NutropinAq

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 

NutropinAq 10 mg/2 ml (30 IU) solution for injection. 
 
 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One ml contains 5 mg of somatropin* 
One cartridge contains 10 mg (30 IU) of somatropin 
* Somatropin is a human growth hormone produced in Escherichia coli cells by recombinant DNA 
technology. 

 
For the full list of excipients, see section 6.1. 

 
 

3. PHARMACEUTICAL FORM 
 

Solution for injection. 
Clear and colourless solution. 

 
 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Paediatric population 
 

- Long-term treatment of children with growth failure due to inadequate endogenous growth 
hormone secretion. 
 

- Long-term treatment of girls from 2 years old with growth failure associated with Turner 
syndrome. 
 

- Treatment of prepubertal children with growth failure associated with chronic renal 
insufficiency up to the time of renal transplantation. 

 
Adult population 

 
- Replacement of endogenous growth hormone in adults with growth hormone deficiency of 

either childhood or adult-onset etiology. Growth hormone deficiency should be confirmed 
appropriately prior to treatment. 
In adults with growth hormone deficiency the diagnosis should be established depending on 
the etiology: 
Adult-onset: The patient must have growth hormone deficiency as a result of hypothalamic or 
pituitary disease, and at least one other hormone deficiency diagnosed (except for prolactin). 
Test for growth hormone deficiency should not be performed until adequate replacement 
therapy for other hormone deficiencies have been instituted. 
Childhood-onset: Patients who have had growth hormone deficiency as a child should be 
retested to confirm growth hormone deficiency in adulthood before replacement therapy with 
NutropinAq is started. 

 
4.2 Posology and method of administration 

 
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 the 
therapeutic indication of use. 
 



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Posology 
 

The NutropinAq dosage and administration schedule should be individualised for each patient. 
 

Paediatric population 
 

Growth failure in children due to inadequate growth hormone secretion 
0.025 - 0.035 mg/kg bodyweight given as a daily subcutaneous injection. 
Somatropin therapy should be continued in children and adolescents until their epiphysis are closed. 

 
Growth failure associated with Turner syndrome 
Up to 0.05 mg/kg bodyweight given as a daily subcutaneous injection. 
Somatropin therapy should be continued in children and adolescents until their epiphysis are closed. 

 
Growth failure associated with chronic renal insufficiency 
Up to 0.05 mg/kg bodyweight given as a daily subcutaneous injection. 
Somatropin therapy should be continued in children and adolescents until their epiphysis are closed, 
or up to the time of renal transplantation. 

 
Adult population 

 
Growth hormone deficiency in adults 
At the start of somatropin therapy, low initial doses of 0.15 - 0.3 mg are recommended, given as a 
daily subcutaneous injection. The dose should be adjusted stepwise, controlled by serum Insulin-like 
Growth Factor-1 (IGF-I) values. The recommended final dose seldom exceeds 1.0 mg/day. In 
general, the lowest efficacious dose should be administered. In older or overweight patients, lower 
doses may be necessary. 
 
Women may require higher doses than men, with men showing an increasing IGF-I sensitivity over 
time. This means that there is a risk that women, especially those on oral oestrogen therapy, are under-
treated while men are over-treated.  

 
Method of administration 

 
The solution for injection should be administered subcutaneously each day. The site of injection 
should be changed. 

 
Precaution to be taken before manipulating or administering the product 
 
NutropinAq is supplied as a multi-dose solution. After removal from the refrigerator, if the solution is 
cloudy, the content must not be injected. Gently swirl. Do not shake vigorously as it could denature 
the protein. NutropinAq is intended for use only with the NutropinAq Pen. 

 
For instructions for use and handling of the medicinal product, see section 6.6. 

 
4.3 Contraindications 

 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Somatropin 
should not be used for growth promotion in patients with closed epiphyses. 
 
Somatropin must not be used when there is any evidence of activity of a tumour. Intracranial tumours 
must be inactive and antitumour therapy must be completed prior to starting GH therapy. Treatment 
should be discontinued if there is evidence of tumour growth. 

 
Growth hormone should not be initiated to treat patients with acute critical illness due to 
complications following open-heart or abdominal surgery, multiple accidental traumas or to treat 
patients having acute respiratory failure. 



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4.4 Special warnings and precautions for use 
 
The maximum recommended daily dose should not be exceeded (see section 4.2).  
 
Neoplasm 
In patients with previous malignant disease, special attention should be given to signs and symptoms 
of relapse. 
 
Patients with pre-existing tumors or growth hormone deficiency secondary to an intracranial lesion 
should be examined routinely for progression or recurrence of the underlying disease process. In 
childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients 
treated with somatropin after their first neoplasm. Intracranial tumors, in particular meningiomas, in 
patients treated with radiation to the head for their first neoplasm, were the most common of these 
second neoplasms. 

 
Prader-Willi syndrome 
NutropinAq is not indicated for the long-term treatment of paediatric patients who have growth 
failure due to genetically confirmed Prader-Willi syndrome, unless they also have a diagnosis of 
growth hormone deficiency. There have been reports of sleep apnoea and sudden death after 
initiating therapy with growth hormone in paediatric patients with Prader-Willi syndrome who had 
one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep 
apnoea, or unidentified respiratory infection. 

 
Acute critical illness 
The effects of growth hormone on recovery were studied in two placebo-controlled clinical trials 
involving 522 adult patients who were critically ill due to complications following open-heart or 
abdominal surgery, multiple accidental traumas, or who were having acute respiratory failure. 
Mortality was higher (41.9 % vs. 19.3 %) among growth hormone treated patients (doses 5.3 - 
8 mg/day) compared to those receiving placebo. 
 
The safety of continuing somatropin treatment in patients with acute critical illness in intensive care 
units due to complications following open-heart or abdominal surgery, multiple accidental trauma or 
acute respiratory failure receiving replacement doses for approved indications has not been 
established. Therefore, the benefit-risk assessment for continuing treatment should be performed 
carefully. 

 
Chronic renal insufficiency 
Patients with growth hormone failure secondary to CRI should be examined periodically for evidence 
of progression of renal osteodystrophy. Slipped capital femoral epiphyses and aseptic necrosis of the 
femoral head may be seen in children with advanced renal osteodystrophy and in growth hormone 
deficiency, and it is uncertain whether these problems are affected by GH therapy. Physicians and 
parents should be alert to the development of a limp or complaints of hip or knee pain in patients 
treated with NutropinAq. 

 
Scoliosis 
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. 

 
Glycaemic control 
Because somatropin may reduce insulin sensitivity, patients should be monitored for evidence of 
glucose intolerance. For patients with diabetes mellitus, the insulin dose may require adjustment after 
NutropinAq therapy is instituted. Patients with diabetes or glucose intolerance should be monitored 
closely during somatropin therapy. Somatropin therapy is not indicated in diabetic patients with 
active proliferative or severe non-proliferative retinopathy. 
 



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Intracranial hypertension 
Intracranial hypertension with papilloedema, visual changes, headache, nausea and/or vomiting has 
been reported in a small number of patients treated with somatropin. Symptoms usually occur within 
the first eight weeks of the initiation of NutropinAq therapy. In all reported cases, intracranial 
hypertension-associated signs and symptoms resolved after reduction of the somatropin dose or 
termination of the therapy. Funduscopic examination is recommended at the initiation and 
periodically during the course of treatment. 

 
Hypothyroidism 
Hypothyroidism may develop during treatment with somatropin, and untreated hypothyroidism may 
prevent optimal response to NutropinAq. Therefore, patients should have periodic thyroid function 
tests and should be treated with thyroid hormone when indicated. Patients with severe 
hypothyroidism should be treated accordingly prior to the start of NutropinAq therapy. 

 
Renal transplantation 
Since somatropin therapy following renal transplantation has not been adequately tested, NutropinAq 
treatment should be terminated after that surgery. 

 
Glucocorticoids use 
Concomitant treatment with glucocorticoids inhibits the growth-promoting effects of NutropinAq. 
Patients with ACTH deficiency should have their glucocorticoid replacement therapy carefully 
adjusted to avoid any inhibitory effect on growth. The use of NutropinAq in patients with chronic 
renal insufficiency receiving glucocorticoid therapy has not been evaluated. 

