ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Omnitrope 1.3 mg/ml powder and solvent for solution for injection
2.
After reconstitution, one vial contains 1.3 mg somatropin* (corresponding to 4 IU) per ml.
* produced in
Escherichia coli
by recombinant DNA technology.
For a full list of excipients, see section 6.1.
3.
Powder and solvent for solution for injection.
The powder is white.
The solvent is clear and colourless.
4.
Infants, children and adolescents
-
Growth disturbance due to insufficient secretion of growth hormone (GH).
-
Growth disturbance associated with Turner syndrome.
-
Growth disturbance associated with chronic renal insufficiency.
-
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted
SDS < -1) in short children/adolescents born small for gestational age (SGA), with a birth
weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth
(height velocity (HV) SDS < 0 during the last year) by 4 years of age or later.
-
Prader-Willi syndrome (PWS), for improvement of growth and body composition. The
diagnosis of PWS should be confirmed by appropriate genetic testing.
Adults
-
Replacement therapy in adults with pronounced growth hormone deficiency. Patients with
severe growth hormone deficiency in adulthood are defined as patients with known
hypothalamic pituitary pathology and at least one known deficiency of a pituitary hormone not
being prolactin. These patients should undergo a single dynamic test in order to diagnose or
exclude a growth hormone deficiency. In patients with childhood onset isolated GH deficiency
(no evidence of hypothalamic-pituitary disease or cranial irradiation), two dynamic tests should
be recommended, except for those having low IGF-I concentrations (SDS < -2) who may be
considered for one test. The cut-off point of the dynamic test should be strict.
Diagnosis and therapy with somatropin should be initiated and monitored by physicians who are
appropriately qualified and experienced in the diagnosis and management of patients with growth
disorders.
2
Posology
Paediatric population
The posology and administration schedule should be individualised.
Growth disturbance due to insufficient secretion of growth hormone in paediatric patients
Generally a dose of 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m
2
body surface area per
day is recommended. Even higher doses have been used.
Prader-Willi syndrome, for improvement of growth and body composition in paediatric patients
Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m
2
body surface area per day is
recommended. Daily doses of 2.7 mg should not be exceeded. Treatment should not be used in
paediatric patients with a growth velocity less than 1 cm per year and near closure of epiphyses.
Growth disturbance due to Turner syndrome
A dose of 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m
2
body surface area per day is
recommended.
Growth disturbance in chronic renal insufficiency
A dose of 1.4 mg/m
2
body surface area per day (0.045 - 0.050 mg/kg body weight per day) is
recommended. Higher doses may be needed if growth velocity is too low. A dose correction may be
needed after six months of treatment (see section 4.4).
Growth disturbance in short children/adolescents born small for gestational age (SGA)
A dose of 0.035 mg/kg body weight per day (1 mg/m
2
body surface area per day) is usually
recommended until final height is reached (see section 5.1). 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 epiphyseal closure.
Dose recommendations for paediatric patients
Indication
mg/kg body weight dose
per day
mg/m² body surface
area dose per day
Growth hormone deficiency
0.025 - 0.035
0.7 - 1.0
Prader-Willi syndrome
0.035
1.0
Turner syndrome
0.045 - 0.050
1.4
Chronic renal insufficiency
0.045 - 0.050
1.4
Children/adolescents born small for
gestational age (SGA)
0.035
1.0
Growth hormone deficient adult patients
Therapy should start with a low dose, 0.15 - 0.3 mg per day. The dose should be gradually increased
according to individual patient requirements as determined by the IGF-I concentration. Treatment goal
should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean
of healthy adults. Patients with normal IGF-I concentrations at the start of the treatment should be
administered growth hormone up to an IGF-I level into the upper range of normal, not exceeding the
2 SDS. Clinical response and side effects may also be used as guidance for dose titration. The daily
maintenance dose rarely exceeds 1.0 mg per day. Women may require higher doses than men, while
men show an increasing IGF-I sensitivity over time. This means that there is a risk that women,
especially those on oral oestrogen replacement are under-treated while men are over-treated. The
accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal
physiological growth hormone production decreases with age, dose requirements may be reduced. The
minimum effective dose should be used.
3
Special populations
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.
Method of administration
The injection should be given subcutaneously and the site varied to prevent lipoatrophy.
For instructions for use and handling see section 6.6.
-
Hypersensitivity to somatropin or to any of the excipients.
-
Somatropin must not be used when there is any evidence of tumour activity and anti-tumour
therapy must be completed prior to starting therapy.
-
Somatropin must not be used for growth promotion in patients with closed epiphyses.
-
Patients with acute critical illness suffering complications following open heart surgery,
abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions
must not be treated with somatropin. With regard to patients undergoing substitution therapy,
see section 4.4.
Insulin sensitivity
Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore
patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria
for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such
as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired
glucose tolerance have been present in most cases where this occurred. In patients with already
manifested diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is
instituted.
Thyroid function
During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result
in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral
thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of
somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical
hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving
replacement therapy with thyroxin mild hyperthyroidism may occur. It is therefore particularly
advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.
4
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or
by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless,
corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.
In growth hormone deficiency, secondary to treatment of malignant disease, it is recommended to pay
attention to signs of relapse of the malignancy.
In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the
hip may occur more frequently than in the general population. Patients limping during treatment with
somatropin, should be examined clinically.
Benign intracranial hypertension
In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for
papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial
hypertension should be considered and, if appropriate, the growth hormone treatment should be
discontinued. At present there is insufficient evidence to give specific advice on the continuation of
growth hormone treatment in patients with resolved intracranial hypertension. However, clinical
experience has shown that reinstitution of the therapy is often possible without recurrence of the
intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms
of intracranial hypertension is necessary.
Paediatric population
Prader-Willi syndrome
In patients with PWS, treatment should always be in combination with a calorie-restricted diet.
There have been reports of fatalities associated with the use of growth hormone in paediatric patients
with PWS who had one or more of the following risk factors: severe obesity, history of respiratory
impairment, sleep apnoea or unidentified respiratory infection. Patients with PWS and one or more of
these risk factors may be at greater risk.
Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory
infections before initiation of treatment with somatropin.
In case of signs of upper airway obstruction, the problem should be solved by a specialist before
starting treatment with somatropin.
Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods
such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.
If during treatment with somatropin patients show signs of upper airway obstruction (including onset
of or increased snoring), treatment should be interrupted, and a new ENT assessment performed.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is
suspected.
All patients with PWS should be monitored for signs of respiratory infections which should be
diagnosed as early as possible and treated aggressively.
All patients with PWS should have effective weight control before and during treatment with
somatropin.
Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth.
Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not
been shown to increase the incidence or severity of scoliosis.
Experience with long term treatment in adults and in patients with PWS is limited.
5
Small for gestational age
In short children/adolescents born SGA, other medical reasons or treatments that could explain growth
disturbance should be ruled out before starting treatment.
In SGA children/adolescents it is recommended to measure fasting insulin and blood glucose before
start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g.
familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose
tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not
be administered.
In SGA children/adolescents it is recommended to measure the IGF-I level before start of treatment
and twice a year thereafter. If on repeated measurements IGF-I levels 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.
Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not
recommended to initiate treatment near onset of puberty. Experience in patients with Silver-Russell
syndrome is limited.
Some of the height gain obtained with treating short children/adolescents born SGA with growth
hormone may be lost if treatment is stopped before final height is reached.
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.
Data from an interaction study performed in growth hormone deficient adults suggests that somatropin
administration may increase the clearance of compounds known to be metabolised by cytochrome
P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex
steroids, corticosteroids, anticonvulsants and ciclosporin) may be especially increased resulting in
lower plasma levels of these compounds. The clinical significance of this is unknown.
Also see section 4.4 for statements regarding diabetes mellitus and thyroid disorder and section 4.2 for
statement on oral oestrogen replacement therapy.
Pregnancy
For Omnitrope no clinical data on exposed pregnancies are available. Animal experimental data on
reproductive toxicity of Omnitrope are not available. Treatment with Omnitrope should be interrupted
if pregnancy occurs.
During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks,
being replaced almost entirely by placental growth hormone by 30 weeks. In view of this, it is unlikely
that continued replacement therapy with somatropin would be necessary in growth hormone deficient
women in the third trimester of pregnancy.
6
Breastfeeding
It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the
gastrointestinal tract of the infant is extremely unlikely.
Caution should be exercised when Omnitrope is administered to breast-feeding women.
Fertility
Fertility studies with Omnitrope have not been performed.
No studies on the effects on the ability to drive and use machines have been performed.
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
7
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.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdose could result in signs and symptoms consistent with the known effects of human
growth hormone excess.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, anterior pituitary
lobe hormones and analogues. ATC code: H01AC01.
Omnitrope is a biosimilar medicinal product. Detailed information is available on the website of the
European Medicines Agency
http://www.ema.europa.eu
Mechanism of action
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
mobilisation 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 (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor
Binding Protein 3) are increased by somatropin. In addition, the following actions have been
demonstrated.
Pharmacodynamic effects
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
reduction in serum LDL and apolipoprotein B. A reduction in serum total cholesterol may also be
observed.
8
Carbohydrate metabolism
Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with
hypopituitarism may experience fasting hypoglycaemia. 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 osteopoenia 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.
Clinical efficacy and safety
In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg somatropin/kg
body weight per day have been used for treatment until final height is reached. In 56 patients who are
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/adolescents without early spontaneous
catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.
5.2 Pharmacokinetic properties
Absorption
The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy
subjects and growth hormone deficient patients. A subcutaneous dose of 5 mg of Omnitrope powder
and solvent for solution for injection in healthy adults results in plasma Cmax values of 71 ± 24 µg/l
(mean ± SD) and median tmax value of 4 hours (range 2-8 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 of Omnitrope powder
and solvent for solution for injection, a half-life of 3 hours is 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
subcutaneous 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.
5.3 Preclinical safety data
In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant
effects have been observed.
In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity
no clinically relevant effects have been observed.
9
With somatropins, 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 medicinal product bleomycin. The clinical significance of this finding is unclear.
In another study with somatropin, no increase in chromosomal abnormalities was found in the
lymphocytes of patients who had received long-term somatropin therapy.
6.
6.1 List of excipients
Powder:
glycine
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
Solvent:
water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
2 years.
Shelf life after reconstitution:
After reconstitution, from a microbiological point of view, an immediate use is recommended.
However, the in-use stability has been demonstrated for up to 24 hours at 2°C - 8°C, in the original
package. Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original package in
order to protect from light.
6.4 Special precautions for storage
Unopened vial: Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original
package in order to protect from light.
For storage conditions of the in-use medicinal product, see section 6.3.
6.5 Nature and contents of container
Powder in a vial (type I glass) with a stopper (fluor-resin laminated butyl rubber), a strip (aluminium)
and a cap (violet polypropylene flip-off), and 1 ml of solvent in a vial (type I glass) with a stopper
(fluor-resin laminated chlorobutyl elastomer), a strip (lacquered aluminium) and a cap (white
polypropylene flip-off).
Pack size of 1.
6.6 Special precautions for disposal and other handling
Omnitrope 1.3 mg/ml is supplied in a vial containing the active substance as a powder and the solvent
filled in a vial for single use. Each vial must be reconstituted with the accompanying solvent only.
The reconstituted solution should be administered using sterile, disposable syringes.
10
The following is a general description of the reconstitution and administration process. Reconstitution
should be performed in accordance with good practice rules, particularly in the respect of asepsis.
1.
Hands should be washed.
2.
Flip off the plastic protective caps from the vials.
3.
The top of the vials should be wiped with an antiseptic solution to prevent contamination of the
contents.
4.
Use a sterile, disposable syringe (e.g. 2 ml syringe) and needle (e.g. 0.33 mm x 12.7 mm) to
withdraw all the solvent from the vial.
5.
Take the vial with the powder, push the needle through the rubber closure and inject the solvent
slowly into the vial aiming the stream of liquid against the glass wall in order to avoid foam.
6.
Gently swirl the vial a few times until the content is completely dissolved. Do not shake; this
may cause denaturation of the active substance.
7.
If the solution is cloudy or contains particulate matter, it should not be used. The content must
be clear and colourless after reconstitution.
8.
Turn the vial upside down and using another sterile, disposable syringe of appropriate size (e.g.
1 ml syringe) and injection needle (e.g. 0.25 mm x 8 mm) withdraw a bit more than the dose
needed back into the syringe. Remove any air bubbles from the syringe. Bring the syringe to the
correct dose needed.
9.
Clean the injection site with an alcohol swab and administer Omnitrope by subcutaneous
injection.
The solution is for single use only. Any unused product or waste material should be disposed of in
accordance with local requirements.
7.
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
8.
EU/1/06/332/001
9.
Date of first authorisation: 12 April 2006
Date of latest renewal:
Detailed information on this product is available on the website of the European Medicines Agency
11
1.
Omnitrope 5 mg/ml powder and solvent for solution for injection
2.
After reconstitution, one vial contains 5 mg somatropin* (corresponding to 15 IU) per ml.
* produced in
Escherichia coli
by recombinant DNA technology.
Excipients:
After reconstitution, one ml contains 15 mg benzyl alcohol.
For a full list of excipients, see section 6.1.
3.
Powder and solvent for solution for injection
The powder is white.
The solvent is clear and colourless.
4.
Infants, children and adolescents
-
Growth disturbance due to insufficient secretion of growth hormone (GH).
-
Growth disturbance associated with Turner syndrome.
-
Growth disturbance associated with chronic renal insufficiency.
-
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted
SDS < -1) in short children/adolescents born small for gestational age (SGA), with a birth
weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth
(height velocity (HV) SDS < 0 during the last year) by 4 years of age or later.
-
Prader-Willi syndrome (PWS), for improvement of growth and body composition. The
diagnosis of PWS should be confirmed by appropriate genetic testing.
Adults
-
Replacement therapy in adults with pronounced growth hormone deficiency. Patients with
severe growth hormone deficiency in adulthood are defined as patients with known
hypothalamic pituitary pathology and at least one known deficiency of a pituitary hormone not
being prolactin. These patients should undergo a single dynamic test in order to diagnose or
exclude a growth hormone deficiency. In patients with childhood onset isolated GH deficiency
(no evidence of hypothalamic-pituitary disease or cranial irradiation), two dynamic tests should
be recommended, except for those having low IGF-I concentrations (SDS < -2) who may be
considered for one test. The cut-off point of the dynamic test should be strict.
Diagnosis and therapy with somatropin should be initiated and monitored by physicians who are
appropriately qualified and experienced in the diagnosis and management of patients with growth
disorders.
12
Posology
Paediatric population
The posology and administration schedule should be individualised.
Growth disturbance due to insufficient secretion of growth hormone in paediatric patients
Generally a dose of 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m
2
body surface area per
day is recommended. Even higher doses have been used.
Prader-Willi syndrome, for improvement of growth and body composition in paediatric patients
Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m
2
body surface area per day is
recommended. Daily doses of 2.7 mg should not be exceeded. Treatment should not be used in
paediatric patients with a growth velocity less than 1 cm per year and near closure of epiphyses.
Growth disturbance due to Turner syndrome
A dose of 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m
2
body surface area per day is
recommended.
Growth disturbance in chronic renal insufficiency
A dose of 1.4 mg/m
2
body surface area per day (0.045 - 0.050 mg/kg body weight per day) is
recommended. Higher doses may be needed if growth velocity is too low. A dose correction may be
needed after six months of treatment (see section 4.4).
Growth disturbance in short children/adolescents born small for gestational age (SGA)
A dose of 0.035 mg/kg body weight per day (1 mg/m
2
body surface area per day) is usually
recommended until final height is reached (see section 5.1). 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 epiphyseal closure.
