Symptoms:
Acute overdosage could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdosage could result in signs and symptoms consistent with the known effects of human growth hormone excess.
3 years.
After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Powder (front compartment):
Glycine (E640)
Sodium dihydrogen phosphate anhydrous (E339)
Disodium phosphate anhydrous (E339)
Mannitol (E421)
Solvent (rear compartment):
Water for injections
Mannitol (E421)
In studies regarding general toxicity, local tolerance and reproduction toxicity no clinically relevant effects have been observed.
In vitro and in vivo genotoxicity studies on gene mutations and induction of chromosome aberrations have been negative.
An increased chromosome fragility has been observed in one in-vitro study on lymphocytes taken from patients after long term treatment with somatropin and following the addition of the radiomimetic drug bleomycin.The clinical significance of this finding is unclear.
In another study, no increase in chromosomal abnormalities was found in the lymphocytes of patients who had received long term somatropin therapy.
Pharmacotherapeutic group: Anterior pituitary lobe hormones and analogues, ATC code: H01A C01
Somatropin is a potent metabolic hormone of importance for the metabolism of lipids, carbohydrates and proteins. In children with inadequate endogenous growth hormone, somatropin stimulates linear growth and increases growth rate. In adults, as well as in children, somatropin maintains a normal body composition by increasing nitrogen retention and stimulation of skeletal muscle growth, and by mobilization of body fat. Visceral adipose tissue is particularly responsive to somatropin. In addition to enhanced lipolysis, somatropin decreases the uptake of triglycerides into body fat stores. Serum concentrations of IGF-I ,and IGFBP3 (Insulin-like Growth Factor Binding Protein 3) are increased by somatropin. In addition, the following actions have been demonstrated:
- Lipid metabolism: Somatropin induces hepatic LDL cholesterol receptors, and affects the profile of serum lipids and lipoproteins. In general, administration of somatropin to growth hormone deficient patients results in reductions in serum LDL and apolipoprotein B. A reduction in serum total cholesterol may also be observed.
- Carbohydrate metabolism: Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with hypopituitarism may experience fasting hypoglycemia. This condition is reversed by somatropin.
- Water and mineral metabolism: Growth hormone deficiency is associated with decreased plasma and extracellular volumes. Both are rapidly increased after treatment with somatropin. Somatropin induces the retention of sodium, potassium and phosphorus.
- Bone metabolism: Somatropin stimulates the turnover of skeletal bone. Long-term administration of somatropin to growth hormone deficient patients with osteopenia results in an increase in bone mineral content and density at weight-bearing sites.
- Physical capacity: Muscle strength and physical exercise capacity are improved after long-term treatment with somatropin. Somatropin also increases cardiac output, but the mechanism has yet to be clarified. A decrease in peripheral vascular resistance may contribute to this effect.
In clinical trials in short children born SGA doses of 0.033 and 0.067 mg/kg body weight per day have been used for treatment until final height. In 56 patients who were continuously treated and have reached (near) final height, the mean change from height at start of treatment was +1.90 SDS (0.033 mg/kg body weight per day) and +2.19 SDS (0.067 mg/kg body weight per day). Literature data from untreated SGA children without early spontaneous catch-up suggest a late growth of 0.5 SDS.
Absorption
The bioavailability of subcutaneously administered somatropin is approximately 80 % in both healthy subjects and growth hormone deficient patients. A subcutaneous dose of 0.035 mg/kg of somatropin results in plasma Cmax and tmax values in the range of 13-35 ng/ml and 3-6 hours respectively.
Elimination
The mean terminal half-life of somatropin after intravenous administration in growth hormone deficient adults is about 0.4 hours. However, after subcutaneous administration, half-lives of 2-3 hours are achieved. The observed difference is likely due to slow absorption from the injection site following subcutaneous administration.
Sub-populations
The absolute bioavailability of somatropin seems to be similar in males and females following s.c. administration.
Information about the pharmacokinetics of somatropin in geriatric and paediatric populations, in different races and in patients with renal, hepatic or cardiac insufficiency is either lacking or incomplete.
04/2018
Pfizer Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ
United Kingdom
Before reconstitution:
Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the syringe in the outer carton in order to protect from light.
Before opening, the product may be taken out of the refrigerator, without being replaced, for a maximum period of 6 months at a temperature not above 25°C. The date when the medicinal product is taken out and the new expiry date should be written on the outer packaging. This new expiry date should never exceed the one initially mentioned on the outer carton. If the medicinal product has not been used before the new expiry date, it should be disposed of.
After reconstitution:
Do not freeze.
Powder and 0.25 ml solvent in a two chamber glass cartridge (type I glass) separated by a rubber plunger (bromobutyl), supplied as a single dose syringe. The cartridge is sealed at both ends with rubber stoppers (bromobutyl) and is enclosed in a plastic sleeve with a plunger rod and a finger grip.
7 x 0.2 mg, 28 (4 x 7 x 0.2 mg)
Not all pack sizes may be marketed.
PL 00057/0989
Only reconstitute the powder with the solvent supplied.
The solution is prepared by screwing the plunger rod inwards so that the solvent will be mixed with the powder in the two chamber cartridge. Do not shake vigorously; this might cause denaturation of the active ingredient. The injection needle should be screwed on before reconstitution. The reconstituted solution is colourless or slightly opalescent. The reconstituted solution for injection is to be inspected prior to use and only clear solutions without particles should be used.
Comprehensive instructions for the preparation and administration of the reconstituted Genotropin product are given in the package leaflet, section 3, “Injecting genotropin†and in the relevant Instructions for Use.
GENOTROPIN MINIQUICK is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
14 September 1998/20 April 2010