 
Leukaemia 
Leukaemia has been reported in a small number of growth hormone deficient patients treated with 
growth hormone. A causal relationship to somatropin therapy has not been established. 

 
Pancreatitis in children 
Children treated with somatropin have an increased risk of developing pancreatitis compared to 
adults treated with somatropin. Although rare, pancreatitis should be considered in somatropin-
treated children who develop abdominal pain. 
 
Use with oral oestrogen therapy 
If a woman taking NutropinAq begins oral oestrogen therapy, the dose of NutropinAq may need to 
be increased to maintain the serum IGF-1 levels within the normal age appropriate range. 
Conversely, if a woman on NutropinAq discontinues oral oestrogen therapy, the dose of NutropinAq 
may need to be reduced to avoid excess of growth hormone and/or side effects (see section 4.5). 

 
Excipients 
This medicinal product contains less than 1 mmol sodium (23 mg) per cartridge, i.e. essentially 
“sodium- free‟. 
 
Traceability 

In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Limited published data indicate that growth hormone treatment increases cytochrome P450 mediated 
antipyrine clearance in man. Monitoring is advisable when somatropin is administered in 
combination with medicinal products known to be metabolised by CYP450 liver enzymes, such as 
corticosteroids, sex steroids, anticonvulsants, and cyclosporin. 

 
In patients treated with somatropin, previously undiagnosed central (secondary) hypoadrenalism may 
be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with 
glucocortocoid replacement therapy for previously diagnosed hypoadrenalism may require an 
increase in their maintenance or stress doses, following initiation of somatropin treatment (see 



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section 4.4). 
 
In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral 
hypoglycemic medicinal product may require adjustment when somatropin therapy is initiated (see 
section 4.4). 
 
In women on oral oestrogen replacement, a higher dose of growth hormone may be required to 
achieve the treatment goal (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 

 
Pregnancy 
There are no or limited data from the use of somatropin in pregnant women. Thus, the risk for 
humans is unknown. 
Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). 
Somatropin is not recommended during pregnancy and should be discontinued if pregnancy occurs. 
During pregnancy, maternal somatropin will largely be replaced by placental growth hormone. 

 
Breast-feeding 
It is unknown whether somatropin/metabolites are excreted in human milk. No animal data are 
available. 
Caution should be exercised while breast-feeding during treatment with NutropinAq. 

 
Fertility 
The effect of NutropinAq has not been assessed in conventional animal fertility studies (see section 
5.3) or clinical studies. 

 
4.7 Effects on ability to drive and use machines 

 
Somatropin has no known effect on the ability to drive or to use machines. 

 
4.8 Undesirable effects 

 
Summary of the safety profile 
 
The adverse reactions reported in both adults and children receiving Nutropin, NutropinAq, Nutropin 
Depot or Protropin (somatrem) are listed in the table below, based on experience from clinical trials 
all approved indications (642 patients) and post-marketing sources which included a surveillance 
survey (National Cooperative Growth Study [NCGS] in 35,344 patients). Approximately 2.5 % of 
patients from the NCGS have experienced drug related adverse reactions. 

 
The most frequently reported adverse reactions from the pivotal and supportive clinical trials were 
hypothyroidism, impaired glucose tolerance, headache, hypertonia, arthralgia, myalgia, peripheral 
oedema, oedema, asthenia, injection site reaction and the presence of drug specific antibodies. 

 
The most serious adverse reactions from the pivotal and supportive clinical trials were neoplasm and 
intracranial hypertension. 

 
Neoplasms (malignant and benign) were reported in both the pivotal and supportive clinical trials and 
in the post-marketing surveillance survey (see sections 4.3 and 4.4). The majority of neoplasms 
reported were recurrence of previous neoplasms and second neoplasms. 

 
Intracranial hypertension was reported in the post-marketing surveillance survey. It is typically 
associated with papilloedema, visual changes, headache, nausea, and/or vomiting and symptoms 
usually occur within eight weeks of initiation of therapy with NutropinAq. 

 
NutropinAq reduces insulin sensitivity; glucose tolerance impairment was reported in both the pivotal 



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and supportive clinical trials and the post-marketing surveillance survey. Events of diabetes mellitus 
and hyperglycaemia were reported in the post-marketing surveillance survey (see section 4.4). 

 
Injection site reactions such as haemorrhage, atrophy, urticaria and pruritus were reported in the 
pivotal and supportive clinical trials and/or the post-marketing surveillance survey. These events can 
be avoided by correct injection technique and rotation of injection sites. 
A small percentage of patients may develop antibodies to the protein somatropin. The binding capacity 
of growth hormone antibodies was lower than 2 mg/l in NutropinAq subjects tested, which has not 
been associated with adversely affected growth rate. 

 
Tabulated summary of adverse reactions 

 
Table 1 contains very common (≥ 1/10), common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); 
rare (≥ 1/10,000, < 1/1,000) adverse reactions which occurred in clinical trials and a post-marketing 
surveillance survey. Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. Other adverse reactions have been identified during post approval use of 
NutropinAq. Because these reactions are reported voluntarily from a population of uncertain size, it is 
not possible to reliably estimate their frequency. 

 
System Organ Class Reactions observed in Pivotal and 

Supportive Clinical Trials (in 642 
patients) 

Reactions observed from the post 
marketing environment 

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

Uncommon: Neoplasm malignant, 
neoplasm benign 

Rare: Neoplasm malignant 
recurrence, melanocytic naevus 

Blood and lymphatic 
system disorders 

Uncommon: Anaemia  

Endocrine disorders Common: Hypothyroidism Rare: Hypothyroidism 
Metabolism and 
nutrition disorders 

Common: Glucose tolerance impaired 
Uncommon: Hypoglycaemia, 
hyperphosphatemia 

Rare: Diabetes mellitus, 
hyperglycaemia, hypoglycaemia, 
glucose tolerance impaired 

Psychiatric disorders Uncommon: Personality disorder Rare: Abnormal behaviour, 
depression, insomnia 

Nervous system 
disorders 

Common: Headache, hypertonia, 
Uncommon: Carpal tunnel syndrome, 
somnolence, nystagmus 

Uncommon: Headache Rare: Benign 
intracranial 
hypertension, intracranial pressure 
increased, migraine, carpal tunnel 
syndrome, paraesthesia, dizziness 

Eye disorders Uncommon: Papilloedema, diplopia Rare: Papilloedema, vision blurred 
Ear and labyrinth 
disorders 

Uncommon: Vertigo  

Cardiac disorders Uncommon: Tachycardia  
Vascular disorders Uncommon: Hypertension Rare: Hypertension 
Respiratory thoracic 
and mediastinal 
disorders 

 Rare: Tonsillar hypertrophy 
Uncommon: Adenoidal hypertrophy 

Gastrointestinal 
disorders 

Uncommon: Abdominal pain, 
vomiting, nausea, flatulence 

Rare: Abdominal pain, diarrhoea, 
nausea, vomiting 

Skin and subcutaneous 
tissue disorders 

Uncommon: Exfoliative dermatitis, 
skin atrophy, skin hypertrophy, 
hirsutism, lipodystrophy, urticaria 

Rare: Generalised pruritus, urticaria, 
rash 



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Musculoskeletal and 
connective tissue 
disorders 

Very common in adults, common in 
children: Arthralgia, myalgia 
Uncommon: Muscle atrophy, bone 
pain 

Uncommon: Slipped capital femoral 
epiphysis, scoliosis progression, 
arthralgia 
Rare: Bone development abnormal, 
osteochondrosis, muscular weakness, 
pain in extremity 

Renal and urinary 
disorders 

Uncommon: Urinary incontinence, 
pollakiuria, polyuria, urine 
abnormality 

 

Reproductive system 
and breast disorders 

Uncommon: Uterine haemorrhage, 
genital discharge 

Rare: Gynaecomastia 

General disorders and 
administration site 
conditions 

Very common in adults, common in 
children: Peripheral oedema, oedema 
Common: Asthenia, injection site 
reaction 
Uncommon: Injection site 
haemorrhage, injection site atrophy, 
injection site mass, hypertrophy 

Uncommon: Peripheral oedema, 
oedema, injection site reaction 
(irritation, pain) 
Rare: Asthenia, face oedema, fatigue, 
irritability, pain, pyrexia, injection 
site reaction (haemorrhage, 
haematoma, atrophy, urticaria, 
pruritus, swelling, erythema) 

Investigations Common: Drug specific antibody 
present 

Rare: Blood glucose increased, 
weight increased 

 
Description of selected adverse reactions 

 
Neoplasm 
There is a risk of neoplasia due to treatment with GH. The underlying risk varies according to the 
underlying cause for growth hormone deficiency (e.g. secondary to intracranial lesion), associated 
co- morbidities and treatment(s) undertaken. NutropinAq therapy must not be initiated when there is 
evidence of tumour activity. Patients with pre-existing tumours or growth hormone deficiency 
secondary to an intracranial lesion should be examined routinely for progression or recurrence of the 
underlying disease process. Treatment must be discontinued if there is evidence of tumour growth. 
 