Dose recommendations for paediatric patients
Indication
mg/kg body weight dose
per day
mg/m² body surface
area dose per day
Growth hormone deficiency
0.025 - 0.035
0.7 - 1.0
Prader-Willi syndrome
0.035
1.0
Turner syndrome
0.045 - 0.050
1.4
Chronic renal insufficiency
0.045 - 0.050
1.4
Children/adolescents born small for
gestational age (SGA)
0.035
1.0
Growth hormone deficient adult patients
Therapy should start with a low dose, 0.15 - 0.3 mg per day. The dose should be gradually increased
according to individual patient requirements as determined by the IGF-I concentration. Treatment goal
should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean
of healthy adults. Patients with normal IGF-I concentrations at the start of the treatment should be
administered growth hormone up to an IGF-I level into the upper range of normal, not exceeding the
2 SDS. Clinical response and side effects may also be used as guidance for dose titration. The daily
maintenance dose rarely exceeds 1.0 mg per day. Women may require higher doses than men, while
men show an increasing IGF-I sensitivity over time. This means that there is a risk that women,
especially those on oral oestrogen replacement are under-treated while men are over-treated. The
accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal
physiological growth hormone production decreases with age, dose requirements may be reduced. The
minimum effective dose should be used.
13
Special populations
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.
Method of administration
The injection should be given subcutaneously and the site varied to prevent lipoatrophy.
For instructions for use and handling see section 6.6.
-
Hypersensitivity to somatropin or to any of the excipients.
-
Somatropin must not be used when there is any evidence of tumour activity and anti-tumour
therapy must be completed prior to starting therapy.
-
Somatropin must not be used for growth promotion in patients with closed epiphyses.
-
Patients with acute critical illness suffering complications following open heart surgery,
abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions
must not be treated with somatropin. With regard to patients undergoing substitution therapy,
see section 4.4.
Insulin sensitivity
Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore
patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria
for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such
as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired
glucose tolerance have been present in most cases where this occurred. In patients with already
manifested diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is
instituted.
Thyroid function
During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result
in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral
thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of
somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical
hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving
replacement therapy with thyroxin mild hyperthyroidism may occur. It is therefore particularly
advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.
14
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or
by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless,
corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.
In growth hormone deficiency, secondary to treatment of malignant disease, it is recommended to pay
attention to signs of relapse of the malignancy.
In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the
hip may occur more frequently than in the general population. Patients limping during treatment with
somatropin, should be examined clinically.
Benign intracranial hypertension
In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for
papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial
hypertension should be considered and, if appropriate, the growth hormone treatment should be
discontinued. At present there is insufficient evidence to give specific advice on the continuation of
growth hormone treatment in patients with resolved intracranial hypertension. However, clinical
experience has shown that reinstitution of the therapy is often possible without recurrence of the
intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms
of intracranial hypertension is necessary.
Paediatric population
Prader-Willi syndrome
In patients with PWS, treatment should always be in combination with a calorie-restricted diet.
There have been reports of fatalities associated with the use of growth hormone in paediatric patients
with PWS who had one or more of the following risk factors: severe obesity, history of respiratory
impairment, sleep apnoea or unidentified respiratory infection. Patients with PWS and one or more of
these risk factors may be at greater risk.
Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory
infections before initiation of treatment with somatropin.
In case of signs of upper airway obstruction, the problem should be solved by a specialist before
starting treatment with somatropin.
Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods
such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.
If during treatment with somatropin patients show signs of upper airway obstruction (including onset
of or increased snoring), treatment should be interrupted, and a new ENT assessment performed.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is
suspected.
All patients with PWS should be monitored for signs of respiratory infections which should be
diagnosed as early as possible and treated aggressively.
All patients with PWS should have effective weight control before and during treatment with
somatropin.
Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth.
Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not
been shown to increase the incidence or severity of scoliosis.
Experience with long term treatment in adults and in patients with PWS is limited.
15
Small for gestational age
In short children/adolescents born SGA, other medical reasons or treatments that could explain growth
disturbance should be ruled out before starting treatment.
In SGA children/adolescents it is recommended to measure fasting insulin and blood glucose before
start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g.
familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose
tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not
be administered.
In SGA children/adolescents it is recommended to measure the IGF-I level before start of treatment
and twice a year thereafter. If on repeated measurements IGF-I levels 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.
Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not
recommended to initiate treatment near onset of puberty. Experience in patients with Silver-Russell
syndrome is limited.
Some of the height gain obtained with treating short children/adolescents born SGA with growth
hormone may be lost if treatment is stopped before final height is reached.
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.
Because of the presence of benzyl alcohol the medicinal product must not be given to premature
babies or neonates. It may cause toxic reactions and anaphylactoid reactions in infants and children up
to 3 years old.
Data from an interaction study performed in growth hormone deficient adults suggests that somatropin
administration may increase the clearance of compounds known to be metabolised by cytochrome
P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex
steroids, corticosteroids, anticonvulsants and ciclosporin) may be especially increased resulting in
lower plasma levels of these compounds. The clinical significance of this is unknown.
Also see section 4.4 for statements regarding diabetes mellitus and thyroid disorder and section 4.2 for
statement on oral oestrogen replacement therapy.
Pregnancy
For Omnitrope no clinical data on exposed pregnancies are available. Animal experimental data on
reproductive toxicity of Omnitrope are not available. Treatment with Omnitrope should be interrupted
if pregnancy occurs.
16
During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks,
being replaced almost entirely by placental growth hormone by 30 weeks. In view of this, it is unlikely
that continued replacement therapy with somatropin would be necessary in growth hormone deficient
women in the third trimester of pregnancy.
Breastfeeding
It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the
gastrointestinal tract of the infant is extremely unlikely.
Caution should be exercised when Omnitrope is administered to breast-feeding women.
Fertility
Fertility studies with Omnitrope have not been performed.
No studies on the effects on the ability to drive and use machines have been performed.
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
17
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.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdose could result in signs and symptoms consistent with the known effects of human
growth hormone excess.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, anterior pituitary
lobe hormones and analogues. ATC code: H01AC01.
Omnitrope is a biosimilar medicinal product. Detailed information is available on the website of the
European Medicines Agency
http://www.ema.europa.eu
Mechanism of action
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
mobilisation 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 (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor
Binding Protein 3) are increased by somatropin. In addition, the following actions have been
demonstrated.
18
Pharmacodynamic effects
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
reduction 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 hypoglycaemia. 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 osteopoenia 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.
Clinical efficacy and safety
In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg somatropin/kg
body weight per day have been used for treatment until final height is reached. In 56 patients who are
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/adolescents without early spontaneous
catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.
5.2 Pharmacokinetic properties
Absorption
The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy
subjects and growth hormone deficient patients. A subcutaneous dose of 5 mg of Omnitrope powder
and solvent for solution for injection in healthy adults results in plasma Cmax values of 71 ± 24 µg/l
(mean ± SD) and median tmax value of 4 hours (range 2-8 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 of Omnitrope 5 mg/ml
powder and solvent for solution for injection, a half-life of 3 hours is 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
subcutaneous administration.
19
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.
5.3 Preclinical safety data
In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant
effects have been observed.
In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity
no clinically relevant effects have been observed.
With somatropins, 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 medicinal product bleomycin. The clinical significance of this finding is unclear.
In another study with somatropin, no increase in chromosomal abnormalities was found in the
lymphocytes of patients who had received long-term somatropin therapy.
6.
6.1 List of excipients
Powder:
glycine
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
Solvent:
water for injections
benzyl alcohol
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
3 years.
Shelf life after reconstitution:
After reconstitution and the first use the cartridge should remain in the pen and has to be kept in a
refrigerator (2°C - 8°C) for a maximum of 21 days. Store and transport refrigerated (2°C - 8°C). Do
not freeze. Store in the original pen in order to protect from light.
6.4 Special precautions for storage
Unopened vial: Store and transport refrigerated (2°C – 8°C). Do not freeze. Store in the original
package in order to protect from light.
For storage conditions of the in-use medicinal product, see section 6.3.
20
6.5 Nature and contents of container
Powder in a vial (type I glass) with a stopper (fluor-resin laminated butyl rubber), a strip (aluminium)
and a cap (green polypropylene flip-off), and 1 ml of solvent in a cartridge (type I glass) with a
stopper (fluor-resin laminated chlorobutyl elastomer), a strip (lacquered aluminium) and a cap (white
polypropylene flip-off).
Pack sizes of 1 and 5.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Omnitrope 5 mg/ml is supplied in a vial containing the active substance as a powder and the solvent
filled in a cartridge. It should be reconstituted with a transfer set as recommended in the information
provided with the transfer set.
This presentation is intended for multiple use. It should only be administered with the
Omnitrope
Pen L, an injection device specifically developed for use with Omnitrope 5 mg/ml
reconstituted solution for injection. It has to be administered using sterile, disposable pen needles.
Patients and caregivers have to receive appropriate training and instruction on the proper use of the
Omnitrope vials, the cartridges with solvent, the transfer set and the pen from the physician or other
suitable qualified health professionals.
The following is a general description of the reconstitution and administration process. The
manufacturer’s instructions with each individual transfer set and pen must be followed for
reconstituting Omnitrope 5 mg/ml powder for solution for injection, loading the cartridge, attaching
the injection needle and for the administration.
1.
Hands should be washed.
2.
Flip off the plastic protective cap from the vial. The top of the vial and of the cartridge should
be wiped with an antiseptic solution in order to prevent contamination of the contents.
3.
Use the transfer set for transferring the solvent from the cartridge into the vial.
4.
Gently swirl the vial a few times until the content is completely dissolved. Do not shake; this
may cause denaturation of the active substance.
5.
If the solution is cloudy or contains particulate matter, it should not be used. The content must
be clear and colourless after reconstitution.
6.
Transfer the solution back into the cartridge using the transfer set.
7.
Assemble the pen following the instructions for use.
8.
Eliminate air bubbles if necessary.
9.
Clean the site of injection with an alcohol swab.
10.
Administer the appropriate dose by subcutaneous injection using a sterile pen needle. Remove
the pen needle and dispose of it in accordance with local requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
8.
EU/1/06/332/002
EU/1/06/332/003
21
9.
Date of first authorisation: 12 April 2006
Date of latest renewal:
Detailed information on this product is available on the website of the European Medicines Agency
22
1.
Omnitrope 3.3 mg/ml solution for injection
2.
Each ml of solution contains 3.3 mg of somatropin* (corresponding to 10 IU)
One cartridge contains 1.5 ml corresponding to 5 mg somatropin* (15 IU).
* produced in
Escherichia coli
by recombinant DNA technology.
Excipients:
One ml contains 9 mg benzyl alcohol.
For a full list of excipients, see section 6.1.
3.
Solution for injection
The solution is clear and colourless.
4.
Infants, children and adolescents
-
Growth disturbance due to insufficient secretion of growth hormone (GH).
-
Growth disturbance associated with Turner syndrome.
-
Growth disturbance associated with chronic renal insufficiency.
-
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted
SDS < -1) in short children/adolescents born small for gestational age (SGA), with a birth
weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth
(height velocity (HV) SDS < 0 during the last year) by 4 years of age or later.
-
Prader-Willi syndrome (PWS), for improvement of growth and body composition. The
diagnosis of PWS should be confirmed by appropriate genetic testing.
Adults
-
Replacement therapy in adults with pronounced growth hormone deficiency. Patients with
severe growth hormone deficiency in adulthood are defined as patients with known
hypothalamic pituitary pathology and at least one known deficiency of a pituitary hormone not
being prolactin. These patients should undergo a single dynamic test in order to diagnose or
exclude a growth hormone deficiency. In patients with childhood onset isolated GH deficiency
(no evidence of hypothalamic-pituitary disease or cranial irradiation), two dynamic tests should
be recommended, except for those having low IGF-I concentrations (SDS < -2) who may be
considered for one test. The cut-off point of the dynamic test should be strict.
Diagnosis and therapy with somatropin should be initiated and monitored by physicians who are
appropriately qualified and experienced in the diagnosis and management of patients with growth
disorders.
23
Posology
Paediatric population
The posology and administration schedule should be individualised.
Growth disturbance due to insufficient secretion of growth hormone in paediatric patients
Generally a dose of 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m
2
body surface area per
day is recommended. Even higher doses have been used.
Prader-Willi syndrome, for improvement of growth and body composition in paediatric patients
Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m
2
body surface area per day is
recommended. Daily doses of 2.7 mg should not be exceeded. Treatment should not be used in
paediatric patients with a growth velocity less than 1 cm per year and near closure of epiphyses.
Growth disturbance due to Turner syndrome
A dose of 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m
2
body surface area per day is
recommended.
Growth disturbance in chronic renal insufficiency
A dose of 1.4 mg/m
2
body surface area per day (0.045 - 0.050 mg/kg body weight per day) is
recommended. Higher doses may be needed if growth velocity is too low. A dose correction may be
needed after six months of treatment (see section 4.4).
Growth disturbance in short children/adolescents born small for gestational age (SGA)
A dose of 0.035 mg/kg body weight per day (1 mg/m
2
body surface area per day) is usually
recommended until final height is reached (see section 5.1). 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 epiphyseal closure.
Dose recommendations for paediatric patients
Indication
mg/kg body weight dose
per day
mg/m² body surface
area dose per day
Growth hormone deficiency
0.025 - 0.035
0.7 - 1.0
Prader-Willi syndrome
0.035
1.0
Turner syndrome
0.045 - 0.050
1.4
Chronic renal insufficiency
0.045 - 0.050
1.4
Children/adolescents born small for
gestational age (SGA)
0.035
1.0
Growth hormone deficient adult patients
Therapy should start with a low dose, 0.15 - 0.3 mg per day. The dose should be gradually increased
according to individual patient requirements as determined by the IGF-I concentration. Treatment goal
should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean
of healthy adults. Patients with normal IGF-I concentrations at the start of the treatment should be
administered growth hormone up to an IGF-I level into the upper range of normal, not exceeding the
2 SDS. Clinical response and side effects may also be used as guidance for dose titration. The daily
maintenance dose rarely exceeds 1.0 mg per day. Women may require higher doses than men, while
men show an increasing IGF-I sensitivity over time. This means that there is a risk that women,
especially those on oral oestrogen replacement are under-treated while men are over-treated. The
accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal
physiological growth hormone production decreases with age, dose requirements may be reduced. The
minimum effective dose should be used.
24
Special populations
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.
Method of administration
The injection should be given subcutaneously and the site varied to prevent lipoatrophy.
For instructions for use and handling see section 6.6.
-
Hypersensitivity to somatropin or to any of the excipients.
-
Somatropin must not be used when there is any evidence of tumour activity and anti-tumour
therapy must be completed prior to starting therapy.
-
Somatropin must not be used for growth promotion in patients with closed epiphyses.
-
Patients with acute critical illness suffering complications following open heart surgery,
abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions
must not be treated with somatropin. With regard to patients undergoing substitution therapy,
see section 4.4.
Insulin sensitivity
Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore
patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria
for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such
as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired
glucose tolerance have been present in most cases where this occurred. In patients with already
manifested diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is
instituted.
Thyroid function
During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result
in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral
thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of
somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical
hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving
replacement therapy with thyroxin mild hyperthyroidism may occur. It is therefore particularly
advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.
25
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or
by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless,
corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.
In growth hormone deficiency, secondary to treatment of malignant disease, it is recommended to pay
attention to signs of relapse of the malignancy.
In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the
hip may occur more frequently than in the general population. Patients limping during treatment with
somatropin, should be examined clinically.
Benign intracranial hypertension
In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for
papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial
hypertension should be considered and, if appropriate, the growth hormone treatment should be
discontinued. At present there is insufficient evidence to give specific advice on the continuation of
growth hormone treatment in patients with resolved intracranial hypertension. However, clinical
experience has shown that reinstitution of the therapy is often possible without recurrence of the
intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms
of intracranial hypertension is necessary.
