ZOMACTON- somatropin
Ferring Pharmaceuticals Inc.
DESCRIPTION
ZOMACTON� [somatropin (rDNA origin)] for Injection, a polypeptide of recombinant DNA origin, has 191 amino acid residues and a molecular weight of about 22,124 daltons. It has an amino acid sequence identical to that of human growth hormone of pituitary origin. ZOMACTON is a strain of Escherichia coli modified by insertion of the human growth hormone gene.
ZOMACTON is a sterile, white, lyophilized powder, intended for subcutaneous administration, after reconstitution with the accompanying diluent.
ZOMACTON 5 mg vial contains recombinant somatropin 5 mg and mannitol 30 mg. The 5 mg vial is supplied in a combination package with an accompanying 5 mL vial of diluting solution. The diluent contains bacteriostatic 0.9% sodium chloride injection, USP, (normal saline), 0.9% benzyl alcohol as a preservative, and water for injection.
ZOMACTON 10 mg vial contains recombinant somatropin 10 mg, mannitol 10 mg, disodium phosphate dodecahydrate 3.57 mg, and sodium dihydrogen phosphate dehydrate 0.79 mg. The 10 mg vial is supplied in a combination package with an accompanying 1 mL syringe of diluting solution. The diluent contains bacteriostatic water for injection with 0.33% metacresol as a preservative.
ZOMACTON is a highly-purified preparation. Reconstituted solutions have a pH in the range of 7.0 to 9.0.
CLINICAL PHARMACOLOGY
Clinical trials have demonstrated that ZOMACTON is equivalent in its therapeutic effectiveness and in its pharmacokinetic profile to those of human growth hormone of pituitary origin (somatropin). ZOMACTON stimulates linear growth in children who lack adequate levels of endogenous growth hormone. Treatment of growth hormone-deficient children with ZOMACTON produces increased growth rates and IGF-1 (Insulin-Like Growth Factor-1) concentrations that are similar to those seen after therapy with human growth hormone of pituitary origin.
Both ZOMACTON and somatropin have also been shown to have other actions including:
A.
Tissue Growth
Skeletal Growth. ZOMACTON stimulates skeletal growth in patients with growth hormone deficiency. The measurable increase in body length after administration of ZOMACTON results from its effect on the epiphyseal growth plates of long bones. Concentration of IGF-1, which may play a role in skeletal growth, are low in the serum of growth hormone-deficient children but increase during treatment with ZOMACTON. Mean serum alkaline phosphatase concentrations are increased.
Cell Growth. It has been shown that there are fewer skeletal muscle cells in short statured children who lack endogenous growth hormone as compared with normal children. Treatment with somatropin results in an increase in both the number and size of muscle cells.
Organ Growth. Somatropin influences the size of internal organs and it also increases red cell mass.
B.
Protein Metabolism
Linear growth is facilitated, in part, by increased cellular protein synthesis. Nitrogen retention, as demonstrated by decreased urinary nitrogen excretion and serum urea nitrogen, results from treatment with somatropin.
C.
Carbohydrate Metabolism
Children with hypopituitarism sometimes experience fasting hypoglycemia that is improved by treatment with somatropin. Large doses of somatropin may impair glucose tolerance.
D.
Lipid Metabolism
Administration of somatropin to growth hormone-deficient patients mobilizes lipid, reduces body fat stores, and increases plasma fatty acids.
E.
Mineral Metabolism
Sodium, potassium, and phosphorous are conserved by somatropin. Serum concentrations of inorganic phosphates increased in patients with growth hormone deficiency after therapy with ZOMACTON or somatropin. Serum calcium concentrations are not significantly altered in patients treated with either somatropin or ZOMACTON.
F.
Connective Tissue Metabolism
Somatropin stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.
PHARMACOKINETICS
Following intravenous administration of 0.1 mg/kg of ZOMACTON, the elimination half-life was about 0.42 hours (approximately 25 minutes) and the mean plasma clearance (�SD) was 133 (�16) mL/min in healthy male volunteers.
In the same volunteers, after a subcutaneous injection of 0.1 mg/kg ZOMACTON to the forearm, the mean peak serum concentration (�SD) was 80 (�50) ng/mL which occurred approximately 7 hours post-injection and the apparent elimination half-life was approximately 2.7 hours. Compared to intravenous administration, the extent of systemic availability from subcutaneous administration was approximately 70%.
INDICATION AND USAGE
ZOMACTON is indicated for the treatment of children who have growth failure due to an inadequate secretion of normal endogenous growth hormone.
DOSAGE AND ADMINISTRATION
The recommended dose is up to 0.1 mg/kg administered subcutaneously three (3) times per week ( up to 0.3 mg/kg/week).
ZOMACTON 5 mg should be reconstituted with 1-5 mL of bacteriostatic 0.9% sodium chloride for injection, USP (benzyl alcohol preserved). Reconstituted ZOMACTON 5 mg vials should not be used if the patient has a known sensitivity to benzyl alcohol. Benzyl alcohol as a preservative in bacteriostatic normal saline, USP, has been associated with toxicity in newborns. WHEN ADMINISTERING ZOMACTON TO NEWBORNS, RECONSTITUTE WITH STERILE NORMAL SALINE FOR INJECTION, USP.
ZOMACTON 10 mg should be reconstituted with 1 mL syringe of bacteriostatic water for injection containing 0.33% metacresol as a preservative. Reconstituted ZOMACTON 10 mg vials should not be used if the patient is allergic to metacresol.
The stream of normal saline should be aimed against the side of the vial to prevent foaming. Swirl the vial with a GENTLE rotary motion until the contents are completely dissolved and the solution is clear. DO NOT SHAKE. Since ZOMACTON is a protein, shaking or vigorous mixing will cause the solution to be cloudy. If the resulting solution is cloudy or contains particulate matter, the contents MUST NOT be injected.
Occasionally, after refrigeration, some cloudiness may occur. This is not unusual for proteins like ZOMACTON. Allow the product to warm to room temperature. If cloudiness persists or particulate matter is noted, the contents MUST NOT be used.
Before and after injection, the septum of the vial should be wiped with rubbing alcohol or an alcoholic antiseptic solution to prevent contamination of the contents by repeated needle insertions.
ZOMACTON 5 mg and 10 mg can be administered using a standard sterile disposable syringe or a ZOMA-Jet� Needle-Free injection device. For proper use, please refer to the User's Manual provided with the administration device.
STABILITY AND STORAGE
Before Reconstitution
Vials of ZOMACTON (5 and 10 mg) are stable when refrigerated at 36� to 46�F (2� to 8�C). Avoid freezing the accompanying diluent. Expiration dates are stated on the labels.