Intracranial hypertension 
In all reported cases, intracranial hypertension associated signs and symptoms resolved after 
reduction of the NutropinAq dose or termination of therapy (see section 4.4). Fundoscopic 
examination is recommended at the initiation and periodically during the course of treatment. 
 
Hypothyroidism 
Hypothyroidism may develop during treatment with NutropinAq and untreated hypothyroidism may 
prevent optimal response to NutropinAq. Patients should have periodic thyroid function tests and 
should be treated with thyroid hormone when required. Patients with pre-existing hypothyroidism 
should be treated prior to the start of NutropinAq therapy. 
 
Glycaemic control 
As NutropinAq may reduce insulin sensitivity, patients should be monitored for evidence of glucose 
intolerance. For patients with diabetes mellitus, the dose of insulin may need adjustment after 
NutropinAq therapy is initiated. Patients with diabetes or glucose intolerance should be monitored 
closely during somatropin therapy. 
 
Injection site reactions 
Injection site reactions may be avoided by using the correct injection technique and rotation of 
injection sites. 
 

Slipped capital femoral epiphysis 



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Patients with endocrinological disorders are more prone to develop a slipped capital femoral 
epiphysis. 

 
Indication-specific adverse drug reactions from clinical trials 

 
Paediatric population 

 
Children with growth failure due to inadequate growth hormone secretion (n=236) 
Common: central nervous system neoplasm (2 patients experienced a recurrent medulloblastoma, 1 
patient experienced a histiocytoma). See also section 4.4. 

 
Girls with growth failure associated with Turner syndrome (n=108) 
Common: menorrhagia. 

 
Children with growth failure associated with chronic renal insufficiency (n=171) 
Common: renal failure, peritonitis, osteonecrosis, blood creatinine increase. Children with chronic 
renal insufficiency receiving NutropinAq are more likely to develop intracranial hypertension, 
although children with organic GHD and Turner syndrome also have an increased incidence. The 
greatest risk is at the beginning of treatment. 

 
Adult population 

 
Adults with growth hormone deficiency (n=127) 
Very common: paraesthesia. 
Common: hyperglycaemia, hyperlipidaemia, insomnia, synovial disorder, arthrosis, muscular 
weakness, back pain, breast pain, gynaecomastia. 

 
Reporting of suspected adverse reactions 

 
Reporting of suspected adverse reactions after authorization of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 

 
4.9 Overdose 

 
Symptoms 

 
Acute overdose could lead to hyperglycaemia. Long-term overdose could result in signs and 
symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth 
hormone. 

 
Management 

 
Treatment is symptomatic and supportive. There is no antidote for somatropin overdose. It is 
recommended to monitor thyroid function following an overdose. 
 
 
5. PHARMACOLOGICAL PROPERTIES 

 
5.1 Pharmacodynamic properties 

 
Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, Somatropin and 
analogues, ATC Code: H01 AC 01 

 
Mechanism of action 

 



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Somatropin stimulates growth rate and increases adult height in children who lack endogenous 
growth hormone and in children who have growth failure due to Turner Syndrome or CRI. Treatment 
of growth hormone deficient adults with somatropin results in reduced fat mass, increased lean body 
mass and increased spine bone mineral density. Metabolic alterations in these patients include 
normalisation of IGF-I serum levels. 

 
Pharmacodynamic effects 

 
In vitro and in vivo preclinical and clinical tests have demonstrated that somatropin is therapeutically 
equivalent to human growth hormone of pituitary origin. 

 
Actions that have been demonstrated for human growth hormone include: 

 
Tissue Growth 
1. Skeletal growth: growth hormone and its mediator IGF-I stimulate skeletal growth in growth 
hormone deficient children by an effect on the epiphyseal plates of long bones. This results in a 
measurable increase in body length until these growth plates fuse at the end of puberty. 
2. Cell growth: Treatment with somatropin results in an increase in both the number and size of 
skeletal muscle cells. 
3. Organ growth: Growth hormone increases the size of internal organs, including kidneys, and 
increases red blood cell mass. 

 
Protein metabolism 
Linear growth is facilitated in part by growth hormone-stimulated protein synthesis. This is reflected 
by nitrogen retention as demonstrated by a decline in urinary nitrogen excretion and blood urea 
nitrogen during growth hormone therapy. 

 
Carbohydrate metabolism 
Patients with inadequate growth hormone secretion sometimes experience fasting hypoglycaemia that 
is improved by treatment with somatropin. Growth hormone therapy may decrease insulin sensitivity 
and impair glucose tolerance. 

 
Mineral metabolism 
Somatropin induces retention of sodium, potassium and phosphorus. Serum concentration of 
inorganic phosphorus are increased in patients with growth hormone deficiency after NutropinAq 
therapy due to metabolic activity associated with bone growth and increased tubular reabsorption in 
the kidney. Serum calcium is not significantly altered by somatropin. Adults with growth hormone 
deficiency show low bone mineral density and in the childhood-onset patient, NutropinAq has been 
shown to increase spine bone mineral density in a dose-dependent manner. 

 
Connective tissue metabolism 
Somatropin stimulates the synthesis of chondroitin sulphate and collagen as well as the urinary 
excretion of hydroxyproline. 

 
Body composition 
Adult growth hormone deficient patients treated with somatropin at a mean dosage of 0.014 mg/kg 
bodyweight daily demonstrate a decrease in fat mass and increase in lean body mass. When these 
alterations are coupled with the increase in total body water and bone mass, the overall effect of 
somatropin therapy is to modify body composition, an effect that is maintained with continued 
treatment. 

 
Clinical efficacy and safety 

 
Growth failure in children 

 
Two pivotal, open label, uncontrolled, multicentre studies have been conducted, one exclusively 
in previously untreated patients (n=67), and the other in previously untreated patients (n=63) 



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and in children previously treated with somatropin (n=9). The dose in both studies was 0.043 
mg/kg/day, administered subcutaneously (s.c.). Doses used in these US based studies are consistent 
with the US approved dose regimen. Of the 139 patients included, 128 completed the first 12 
months of therapy, with an average treatment time of 3.2 and 4.6 years and a total exposure of 542 
patient years. In both studies there was a significant improvement in growth rate in the naïve 
patients, increasing from 4.2 to 10.9 cm/year in one study and from 4.8 to 11.2 cm/year in the other 
at 12 months. The growth rate decreased after the first year in both studies, but continued to be 
greater than pretreatment levels for up to 48 months treatment (7.1 cm/year). The height standard 
deviation score (SDS) improved each year, increasing from -3.0 to -2.7 at baseline to -1.0 to -0.8 at 
Month 36. The improvements in growth were not accompanied by undue advancement of bone 
age, which would jeopardise future growth potential. Predicted adult height (PAH) increased from 
157.7-161.0 cm at baseline to 161.4-167.4 cm at Month 12 and 166.2-171.1 cm at Month 36. 

 
Supportive data are provided by two other studies, in which patients were given a dose of 0.3 
or 0.6 mg/kg/week either as a daily injection or three times per week, or 0.029 mg/kg/day. The 
data on growth rate and height SDS were broadly similar to those observed in the pivotal studies. 

 
For 51 patients who achieved near-adult height after an average duration of treatment of 6 years 
in males and 5 years in females, the mean near-adult height SDS was -0.7 in males and -1.2 in 
females. 

 
IGF-I levels increased from a baseline of 43 ng/ml to 252 ng/ml at 36 months, which approximate 
to the normal levels expected in children of this age. 