Paediatric population
Prader-Willi syndrome
In patients with PWS, treatment should always be in combination with a calorie-restricted diet.
There have been reports of fatalities associated with the use of growth hormone in paediatric patients
with PWS who had one or more of the following risk factors: severe obesity, history of respiratory
impairment, sleep apnoea or unidentified respiratory infection. Patients with PWS and one or more of
these risk factors may be at greater risk.
Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory
infections before initiation of treatment with somatropin.
In case of signs of upper airway obstruction, the problem should be solved by a specialist before
starting treatment with somatropin.
Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods
such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.
If during treatment with somatropin patients show signs of upper airway obstruction (including onset
of or increased snoring), treatment should be interrupted, and a new ENT assessment performed.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is
suspected.
All patients with PWS should be monitored for signs of respiratory infections which should be
diagnosed as early as possible and treated aggressively.
All patients with PWS should have effective weight control before and during treatment with
somatropin.
Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth.
Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not
been shown to increase the incidence or severity of scoliosis.
Experience with long term treatment in adults and in patients with PWS is limited.
26
Small for gestational age
In short children/adolescents born SGA, other medical reasons or treatments that could explain growth
disturbance should be ruled out before starting treatment.
In SGA children/adolescents it is recommended to measure fasting insulin and blood glucose before
start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g.
familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose
tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not
be administered.
In SGA children/adolescents it is recommended to measure the IGF-I level before start of treatment
and twice a year thereafter. If on repeated measurements IGF-I levels 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.
Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not
recommended to initiate treatment near onset of puberty. Experience in patients with Silver-Russell
syndrome is limited.
Some of the height gain obtained with treating short children/adolescents born SGA with growth
hormone may be lost if treatment is stopped before final height is reached.
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.
Because of the presence of benzyl alcohol the medicinal product must not be given to premature
babies or neonates. It may cause toxic reactions and anaphylactoid reactions in infants and children up
to 3 years old.
Data from an interaction study performed in growth hormone deficient adults suggests that somatropin
administration may increase the clearance of compounds known to be metabolised by cytochrome
P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex
steroids, corticosteroids, anticonvulsants and ciclosporin) may be especially increased resulting in
lower plasma levels of these compounds. The clinical significance of this is unknown.
Also see section 4.4 for statements regarding diabetes mellitus and thyroid disorder and section 4.2 for
statement on oral oestrogen replacement therapy.
Pregnancy
For Omnitrope no clinical data on exposed pregnancies are available. Animal experimental data on
reproductive toxicity of Omnitrope are not available. Treatment with Omnitrope should be interrupted
if pregnancy occurs.
27
During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks,
being replaced almost entirely by placental growth hormone by 30 weeks. In view of this, it is unlikely
that continued replacement therapy with somatropin would be necessary in growth hormone deficient
women in the third trimester of pregnancy.
Breastfeeding
It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the
gastrointestinal tract of the infant is extremely unlikely.
Caution should be exercised when Omnitrope is administered to breast-feeding women.
Fertility
Fertility studies with Omnitrope have not been performed.
No studies on the effects on the ability to drive and use machines have been performed.
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
28
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.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdose could result in signs and symptoms consistent with the known effects of human
growth hormone excess.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, anterior pituitary
lobe hormones and analogues. ATC code: H01AC01.
Omnitrope is a biosimilar medicinal product. Detailed information is available on the website of the
European Medicines Agency
http://www.ema.europa.eu
Mechanism of action
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
mobilisation 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 (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor
Binding Protein 3) are increased by somatropin. In addition, the following actions have been
demonstrated.
29
Pharmacodynamic effects
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
reduction 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 hypoglycaemia. 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 osteopoenia 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.
Clinical efficacy and safety
In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg somatropin/kg
body weight per day have been used for treatment until final height is reached. In 56 patients who are
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/adolescents without early spontaneous
catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.
5.2 Pharmacokinetic properties
Absorption
The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy
subjects and growth hormone deficient patients. A subcutaneous dose of 5 mg of Omnitrope
3.3 mg/ml solution for injection in healthy adults results in plasma Cmax and tmax values of
72 ± 28 µg/l and 4.0 ± 2.0 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 of Omnitrope
3.3 mg/ml solution for injection, a half-life of 3 hours is 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
subcutaneous 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.
30
5.3 Preclinical safety data
In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant
effects have been observed.
In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity
no clinically relevant effects have been observed.
With somatropins, 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 medicinal product bleomycin. The clinical significance of this finding is unclear.
In another study with somatropin, no increase in chromosomal abnormalities was found in the
lymphocytes of patients who had received long-term somatropin therapy.
6.
6.1 List of excipients
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
mannitol
poloxamer 188
water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
2 years.
Shelf life after first use:
After first use the cartridge should remain in the pen and has to be kept in a refrigerator (2°C - 8°C)
for a maximum of 28 days. Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the
original pen in order to protect from light.
6.4 Special precautions for storage
Unopened cartridge: Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original
package in order to protect from light.
For storage conditions of the in-use medicinal product, see section 6.3.
6.5 Nature and contents of container
1.5 ml of solution in a cartridge (colourless type I glass) with plunger on one side (siliconised
bromobutyl), a disc (bromobutyl) and a cap (aluminium) on the other side.
Pack sizes of 1, 5 and 10.
Not all pack sizes may be marketed.
31
benzyl alcohol
6.6 Special precautions for disposal and other handling
Omnitrope 3.3 mg/ml solution for injection is a sterile, ready-to-use solution for subcutaneous
injection filled in a glass cartridge.
This presentation is intended for multiple use. It should only be administered with the
Omnitrope Pen 5, an injection device specifically developed for use with Omnitrope 3.3 mg/ml
solution for injection. It has to be administered using sterile, disposable pen needles. Patients and
caregivers have to receive appropriate training and instruction on the proper use of the Omnitrope
cartridges and the pen from the physician or other suitable qualified health professionals.
The following is a general description of the administration process. The manufacturer’s instructions
with each pen must be followed for loading the cartridge, attaching the injection needle and for the
administration.
1.
Hands should be washed.
2.
If the solution is cloudy or contains particulate matter, it should not be used. The content must
be clear and colourless.
3.
Disinfect the rubber membrane of the cartridge with a cleansing swab
4.
Insert the cartridge into the Omnitrope Pen 5 following the instructions for use provided with
the pen.
5.
Clean the site of injection with an alcohol swab.
6.
Administer the appropriate dose by subcutaneous injection using a sterile pen needle. Remove
the pen needle and dispose of it in accordance with local requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
8.
EU/1/06/332/004
EU/1/06/332/005
EU/1/06/332/006
9.
Date of first authorisation: 12 April 2006
Date of latest renewal:
Detailed information on this product is available on the website of the European Medicines Agency
32
1.
Omnitrope 6.7 mg/ml solution for injection
2.
Each ml of solution contains 6.7 mg of somatropin* (corresponding to 20 IU)
One cartridge contains 1.5 ml corresponding to 10 mg somatropin* (30 IU).
* produced in
Escherichia coli
by recombinant DNA technology.
For a full list of excipients, see section 6.1.
3.
Solution for injection
The solution is clear and colourless.
4.
Infants, children and adolescents
-
Growth disturbance due to insufficient secretion of growth hormone (GH).
-
Growth disturbance associated with Turner syndrome.
-
Growth disturbance associated with chronic renal insufficiency.
-
Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted
SDS < -1) in short children/adolescents born small for gestational age (SGA), with a birth
weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth
(height velocity (HV) SDS < 0 during the last year) by 4 years of age or later.
-
Prader-Willi syndrome (PWS), for improvement of growth and body composition. The
diagnosis of PWS should be confirmed by appropriate genetic testing.
Adults
-
Replacement therapy in adults with pronounced growth hormone deficiency. Patients with
severe growth hormone deficiency in adulthood are defined as patients with known
hypothalamic pituitary pathology and at least one known deficiency of a pituitary hormone not
being prolactin. These patients should undergo a single dynamic test in order to diagnose or
exclude a growth hormone deficiency. In patients with childhood onset isolated GH deficiency
(no evidence of hypothalamic-pituitary disease or cranial irradiation), two dynamic tests should
be recommended, except for those having low IGF-I concentrations (SDS < -2) who may be
considered for one test. The cut-off point of the dynamic test should be strict.
Diagnosis and therapy with somatropin should be initiated and monitored by physicians who are
appropriately qualified and experienced in the diagnosis and management of patients with growth
disorders.
33
Posology
Paediatric population
The posology and administration schedule should be individualised.
Growth disturbance due to insufficient secretion of growth hormone in paediatric patients
Generally a dose of 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m
2
body surface area per
day is recommended. Even higher doses have been used.
Prader-Willi syndrome, for improvement of growth and body composition in paediatric patients
Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m
2
body surface area per day is
recommended. Daily doses of 2.7 mg should not be exceeded. Treatment should not be used in
paediatric patients with a growth velocity less than 1 cm per year and near closure of epiphyses.
Growth disturbance due to Turner syndrome
A dose of 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m
2
body surface area per day is
recommended.
Growth disturbance in chronic renal insufficiency
A dose of 1.4 mg/m
2
body surface area per day (0.045 - 0.050 mg/kg body weight per day) is
recommended. Higher doses may be needed if growth velocity is too low. A dose correction may be
needed after six months of treatment (see section 4.4).
Growth disturbance in short children/adolescents born small for gestational age (SGA)
A dose of 0.035 mg/kg body weight per day (1 mg/m
2
body surface area per day) is usually
recommended until final height is reached (see section 5.1). 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 epiphyseal closure.
Dose recommendations for paediatric patients
Indication
mg/kg body weight dose
per day
mg/m² body surface
area dose per day
Growth hormone deficiency
0.025 - 0.035
0.7 - 1.0
Prader-Willi syndrome
0.035
1.0
Turner syndrome
0.045 - 0.050
1.4
Chronic renal insufficiency
0.045 - 0.050
1.4
Children/adolescents born small for
gestational age (SGA)
0.035
1.0
Growth hormone deficient adult patients
Therapy should start with a low dose, 0.15 - 0.3 mg per day. The dose should be gradually increased
according to individual patient requirements as determined by the IGF-I concentration. Treatment goal
should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean
of healthy adults. Patients with normal IGF-I concentrations at the start of the treatment should be
administered growth hormone up to an IGF-I level into the upper range of normal, not exceeding the
2 SDS. Clinical response and side effects may also be used as guidance for dose titration. The daily
maintenance dose rarely exceeds 1.0 mg per day. Women may require higher doses than men, while
men show an increasing IGF-I sensitivity over time. This means that there is a risk that women,
especially those on oral oestrogen replacement are under-treated while men are over-treated. The
accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal
physiological growth hormone production decreases with age, dose requirements may be reduced. The
minimum effective dose should be used.
34
Special populations
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.
Method of administration
The injection should be given subcutaneously and the site varied to prevent lipoatrophy.
For instructions for use and handling see section 6.6.
-
Hypersensitivity to somatropin or to any of the excipients.
-
Somatropin must not be used when there is any evidence of tumour activity and anti-tumour
therapy must be completed prior to starting therapy.
-
Somatropin must not be used for growth promotion in patients with closed epiphyses.
-
Patients with acute critical illness suffering complications following open heart surgery,
abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions
must not be treated with somatropin. With regard to patients undergoing substitution therapy,
see section 4.4.
Insulin sensitivity
Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore
patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria
for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such
as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired
glucose tolerance have been present in most cases where this occurred. In patients with already
manifested diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is
instituted.
Thyroid function
During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result
in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral
thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of
somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical
hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving
replacement therapy with thyroxin mild hyperthyroidism may occur. It is therefore particularly
advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.
35
Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or
by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless,
corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.
In growth hormone deficiency, secondary to treatment of malignant disease, it is recommended to pay
attention to signs of relapse of the malignancy.
In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the
hip may occur more frequently than in the general population. Patients limping during treatment with
somatropin, should be examined clinically.
Benign intracranial hypertension
In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for
papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial
hypertension should be considered and, if appropriate, the growth hormone treatment should be
discontinued. At present there is insufficient evidence to give specific advice on the continuation of
growth hormone treatment in patients with resolved intracranial hypertension. However, clinical
experience has shown that reinstitution of the therapy is often possible without recurrence of the
intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms
of intracranial hypertension is necessary.
Paediatric population
Prader-Willi syndrome
In patients with PWS, treatment should always be in combination with a calorie-restricted diet.
There have been reports of fatalities associated with the use of growth hormone in paediatric patients
with PWS who had one or more of the following risk factors: severe obesity, history of respiratory
impairment, sleep apnoea or unidentified respiratory infection. Patients with PWS and one or more of
these risk factors may be at greater risk.
Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory
infections before initiation of treatment with somatropin.
In case of signs of upper airway obstruction, the problem should be solved by a specialist before
starting treatment with somatropin.
Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods
such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.
If during treatment with somatropin patients show signs of upper airway obstruction (including onset
of or increased snoring), treatment should be interrupted, and a new ENT assessment performed.
All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is
suspected.
All patients with PWS should be monitored for signs of respiratory infections which should be
diagnosed as early as possible and treated aggressively.
All patients with PWS should have effective weight control before and during treatment with
somatropin.
Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth.
Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not
been shown to increase the incidence or severity of scoliosis.
Experience with long term treatment in adults and in patients with PWS is limited.
36
Small for gestational age
In short children/adolescents born SGA, other medical reasons or treatments that could explain growth
disturbance should be ruled out before starting treatment.
In SGA children/adolescents it is recommended to measure fasting insulin and blood glucose before
start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g.
familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose
tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not
be administered.
In SGA children/adolescents it is recommended to measure the IGF-I level before start of treatment
and twice a year thereafter. If on repeated measurements IGF-I levels 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.
Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not
recommended to initiate treatment near onset of puberty. Experience in patients with Silver-Russell
syndrome is limited.
Some of the height gain obtained with treating short children/adolescents born SGA with growth
hormone may be lost if treatment is stopped before final height is reached.
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.
Data from an interaction study performed in growth hormone deficient adults suggests that somatropin
administration may increase the clearance of compounds known to be metabolised by cytochrome
P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex
steroids, corticosteroids, anticonvulsants and ciclosporin) may be especially increased resulting in
lower plasma levels of these compounds. The clinical significance of this is unknown.
Also see section 4.4 for statements regarding diabetes mellitus and thyroid disorder and section 4.2 for
statement on oral oestrogen replacement therapy.
Pregnancy
For Omnitrope no clinical data on exposed pregnancies are available. Animal experimental data on
reproductive toxicity of Omnitrope are not available. Treatment with Omnitrope should be interrupted
if pregnancy occurs.
During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks,
being replaced almost entirely by placental growth hormone by 30 weeks. In view of this, it is unlikely
that continued replacement therapy with somatropin would be necessary in growth hormone deficient
women in the third trimester of pregnancy.
37
Breastfeeding
It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the
gastrointestinal tract of the infant is extremely unlikely.
Caution should be exercised when Omnitrope is administered to breast-feeding women.
Fertility
Fertility studies with Omnitrope have not been performed.
No studies on the effects on the ability to drive and use machines have been performed.
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
38
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.
Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.
Long-term overdose could result in signs and symptoms consistent with the known effects of human
growth hormone excess.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, anterior pituitary
lobe hormones and analogues. ATC code: H01AC01.
Omnitrope is a biosimilar medicinal product. Detailed information is available on the website of the
European Medicines Agency
http://www.ema.europa.eu
Mechanism of action
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
mobilisation 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 (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor
Binding Protein 3) are increased by somatropin. In addition, the following actions have been
demonstrated.
Pharmacodynamic effects
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
reduction in serum LDL and apolipoprotein B. A reduction in serum total cholesterol may also be
observed.
