Saizen®
[somatropin (rDNA origin) for injection]
For subcutaneous or intramuscular injection

DESCRIPTION
Saizen® [somatropin (rDNA origin) for injection] is a human growth hormone produced by recombinant DNA technology.  Saizen® has 191 amino acid residues and a molecular weight of 22,125 daltons.  Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone.  Saizen® is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the human growth hormone gene.  Saizen®, with the correct three-dimensional configuration, is secreted directly through the cell membrane into the cell-culture medium for collection and purification.

Saizen® is a highly purified preparation. Biological potency is determined by measuring the increase in body weight induced in hypophysectomized rats.

Saizen® is a sterile, non pyrogenic, white, lyophilized powder intended for subcutaneous or intramuscular injection after reconstitution with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol).  The reconstituted solution has a pH of 6.5 to 8.5.

Saizen® is available in 5 mg and 8.8 mg vials.  The quantitative composition per vial is:

5 mg vial:

Each vial contains 5.0 mg somatropin, 34.2 mg sucrose and 1.16 mg O-phosphoric acid.  The pH is adjusted with sodium hydroxide or O-phosphoric acid.

8.8 mg vial:

Each vial contains 8.8 mg somatropin, 60.2 mg sucrose and 2.05 mg O-phosphoric acid.  The pH is adjusted with sodium hydroxide or O-phosphoric acid.

The diluent is Bacteriostatic Water for Injection, USP containing 0.9% Benzyl Alcohol added as an antimicrobial preservative.

Saizen® is also available in the click.easy® reconstitution device.  The quantitative composition per vial contained in the click.easy® reconstitution device is:

8.8 mg vial contained in the click.easy® device:

Each vial contains 8.8 mg somatropin, 60.2 mg sucrose and 2.05 mg O-phosphoric acid.  The pH is adjusted with sodium hydroxide or O-phosphoric acid.

The diluent contained in click.easy® device is 0.3% (w/v) metacresol in Sterile Water for Injection added as an antimicrobial preservative.  The reconstituted solution has a pH of 6.5 to 8.5.

CLINICAL PHARMACOLOGY
General

In vitro, preclinical, and clinical testing have demonstrated that Saizen® [somatropin (rDNA origin) for injection] is therapeutically equivalent to pituitary-derived human growth hormone.  Clinical studies in normal adults also demonstrated equivalent pharmacokinetics.

Actions that have been demonstrated for Saizen®, somatrem, and/or pituitary-derived human growth hormone include:

Tissue Growth–
Skeletal Growth:  Saizen® stimulates skeletal growth in prepubertal children with pituitary growth hormone deficiency.  Skeletal growth is accomplished at the epiphyseal plates at the ends of long bone.  Growth and metabolism of epiphyseal plate cells are directly stimulated by growth hormone and one of its mediators, insulin-like growth factor-I.  Serum levels of insulin-like growth factor-I (IGF-I) are low in children and adolescents who are growth hormone deficient, but increase during treatment with Saizen®.  Linear growth continues until the