 
The most common adverse events (AEs) observed in the pivotal studies were infection, 
headache, otitis media, fever, pharyngitis, rhinitis and gastroenteritis and vomiting. 

 
Growth failure associated with chronic renal insufficiency 

 
Two pivotal, multicentre, controlled studies have been conducted in patients with growth 
failure associated with chronic renal insufficiency (CRI). Each study had a two year treatment 
period which included a placebo arm, followed by an open label uncontrolled extension in 
which all patients received somatropin. The dose was 0.05 mg/kg/day s.c. in both studies. The 
results of both studies were similar. 

 
In total, 128 patients received somatropin over the 24 month controlled phase of the 2 studies, 
and 139 patients were treated with somatropin in the open extension phases. Overall, 171 patients 
were exposed to somatropin for an average of 3.5 or 2.8 years. 

 
Both studies demonstrated a statistically significant increase in growth rate compared to placebo 
over the first year (9.1-10.9 cm/year vs 6.2-6.6 cm/year), which decreased slightly in the 
second year (7.4-7.9 cm/year vs 5.5-6.6 cm/year). There was also a significant increase in height 
SDS in somatropin-treated patients, from -2.9 to -2.7 at baseline to -1.6 to -1.4 at 24 months. 
Height gains were maintained in the patients treated for 36 or 48 months. A total of 58% and 
65% of somatropin-treated patients, who were below normal range at baseline, had reached heights 
within the normal range by Month 24. 
The results to Month 60 show continued improvement, and more patients reached height SDS in 
the normal range. The average change in height SDS after 5 years of treatment was close to 2 
standard deviations (SDs). A statistically significant increase in mean PAH SDS was observed, 
from -1.6 or 
-1.7 at baseline to -0.7 or -0.9 at Month 24. This continued to increase in those patients treated for 
36 and 48 months. 

 
IGF-I levels, which were low at study entry, were restored to within the normal range with 
somatropin therapy. 

 
The most frequently reported AEs were associated with both NutropinAq and placebo and were 



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fever, infection, vomiting, cough increased, pharyngitis, rhinitis and otitis media. There was a high 
incidence of urinary tract infections. 

 
Growth failure associated with Turner Syndrome 

 
One pivotal, multicentre, open label, controlled study has been conducted in Turner Syndrome. 
Patients received an s.c. dose of 0.125 mg/kg three times a week or 0.054 mg/kg/day, both regimens 
giving a cumulative weekly dose of approximately 0.375 mg/kg. Patients under 11 years of age were 
also randomised to receive oestrogen therapy, either in late (aged 15 years) or early (aged 12 years) 
adolescence. 

 
A total of 117 patients were treated with somatropin; 36 received somatropin 0.125 mg/kg three times 
a week and 81 patients received 0.054 mg/kg somatropin daily. The average treatment time was 4.7 
years in the somatropin three times a week group and 4.6 years in the somatropin daily group. 

 
Growth rate increased significantly from 3.6-4.1 cm/year at baseline to 6.7-8.1 cm/year at Month 12, 
6.7-6.8 cm/year at Month 24 and 4.5-5.1 cm/year at Month 48. This was accompanied by a significant 
increase in height SDS from -0.1 to 0.5 at baseline to 0.0 to 0.7 at Month 12 and 1.6 to 1.7 at Month 
48. Compared with matched historical controls, early somatropin therapy (mean duration of 5.6 years) 
combined with oestrogen replacement at age 12 years resulted in an adult height gain of 5.9 cm 
(n=26), whereas girls who initiated oestrogen at age 15 years (mean duration of somatropin therapy 
6.1 years) had a mean adult height gain of 8.3 cm (n=29). Thus, the greatest improvement in adult 
height was observed in patients who received early GH treatment and oestrogen after age 14 years. 

 
The most commonly reported AEs were flu syndrome, infection, headache, pharyngitis, rhinitis and 
otitis media. These events are expected in children and were mild/moderate AEs. 

 
Growth hormone deficiency in adults 

 
Two pivotal, multicentre, placebo-controlled, double-blind studies have been conducted in patients 
diagnosed with adult growth hormone deficiency (AGHD), one in adult-onset AGHD (n=166) and the 
other in childhood-onset AGHD (n=64). The dose of somatropin was 0.0125 mg/kg/day sc in adult-
onset AGHD and 0.0125 or 0.025 mg/kg/day in childhood-onset AGHD. 
In both studies, somatropin treatment resulted in significant changes compared to placebo in total 
body % fat (-6.3 to -3.6 vs +0.2 to-0.1), trunk % fat (-7.6 to -4.3 vs +0.6 to 0.0) and total body % lean 
(+3.6 to +6.4 vs -0.2 to +0.2). These changes were highly significant at the 12-month time point in 
both studies, and at the 24-month time point in the childhood-onset study. At the 12-month time point, 
the percentage change was higher in the childhood-onset study than in the adult-onset study. No 
significant changes in bone mineral density (BMD) were observed in adult-onset AGHD patients, 
however in the childhood-onset study, all groups had an increase in BMD at 24 months, although 
there was no statistically significant dose response for total body BMD. Lumbar spine BMD had 
statistically significant increases in both treated groups, and the increase was dose dependent. 

 
Supporting data from a study on adult-onset GHD patients were generally consistent with those of the 
pivotal studies, with some improvements in BMD. 
The most frequently reported AEs in the two pivotal studies were headache, oedema, 
arthralgia/arthrosis, tenosynovitis, paraesthesia and allergic reaction/rash. The incidence of these AEs 
was also high in the placebo groups. 

 
5.2 Pharmacokinetic properties 

 
The pharmacokinetic properties of NutropinAq have only been investigated in healthy adult males.  
 
General characteristics 
 
Absorption 
The absolute bioavailability of recombinant human growth hormone after subcutaneous 



13  

administration is about 80%. 
 

Distribution  
Animal studies with somatropin showed that growth hormone localises to highly perfused organs, 
particularly the liver and kidney. The volume of distribution at steady state for somatropin in 
healthy adult males is about 50 ml/kg bodyweight, approximating the serum volume. 

 
Biotransformation  
Both the liver and the kidney have been shown to be important protein catabolising organs for 
growth hormone. Animal studies suggest that the kidney is the dominant organ of clearance. Growth 
hormone is filtered at the glomerulus and reabsorbed in the proximal tubules. It is then cleaved 
within renal cells into its constituent amino acids, which return to the systemic circulation. 

 
Elimination  
After subcutaneous bolus administration, the mean terminal half-life t½ of somatropin is about 2.3 
hours. After intravenous bolus administration of somatropin, the mean terminal half-life t½β or 
t½γ is about 20 minutes and the mean clearance is reported to be in the range of 116 - 174 ml/h/kg. 
Available literature data suggest that somatropin clearance is similar in adults and children. 

 
Special populations 

 
Information about the pharmacokinetics of somatropin in elderly and paediatric populations, in 
different races or genders and in patients with renal or hepatic impairment is incomplete. 

 
Paediatric population 
Available literature data suggests that somatropin clearances are similar in adults and children. 

 
Older people 
Limited published data suggest that the plasma clearance and average steady-state plasma 
concentration of somatropin may not be different between young and elderly patients. 

 
Race 
Reported values for half-lives for endogenous GH in normal adult black males are not different from 
observed values for normal adult white males.  No data for other races are available. 

 
Growth hormone deficiency 
Clearance and mean terminal half-life t½ of somatropin in adult and paediatric growth hormone 
deficient patients are similar to those observed in healthy subjects. 

 
Renal impairment 
Children and adults with chronic renal failure and end-stage renal disease tend to have decreased 
clearance compared to normal subjects. Endogenous growth hormone production may also increase 
in some individuals with end-stage renal disease. However, no somatropin accumulation has been 
reported in children with chronic renal failure or end-stage renal disease dosed with current 
regimens. 

 
Turner syndrome 
Limited published data for exogenously-administered somatropin suggest absorption and elimination 
half-lives and time of maximum concentration tmax in Turner patients are similar to those observed in 
both normal and growth hormone deficient populations. 

 
Hepatic impairment 
In patients with severe liver dysfunction a reduction in somatropin clearance has been noted. The 
clinical significance of this decrease is unknown. 

 
Gender 
No gender-specific pharmacokinetic studies have been done with NutropinAq. The available 



14  

literature indicates that the pharmacokinetics of somatropin are similar in men and women. 
 

5.3 Preclinical safety data 
 

Non-clinical data reveal no special hazard for human based on conventional acute and repeated-dose 
toxicity studies. 

 
Carcinogenic potential 

 
Carcinogenicity and genotoxicity studies have not been conducted with Nutropin Aq. In genotoxicity 
studies with other recombinant growth hormone preparations, there was no evidence of gene 
mutation in bacterial reverse mutation assays, chromosomal damage in human lymphocyte and 
mouse bone marrow cells, gene conversion in yeast or unscheduled DNA synthesis in human 
carcinoma cells. In carcinogenicity studies testing biologically recombinant active growth hormone in 
rats and mice, no increase in the incidence of tumors was shown. 

 
Toxicity to reproduction and development 

 
No conventional reproduction studies were performed. Somatropin is known to be associated with 
inhibition of the reproduction in male and female rats at doses of 3 IU/kg/day (1 mg/kg/day) or more, 
with reduced copulation and conception rates, lengthened or absent oestrous cycles, and at 
10 IU/kg/day (3.3 mg/kg/day). Long-term treatment of monkeys during pregnancy and lactation and 
of newborn animals until adolescence, sexual maturity and reproduction did not indicate substantial 
disturbances of fertility, pregnancy, delivery, nursing or development of progeny. 

 
Environmental risk assessment (ERA) 

 
Under the proposed indications, the use of somatropin is not expected to result in an unacceptable 
risk to the environment. 

 
 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Sodium Chloride  
Liquified Phenol 
Polysorbate 20  
Sodium Citrate Dihydrate 
Citric Acid, Anhydrous  
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 

 
Chemical and physical in-use stability has been demonstrated for 28 days at 2°C - 8°C. 

 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 
days at 2°C - 8°C. NutropinAq is designed to withstand a nominal (one hour maximum) period of 
time outside of the refrigerator on a daily basis. 

 



15  

6.4 Special precautions for storage 
 

Store in a refrigerator (2°C - 8°C). Do not freeze. 
Keep the blister in the outer carton 

 
For in-use storage conditions of the medicinal product, see section 6.3. 

 
6.5 Nature and contents of container 

 
2 ml of solution in a cartridge (Type I glass) closed with a stopper (butyl rubber) and a seal (rubber). 
Pack sizes of 1, 3 and 6 cartridges. 
Not all pack sizes may be marketed. 

 
6.6 Special precautions for disposal 

 
No special requirements. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 
Instructions for use and handling 

 
NutropinAq is supplied as a multi-dose solution. After removal from the refrigerator, if the solution 
is cloudy, the content must not be injected. Gently swirl. Do not shake vigorously as it could 
denature the protein. 

 
NutropinAq is intended for use only with the NutropinAq Pen. Wipe the rubber seal of the 
NutropinAq with rubbing alcohol or an antiseptic solution to prevent contamination of the contents 
by microorganisms that may be introduced by repeated needle insertions. It is recommended that 
NutropinAq be administered using sterile, disposable needles. 

 
The NutropinAq Pen allows for administration of a minimum dose of 0.1 mg to a maximum dose of 
4.0 mg, in 0.1 mg increments. 

 
A cartridge that is in the pen should not be removed during injections. 
 
 
7. MARKETING AUTHORISATION HOLDER 

 
Ipsen Pharma 
65 quai Georges Gorse,  
92100 Boulogne-Billancourt,  
France 

 
 

8. MARKETING AUTHORISATION NUMBERS 
 

EU/1/00/164/003  
EU/1/00/164/004  
EU/1/00/164/005 

 
 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 16 February 2001  
Date of latest renewal: 16 February 2006 

 
 



16  

10. DATE OF REVISION OF THE TEXT 
 

DD/MM/YYYY 
 

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



17  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 



18  

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 

 
Genentech Inc.  
1 DNA Way 
South San Francisco  
CA 94080-4990  
USA 

 
Name and address of the manufacturer responsible for batch release 

 
Ipsen Pharma Biotech SAS 
Parc d’Activités du Plateau de Signes, 
Chemin Départemental no 402, 
83870 Signes  
France 

 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 

 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

• Phamacovigilance System 
 

The marketing authorisation holder (MAH) must ensure that the system of 
pharmacovigilance, presented in Module 1.8.1 of the Marketing Authorisation, is in place 
and functioning before and whilst the medicinal product is on the market. 

 
• Periodic safety update reports (PSURs) 

 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-
portal. 

 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
• Risk management plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed 
in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed 
subsequent updates of the RMP. 

 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



19  

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 



20  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



21  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



22  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
{CARTON - 1 CARTRIDGE} 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 

NutropinAq 10 mg/2 ml (30 IU), solution for injection  
somatropin 

 
 

2. STATEMENT OF ACTIVE SUBSTANCE 
 

One ml contains 5 mg of somatropin 
One cartridge contains 10 mg (30 IU) of somatropin 
 
 
3. LIST OF EXCIPIENTS 

 
Other ingredients: sodium chloride, liquefied phenol, polysorbate 20, sodium citrate dihydrate, citric 
acid anhydrous and water for injections. 

 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 

1 cartridge containing 2 ml solution for injection 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Subcutaneous use 
Read the package leaflet before use. 

 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 

 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 

8. EXPIRY DATE 
 

EXP: {date} 
After first opening, use before 28 days at 2°C – 8°C. 



23  

9. SPECIAL STORAGE CONDITIONS 
 

Store in a refrigerator. Do not freeze. 
Keep the blister in the outer carton. 

 
Chemical and physical in-use stability has been demonstrated for 28 days at 2°C - 8°C. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 
days at 2°C - 8°C. 

 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, France 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/00/164/003 1 cartridge 
EU/1/00/164/004 3 cartridges 
EU/1/00/164/005 6 cartridges 

 
 

13. BATCH NUMBER 
 

Lot: {number} 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 

Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 
 

16. INFORMATION IN BRAILLE 
 

NutropinAq 10 mg/2 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 

 
<2D barcode carrying the unique identifier included> 

 
 



24  

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 

< PC: {number} 
SN: {number} 
NN: {number} 



25  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
{CARTON - 3 CARTRIDGES} 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 

NutropinAq 10 mg/2 ml (30 IU), solution for injection  
somatropin 

 
 

2. STATEMENT OF ACTIVE SUBSTANCE 
 

One ml contains 5 mg of somatropin 
One cartridge contains 10 mg (30 IU) of somatropin 

 
 

3. LIST OF EXCIPIENTS 
 

Other ingredients: sodium chloride, liquefied phenol, polysorbate 20, sodium citrate dihydrate, citric 
acid anhydrous and water for injections. 

 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 

3 cartridges containing 2 ml solution for injection 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Subcutaneous use. 
Read the package leaflet before use. 

 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 

 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 

8. EXPIRY DATE 
 

EXP: {date} 
After first opening, use before 28 days at 2°C – 8°C. 



26  

9. SPECIAL STORAGE CONDITIONS 
 

Store in a refrigerator. Do not freeze. 
Keep the blister in the outer carton. 

 
Chemical and physical in-use stability has been demonstrated for 28 days at 2°C - 8°C. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 
days at 2°C - 8°C. 

 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, France 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/00/164/003 1 cartridge 
EU/1/00/164/004 3 cartridges 
EU/1/00/164/005 6 cartridges 

 
 

13. BATCH NUMBER 
 

Lot: {number} 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 

Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 
 

16. INFORMATION IN BRAILLE 
 

NutropinAq 10 mg/2 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 

 
<2D barcode carrying the unique identifier included> 

 
 



27  

 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 
< PC: {number} 
SN: {number} 
NN: {number} 

 



28  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
{CARTON - 6 CARTRIDGES} 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 

NutropinAq 10 mg/2 ml (30 IU), solution for injection  
somatropin 

 
 

2. STATEMENT OF ACTIVE SUBSTANCE 
 

One ml contains 5 mg of somatropin 
One cartridge contains 10 mg (30 IU) of somatropin 

 
 

3. LIST OF EXCIPIENTS 
 

Other ingredients: sodium chloride, liquefied phenol, polysorbate 20, sodium citrate dihydrate, citric 
acid anhydrous and water for injections. 