39
Carbohydrate metabolism
Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with
hypopituitarism may experience fasting hypoglycaemia. 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 osteopoenia 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.
Clinical efficacy and safety
In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg somatropin/kg
body weight per day have been used for treatment until final height is reached. In 56 patients who are
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/adolescents without early spontaneous
catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.
5.2 Pharmacokinetic properties
Absorption
The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy
subjects and growth hormone deficient patients. A subcutaneous dose of 5 mg of Omnitrope
6.7 mg/ml solution for injection in healthy adults results in plasma Cmax and tmax values of
74 ± 22 µg/l and 3.9 ± 1.2 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 of Omnitrope
6.7 mg/ml solution for injection, a half-life of 3 hours is 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
subcutaneous 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.
5.3 Preclinical safety data
In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant
effects have been observed.
In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity
no clinically relevant effects have been observed.
40
With somatropins, 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 medicinal product bleomycin. The clinical significance of this finding is unclear.
In another study with somatropin, no increase in chromosomal abnormalities was found in the
lymphocytes of patients who had received long-term somatropin therapy.
6.
6.1 List of excipients
disodium hydrogen phosphate heptahydrate
glycine
poloxamer 188
phenol
water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
18 months.
Shelf life after first use:
After first use the cartridge should remain in the pen and has to be kept in a refrigerator (2°C - 8°C)
for a maximum of 28 days. Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the
original pen in order to protect from light.
6.4 Special precautions for storage
Unopened cartridge: Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original
package in order to protect from light.
For storage conditions of the in-use medicinal product, see section 6.3.
6.5 Nature and contents of container
1.5 ml of solution in a cartridge (colourless type I glass) with plunger on one side (siliconised
bromobutyl), a disc (bromobutyl) and a cap (aluminium) on the other side.
Pack sizes of 1, 5 and 10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Omnitrope 6.7 mg/ml solution for injection is a sterile, ready-to-use solution for subcutaneous
injection filled in a glass cartridge.
This presentation is intended for multiple use. It should only be administered with the
Omnitrope Pen 10, an injection device specifically developed for use with Omnitrope 6.7 mg/ml
solution for injection. It has to be administered using sterile, disposable pen needles. Patients and
41
sodium dihydrogen phosphate dihydrate
caregivers have to receive appropriate training and instruction on the proper use of the Omnitrope
cartridges and the pen from the physician or other suitable qualified health professionals.
The following is a general description of the administration process. The manufacturer’s instructions
with each pen must be followed for loading the cartridge, attaching the injection needle and for the
administration.
1.
Hands should be washed.
2.
If the solution is cloudy or contains particulate matter, it should not be used. The content must
be clear and colourless.
3.
Disinfect the rubber membrane of the cartridge with a cleansing swab
4.
Insert the cartridge into the Omnitrope Pen 10 following the instructions for use provided with
the pen.
5.
Clean the site of injection with an alcohol swab.
6.
Administer the appropriate dose by subcutaneous injection using a sterile pen needle. Remove
the pen needle and dispose of it in accordance with local requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
8.
EU/1/06/332/007
EU/1/06/332/008
EU/1/06/332/009
9.
Date of first authorisation: 12 April 2006
Date of latest renewal:
Detailed information on this product is available on the website of the European Medicines Agency
42
ANNEX II
A.
MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR
BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
43
A
MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer of the biological active substance
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl
Austria
Name and address of the manufacturer responsible for batch release
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl
Austria
B
CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to restricted medical prescription. (See Annex I: Summary of Product
Characteristics, section 4.2).
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as presented in Module 1.8.1. of the
Marketing Authorisation, is in place and functioning before and whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 8.0 of the Risk Management Plan (RMP) presented
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
-
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
-
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
44
-
At the request of the European Medicines Agency
45
ANNEX III
LABELLING AND PACKAGE LEAFLET
46
A. LABELLING
47
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON LABEL
1.
Omnitrope 1.3 mg/ml powder and solvent for solution for injection
Somatropin
2.
STATEMENT OF ACTIVE SUBSTANCE
Somatropin 1.3 mg (4 IU)/ml in a vial. After reconstitution, one vial contains 1.3 mg somatropin
(corresponding to 4 IU) per ml.
3.
LIST OF EXCIPIENTS
Other ingredients:
Powder: glycine, disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate dihydrate
Solvent: water for injections
4.
Powder and solvent for solution for injection.
1 vial of 1.3 mg powder
1 vial of 1 ml solvent
Pack size of 1.
5.
METHOD AND ROUTE OF ADMINISTRATION
For single use only. Use only clear solution.
Read package leaflet before use.
Subcutaneous use after reconstitution.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING, IF NECESSARY
8.
EXPIRY DATE
EXP
After reconstitution, use within 24 hours.
48
9.
SPECIAL STORAGE CONDITIONS
Store and transport refrigerated (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
12. MARKETING AUTHORISATION NUMBER
EU/1/06/332/001
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Omnitrope 1.3 mg/ml
49
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OMNITROPE VIAL LABEL
1.
Omnitrope 1.3 mg/ml powder for solution for injection
Somatropin
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
For single use only.
3.
EXPIRY DATE
EXP
After reconstitution, use within 24 hours.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1.3 mg
6.
OTHER
50
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
SOLVENT VIAL LABEL
1.
Solvent for Omnitrope (water for injections)
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
For single use only.
3.
EXPIRY DATE
EXP
After reconstitution, use within 24 hours.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
51
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON LABEL
1.
Omnitrope 5 mg/ml powder and solvent for solution for injection
Somatropin
2.
STATEMENT OF ACTIVE SUBSTANCE
Somatropin 5 mg (15 IU)/ml in a vial. After reconstitution, one cartridge contains 5 mg somatropin
(corresponding to 15 IU) per ml.
3.
LIST OF EXCIPIENTS
Other ingredients:
Powder: glycine, disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate dihydrate
Solvent: benzyl alcohol, water for injections
Contains benzyl alcohol. See leaflet for further information.
4.
Powder and solvent for solution for injection.
1 vial of 5 mg powder
1 cartridge of 1 ml solvent
Pack sizes of 1 and 5.
5.
METHOD AND ROUTE OF ADMINISTRATION
Use only clear solution. Use only with Omnitrope Pen L.
Read package leaflet before use.
Subcutaneous use after reconstitution.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING, IF NECESSARY
8.
EXPIRY DATE
EXP
After reconstitution, use within 21 days.
52
9.
SPECIAL STORAGE CONDITIONS
Store and transport refrigerated (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
12. MARKETING AUTHORISATION NUMBERS
EU/1/06/332/002
EU/1/06/332/003
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Omnitrope 5 mg/ml
53
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OMNITROPE VIAL LABEL
1.
Omnitrope 5 mg/ml powder for solution for injection
Somatropin
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP
After reconstitution, use within 21 days.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
5 mg
6.
OTHER
54
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
SOLVENT CARTRIDGE LABEL
1.
Solvent for Omnitrope (water for injections with 1.5% benzyl alcohol)
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP
After reconstitution, use within 21 days.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
55
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON LABEL
1.
Omnitrope 3.3 mg/ml solution for injection
Somatropin
2.
STATEMENT OF ACTIVE SUBSTANCE
Somatropin 3.3 mg (10 IU)/ml.
One cartridge contains 1.5 ml corresponding to 5 mg somatropin (15 IU).
3.
LIST OF EXCIPIENTS
Other ingredients: disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate
dihydrate, mannitol, poloxamer 188, benzyl alcohol, water for injections
Contains benzyl alcohol. See leaflet for further information.
4.
Solution for injection.
1 cartridge of 1.5 ml
Pack sizes of 1, 5 and 10.
5.
METHOD AND ROUTE OF ADMINISTRATION
Use only clear solution. Use only with Omnitrope Pen 5.
Read package leaflet before use.
For subcutaneous use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING, IF NECESSARY
8.
EXPIRY DATE
EXP
After first opening, use within 28 days.
56
9.
SPECIAL STORAGE CONDITIONS
Store and transport refrigerated (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
12. MARKETING AUTHORISATION NUMBERS
EU/1/06/332/004
EU/1/06/332/005
EU/1/06/332/006
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Omnitrope 3.3 mg/ml
57
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OMNITROPE CARTRIDGE LABEL
1.
Omnitrope 3.3 mg/ml solution for injection
Somatropin
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP
After first opening, use within 28 days.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
5 mg
6.
OTHER
58
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON LABEL
1.
Omnitrope 6.7 mg/ml solution for injection
Somatropin
2.
STATEMENT OF ACTIVE SUBSTANCE
Somatropin 6.7 mg (20 IU)/ml.
One cartridge contains 1.5 ml corresponding to 10 mg somatropin (30 IU).
3.
LIST OF EXCIPIENTS
Other ingredients: disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate
dihydrate, glycine, poloxamer 188, phenol, water for injections
4.
Solution for injection.
1 cartridge of 1.5 ml
Pack sizes of 1, 5 and 10.
5.
METHOD AND ROUTE OF ADMINISTRATION
Use only clear solution. Use only with Omnitrope Pen 10.
Read package leaflet before use.
For subcutaneous use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING, IF NECESSARY
8.
EXPIRY DATE
EXP
After first opening, use within 28 days.
59
9.
SPECIAL STORAGE CONDITIONS
Store and transport refrigerated (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
12. MARKETING AUTHORISATION NUMBERS
EU/1/06/332/007
EU/1/06/332/008
EU/1/06/332/009
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Omnitrope 6.7 mg/ml
60
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OMNITROPE CARTRIDGE LABEL
1.
Omnitrope 6.7 mg/ml solution for injection
Somatropin
Subcutaneous use
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP
After first opening, use within 28 days.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
10 mg
6.
OTHER
61
B. PACKAGE LEAFLET
62
PACKAGE LEAFLET: INFORMATION FOR THE USER
Omnitrope 1.3 mg/ml powder and solvent for solution for injection
Somatropin
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Omnitrope is and what it is used for
2.
Before you use Omnitrope
3.
How to use Omnitrope
4.
Possible side effects
5.
How to store Omnitrope
6.
Further information
1.
WHAT OMNITROPE IS AND WHAT IT IS USED FOR
Omnitrope is a recombinant human growth hormone (also called somatropin). It has the same structure
as natural human growth hormone which is needed for bones and muscles to grow. It also helps your
fat and muscle tissues to develop in the right amounts. It is recombinant meaning it is not made from
human or animal tissue.
In children Omnitrope is used to treat the following growth disturbances:
•
If you are not growing properly and you do not have enough of your own growth hormone.
•
If you have Turner syndrome. Turner syndrome is a genetic disorder in girls that can affect
growth-your doctor will have told you if you have this.
•
If you have chronic renal (kidney) insufficiency. As kidneys lose their ability to function
normally this can affect growth.
•
If you were small or too light at birth. Growth hormone can help you grow taller if you have not
been able to catch up or maintain normal growth by 4 years of age or later.
•
If you have Prader-Willi syndrome (a genetic disorder). Growth hormone will help you grow
taller if you are still growing, and will also improve your body composition. Your excessive fat
will decrease and your reduced muscle mass will improve.
In adults Omnitrope is used to
•
Treat persons with pronounced growth hormone deficiency. This can start during either adult
life or it can continue from childhood.
If you have been treated with Omnitrope for growth hormone deficiency during childhood, your
growth hormone status will be retested after completion of growth. If severe growth hormone
deficiency is confirmed, your doctor will propose continuation of Omnitrope treatment
63
2.
BEFORE YOU USE OMNITROPE
Do not use Omnitrope
•
If you are allergic (hypersensitive) to somatropin or to any of the other ingredients of
Omnitrope.
•
If you have an active tumour (cancer). Tumours must be inactive and you must have finished
your ant-tumour treatment before you start using Omnitrope. .
•
To stimulate growth if growing is already finished (closed epiphyses).
•
If you are seriously ill (for example, complications following open-heart surgery, abdominal
surgery, accidental trauma, acute respiratory failure, or similar conditions). If you are about to
have, or have had, a major operation, or go into hospital for any reason, tell your doctor and
remind other doctors you are seeing that you use growth hormone.
Take special care with Omnitrope
•
If you are at risk of developing diabetes, your doctor will need to monitor your blood sugar
level during therapy with somatropin.
•
If you have diabetes, you should closely monitor your blood sugar level during treatment with
somatropin and discuss the results with your doctor to determine whether you need to change
the dose of your medicines to treat diabetes.
•
After starting somatropin treatment some patients may need to start thyroid hormone
replacement.
•
If you are receiving treatment with thyroid hormones it may become necessary to adjust your
thyroid hormone dose.
•
If you have raised intracranial pressure ( which causes symptoms, such as strong headache,
visual problems, or vomiting) you should inform your doctor about it..
•
If you walk with a limp or if you start to limp during your growth hormone treatment, you
should inform your doctor.
•
If you are receiving somatropin for growth hormone deficiency following a previous tumour
(cancer), you should be examined regularly for recurrence of the tumour.
•
If you are over 60 years old. Elderly persons may be more sensitive to the action of somatropin,
and therefore may be more prone to develop side effects.
Children with chronic renal (kidney) insufficiency
•
Your doctor should examine your kidney function and your growth rate before starting
somatropin. Medical treatment for your kidney should be continued. Somatropin treatment
should be stopped at kidney transplantation.
Children with Prader-Willi syndrome
•
Your doctor will give you diet restrictions to follow to control your weight.
•
Your doctor will assess you for signs of upper airway obstruction, sleep apnoea (where your
breathing is interrupted during sleep), or respiratory infection before you start treatment with
somatropin.
•
During treatment with somatropin, tell your doctor if you show signs of upper airway
obstruction (including starting to snore or worsening of snoring), your doctor will need to
examine you and may interrupt treatment with somatropin.
•
During treatment, your doctor will check you for signs of scoliosis, a type of spinal deformity.
•
During treatment, if you develop a lung infection, tell your doctor so that he can treat the
infection.
Children born small or too light at birth
•
If you were too small or too light at birth and are aged between 9 and 12 years, ask your doctor
for specific advice relating to puberty and treatment with this medicine.
•
Treatment should be continued until you have stopped growing.
64
•
Your doctor will check your blood sugar and insulin levels before the start of treatment and
every year during treatment.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
You should tell your doctor if you are using:
•
medicine to treat diabetes,
•
thyroid hormones,
•
medicines to control epilepsy (anticonvulsants),
•
ciclosporin (a medicine that weakens the immune system after transplantation),
•
sex hormones (for example oestrogens),
•
synthetic adrenal hormones (corticosteroids).
Your doctor may need to adjust the dose of these medicines or the dose of somatropin.
Pregnancy and breast-feeding
You should not use Omnitrope if you are pregnant or trying to become pregnant.
Ask your doctor or pharmacist for advice before using this medicine while breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Important information about some of the ingredients of Omnitrope
This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially ‘sodium- free’.
3.
HOW TO USE OMNITROPE
You should only be given this medicine by a doctor who has experience with growth hormone
treatment and who has confirmed your diagnosis.
Recommended dosage
The dose depends on your size, the condition for which you are being treated and how well growth
hormone works for you. Your doctor will advise you about your individualised dose of Omnitrope in
milligrams (mg) from either your body weight in kilograms (kg) or your body surface area calculated
from your height and weight in square metres (m2), as well as your treatment schedule. Do not change
the dosage and treatment schedule without consulting your doctor.
Children with growth hormone deficiency:
0.025-0.035 mg/kg body weight per day or 0.7-1.0 mg/m2 body surface area per day. Higher doses
can be used. When growth hormone deficiency continues into adolescence, Omnitrope should be
continued until completion of physical development.
Children with Turner syndrome:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day.
