GENOTROPIN (somatropin for injection) is a polypeptide hormone of recombinant DNA origin. It has 191 amino acid residues, a molecular weight of 22,124 daltons, and an isoelectric point (pH) of 5.0. The amino acid sequence of the product is identical to that of human growth hormone of pituitary origin (somatropin). GENOTROPIN is synthesized in a strain of Escherichia coli that has been modified by the addition of the gene for human growth hormone.

GENOTROPIN (somatropin for injection) is indicated for:

Children

The long‑term treatment of children who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency (GHD)). Other causes of short stature should be excluded.

SGA Indication

GENOTROPIN is indicated for the treatment of growth failure (current height standard deviation score [SDS] < - 2) in short children born SGA (birth weight and/or length below -2 SD) and who fail to achieve catch-up growth (height velocity SDS < 0 during the last year) by 2 to 4 years or later.

TS Indication

The treatment of short stature associated with Turner syndrome in patients whose epiphyses are not closed.

ISS Indication

The long-term treatment of idiopathic short stature (ISS), also called non-growth hormone-deficient short stature, defined by height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in pediatric patients for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means. Genotropin treatment for ISS should be prescribed only for those patients whose epiphyses are not closed.

PWS Indication

GENOTROPIN is indicated for the treatment of pediatric patients who have growth failure due to Prader-Willi syndrome (PWS). The diagnosis of PWS should be confirmed by appropriate genetic testing. GENOTROPIN is also indicated for improvement of body composition in children with Prader-Willi syndrome.

Adults

GENOTROPIN (somatropin [rDNA origin] for injection) is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following two criteria:

Adult Onset (AO): Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or

Childhood Onset (CO): Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes.

Patients who were treated with somatropin for growth hormone deficiency in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for growth hormone deficient adults. According to current standards, confirmation of the diagnosis of adult growth hormone deficiency in both groups involves an appropriate growth hormone provocative test with two exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

Geriatrics

The safety and effectiveness of GENOTROPIN in patients aged 65 and over have not been evaluated in clinical studies. (see WARNINGS AND PRECAUTIONS, Special Populations, Geriatrics).

Therapy with GENOTROPIN (somatropin for injection) should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with growth failure associated with growth hormone deficiency (GHD), Turner syndrome (TS), those who were born small for gestational age (SGA) or Idiopathic Short Stature (ISS), and adult patients with either childhood onset or adult onset GHD.

The GENOTROPIN dosage and administration schedule should be individualized based on the growth response of each patient.

Response to somatropin therapy in pediatric patients tends to decrease with time. However, in pediatric patients, the failure to increase growth rate, particularly during the first year of therapy, indicates the need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age and antibodies to recombinant human GH (rhGH).

Treatment with GENOTROPIN for short stature should be discontinued when the epiphyses are fused.

Recommended Dose and Dosage Adjustment

The recommended dosage of GENOTROPIN

Adults Growth Hormone Deficiency
Clinical response, side effects and determination of IGF-1 in serum may be used as guidance for dose titration. The level of IGF-1 should not exceed the upper limit of normal IGF-1 levels matched to age and sex.

It is recommended that IGF-I concentrations be monitored regularly and GH dose be reduced in children with a plasma IGF-1 above + 2SD.

Small for Gestational Age
Recent literature has recommended initial treatment with larger doses of somatropin (e.g., 0.48 mg/kg/week), especially in very short children (i.e., height SDS <–3), and/or older/ pubertal children, and that a reduction in dosage (e.g., gradually towards 0.24 mg/kg/week) should be considered if substantial catch-up growth is observed during the first few years of therapy. On the other hand, in younger SGA children (e.g., approximately

Dosing should continue until final height is reached (see DETAILED PHARMACOLOGY, Human Pharmacology, Pharmacodynamics). Treatment should be discontinued after the first year of treatment if the height velocity SDS is below + 1. 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.

In short children born SGA, it is recommended that IGF I concentration be measured before initiation of treatment and monitored every 6 months thereafter. If on repeated measurements IGF-I concentrations 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.

Administration

See CONSUMER INFORMATION for detailed information.

All parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. If the solution is cloudy, the contents MUST NOT be injected.