 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 

6 cartridges containing 2 ml solution for injection 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Subcutaneous use. 
Read the package leaflet before use. 

 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 

 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 

8. EXPIRY DATE 
 

EXP: {date} 
After first opening, use before 28 days at 2°C – 8°C. 



29  

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Keep the blister in the outer carton. 

 
Chemical and physical in-use stability has been demonstrated for 28 days at 2°C - 8°C. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 
days at 2°C - 8°C. 

 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, France 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/00/164/003 1 cartridge 
EU/1/00/164/004 3 cartridges 
EU/1/00/164/005 6 cartridges 

 
 

13. BATCH NUMBER 
 

Lot: {number} 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 

Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 
 

16. INFORMATION IN BRAILLE 
 

NutropinAq 10 mg/2 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 

 
<2D barcode carrying the unique identifier included> 

 
 



30  

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 

< PC: {number} 
SN: {number} 
NN: {number} 

 



31  

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
{BLISTER} 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 

NutropinAq 10 mg/2 ml (30 IU) solution for injection  
somatropin 

 
 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 

Ipsen Pharma. 
 
 

3. EXPIRY DATE 
 

EXP: {date} 
 
 

4. BATCH NUMBER 
 

Lot: {number} 
 
 

5. OTHER 
 

Subcutaneous use. 
Read the package leaflet before use. Store in a refrigerator. 



32  

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
{CARTRIDGE} 

 
 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 

NutropinAq 10 mg/2 ml  
SC 

 
 

2. METHOD OF ADMINISTRATION 
 
 
 

3. EXPIRY DATE 
 

EXP: {date} 
 
 

4. BATCH NUMBER 
 

Lot: {number} 
 
 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 

2 ml 
 

6. OTHER 
 
 
 



33  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



34  

Package leaflet: Information for the user 
 

NutropinAq 10 mg/2 ml (30 IU) solution for injection 
somatropin 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- 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 only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 

What is in this leaflet 
1. What NutropinAq is and what it is used for 
2. What you need to know before you use NutropinAq 
3. How to use NutropinAq 
4. Possible side effects 
5. How to store NutropinAq 
6. Contents of the pack and other information 

 
 

1. What NutropinAq is and what it is used for 
 

NutropinAq contains somatropin which is a recombinant growth hormone similar to the human’s 
natural growth hormone made by your body. It is recombinant, meaning it is made outside of the 
body by a special process. Growth Hormone (GH) is a chemical messenger made by a small gland in 
your brain called the pituitary. In children it tells the body to grow, help the bones to develop 
normally and, in later adult life, GH helps to maintain a normal body shape and metabolism. 

 
In children, NutropinAq is used: 
• When your body does not make enough growth hormone and for this reason you are not 

growing properly. 
• When you have Turner syndrome. Turner syndrome is a genetic abnormality in girls (absence 

of female sexual chromosome(s)) that prevents growth. 
• When your kidneys are damaged and they lose their ability to function normally with an impact 

on growth. 
 

In adults NutropinAq is used for: 
• If your body does not make enough growth hormone as an adult. This can start during adult life 

or continue from when you were a child. 
 
Benefits if using this medicine 
 
In children, it helps the body to grow and the bones to develop normally. 
In adults, it helps to maintain normal body shape and metabolism for example lipid profile and 
glucose levels. 
 
 
2. What you need to know before you use NutropinAq  
 
Do not use NutropinAq: 
• if you are allergic to somatropin or any of the other ingredients of this medicine (listed in 

section 6). 
• in children if the bones have already stopped growing. 
• if you have an active tumour (cancer). Tell your doctor if you have or have had an active 



35  

tumour. Tumours must be inactive and you must have finished your anti-tumour treatment 
before you start treatment with NutropinAq. 

• if you have complications after a major surgery (open-heart or abdominal surgery), a multiple 
trauma, acute respiratory failure, or similar conditions. 

 
Warning and Precautions 
 
Talk to you doctor or pharmacist before using NutropinAq. 

 
• If you experience visual changes, bad or frequent headache, associated with feeling sick 

(nausea) or vomiting, especially at the start of treatment, tell your doctor immediately. These 
could be signs of a temporary increase in pressure within the brain (intracranial hypertension). 

• If during growing, a limp or hip or knee pain develops, ask the doctor for advice. 
• If you notice a curve of your spine (scoliosis) you will need to be checked often by your doctor 

as scoliosis may progress in any child during rapid growth. 
• Your doctor should monitor you for high blood sugar levels (hyperglycemia) during treatment 

with NutropinAq. If you are treated with insulin, your doctor may need to adjust your insulin 
dose. If you have diabetes and associated severe/worsening eye disease you should not be 
treated with NutropinAq. 

• Your doctor should check your thyroid function periodically and if necessary prescribe 
adequate treatment. If you have an underactive thyroid gland leading to low levels of thyroid 
hormone (hypothyroidism) it should be treated before you start NutropinAq treatment. If your 
hypothyroidism is not treated, it could stop NutropinAq from working. 

• If you have a replacement therapy with glucocorticoids you should consult your doctor 
regularly as you may need adjustment of your glucocorticoid dose. 

• If you have had a tumour (cancer) in the past, specially a tumour affecting the brain, your 
doctor should pay special attention and examine you regularly for a possible return of the 
tumour. 

• A small number of growth hormones deficient patients treated with growth hormone have had 
leukaemia (blood cancer). However, no cause and effect relationship with growth hormone 
treatment has been proven. 

• If you undergo a kidney transplant NutropinAq treatment should be stopped. 
• If you have complications after major surgery (open-heart or abdominal surgery), multiple 

trauma, acute respiratory failure, or similar conditions, your doctor should decide whether it is 
safe to continue NutropinAq treatment. 

• There may be an increased risk of developing an inflammation of the pancreas (pancreatitis) in 
children compared to adults treated with growth hormone. In case of severe and persistent 
abdominal pain, consult your doctor. 

• If you have Prader-Willi syndrome, you should not be treated with NutropinAq unless you 
have growth hormone deficiency. 

 
 
Other medicines and NutropinAq 
 
Tell your doctor or pharmacist if you are using, have recently used or might take any other medicines. 

 
• if you have a replacement therapy with glucocorticoids it may reduce the effect of NutropinAq 

on growth. You should consult your doctor regularly as you may need adjustment of your 
glucocorticoid dose. 

 
• if you are treated with insulin, your doctor may need to adjust your insulin dose. 

 
• if you are treated with sex steroids, anticonvulsants or cyclosporin ask the doctor for advice. If 

you are diagnosed with adrenal insufficiency during NutropinAq treatment, you require steroid 
treatment. If you are already treated for adrenal insufficiency you may require an adjustment 
of your steroid dose. 



36  

 
• in particular, inform your doctor if you are taking or have recently taken any of the following 

medicines. Your doctor may need to adjust the dose of NutropinAq or of the other medicines: 
- Oestrogen taken orally or other sex hormones 

 
Pregnancy and breast-feeding 

 
You should stop taking NutropinAq if you are pregnant. 
Caution should be exercised while breast-feeding during treatment with NutropinAq. 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 

 
Driving and using machines 

 
No effect on ability to drive or use machines has been noticed while using NutropinAq. 

 
NutropinAq is essentially “sodium free” 

 
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially “sodium-
free”. 

 
 

3. How to use NutropinAq 
 

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. NutropinAq therapy should be carried out under regular guidance 
of a doctor who is experienced in growth hormone deficiency. 
 
The dose of NutropinAq to be injected will be decided by your doctor. Do not change the dosage 
without consulting your doctor. The recommended dose is: 
 
In children with growth hormone deficiency: 
0.025 - 0.035 mg/kg bodyweight injected each day under the skin (subcutaneous injection). 

 
In girls with Turner syndrome: 
Up to 0.05 mg/kg bodyweight injected each day under the skin (subcutaneous injection). 

 
In children with chronic renal insufficiency: 
Up to 0.05 mg/kg bodyweight injected each day under the skin (subcutaneous injection).  You can 
continue treatment with NutropinAq until you have a kidney transplant. 