Children with chronic renal (kidney) insufficiency:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day). Higher doses may
be necessary if the rate of growth is too low. Dosage adjustment may be necessary after 6 months of
treatment.
Children with Prader-Willi syndrome:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day. The daily dosage should
not exceed 2.7 mg. Treatment should not be used in children who have almost stopped growing after
puberty.
65
Children born smaller or lighter than expected and with growth disturbance:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day). It is important to continue
treatment until final height is reached. Treatment should be discontinued after the first year if you are
not responding or if you have reached your final height and stopped growing
Adults with growth hormone deficiency:
If your growth hormone deficiency starts during adult life you should start with 0.15-0.3 mg per day.
This dosage should be gradually increased according to blood test results as well as clinical response
and side effects. The daily maintenance dose seldom exceeds 1.0 mg per day. Women may require
higher doses than men. Dosage should be monitored every 6 months. The minimum effective dose
should be used. Follow the instructions given to you by your doctor.
Injecting Omnitrope
Omnitrope is intended for subcutaneous use. This means that it is injected through a short injection
needle into the fatty tissue just under your skin. Your doctor should have already shown you how to
use Omnitrope. Always inject Omnitrope exactly as your doctor has told you. You should check with
your doctor or pharmacist if you are not sure.
How to inject Omnitrope 1.3 mg/ml
The following instructions explain how to inject Omnitrope 1.3 mg/ml yourself. Please read the
instructions carefully and follow them step by step. Your doctor will show you how to inject
Omnitrope. Do not attempt to inject unless you are sure you understand the procedure and
requirements for injection.
-
After reconstitution, Omnitrope is given as an injection under the skin.
-
Change the injection sites to minimise the risk of local lipoatrophy (local reduction of fatty
tissue under the skin).
Preparation
Collect necessary items before you begin:
-
a vial with Omnitrope 1.3 mg/ml powder for solution for injection.
-
a vial with solvent (liquid) for Omnitrope 1.3 mg/ml.
-
a sterile, disposable syringe (e.g. 2 ml syringe) and needle (e.g.
0.33 mm x 12.7 mm) for withdrawing the solvent from the vial (not
supplied in the pack).
-
a sterile, disposable syringe of appropriate size (e.g. 1 ml syringe)
and injection needle (e.g. 0.25 mm x 8 mm) for subcutaneous
injection (not supplied in the pack).
-
2 cleansing swabs (not supplied in the pack).
Wash your hands before you continue with the next steps.
Reconstituting Omnitrope
-
Remove the protective caps from the two vials in the box. With a
cleansing swab, disinfect the rubber membranes of both the
powder-filled and the solvent-filled vial.
-
Take the vial with solvent and the sterile, disposable syringe (e.g.
2 ml syringe) and needle (e.g. 0.33 mm x 12.7 mm). Push the
needle fitted to the syringe through the rubber membrane.
-
Turn the vial with the solvent upside down and withdraw all the
solvent from the vial.
66
-
Carefully inspect the solution before injecting it and use only if clear and colourless.
-
Take the vial with the powder and push the needle through the
rubber membrane of the vial. Inject the solvent slowly. Aim the
stream of liquid against the glass wall in order to avoid foam.
Remove the syringe and needle.
-
Gently swirl the reconstituted vial until the content is completely
dissolved.
Do not shake.
-
If the solution is cloudy (and the cloudiness does not disappear
within ten minutes) or contains particles, it should not be used. The
contents must be clear and colourless.
-
Use the solution immediately.
Measuring the dose of Omnitrope to be injected
-
Take the sterile, disposable syringe of appropriate size (e.g. 1 ml
syringe) and injection needle (e.g. 0.25 mm x 8 mm).
-
Push the needle through the rubber stopper of the vial with the
reconstituted solution.
-
Turn the vial and the syringe upside down in one hand.
-
Be sure that the tip of the syringe is in the Omnitrope reconstituted
solution. Your other hand will be free to move the plunger.
-
Pull back on the plunger slowly and withdraw just a bit more than
the dose prescribed by your doctor into the syringe.
-
Hold the syringe with the needle in the vial pointing up and remove
the syringe from the vial.
-
Check for air bubbles in the syringe. If you see any bubbles, pull
the plunger slightly back; tap the syringe gently, with the needle
pointing upwards, until the bubbles disappear. Push up the plunger
slowly back to the correct dose.
-
Inspect the reconstituted solution visually prior to administration.
Do not use if the solution is cloudy or contains particles
.
You
are now ready to inject the dose.
Injecting Omnitrope
-
Select the site of injection. The best sites for injection are tissues
with a layer of fat between skin and muscle, such as the thigh or
belly (except the navel or waistline).
-
Make sure you inject at least 1 cm from your last injection site and
that you change the places where you inject, as you have been
taught.
-
Before you make an injection, clean your skin well with an alcohol
swab. Wait for the area to dry.
-
With one hand, pitch a fold of loose skin. With your other hand,
hold the syringe as you would a pencil. Insert the needle into the
pinched skin at an angle of 45° to 90°. After the needle is in,
remove the hand used to pinch the skin and use it to hold the
syringe barrel. Pull back the plunger very slightly with one hand. If
blood comes into the syringe, the needle has entered a blood vessel.
Do not inject into this site; withdraw the needle and repeat this
step. Inject the solution by pushing the plunger all the way down
gently.
-
Pull the needle straight out of the skin.
67
After injecting
-
After injection, press the injection site with a small bandage or
sterile gauze for several seconds. Do not massage the injection site.
-
The residual solution, vials, and injection materials intended for
single use must be discarded. Dispose of the syringes safely in a
closed container.
If you use more Omnitrope than you should
If you inject much more than you should, contact your doctor or pharmacist as soon as possible. Your
blood sugar level could fall too low and later rise too high. You might feel shaky, sweaty, sleepy or
“not yourself”, and you might faint.
If you forget to use Omnitrope
Do not use a double dose to make up for a forgotten dose. It is best to use your growth hormone
regularly. If you forget to use a dose, have your next injection at the usual time the next day. Keep a
note of any missed injections and tell your doctor at your next check-up.
If you stop using Omnitrope
Ask your doctor for advice before you stop using somatropin.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Omnitrope can cause side effects, although not everybody gets them.
Common side effects (likely to occur in fewer than 1 in 10 patients) include:
Formation of antibodies to the injected growth hormone but these do not seem to stop the growth
hormone from working.
In children
•
Temporary reddening, itchiness or pain at the injection site.
In adults
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment). These symptoms may be seen at the beginning of treatment, but they disappear
spontaneously or when the dosage is lowered.
These common side effects in adults may start within the first months of treatment and may either stop
spontaneously or if your dose is reduced.
Uncommon side effects (likely to occur in fewer than 1 in 100 patients) include:
In children
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment).
In adults
•
pain or burning sensation in the hands or underarms (known as Carpal Tunnel Syndrome)
68
Rare side effects (likely to occur in fewer than 1 in 1,000 patients) include
•
Increased intracranial pressure (which causes symptoms, such as strong headache, visual
problems, or vomiting).
Very rare side effects (likely to occur in fewer than 1 in 10,000 patients) include
•
Cancer of white blood cells (leukemia)
The skin around the injection area can get uneven or lumpy, but this should not happen if you inject in
a different place each time.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE OMNITROPE
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton after EXP. The expiry date
refers to the last day of that month.
•
Store and transport refrigerated (2°C - 8°C).
•
Do not freeze.
•
Store in the original package in order to protect from light.
•
After reconstitution, from a microbiological point of view, the product should be used
immediately. However, the in-use stability has been demonstrated for up to 24 hours at
2°C - 8°C, in the original package.
•
For single use only.
Do not use Omnitrope if it was frozen or subject to high temperatures.
Do not use Omnitrope if you notice that the solution is cloudy.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Omnitrope contains
The active substance of Omnitrope is somatropin.
One vial contains 1.3 mg (corresponding to 4 IU) of somatropin after reconstitution with 1 ml solvent.
The other ingredients are:
Powder:
disodium hydrogen phosphate heptyhydrate
sodium dihydrogen phosphate dihydrate
Solvent:
water for injections
What Omnitrope looks like and contents of the pack
Powder and solvent for solution for injection (powder in a vial (1.3 mg), solvent in a vial (1 ml)).
Pack size of 1.
The powder is white and the solvent is a clear, colourless solution.
69
-
Type 2 diabetes mellitus
glycine
Marketing Authorisation Holder and Manufacturer
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Sandoz nv-sa
Telecom Gardens
Medialaan 40
B-1800 Vilvoorde
Tél/Tel: + 32 (0)2 722 97 97
Luxembourg/Luxemburg
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
България
Διaνοµέaς Κύpρου
Π.T.Χatζηγeωργίου SΙΑ ΛΤΔ
Gιλtίζ 31- 3042 Λeµesός
Τηλέfωνο: +357 25372425
Magyarország
Sandoz Hungaria Kft.
Bartók Béla út 43-47
H-1114 Budapest
Tel.: +36 1 430 2890
Česká republika
Sandoz s.r.o.
U Nákladového nádraží 10
CZ 130 00 Praha 3
Tel: +420 221 421 611
Malta
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
Danmark
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Danmark
Tlf: + 45 6395 1000
Nederland
Sandoz B.V.
Veluwezoom 22
NL-1327 AH Almere
Tel: + 31 36 52 41 600
Deutschland
Sandoz Pharmaceuticals GmbH
Raiffeisenstr. 11
D-83607 Holzkirchen
Tel: + 49 (0)8024 902 40 00
E-Mail: info@sandoz.de
Norge
Sandoz A/S
Edvard Thomsens Vej 14
DK-2300 København S
Danmark
Tlf: + 45 6395 1000
Eesti
Sandoz d.d. Eesti filiaal
Pärnu mnt 105
EE - 11312 Tallinn
Tel: +372 665 2400
Österreich
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Tel: + 43-(0)5338 2000
Ελλάδα
Sambrook Φαρμακευτική Α.Ε.
Καζαντζάκη 4 & Αγ. Παντελεήμονος
Τ.Κ. 135 61
Αγ. Ανάργυροι
Τηλ: + 30 210 8323 372
Polska
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
PL – 02 672 Warszawa
Tel.: + 48-22 549 15 00
70
España
Sandoz Farmacéutica, SA
Avda. Osa Mayor, 4
E-28023 Aravaca (Madrid)
Tel: + 34 91 740 12 80
Portugal
Sandoz Farmacêutica Lda.
Alameda da Beloura, Edifício 1
2
o
andar – Escritório 15
P-2710-693 Sintra
Tel: + 351 21 000 86 00
France
Sandoz S.A.S.
49 Avenue Georges Pompidou
F-92593 Levallois Perret
Tél: + 33 (0)1 49 64 48 00
România
Sandoz SRL
str. Livezeni, Nr 7A
Târgu Mureş 540472 – RO
Tel: + 40 265 208 120
Ireland
Rowex Ltd
Bantry
Co. Cork - IRL
Tel: + 353 (0) 27 50077
Email: reg@rowa-pharma.ie
Slovenija
Lek farmacevtska družba d.d.
Verovškova 57
SI-1526 Ljubljana
Tel: + 386 (0)1 580 21 11
Ísland
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Denmark
Tlf: + 45 6395 1000
Slovenská republika
Sandoz d.d. organizačná zložka
Galvaniho 15/C
SK-821 04 Bratislava
Tel: + 421-2-48 200 600
Italia
Sandoz S.p.A.
Largo U. Boccioni, 1
I-21040 Origgio (Va)
Tel: + 39 02 96541
Suomi/Finland
Sandoz A/S
Edvard Thomsens Vej 14
2300 Kööpenhamina S
Tanska
Puh/Tel: +45 6395 1000
Κύπρος
Distributors for Cyprus
P.T. Hadjigeorgiou co ltd
Yildiz 31-3042 Limassol
Tel: +357 25372425
Sverige
Sandoz A/S
Edvard Thomsens Vej 14
2300 Köpenhamn S
Danmark
Tel: +45 6395 1000
Latvija
Sandoz d.d. Pārstāvniecība Latvijā
K. Valdemāra 33-30
Riga, LV-1010
Tel: + 371 67 892 006
United Kingdom
Sandoz Limited
Frimley Business Park
Frimley/Camberley
Surrey GU16 7SR– UK
Tel: + 44 1276 69 8020
Lietuva
Sandoz Pharmaceuticals d.d. Branch Office
Seimyniskiu str. 3A
LT 09312 Vilnius
Tel: +370 5 2636 038
71
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
72
PACKAGE LEAFLET: INFORMATION FOR THE USER
Omnitrope 5 mg/ml powder and solvent for solution for injection
Somatropin
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Omnitrope is and what it is used for
2.
Before you use Omnitrope
3.
How to use Omnitrope
4.
Possible side effects
5.
How to store Omnitrope
6.
Further information
1.
WHAT OMNITROPE IS AND WHAT IT IS USED FOR
Omnitrope is a recombinant human growth hormone (also called somatropin). It has the same structure
as natural human growth hormone which is needed for bones and muscles to grow. It also helps your
fat and muscle tissues to develop in the right amounts. It is recombinant meaning it is not made from
human or animal tissue.
In children Omnitrope is used to treat the following growth disturbances:
•
If you are not growing properly and you do not have enough of your own growth hormone.
•
If you have Turner syndrome. Turner syndrome is a genetic disorder in girls that can affect
growth-your doctor will have told you if you have this.
•
If you have chronic renal (kidney) insufficiency. As kidneys lose their ability to function
normally this can affect growth.
•
If you were small or too light at birth. Growth hormone can help you grow taller if you have not
been able to catch up or maintain normal growth by 4 years of age or later.
•
If you have Prader-Willi syndrome (a genetic disorder). Growth hormone will help you grow
taller if you are still growing, and will also improve your body composition. Your excessive fat
will decrease and your reduced muscle mass will improve.
In adults Omnitrope is used to
•
Treat persons with pronounced growth hormone deficiency. This can start during either adult
life or it can continue from childhood.
If you have been treated with Omnitrope for growth hormone deficiency during childhood, your
growth hormone status will be retested after completion of growth. If severe growth hormone
deficiency is confirmed, your doctor will propose continuation of Omnitrope treatment
73
2.
BEFORE YOU USE OMNITROPE
Do not use Omnitrope
•
If you are allergic (hypersensitive) to somatropin or to any of the other ingredients of
Omnitrope.
•
If you have an active tumour (cancer). Tumours must be inactive and you must have finished
your ant-tumour treatment before you start using Omnitrope. .
•
To stimulate growth if growing is already finished (closed epiphyses).
•
If you are seriously ill (for example, complications following open-heart surgery, abdominal
surgery, accidental trauma, acute respiratory failure, or similar conditions). If you are about to
have, or have had, a major operation, or go into hospital for any reason, tell your doctor and
remind other doctors you are seeing that you use growth hormone.
Take special care with Omnitrope
•
If you are at risk of developing diabetes, your doctor will need to monitor your blood sugar
level during therapy with somatropin.
•
If you have diabetes, you should closely monitor your blood sugar level during treatment with
somatropin and discuss the results with your doctor to determine whether you need to change
the dose of your medicines to treat diabetes.
•
After starting somatropin treatment some patients may need to start thyroid hormone
replacement.
•
If you are receiving treatment with thyroid hormones it may become necessary to adjust your
thyroid hormone dose.
•
If you have raised intracranial pressure ( which causes symptoms, such as strong headache,
visual problems, or vomiting) you should inform your doctor about it..
•
If you walk with a limp or if you start to limp during your growth hormone treatment, you
should inform your doctor.
•
If you are receiving somatropin for growth hormone deficiency following a previous tumour
(cancer), you should be examined regularly for recurrence of the tumour.
•
If you are over 60 years old. Elderly persons may be more sensitive to the action of somatropin,
and therefore may be more prone to develop side effects.
