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        4.3     Contraindications

-                 Somatropin must not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and anti tumour therapy must be completed prior to starting GH therapy. Treatment should be discontinued if there is evidence of tumour growth.


4.4     Special warnings and precautions for use

Acute critical illness

The effects of somatropin on recovery were studied in two placebo controlled trials involving 522 critically ill adult patients suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. Mortality was higher in patients treated with 5.3 or 8 mg somatropin daily compared to patients receiving placebo, 42% vs. 19%. Based on this information, these types of patients should not be treated with somatropin. As there is no information available on the safety of growth hormone substitution therapy in acutely critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved.

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

The maximum recommended daily dose should not be exceeded (see section 4.2).

Elderly

Experience in patients above 60 years is limited.

Renal impairment

In chronic renal insufficiency, renal function should be below 50 percent of normal before institution of therapy. To verify growth disturbance, growth should be followed for a year preceding institution of therapy. During this period, conservative treatment for renal insufficiency (which includes control of acidosis, hyperparathyroidism and nutritional status) should have been established and should be maintained during treatment.

The treatment should be discontinued at renal transplantation.

To date, no data on final height in patients with chronic renal insufficiency treated with Omnitrope are available.

4.6     Fertility, pregnancy and lactation

Fertility

Fertility studies with Omnitrope have not been performed.

4.8     Undesirable effects

Patients with growth hormone deficiency are characterized by extracellular volume deficit. When treatment with somatropin is started this deficit is rapidly corrected. In adult patients adverse effects related to fluid retention, such as peripheral oedema, stiffness in the extremities, arthralgia, myalgia and paraesthesia are common. In general these adverse effects are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose-reduction.

The incidence of these adverse effects is related to the administered dose, the age of patients, and possibly inversely related to the age of patients at the onset of growth hormone deficiency. In children such adverse effects are uncommon.

Omnitrope has given rise to the formation of antibodies in approximately 1 % of the patients. The binding capacity of these antibodies has been low and no clinical changes have been associated with their formation, see section 4.4.

The following undesirable effects have been observed and reported during treatment with Omnitrope with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Neoplasms benign, malignant and unspecified (including cysts and polyps):

Very rare: Leukemia*

Immune system disorders:

Common: Formation of antibodies

Endocrine disorders:

Rare: Diabetes mellitus type II

Nervous system disorders:

Common: In adults: paraesthesia

Uncommon: In adults: carpal tunnel syndrome. In children: paraesthesia

Rare: Benign intracranial hypertension

Skin and subcutaneous tissue disorders:

Common: In children: transient local skin reactions

Musculoskeletal and connective tissue disorders:

Common: In adults: stiffness in the extremities, arthralgia, myalgia

Uncommon: In children: stiffness in the extremities, arthralgia, myalgia

General disorders and administration site conditions:

Common: In adults: peripheral oedema

Uncommon: In children: peripheral oedema

Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increased hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of therapy.

^*Very rare cases of leukemia have been reported in growth hormone deficient children treated with Omnitrope, but the incidence appears to be similar to that in children without growth hormone deficiency, see section 4.4.

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 12 April 2006

Date of latest renewal:  28 February 2011

11.             DATE OF REVISION OF THE TEXT

28 February 2011

Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu/