pfizer (Genotropin): growth hormone deficiency; Turner syndrome; CRI; Prader–Willi syndrome and short children born small for gestational age.

• Sandoz (Omnitrope): growth hormone deficiency; Turner syndrome; CRI; Prader–Willi syndrome and short children born small for gestational age. Note: Omnitrope is a 'similar biological medicinal product' or 'biosimilar'. Genotropin is the biological reference medicine for Omnitrope. British national formulary 58 states the following: A similar biological medicinal product is a new biological product that is similar to a medicine that has already been authorised to be marketed (the 'biological reference medicine') in the European Union. The active substance of a biosimilar medicine is similar, but not identical, to the biological reference medicine. Biological products are different from standard chemical products in terms of their complexity and although theoretically there should be no important differences between the biosimilar and the biological reference medicine in terms of safety or efficacy, when prescribing biological products, it is good practice to use the brand name. This will ensure that substitution of a biosimilar medicine does not occur when the medicine is dispensed.

• Merck Serono (Saizen): growth hormone deficiency; Turner syndrome; CRI and short children born small for gestational age.

The summary of product characteristics for somatropin states that the dosage and the administration of somatropin should be tailored to the needs of each individual child. The dosage varies according to the condition being treated: 23 to 39 microgram per kg daily or 0.7 to 1.0 mg per m² daily for growth hormone deficiency; 45 to 50 microgram per kg daily or 1.4 mg per m² daily for Turner syndrome and CRI; 35 microgram/kg daily or 1.0 mg per m² daily for growth disturbance in children born small for gestational age; 35 microgram per kg daily or 1.0 mg per m² daily (with a maximum of 2.7 mg daily) for Prader–Willi syndrome; and 45 to 50 microgram per kg daily for SHOX deficiency. Somatropin is self‑administered or given to the child by an adult, at home, usually as a subcutaneous injection, 6 to 7 times a week.

The summary of product characteristics for somatropin states that side effects include headache, visual problems, nausea and vomiting, fluid retention (peripheral oedema), arthralgia, myalgia, carpal tunnel syndrome, paraesthesia, antibody formation, hypothyroidism and reactions at injection site. Paediatricians should pay particular attention when giving somatropin to children with diabetes mellitus or its risk factors, slipped capital epiphyses, idiopathic intracranial hypertension or malignancies. For full details of side effects and contraindications, see the summary of product characteristics.

The cost of treatment with somatropin depends on the dose, which is determined by the weight or body surface area of the child as well as by the indication for growth hormone treatment. The costs of the different somatropin products (excluding VAT; BNF edition 58) are: £23.18 per mg for Genotropin, £18.00 per mg for Humatrope, £21.39 per mg for Norditropin (since January 2010 £21.27 per mg), £20.70 per mg for Nutropin, £18.26 per mg for Omnitrope, £23.18 per mg for Saizen and £19.92 per mg for Zomacton. Costs may vary in different settings because of negotiated procurement discounts.