Children with chronic renal (kidney) insufficiency
•
Your doctor should examine your kidney function and your growth rate before starting
somatropin. Medical treatment for your kidney should be continued. Somatropin treatment
should be stopped at kidney transplantation.
Children with Prader-Willi syndrome
•
Your doctor will give you diet restrictions to follow to control your weight.
•
Your doctor will assess you for signs of upper airway obstruction, sleep apnoea (where your
breathing is interrupted during sleep), or respiratory infection before you start treatment with
somatropin.
•
During treatment with somatropin, tell your doctor if you show signs of upper airway
obstruction (including starting to snore or worsening of snoring), your doctor will need to
examine you and may interrupt treatment with somatropin.
•
During treatment, your doctor will check you for signs of scoliosis, a type of spinal deformity.
•
During treatment, if you develop a lung infection, tell your doctor so that he can treat the
infection.
Children born small or too light at birth
•
If you were too small or too light at birth and are aged between 9 and 12 years, ask your doctor
for specific advice relating to puberty and treatment with this medicine.
•
Treatment should be continued until you have stopped growing.
74
•
Your doctor will check your blood sugar and insulin levels before the start of treatment and
every year during treatment.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
You should tell your doctor if you are using:
•
medicine to treat diabetes,
•
thyroid hormones,
•
medicines to control epilepsy (anticonvulsants),
•
ciclosporin (a medicine that weakens the immune system after transplantation),
•
sex hormones (for example oestrogens),
•
synthetic adrenal hormones (corticosteroids).
Your doctor may need to adjust the dose of these medicines or the dose of somatropin.
Pregnancy and breast-feeding
You should not use Omnitrope if you are pregnant or trying to become pregnant.
Ask your doctor or pharmacist for advice before using this medicine while breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Important information about some of the ingredients of Omnitrope
This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially ‘sodium- free’.
After reconstitution, one ml contains 15 mg benzyl alcohol.
Because of the presence of benzyl alcohol the medicinal product must not be given to premature
babies or neonates. May cause toxic reactions and allergic reactions in infants and children up to
3 years old.
3.
HOW TO USE OMNITROPE
You should only be given this medicine by a doctor who has experience with growth hormone
treatment and who has confirmed your diagnosis.
Recommended dosage
The dose depends on your size, the condition for which you are being treated and how well growth
hormone works for you. Your doctor will advise you about your individualised dose of Omnitrope in
milligrams (mg) from either your body weight in kilograms (kg) or your body surface area calculated
from your height and weight in square metres (m2), as well as your treatment schedule. Do not change
the dosage and treatment schedule without consulting your doctor.
Children with growth hormone deficiency:
0.025-0.035 mg/kg body weight per day or 0.7-1.0 mg/m2 body surface area per day. Higher doses
can be used. When growth hormone deficiency continues into adolescence, Omnitrope should be
continued until completion of physical development.
Children with Turner syndrome:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day.
75
Children with chronic renal (kidney) insufficiency:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day). Higher doses may
be necessary if the rate of growth is too low. Dosage adjustment may be necessary after 6 months of
treatment.
Children with Prader-Willi syndrome:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day. The daily dosage should
not exceed 2.7 mg. Treatment should not be used in children who have almost stopped growing after
puberty.
Children born smaller or lighter than expected and with growth disturbance:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day). It is important to continue
treatment until final height is reached. Treatment should be discontinued after the first year if you are
not responding or if you have reached your final height and stopped growing.
Adults with growth hormone deficiency:
If your growth hormone deficiency starts during adult life you should start with 0.15-0.3 mg per day.
This dosage should be gradually increased according to blood test results as well as clinical response
and side effects. The daily maintenance dose seldom exceeds 1.0 mg per day. Women may require
higher doses than men. Dosage should be monitored every 6 months. The minimum effective dose
should be used. Follow the instructions given to you by your doctor.
Injecting Omnitrope
Omnitrope 5 mg/ml is intended for multiple use. It should only be administered with the Omnitrope
Pen L, an injection device specifically developed for use with Omnitrope 5 mg/ml powder and solvent
for solution for injection.
Omnitrope is given through a short injection needle into the fatty tissue just under your skin. Your
doctor should have already shown you how to use Omnitrope. Always inject Omnitrope exactly as
your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
How to inject Omnitrope 5 mg/ml
The following instructions explain how to inject Omnitrope 5 mg/ml yourself. Please read the
instructions carefully and follow them step by step. Your doctor will show you how to inject
Omnitrope. Do not attempt to inject unless you are sure you understand the procedure and
requirements for injection.
-
Carefully inspect the solution before injecting it and use only if clear and colourless.
-
Change the injection sites to minimise the risk of local lipoatrophy (local reduction of fatty
tissue under the skin).
Preparation
Collect necessary items before you begin:
-
a vial with Omnitrope 5 mg/ml powder for solution for injection.
-
a cartridge with solvent for Omnitrope 5 mg/ml.
-
a transfer set for mixing and transferring the reconstituted solution
back into the cartridge (see Instructions for Use of the pen injector).
-
the Omnitrope Pen L, an injection device specifically developed for
use with Omnitrope 5 mg/ml reconstituted solution for injection
(not supplied in the pack; see Instructions for Use of the transfer set
and of the injection device).
-
2 cleansing swabs (not supplied in the pack).
Wash your hands before you continue with the next steps.
76
-
After reconstitution, Omnitrope is given as an injection under the skin.
-
a pen needle for subcutaneous injection.
Reconstituting Omnitrope
-
Remove the protective cap from the vial. With a cleansing swab,
disinfect both the rubber membrane of the vial with powder and the
rubber membrane of the cartridge with solvent.
-
Use the transfer set for transferring all the solvent from the
cartridge into the vial. Follow the instructions that come with the
transfer set.
-
Gently swirl the reconstituted vial until the content is completely
dissolved.
Do not shake
-
If the solution is cloudy (and the cloudiness does not disappear
within ten minutes) or contains particles, it should not be used. The
contents must be clear and colourless.
-
Transfer all of the dissolved solution back into the cartridge using
the transfer set.
Injecting Omnitrope
-
Put the cartridge with the dissolved Omnitrope
into the pen for
injection. Follow the Instructions for Use of the pen injector. To
setup the pen dial the dose.
-
Eliminate any air bubbles.
-
Select the site of injection. The best sites for injection are tissues
with a layer of fat between skin and muscle, such as the thigh or
belly (except the navel or waistline).
-
Make sure you inject at least 1 cm from your last injection site and
that you change the places where you inject, as you have been
taught.
-
Before you make an injection, clean your skin well with an alcohol
swab. Wait for the area to dry.
-
Insert the needle into the skin in the way your doctor has taught
you.
After injecting
-
After injection, press the injection site with a small bandage or
sterile gauze for several seconds. Do not massage the injection site.
-
Take the needle off the pen using the outer needle cap, and discard
the needle. This will keep the Omnitrope solution sterile and
prevent leaking. It will also stop air going back into the pen and the
needle clogging up. Do not share your needles. Do not share your
pen.
-
Leave the cartridge in the pen, put the cap on the pen, and store it
in the refrigerator.
-
The solution should be clear after removal from the refrigerator.
Do
not use if the solution is cloudy or contains particles.
If you use more Omnitrope than you should
If you inject much more than you should, contact your doctor or pharmacist as soon as possible. Your
blood sugar level could fall too low and later rise too high. You might feel shaky, sweaty, sleepy or
“not yourself”, and you might faint.
77
If you forget to use Omnitrope
Do not use a double dose to make up for a forgotten dose. It is best to use your growth hormone
regularly. If you forget to use a dose, have your next injection at the usual time the next day. Keep a
note of any missed injections and tell your doctor at your next check-up.
If you stop using Omnitrope
Ask your doctor for advice before you stop using somatropin.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Omnitrope can cause side effects, although not everybody gets them.
Common side effects (likely to occur in fewer than 1 in 10 patients) include:
Formation of antibodies to the injected growth hormone but these do not seem to stop the growth
hormone from working.
In children
•
Temporary reddening, itchiness or pain at the injection site.
In adults
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment). These symptoms may be seen at the beginning of treatment, but they disappear
spontaneously or when the dosage is lowered.
These common side effects in adults may start within the first months of treatment and may either stop
spontaneously or if your dose is reduced.
Uncommon side effects (likely to occur in fewer than 1 in 100 patients) include:
In children
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment).
In adults
•
pain or burning sensation in the hands or underarms (known as Carpal Tunnel Syndrome)
Rare side effects (likely to occur in fewer than 1 in 1,000 patients) include
•
Type 2 diabetes mellitus
-
Increased intracranial pressure (which causes symptoms, such as strong headache, visual
problems, or vomiting).
Very rare side effects (likely to occur in fewer than 1 in 10,000 patients) include
•
Cancer of white blood cells (leukemia)
The skin around the injection area can get uneven or lumpy, but this should not happen if you inject in
a different place each time.
78
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE OMNITROPE
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton after EXP. The expiry date
refers to the last day of that month.
•
Store and transport refrigerated (2°C - 8°C).
•
Do not freeze.
•
Store in the original package in order to protect from light.
•
After the first injection, the cartridge should remain in the pen injector and has to be stored in a
refrigerator (2°C - 8°C) and only used for a maximum of 21 days.
Do not use Omnitrope if it was frozen or subject to high temperatures.
Do not use Omnitrope if you notice that the solution is cloudy.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Omnitrope contains
The active substance of Omnitrope is somatropin.
One cartridge contains 5 mg (corresponding to 15 IU) of somatropin after reconstitution with 1 ml
solvent.
The other ingredients are:
Powder:
glycine
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
Solvent:
water for injections
benzyl alcohol
What Omnitrope looks like and contents of the pack
Powder and solvent for solution for injection (powder in a vial (5 mg), solvent in a cartridge (1 ml))
Pack sizes of 1 and 5.
The powder is white and the solvent is a clear, colourless solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Luxembourg/Luxemburg
79
Sandoz nv-sa
Telecom Gardens
Medialaan 40
B-1800 Vilvoorde
Tél/Tel: + 32 (0)2 722 97 97
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
България
Διaνοµέaς Κύpρου
Π.T.Χatζηγeωργίου SΙΑ ΛΤΔ
Gιλtίζ 31- 3042 Λeµesός
Τηλέfωνο: +357 25372425
Magyarország
Sandoz Hungaria Kft.
Bartók Béla út 43-47
H-1114 Budapest
Tel.: +36 1 430 2890
Česká republika
Sandoz s.r.o.
U Nákladového nádraží 10
CZ 130 00 Praha 3
Tel: +420 221 421 611
Malta
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
Danmark
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Danmark
Tlf: + 45 6395 1000
Nederland
Sandoz B.V.
Veluwezoom 22
NL-1327 AH Almere
Tel: + 31 36 52 41 600
Deutschland
Sandoz Pharmaceuticals GmbH
Raiffeisenstr. 11
D-83607 Holzkirchen
Tel: + 49 (0)8024 902 40 00
E-Mail: info@sandoz.de
Norge
Sandoz A/S
Edvard Thomsens Vej 14
DK-2300 København S
Danmark
Tlf: + 45 6395 1000
Eesti
Sandoz d.d. Eesti filiaal
Pärnu mnt 105
EE - 11312 Tallinn
Tel: +372 665 2400
Österreich
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Tel: + 43-(0)5338 2000
Ελλάδα
Sambrook Φαρμακευτική Α.Ε.
Καζαντζάκη 4 & Αγ. Παντελεήμονος
Τ.Κ. 135 61
Αγ. Ανάργυροι
Τηλ: + 30 210 8323 372
Polska
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
PL – 02 672 Warszawa
Tel.: + 48-22 549 15 00
España
Sandoz Farmacéutica, SA
Avda. Osa Mayor, 4
E-28023 Aravaca (Madrid)
Tel: + 34 91 740 12 80
Portugal
Sandoz Farmacêutica Lda.
Alameda da Beloura, Edifício 1
2
o
andar – Escritório 15
P-2710-693 Sintra
Tel: + 351 21 000 86 00
France
Sandoz S.A.S.
49 Avenue Georges Pompidou
F-92593 Levallois Perret
România
Sandoz SRL
str. Livezeni, Nr 7A
Târgu Mureş 540472 – RO
80
Tél: + 33 (0)1 49 64 48 00
Tel: + 40 265 208 120
Ireland
Rowex Ltd
Bantry
Co. Cork - IRL
Tel: + 353 (0) 27 50077
Email: reg@rowa-pharma.ie
Slovenija
Lek farmacevtska družba d.d.
Verovškova 57
SI-1526 Ljubljana
Tel: + 386 (0)1 580 21 11
Ísland
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Denmark
Tlf: + 45 6395 1000
Slovenská republika
Sandoz d.d. organizačná zložka
Galvaniho 15/C
SK-821 04 Bratislava
Tel: + 421-2-48 200 600
Italia
Sandoz S.p.A.
Largo U. Boccioni, 1
I-21040 Origgio (Va)
Tel: + 39 02 96541
Suomi/Finland
Sandoz A/S
Edvard Thomsens Vej 14
2300 Kööpenhamina S
Tanska
Puh/Tel: +45 6395 1000
Κύπρος
Distributors for Cyprus
P.T. Hadjigeorgiou co ltd
Yildiz 31-3042 Limassol
Tel: +357 25372425
Sverige
Sandoz A/S
Edvard Thomsens Vej 14
2300 Köpenhamn S
Danmark
Tel: +45 6395 1000
Latvija
Sandoz d.d. Pārstāvniecība Latvijā
K. Valdemāra 33-30
Riga, LV-1010
Tel: + 371 67 892 006
United Kingdom
Sandoz Limited
Frimley Business Park
Frimley/Camberley
Surrey GU16 7SR– UK
Tel: + 44 1276 69 8020
Lietuva
Sandoz Pharmaceuticals d.d. Branch Office
Seimyniskiu str. 3A
LT 09312 Vilnius
Tel: +370 5 2636 038
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
81
PACKAGE LEAFLET: INFORMATION FOR THE USER
Omnitrope 3.3 mg/ml solution for injection
Somatropin
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Omnitrope is and what it is used for
2.
Before you use Omnitrope
3.
How to use Omnitrope
4.
Possible side effects
5.
How to store Omnitrope
6.
Further information
1.
WHAT OMNITROPE IS AND WHAT IT IS USED FOR
Omnitrope is a recombinant human growth hormone (also called somatropin). It has the same structure
as natural human growth hormone which is needed for bones and muscles to grow. It also helps your
fat and muscle tissues to develop in the right amounts. It is recombinant meaning it is not made from
human or animal tissue.
In children Omnitrope is used to treat the following growth disturbances:
•
If you are not growing properly and you do not have enough of your own growth hormone.
•
If you have Turner syndrome. Turner syndrome is a genetic disorder in girls that can affect
growth-your doctor will have told you if you have this.
•
If you have chronic renal (kidney) insufficiency. As kidneys lose their ability to function
normally this can affect growth.
•
If you were small or too light at birth. Growth hormone can help you grow taller if you have not
been able to catch up or maintain normal growth by 4 years of age or later.
•
If you have Prader-Willi syndrome (a genetic disorder). Growth hormone will help you grow
taller if you are still growing, and will also improve your body composition. Your excessive fat
will decrease and your reduced muscle mass will improve.
In adults Omnitrope is used to
•
Treat persons with pronounced growth hormone deficiency. This can start during either adult
life or it can continue from childhood.
If you have been treated with Omnitrope for growth hormone deficiency during childhood, your
growth hormone status will be retested after completion of growth. If severe growth hormone
deficiency is confirmed, your doctor will propose continuation of Omnitrope treatment
82
2.
BEFORE YOU USE OMNITROPE
Do not use Omnitrope
•
If you are allergic (hypersensitive) to somatropin or to any of the other ingredients of
Omnitrope.