 
In adults with growth hormone deficiency: 
Low initial doses of 0.15 - 0.3 mg injected each day under the skin (subcutaneous injection). Then 
the doctor can increase the dose depending on your response. The final dose is rarely above 1.0 
mg/day. In general, the lowest dose leading to a response should be given to you. 

 
Treatment with NutropinAq is a long-term therapy. For further information ask your doctor. 

 
How to inject NutropinAq 
 
The dose of NutropinAq to be injected will be decided by your doctor. You have to inject NutropinAq 
every day under the skin (subcutaneous injection). It is important to change the place where you have 
your injection every day to avoid damaging your skin. 
NutropinAq is supplied as a multi-dose solution. After removal from the refrigerator, if the solution is 
cloudy, the content must not be injected. Gently swirl. Do not shake vigorously as it could denature 
the protein. 
 



37  

To inject NutropinAq you should use the NutropinAq Pen. For each injection you should use a new 
sterile injection needle. Read all the instructions for use carefully (on the reverse) before you start 
using NutropinAq Pen. At the start of therapy, it is recommended that a doctor or a nurse give you 
the injection and train you with the NutropinAq Pen. After this training, you will be able to inject 
yourself or be injected by a trained care-giver. 

 
If you use more NutropinAq than you should 
 
If you have injected more NutropinAq than you should have, contact your doctor for advice. If you 
inject too much NutropinAq, your blood sugar level may decrease and become too low and then rise 
too high (hyperglycaemia). 

 
If you inject too much NutropinAq over a long period of time (years), you may experience some 
overgrowth of parts of your body such as ears, nose, lips, tongue and cheekbone (gigantism and/or 
acromegaly). 

 
If you forget to take NutropinAq 
 
Do not take a double dose to make up for a missed dose. Continue with your usual dosage the next 
day and tell your doctor at your next appointment. 

 
If you stop using NutropinAq 
 
Ask advice from you doctor before you stop using NutropinAq. If you stop using NutropinAq too 
early or for too long, the results will not be as expected. 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 
 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 

Tell your doctor immediately if you notice any change or increase in growth of birthmarks and/or 
moles (melanocytic naevus). In case of a tumour or re-growth of previous tumours (confirmed by 
your doctor), treatment with NutropinAq must be stopped immediately. This side effect is 
uncommon, it may affect up to 1 in 100 patients. 

 
Tell your doctor immediately if you experience visual changes, bad or frequent headaches, associated 
with feeling sick (nausea) or vomiting. These could be symptoms of a temporary increase in pressure 
within the brain (intracranial hypertension). If you have intracranial hypertension, your doctor may 
decide to temporarily reduce or discontinue NutropinAq therapy. Then therapy may be started again 
after the episode is over. This side effect is rare, it may affect up to 1 in 1,000 patients. 

 
Other side effects include: 
 
Very common (may affect more than 1 in 10 patients) 
 
Swelling of the hands and feet due to an accumulation of fluid (peripheral oedema) sometimes 
associated with localised muscle pain (myalgia) and pain in joints (arthralgia).  These side effects 
appear usually in adults early in treatment and are short-lived. Oedema was reported as common in 
children. 

 
Common (may affect up to 1 in 10 people) 
 
Underactivity of the thyroid gland leading to low levels of thyroid hormone (hypothyroidism). If your 
hypothyroidism is not treated, it could stop NutropinAq from working. Your doctor should check your 



38  

thyroid function periodically and if necessary prescribe adequate treatment. 
 
Reduced ability to absorb sugar (glucose) from your blood leading to high blood sugar levels 
(hyperglycemia). Your doctor should monitor you for signs of this during treatment with NutropinAq. 
If you are treated with insulin, your doctor may need to adjust your insulin dose. 
 
Feeling of weakness (asthenia) and increased muscle tension (hypertonia) 
 
Pain, bleeding, bruising, rash and itching at the site of injection. These can be avoided by using the 
correct injection technique and changing the sites of injection. 
 
Some patients may develop antibodies (a type of protein produced by the body) to somatropin. When 
these antibodies were found in patients, it did not prevent them from growing. 

 
Uncommon (may affect up to 1 in 100 people) 
 
Decrease in the number of red blood cells in the blood (anaemia), decrease in blood sugar level 
(hypoglycaemia) and increase in phosphate levels (hyperphosphatemia). 
 
Personality changes or abnormal behaviour. 
 
Persistent stinging, burning sensation, pain and/or numbness in the palm of the hand due to a trapped 
nerve at the wrist (carpal tunnel syndrome). 
 
Rapid involuntary movements of the eyes (nystagmus), swelling of the optic nerve in the eye 
(papilloedema), double vision (diplopia), headache, somnolence and vertigo. 
 
Increased heart rate (tachycardia) and high blood pressure (hypertension). Vomiting, stomach pain, 
wind (flatulence) and feeling of sickness (nausea). 
 
Sensitive and dry skin (exfoliative dermatitis), changes in thickness of the skin, excessive growth of 
hair on the face and body (hirsutism), hives (urticaria). 
 
Curvature of the spine (scoliosis). If you have scoliosis, you will need to be frequently checked for an 
increase in the curve. 
 
Bone disorder where the upper leg (femur) moves apart from the hip (slipped capital femoral 
epiphysis). This happens generally in patients who grow rapidly. Patients with endocrinological 
disorders are more prone to develop a slipped capital femoral epiphysis. 
 
Decrease in muscle size (muscle atrophy), joint pain (arthralgia) and bone pain. 
 
Difficulty to hold-in urine (urinary incontinence), high frequency (pollakiuria) and volume (polyuria) 
of urination. 
 
Bleeding from the womb (uterine haemorrhage) and genital discharge. 
 
Localised loss/gain of fat from the skin (lipodystrophy, injection site atrophy/hypertrophy)  
Enlarged adenoids with similar symptoms as enlarged tonsils (see rare). 
 
Rare (may effect up to 1 in 1,000 people) 
 
Increase in blood sugar levels (hyperglycaemia, diabetes mellitus). Diabetes mellitus can lead to 
increased urination, thirst and hunger. If you experience any of these symptoms, you should inform 
your doctor. 
 
Enlarged tonsils leading to snoring, difficulty breathing or swallowing, brief interruption of breathing 



39  

during sleep (sleep apnea), or fluid in the ear, as well as infections of the ear. If this appears to be 
particularly troublesome, you should discuss it with your doctor. 
 
Abnormal sensations of tingling, pricking or numbness (paraesthesia), abnormal bone development, 
disease affecting progress of bone growth (osteochondrosis) and muscle weakness. 
 
Other rare side effects seen with NutropinAq treatment include itching over the whole body, rash, 
blurred vision, increased weight, dizziness, diarrhoea, swelling of the face, fatigue, pain, fever, breast 
enlargement (gynaecomastia), depression and difficulty to sleep (insomnia). 
 
Indication specific side effects seen during clinical trials 
 
In children with growth hormone deficiency brain (central nervous system) tumours were commonly 
reported. From the 236 patients enrolled into the clinical studies 3 patients had a central nervous 
system tumour. Of the 3 patients with a central nervous system tumour, 2 patients experienced a 
recurrent medulloblastoma and 1 patient experienced a histiocytoma. See also section “warning and 
precautions”. 
 
Girls with Turner syndrome commonly reported abnormally heavy bleeding at menstruation. 
 
Children with chronic renal insufficiency commonly reported inflammation of the lining of the abdomen 
(peritonitis), bone necrosis and an increase of creatinine blood levels. They are more likely to develop 
increased pressure in the brain (intracranial hypertension), with the greatest risk at the beginning of 
treatment, although children with organic growth hormone deficiency and Turner syndrome also have 
an increased incidence. 
 
Adults with growth hormone deficiency commonly reported abnormal sensations of tingling, pricking 
or numbness (paraesthesia), abnormally high levels of blood glucose, excess of lipids (fat) in the 
blood, sleeplessness, joint disorders, arthrosis (degenerative joint disease), muscle weakness, back 
pain, breast pain and breast enlargement (gynaecomastia). 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects, you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store NutropinAq 
 
Keep out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label of the cartridge and the 
carton after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
Keep the blister in the outer carton. 
 