•
If you have an active tumour (cancer). Tumours must be inactive and you must have finished
your ant-tumour treatment before you start using Omnitrope. .
•
To stimulate growth if growing is already finished (closed epiphyses).
•
If you are seriously ill (for example, complications following open-heart surgery, abdominal
surgery, accidental trauma, acute respiratory failure, or similar conditions). If you are about to
have, or have had, a major operation, or go into hospital for any reason, tell your doctor and
remind other doctors you are seeing that you use growth hormone.
Take special care with Omnitrope
•
If you are at risk of developing diabetes, your doctor will need to monitor your blood sugar
level during therapy with somatropin.
•
If you have diabetes, you should closely monitor your blood sugar level during treatment with
somatropin and discuss the results with your doctor to determine whether you need to change
the dose of your medicines to treat diabetes.
•
After starting somatropin treatment some patients may need to start thyroid hormone
replacement.
•
If you are receiving treatment with thyroid hormones it may become necessary to adjust your
thyroid hormone dose.
•
If you have raised intracranial pressure ( which causes symptoms, such as strong headache,
visual problems, or vomiting) you should inform your doctor about it..
•
If you walk with a limp or if you start to limp during your growth hormone treatment, you
should inform your doctor.
•
If you are receiving somatropin for growth hormone deficiency following a previous tumour
(cancer), you should be examined regularly for recurrence of the tumour.
•
If you are over 60 years old. Elderly persons may be more sensitive to the action of somatropin,
and therefore may be more prone to develop side effects.
Children with chronic renal (kidney) insufficiency
•
Your doctor should examine your kidney function and your growth rate before starting
somatropin. Medical treatment for your kidney should be continued. Somatropin treatment
should be stopped at kidney transplantation.
Children with Prader-Willi syndrome
•
Your doctor will give you diet restrictions to follow to control your weight.
•
Your doctor will assess you for signs of upper airway obstruction, sleep apnoea (where your
breathing is interrupted during sleep), or respiratory infection before you start treatment with
somatropin.
•
During treatment with somatropin, tell your doctor if you show signs of upper airway
obstruction (including starting to snore or worsening of snoring), your doctor will need to
examine you and may interrupt treatment with somatropin.
•
During treatment, your doctor will check you for signs of scoliosis, a type of spinal deformity.
•
During treatment, if you develop a lung infection, tell your doctor so that he can treat the
infection.
Children born small or too light at birth
•
If you were too small or too light at birth and are aged between 9 and 12 years, ask your doctor
for specific advice relating to puberty and treatment with this medicine.
•
Treatment should be continued until you have stopped growing.
83
•
Your doctor will check your blood sugar and insulin levels before the start of treatment and
every year during treatment.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
You should tell your doctor if you are using:
•
medicine to treat diabetes,
•
thyroid hormones,
•
medicines to control epilepsy (anticonvulsants),
•
ciclosporin (a medicine that weakens the immune system after transplantation),
•
sex hormones (for example oestrogens),
•
synthetic adrenal hormones (corticosteroids).
Your doctor may need to adjust the dose of these medicines or the dose of somatropin.
Pregnancy and breast-feeding
You should not use Omnitrope if you are pregnant or trying to become pregnant.
Ask your doctor or pharmacist for advice before using this medicine while breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Important information about some of the ingredients of Omnitrope
This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially ‘sodium- free’.
One ml contains 9 mg benzyl alcohol.
Because of the presence of benzyl alcohol the medicinal product must not be given to premature
babies or neonates. May cause toxic reactions and allergic reactions in infants and children up to
3 years old.
3.
HOW TO USE OMNITROPE
You should only be given this medicine by a doctor who has experience with growth hormone
treatment and who has confirmed your diagnosis.
Recommended dosage
The dose depends on your size, the condition for which you are being treated and how well growth
hormone works for you. Your doctor will advise you about your individualised dose of Omnitrope in
milligrams (mg) from either your body weight in kilograms (kg) or your body surface area calculated
from your height and weight in square metres (m2), as well as your treatment schedule. Do not change
the dosage and treatment schedule without consulting your doctor.
Children with growth hormone deficiency:
0.025-0.035 mg/kg body weight per day or 0.7-1.0 mg/m2 body surface area per day. Higher doses
can be used. When growth hormone deficiency continues into adolescence, Omnitrope should be
continued until completion of physical development.
Children with Turner syndrome:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day.
84
Children with chronic renal (kidney) insufficiency:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day). Higher doses may
be necessary if the rate of growth is too low. Dosage adjustment may be necessary after 6 months of
treatment.
Children with Prader-Willi syndrome:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day. The daily dosage should
not exceed 2.7 mg. Treatment should not be used in children who have almost stopped growing after
puberty.
Children born smaller or lighter than expected and with growth disturbance:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day). It is important to continue
treatment until final height is reached. Treatment should be discontinued after the first year if you are
not responding or if you have reached your final height and stopped growing.
Adults with growth hormone deficiency:
If your growth hormone deficiency starts during adult life you should start with 0.15-0.3 mg per day.
This dosage should be gradually increased according to blood test results as well as clinical response
and side effects. The daily maintenance dose seldom exceeds 1.0 mg per day. Women may require
higher doses than men. Dosage should be monitored every 6 months. The minimum effective dose
should be used. Follow the instructions given to you by your doctor.
Injecting Omnitrope
Omnitrope 3.3 mg/ml is intended for multiple use. It should only be administered with the Omnitrope
Pen 5, an injection device specifically developed for use with Omnitrope 3.3 mg/ml solution for
injection.
Omnitrope is given through a short injection needle into the fatty tissue just under your skin. Your
doctor should have already shown you how to use Omnitrope. Always inject Omnitrope exactly as
your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
How to inject Omnitrope 3.3 mg/ml
The following instructions explain how to inject Omnitrope 3.3 mg/ml yourself. Please read the
instructions carefully and follow them step by step. Your doctor will show you how to inject
Omnitrope. Do not attempt to inject unless you are sure you understand the procedure and
requirements for injection.
-
Carefully inspect the solution before injecting it and use only if clear and colourless.
-
Change the injection sites to minimise the risk of local lipoatrophy (local reduction of fatty
tissue under the skin).
Preparation
Collect necessary items before you begin:
-
a cartridge with Omnitrope 3.3 mg/ml solution for injection.
-
the Omnitrope Pen 5, an injection device specifically developed for
use with Omnitrope 3.3 mg/ml solution for injection (not supplied
in the pack; see Instructions for Use provided with the
Omnitrope Pen 5).
-
a pen needle for subcutaneous injection.
-
2 cleansing swabs (not supplied in the pack).
Wash your hands before you continue with the next steps.
85
-
Omnitrope is given as an injection under the skin.
Injecting Omnitrope
-
With a cleansing swab, disinfect the rubber membrane of the
cartridge.
-
The contents must be clear and colourless.
-
Insert the cartridge into the pen for injection. Follow the
Instructions for Use of the pen injector. To setup the pen dial the
dose.
-
Select the site of injection. The best sites for injection are tissues
with a layer of fat between skin and muscle, such as the thigh or
belly (except the navel or waistline).
-
Make sure you inject at least 1 cm from your last injection site and
that you change the places where you inject, as you have been
taught.
-
Before you make an injection, clean your skin well with an alcohol
swab. Wait for the area to dry.
-
Insert the needle into the skin in the way your doctor has taught
you.
After injecting
-
After injection, press the injection site with a small bandage or
sterile gauze for several seconds. Do not massage the injection site.
-
Take the needle off the pen using the outer needle cap, and discard
the needle. This will keep the Omnitrope
solution sterile and
prevent leaking. It will also stop air going back into the pen and the
needle clogging up. Do not share your needles. Do not share your
pen.
-
Leave the cartridge in the pen, put the cap on the pen, and store it
in the refrigerator.
-
The solution should be clear after removal from the refrigerator.
Do
not use if the solution is cloudy or contains particles.
If you use more Omnitrope than you should
If you inject much more than you should, contact your doctor or pharmacist as soon as possible. Your
blood sugar level could fall too low and later rise too high. You might feel shaky, sweaty, sleepy or
“not yourself”, and you might faint.
If you forget to use Omnitrope
Do not use a double dose to make up for a forgotten dose. It is best to use your growth hormone
regularly. If you forget to use a dose, have your next injection at the usual time the next day. Keep a
note of any missed injections and tell your doctor at your next check-up.
If you stop using Omnitrope
Ask your doctor for advice before you stop using somatropin.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Omnitrope can cause side effects, although not everybody gets them.
86
Common side effects (likely to occur in fewer than 1 in 10 patients) include:
Formation of antibodies to the injected growth hormone but these do not seem to stop the growth
hormone from working.
In children
•
Temporary reddening, itchiness or pain at the injection site.
In adults
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment). These symptoms may be seen at the beginning of treatment, but they disappear
spontaneously or when the dosage is lowered.
These common side effects in adults may start within the first months of treatment and may either stop
spontaneously or if your dose is reduced.
Uncommon side effects (likely to occur in fewer than 1 in 100 patients) include:
In children
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment).
In adults
•
pain or burning sensation in the hands or underarms (known as Carpal Tunnel Syndrome)
Rare side effects (likely to occur in fewer than 1 in 1,000 patients) include
•
Type 2 diabetes mellitus
-
Increased intracranial pressure (which causes symptoms, such as strong headache, visual
problems, or vomiting).
Very rare side effects (likely to occur in fewer than 1 in 10,000 patients) include
•
Cancer of white blood cells (leukemia)
The skin around the injection area can get uneven or lumpy, but this should not happen if you inject in
a different place each time.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE OMNITROPE
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton after EXP. The expiry date
refers to the last day of that month.
•
Store and transport refrigerated (2°C - 8°C).
•
Do not freeze.
•
Store in the original package in order to protect from light.
•
After the first injection, the cartridge should remain in the pen injector and has to be stored in a
refrigerator (2°C - 8°C) and only used for a maximum of 28 days.
Do not use Omnitrope if it was frozen or subject to high temperatures.
87
Do not use Omnitrope if you notice that the solution is cloudy.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Omnitrope contains
The active substance of Omnitrope is somatropin.
One cartridge contains 5.0 mg (corresponding to 15 IU) of somatropin in 1.5 ml.
The other ingredients are:
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
poloxamer 188
benzyl alcohol
water for injections.
What Omnitrope looks like and contents of the pack
Omnitrope is presented as a solution for injection.
Pack sizes of 1, 5 or 10.
Omnitrope is a clear and colourless solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Sandoz nv-sa
Telecom Gardens
Medialaan 40
B-1800 Vilvoorde
Tél/Tel: + 32 (0)2 722 97 97
Luxembourg/Luxemburg
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
България
Διaνοµέaς Κύpρου
Π.T.Χatζηγeωργίου SΙΑ ΛΤΔ
Gιλtίζ 31- 3042 Λeµesός
Τηλέfωνο: +357 25372425
Magyarország
Sandoz Hungaria Kft.
Bartók Béla út 43-47
H-1114 Budapest
Tel.: +36 1 430 2890
88
mannitol
Česká republika
Sandoz s.r.o.
U Nákladového nádraží 10
CZ 130 00 Praha 3
Tel: +420 221 421 611
Malta
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
Danmark
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Danmark
Tlf: + 45 6395 1000
Nederland
Sandoz B.V.
Veluwezoom 22
NL-1327 AH Almere
Tel: + 31 36 52 41 600
Deutschland
Sandoz Pharmaceuticals GmbH
Raiffeisenstr. 11
D-83607 Holzkirchen
Tel: + 49 (0)8024 902 40 00
E-Mail: info@sandoz.de
Norge
Sandoz A/S
Edvard Thomsens Vej 14
DK-2300 København S
Danmark
Tlf: + 45 6395 1000
Eesti
Sandoz d.d. Eesti filiaal
Pärnu mnt 105
EE - 11312 Tallinn
Tel: +372 665 2400
Österreich
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Tel: + 43-(0)5338 2000
Ελλάδα
Sambrook Φαρμακευτική Α.Ε.
Καζαντζάκη 4 & Αγ. Παντελεήμονος
Τ.Κ. 135 61
Αγ. Ανάργυροι
Τηλ: + 30 210 8323 372
Polska
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
PL – 02 672 Warszawa
Tel.: + 48-22 549 15 00
España
Sandoz Farmacéutica, SA
Avda. Osa Mayor, 4
E-28023 Aravaca (Madrid)
Tel: + 34 91 740 12 80
Portugal
Sandoz Farmacêutica Lda.
Alameda da Beloura, Edifício 1
2
o
andar – Escritório 15
P-2710-693 Sintra
Tel: + 351 21 000 86 00
France
Sandoz S.A.S.
49 Avenue Georges Pompidou
F-92593 Levallois Perret
Tél: + 33 (0)1 49 64 48 00
România
Sandoz SRL
str. Livezeni, Nr 7A
Târgu Mureş 540472 – RO
Tel: + 40 265 208 120
Ireland
Rowex Ltd
Bantry
Co. Cork - IRL
Tel: + 353 (0) 27 50077
Email: reg@rowa-pharma.ie
Slovenija
Lek farmacevtska družba d.d.
Verovškova 57
SI-1526 Ljubljana
Tel: + 386 (0)1 580 21 11
Ísland
Sandoz A/S
Edvard Thomsens Vej 14
Slovenská republika
Sandoz d.d. organizačná zložka
Galvaniho 15/C
89
2300 København S
Denmark
Tlf: + 45 6395 1000
SK-821 04 Bratislava
Tel: + 421-2-48 200 600
Italia
Sandoz S.p.A.
Largo U. Boccioni, 1
I-21040 Origgio (Va)
Tel: + 39 02 96541
Suomi/Finland
Sandoz A/S
Edvard Thomsens Vej 14
2300 Kööpenhamina S
Tanska
Puh/Tel: +45 6395 1000
Κύπρος
Distributors for Cyprus
P.T. Hadjigeorgiou co ltd
Yildiz 31-3042 Limassol
Tel: +357 25372425
Sverige
Sandoz A/S
Edvard Thomsens Vej 14
2300 Köpenhamn S
Danmark
Tel: +45 6395 1000
Latvija
Sandoz d.d. Pārstāvniecība Latvijā
K. Valdemāra 33-30
Riga, LV-1010
Tel: + 371 67 892 006
United Kingdom
Sandoz Limited
Frimley Business Park
Frimley/Camberley
Surrey GU16 7SR– UK
Tel: + 44 1276 69 8020
Lietuva
Sandoz Pharmaceuticals d.d. Branch Office
Seimyniskiu str. 3A
LT 09312 Vilnius
Tel: +370 5 2636 038
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
90
PACKAGE LEAFLET: INFORMATION FOR THE USER
Omnitrope 6.7 mg/ml solution for injection
Somatropin
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Omnitrope is and what it is used for
2.
Before you use Omnitrope
3.
How to use Omnitrope
4.
Possible side effects
5.
How to store Omnitrope
6.
Further information
1.
WHAT OMNITROPE IS AND WHAT IT IS USED FOR
Omnitrope is a recombinant human growth hormone (also called somatropin). It has the same structure
as natural human growth hormone which is needed for bones and muscles to grow. It also helps your
fat and muscle tissues to develop in the right amounts. It is recombinant meaning it is not made from
human or animal tissue.
In children Omnitrope is used to treat the following growth disturbances:
•
If you are not growing properly and you do not have enough of your own growth hormone.
•
If you have Turner syndrome. Turner syndrome is a genetic disorder in girls that can affect
growth-your doctor will have told you if you have this.
•
If you have chronic renal (kidney) insufficiency. As kidneys lose their ability to function
normally this can affect growth.
•
If you were small or too light at birth. Growth hormone can help you grow taller if you have not
been able to catch up or maintain normal growth by 4 years of age or later.
•
If you have Prader-Willi syndrome (a genetic disorder). Growth hormone will help you grow
taller if you are still growing, and will also improve your body composition. Your excessive fat
will decrease and your reduced muscle mass will improve.
In adults Omnitrope is used to
•
Treat persons with pronounced growth hormone deficiency. This can start during either adult
life or it can continue from childhood.
If you have been treated with Omnitrope for growth hormone deficiency during childhood, your
growth hormone status will be retested after completion of growth. If severe growth hormone
deficiency is confirmed, your doctor will propose continuation of Omnitrope treatment
91
2.
BEFORE YOU USE OMNITROPE
Do not use Omnitrope
•
If you are allergic (hypersensitive) to somatropin or to any of the other ingredients of
Omnitrope.
•
If you have an active tumour (cancer). Tumours must be inactive and you must have finished
your ant-tumour treatment before you start using Omnitrope. .
•
To stimulate growth if growing is already finished (closed epiphyses).
•
If you are seriously ill (for example, complications following open-heart surgery, abdominal
surgery, accidental trauma, acute respiratory failure, or similar conditions). If you are about to
have, or have had, a major operation, or go into hospital for any reason, tell your doctor and
remind other doctors you are seeing that you use growth hormone.
Take special care with Omnitrope
•
If you are at risk of developing diabetes, your doctor will need to monitor your blood sugar
level during therapy with somatropin.
•
If you have diabetes, you should closely monitor your blood sugar level during treatment with
somatropin and discuss the results with your doctor to determine whether you need to change
the dose of your medicines to treat diabetes.
•
After starting somatropin treatment some patients may need to start thyroid hormone
replacement.
•
If you are receiving treatment with thyroid hormones it may become necessary to adjust your
thyroid hormone dose.
•
If you have raised intracranial pressure ( which causes symptoms, such as strong headache,
visual problems, or vomiting) you should inform your doctor about it..
•
If you walk with a limp or if you start to limp during your growth hormone treatment, you
should inform your doctor.
•
If you are receiving somatropin for growth hormone deficiency following a previous tumour
(cancer), you should be examined regularly for recurrence of the tumour.
•
If you are over 60 years old. Elderly persons may be more sensitive to the action of somatropin,
and therefore may be more prone to develop side effects.
Children with chronic renal (kidney) insufficiency
•
Your doctor should examine your kidney function and your growth rate before starting
somatropin. Medical treatment for your kidney should be continued. Somatropin treatment
should be stopped at kidney transplantation.
Children with Prader-Willi syndrome
•
Your doctor will give you diet restrictions to follow to control your weight.
•
Your doctor will assess you for signs of upper airway obstruction, sleep apnoea (where your
breathing is interrupted during sleep), or respiratory infection before you start treatment with
somatropin.
•
During treatment with somatropin, tell your doctor if you show signs of upper airway
obstruction (including starting to snore or worsening of snoring), your doctor will need to
examine you and may interrupt treatment with somatropin.
•
During treatment, your doctor will check you for signs of scoliosis, a type of spinal deformity.
•
During treatment, if you develop a lung infection, tell your doctor so that he can treat the
infection.
Children born small or too light at birth
•
If you were too small or too light at birth and are aged between 9 and 12 years, ask your doctor
for specific advice relating to puberty and treatment with this medicine.
•
Treatment should be continued until you have stopped growing.
92
•
Your doctor will check your blood sugar and insulin levels before the start of treatment and
every year during treatment.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
You should tell your doctor if you are using:
•
medicine to treat diabetes,
•
thyroid hormones,
•
medicines to control epilepsy (anticonvulsants),
•
ciclosporin (a medicine that weakens the immune system after transplantation),
•
sex hormones (for example oestrogens),
•
synthetic adrenal hormones (corticosteroids).
Your doctor may need to adjust the dose of these medicines or the dose of somatropin.
Pregnancy and breast-feeding
You should not use Omnitrope if you are pregnant or trying to become pregnant.
Ask your doctor or pharmacist for advice before using this medicine while breast-feeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Important information about some of the ingredients of Omnitrope
This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially ‘sodium- free’.
3.
HOW TO USE OMNITROPE
You should only be given this medicine by a doctor who has experience with growth hormone
treatment and who has confirmed your diagnosis.
Recommended dosage
The dose depends on your size, the condition for which you are being treated and how well growth
hormone works for you. Your doctor will advise you about your individualised dose of Omnitrope in
milligrams (mg) from either your body weight in kilograms (kg) or your body surface area calculated
from your height and weight in square metres (m2), as well as your treatment schedule. Do not change
the dosage and treatment schedule without consulting your doctor.
Children with growth hormone deficiency:
0.025-0.035 mg/kg body weight per day or 0.7-1.0 mg/m2 body surface area per day. Higher doses
can be used. When growth hormone deficiency continues into adolescence, Omnitrope should be
continued until completion of physical development.
Children with Turner syndrome:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day.
Children with chronic renal (kidney) insufficiency:
0.045-0.050 mg/kg body weight per day or 1.4 mg/m2 body surface area per day). Higher doses may
be necessary if the rate of growth is too low. Dosage adjustment may be necessary after 6 months of
treatment.
Children with Prader-Willi syndrome:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day. The daily dosage should
not exceed 2.7 mg. Treatment should not be used in children who have almost stopped growing after
puberty.
93
Children born smaller or lighter than expected and with growth disturbance:
0.035 mg/kg body weight per day or 1.0 mg/m2 body surface area per day). It is important to continue
treatment until final height is reached. Treatment should be discontinued after the first year if you are
not responding or if you have reached your final height and stopped growing.
Adults with growth hormone deficiency:
If your growth hormone deficiency starts during adult life you should start with 0.15-0.3 mg per day.
This dosage should be gradually increased according to blood test results as well as clinical response
and side effects. The daily maintenance dose seldom exceeds 1.0 mg per day. Women may require
higher doses than men. Dosage should be monitored every 6 months. The minimum effective dose
should be used. Follow the instructions given to you by your doctor.
Injecting Omnitrope
Omnitrope 6.7 mg/ml is intended for multiple use. It should only be administered with the Omnitrope
Pen 10, an injection device specifically developed for use with Omnitrope 6.7 mg/ml solution for
injection.
Omnitrope is given through a short injection needle into the fatty tissue just under your skin. Your
doctor should have already shown you how to use Omnitrope. Always inject Omnitrope exactly as
your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
How to inject Omnitrope 6.7 mg/ml
The following instructions explain how to inject Omnitrope 6.7 mg/ml yourself. Please read the
instructions carefully and follow them step by step. Your doctor will show you how to inject
Omnitrope. Do not attempt to inject unless you are sure you understand the procedure and
requirements for injection.
-
Omnitrope is given as an injection under the skin.
-
Carefully inspect the solution before injecting it and use only if clear and colourless.
-
Change the injection sites to minimise the risk of local lipoatrophy (local reduction of fatty
tissue under the skin).
Preparation
Collect necessary items before you begin:
-
a cartridge with Omnitrope 6.7 mg/ml solution for injection.
-
the Omnitrope Pen 10, an injection device specifically developed
for use with Omnitrope 6.7 mg/ml solution for injection (not
supplied in the pack; see Instructions for Use provided with the
Omnitrope Pen 10).
-
a pen needle for subcutaneous injection.
-
2 cleansing swabs (not supplied in the pack).
Wash your hands before you continue with the next steps.
Injecting Omnitrope
-
With a cleansing swab, disinfect the rubber membrane of the
cartridge.
-
The contents must be clear and colourless.
-
Insert the cartridge into the pen for injection. Follow the
Instructions for Use of the pen injector. To setup the pen dial the
dose.
94
-
Select the site of injection. The best sites for injection are tissues
with a layer of fat between skin and muscle, such as the thigh or
belly (except the navel or waistline).
-
Make sure you inject at least 1 cm from your last injection site and
that you change the places where you inject, as you have been
taught.
-
Before you make an injection, clean your skin well with an alcohol
swab. Wait for the area to dry.
-
Insert the needle into the skin in the way your doctor has taught
you.
After injecting
-
After injection, press the injection site with a small bandage or
sterile gauze for several seconds. Do not massage the injection site.
-
Take the needle off the pen using the outer needle cap, and discard
the needle. This will keep the Omnitrope
solution sterile and
prevent leaking. It will also stop air going back into the pen and the
needle clogging up. Do not share your needles. Do not share your
pen.
-
Leave the cartridge in the pen, put the cap on the pen, and store it
in the refrigerator.
-
The solution should be clear after removal from the refrigerator.
Do
not use if the solution is cloudy or contains particles.
If you use more Omnitrope than you should
If you inject much more than you should, contact your doctor or pharmacist as soon as possible. Your
blood sugar level could fall too low and later rise too high. You might feel shaky, sweaty, sleepy or
“not yourself”, and you might faint.
If you forget to use Omnitrope
Do not use a double dose to make up for a forgotten dose. It is best to use your growth hormone
regularly. If you forget to use a dose, have your next injection at the usual time the next day. Keep a
note of any missed injections and tell your doctor at your next check-up.
If you stop using Omnitrope
Ask your doctor for advice before you stop using somatropin.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Omnitrope can cause side effects, although not everybody gets them.
Common side effects (likely to occur in fewer than 1 in 10 patients) include:
Formation of antibodies to the injected growth hormone but these do not seem to stop the growth
hormone from working.
In children
•
Temporary reddening, itchiness or pain at the injection site.
In adults
•
numbness/tingling
95
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment). These symptoms may be seen at the beginning of treatment, but they disappear
spontaneously or when the dosage is lowered.
These common side effects in adults may start within the first months of treatment and may either stop
spontaneously or if your dose is reduced.
Uncommon side effects (likely to occur in fewer than 1 in 100 patients) include:
In children
•
numbness/tingling
•
stiffness in the arms and legs, joint pain, muscle pain,
•
Water retention (which shows as puffy fingers or swollen ankles, for a short time at the start of
treatment).
In adults
•
pain or burning sensation in the hands or underarms (known as Carpal Tunnel Syndrome)
Rare side effects (likely to occur in fewer than 1 in 1,000 patients) include
•
Type 2 diabetes mellitus
-
Increased intracranial pressure (which causes symptoms, such as strong headache, visual
problems, or vomiting).
Very rare side effects (likely to occur in fewer than 1 in 10,000 patients) include
•
Cancer of white blood cells (leukemia)
The skin around the injection area can get uneven or lumpy, but this should not happen if you inject in
a different place each time.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE OMNITROPE
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton after EXP. The expiry date
refers to the last day of that month.
•
Store and transport refrigerated (2°C - 8°C).
•
Do not freeze.
•
Store in the original package in order to protect from light.
•
After the first injection, the cartridge should remain in the pen injector and has to be stored in a
refrigerator (2°C - 8°C) and only used for a maximum of 28 days.
Do not use Omnitrope if it was frozen or subject to high temperatures.
Do not use Omnitrope if you notice that the solution is cloudy.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
96
6.
FURTHER INFORMATION
What Omnitrope contains
The active substance of Omnitrope is somatropin.
One cartridge contains 10.0 mg (corresponding to 30 IU) of somatropin in 1.5 ml.
The other ingredients are:
disodium hydrogen phosphate heptahydrate
sodium dihydrogen phosphate dihydrate
poloxamer 188
phenol
water for injections.
What Omnitrope looks like and contents of the pack
Omnitrope is presented as a solution for injection.
Pack sizes of 1, 5 or 10.
Omnitrope is a clear and colourless solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl
Austria
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
Sandoz nv-sa
Telecom Gardens
Medialaan 40
B-1800 Vilvoorde
Tél/Tel: + 32 (0)2 722 97 97
Luxembourg/Luxemburg
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
България
Διaνοµέaς Κύpρου
Π.T.Χatζηγeωργίου SΙΑ ΛΤΔ
Gιλtίζ 31- 3042 Λeµesός
Τηλέfωνο: +357 25372425
Magyarország
Sandoz Hungaria Kft.
Bartók Béla út 43-47
H-1114 Budapest
Tel.: +36 1 430 2890
Česká republika
Sandoz s.r.o.
U Nákladového nádraží 10
CZ 130 00 Praha 3
Tel: +420 221 421 611
Malta
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Austria
Tel: + 43-(0)5338 2000
Danmark
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Danmark
Nederland
Sandoz B.V.
Veluwezoom 22
NL-1327 AH Almere
Tel: + 31 36 52 41 600
97
glycine
Tlf: + 45 6395 1000
Deutschland
Sandoz Pharmaceuticals GmbH
Raiffeisenstr. 11
D-83607 Holzkirchen
Tel: + 49 (0)8024 902 40 00
E-Mail: info@sandoz.de
Norge
Sandoz A/S
Edvard Thomsens Vej 14
DK-2300 København S
Danmark
Tlf: + 45 6395 1000
Eesti
Sandoz d.d. Eesti filiaal
Pärnu mnt 105
EE - 11312 Tallinn
Tel: +372 665 2400
Österreich
Sandoz GmbH
Biochemiestr. 10
A-6250 Kundl
Tel: + 43-(0)5338 2000
Ελλάδα
Sambrook Φαρμακευτική Α.Ε.
Καζαντζάκη 4 & Αγ. Παντελεήμονος
Τ.Κ. 135 61
Αγ. Ανάργυροι
Τηλ: + 30 210 8323 372
Polska
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
PL – 02 672 Warszawa
Tel.: + 48-22 549 15 00
España
Sandoz Farmacéutica, SA
Avda. Osa Mayor, 4
E-28023 Aravaca (Madrid)
Tel: + 34 91 740 12 80
Portugal
Sandoz Farmacêutica Lda.
Alameda da Beloura, Edifício 1
2
o
andar – Escritório 15
P-2710-693 Sintra
Tel: + 351 21 000 86 00
France
Sandoz S.A.S.
49 Avenue Georges Pompidou
F-92593 Levallois Perret
Tél: + 33 (0)1 49 64 48 00
România
Sandoz SRL
str. Livezeni, Nr 7A
Târgu Mureş 540472 – RO
Tel: + 40 265 208 120
Ireland
Rowex Ltd
Bantry
Co. Cork - IRL
Tel: + 353 (0) 27 50077
Email: reg@rowa-pharma.ie
Slovenija
Lek farmacevtska družba d.d.
Verovškova 57
SI-1526 Ljubljana
Tel: + 386 (0)1 580 21 11
Ísland
Sandoz A/S
Edvard Thomsens Vej 14
2300 København S
Denmark
Tlf: + 45 6395 1000
Slovenská republika
Sandoz d.d. organizačná zložka
Galvaniho 15/C
SK-821 04 Bratislava
Tel: + 421-2-48 200 600
Italia
Sandoz S.p.A.
Largo U. Boccioni, 1
I-21040 Origgio (Va)
Tel: + 39 02 96541
Suomi/Finland
Sandoz A/S
Edvard Thomsens Vej 14
2300 Kööpenhamina S
Tanska
Puh/Tel: +45 6395 1000
Κύπρος
Sverige
98
Distributors for Cyprus
P.T. Hadjigeorgiou co ltd
Yildiz 31-3042 Limassol
Tel: +357 25372425
Sandoz A/S
Edvard Thomsens Vej 14
2300 Köpenhamn S
Danmark
Tel: +45 6395 1000
Latvija
Sandoz d.d. Pārstāvniecība Latvijā
K. Valdemāra 33-30
Riga, LV-1010
Tel: + 371 67 892 006
United Kingdom
Sandoz Limited
Frimley Business Park
Frimley/Camberley
Surrey GU16 7SR– UK
Tel: + 44 1276 69 8020
Lietuva
Sandoz Pharmaceuticals d.d. Branch Office
Seimyniskiu str. 3A
LT 09312 Vilnius
Tel: +370 5 2636 038
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
99
Source: European Medicines Agency
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