After first use, the cartridge may be stored for up to 28 days at 2°C - 8°C. Do not remove the cartridge 
that is being used from the NutropinAq Pen between injections. 
 
Do not use NutropinAq if you notice that the solution is cloudy. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 



40  

 
6. Content of the pack and other information  
 
What NutropinAq contains 
 
The active substance of NutropinAq is somatropin*. 
* Somatropin is a human growth hormone produced in Escherichia coli cells by recombinant DNA 
technology. 
 
The other ingredients are sodium chloride, liquefied phenol, polysorbate 20, sodium citrate dihydrate, 
citric acid anhydrous and water for injections. 
 
What NutropinAq looks like and contents of the pack 
 
NutropinAq is a solution for injection (in a cartridge (10 mg/2 ml) - pack size of 1, 3 and 6). The 
solution for multidose use is clear and colourless. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, 
France 
 
Manufacturer : IPSEN PHARMA BIOTECH S.A.S., Parc d’Activités du Plateau de Signes, CD no 
402, 83870 Signes, France 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
 
België/Belgique/Belgien 
Luxembourg/Luxemburg  
Ipsen NV Guldensporenpark 87 
B-9820 Merelbeke 
België /Belgique/Belgien 
Tél/Tel: + 32 - 9 - 243 96 00 

Latvija  
Ipsen Pharma pārstāvniecība 
Kalnciema iela 33-5 
Rīga LV 1046 
Tel: +371 676 22233 

 
 
Česká republika  
Ipsen Pharma, s.r.o.  
Olbrachtova 2006/9 
140 00 Praha 4 
Česká republika 
Tel: + 420 242 481 821 

 
 
Lietuva 
Ipsen Pharma SAS Lietuvos filialas  
T. Narbuto 5,  
08105 Vilnius 
Tel. +370 700 33305 

 
Danmark, Norge, Suomi/Finland, Sverige, 
Ísland 
Institut Produits Synthèse (IPSEN) AB 
Kista Science Tower Färögatan 33 
SE- 164 51 Kista Sverige/Ruotsi/Svíþjóð 
Tlf/Puh/Tel/Sími: +46 8 451 60 00 

 
Magyarország 
Ipsen Pharma Hungary Kft. 
Váci út 33. IX. em. 
H-1134 Budapest 
Tel.: + 36-1-555-5930 



41  

 
Deutschland, Österreich  
Ipsen Pharma GmbH  
Einsteinstraße 174D-81677 München 
Tel: + 49 89 2620 432 89 

 
Nederland 
Ipsen Farmaceutica B.V.  
Taurusavenue 33b 
NL-2132 LS Hoofddorp  
Tel: + 31 (0) 23 55 41 600 

 
 
Eesti 
CentralPharma Communications OÜ 
Selise 26 – 11, 13522 Tallinn 
Tel: +372 601 5540 

 
 
Polska 
Ipsen Poland Sp. z o.o.  
Al. Jana Pawła II 29 
00-867 Warszawa 
Tel.: + 48 (0) 22 653 6800 

 
Ελλάδα, Κύπρος, Malta 
Ipsen Μονοπρόσωπη EΠΕ 
Αγ. Δημητρίου 63 Άλιμος 
GR-17456 Αθήνα Ελλάδα 
Τηλ: + 30 - 210 - 984 3324 
 

 
Portugal 
Ipsen Portugal – Produtos Farmacêuticos, S.A.  
Alameda Fernão Lopes, nº 16A, 1ºB 
1495-190 Algés 
Portugal 
Tel: + 351 - 21 - 412 3550 

 
España 
Ipsen Pharma S.A. 
Torre Realia, Plaza de Europa, 41-43 08908 
L’Hospitalet de Llobregat, Barcelona 
Tel: + 34 - 936 - 858 100 

 
România  
Ipsen Pharma România SRL 
Sectorul 1, Strada Grigore  
Alexandrescu nr. 59, Etaj 1 
Bucureşti, 010623 
Tel: + 40 (021) 231 27 20 
 

 
France, Hrvatska 
Ipsen Pharma 
65 quai Georges Gorse 
F-92100 Boulogne-Billancourt  
Tél : + 33 - 1 - 58 33 50 00 

Slovenija 
PharmaSwiss d.o.o. 
Brodišče 32 
SI-1236 Trzin 
Tel: + 386 1 236 47 00 

 
Ireland 
Ipsen Pharmaceuticals Limited.  
Blanchardstown Industrial Park  
Blanchardstown 
IRL-Dublin 15 
Tel: +353 (0) 1 809 8256 
 

 
  

 
Slovenská republika 
Ipsen Pharma, organizačná zložka 
Zámocká 3 
SK-811 01 Bratislava 
Tel: + 420 242 481 821 
 

 
 
Italia 
Ipsen SpA 
Via del Bosco Rinnovato n. 6 
Milanofiori Nord Palazzo U7 
20090 Assago (Mi) 
Tel: + 39 - 02 - 39 22 41 

 
 
United Kingdom 
Ipsen Limited. 
190 Bath Road  
Slough,  
Berkshire SL1 3XE 
Tel: + 44 (0)1753 - 62 77 00 



42  

България 
PharmaSwiss EOOD 
16, Troyanski Prohod Street 
Floor 3, Office 8, Lagera 
1612 Sofia 
Тел.: +359 2 8952 110 

 

 
 
This leaflet was last revised in <{Month/YYYY}> 
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

 



43  

NutropinAq Pen Instruction for use with NutropinAq 
 
DO NOT INJECT THE MEDICINE UNTIL YOUR DOCTOR OR NURSE HAS THOROUGHLY 
TRAINED YOU IN THE PROPER TECHNIQUES. 
 
Caution: 
Before using your NutropinAq Pen, please read the following instructions carefully. We also suggest 
you consult your doctor or nurse for a demonstration. 
 
The NutropinAq Pen is designed for use only with cartridges of NutropinAq (for subcutaneous use 
only). 
As shown by the illustrations below, NutropinAq pen and cartridges are available in two designs (with 
or without additional yellow colour). The working of the pen and the content of the cartridges are the 
same for both designs. Either of the NutropinAq cartridge designs can be used with either of the 
NutropinAq Pen designs. 
 

 
 
Only use the pen needles recommended by your doctor or nurse. 
 
The dosage scale located beside the window of the cartridge holder should not be used as a dose 
measurement. It should only be used to estimate the dosage remaining in the cartridge. Always refer to 
the LCD (Liquid Crystal Display), not audible clicks, for setting an injection of NutropinAq. The 
clicks are only audible confirmation that the black dose knob has been moved. 
 
Always store the pen and cartridges in a clean, safe place in the refrigerator at a temperature between 
2-8°C and out of children’s reach and sight. Protect from intense light. Use a cooler to store your 
NutropinAq Pen when travelling. The NutropinAq is designed to withstand a nominal (one hour 
maximum) period of time outside of the refrigerator on a daily basis. Avoid areas of extreme 
temperature. Check the expiry date of the cartridge before use. 
 
 
To guard against the spread of infection, follow these safety measures: 
 

• Wash your hands thoroughly with soap and water before using your pen. 
• Clean the cartridge rubber seal with an alcohol swab or cotton ball saturated with alcohol. 
• Avoid touching the cartridge rubber seal at all times. 
• If you accidentally touch the cartridge rubber seal, clean it with an alcohol swab. 
• Do not use the same needle for more than one person. 
• Use needles only once. 

 
 

NutropinAq Pen Components: 
 
Shown below are the items necessary for giving an injection. Gather all of these components prior to 
use. 



44  

 
Your NutropinAq cartridge and Pen will be supplied separately. 
 
 
Part I: Preparing and Injecting 
 
Follow the instructions in this section if you are using the pen for the first time or are replacing an 
empty cartridge. 
 
Inspect all new cartridges prior to use. Occasionally, after refrigeration, you may notice that small 
colourless particles are present in the NutropinAq solution. This is not unusual for solutions 
containing proteins like NutropinAq and does not affect the strength of the product. Allow the 
cartridge to come to room temperature and gently swirl. Do not shake. If the solution is cloudy or hazy 
or contains any solid matter, the cartridge should not be used. Return the cartridge to your pharmacist 
or prescribing doctor. 
 

1. Remove the green pen cap and unscrew the cartridge holder from the pen. If 
necessary, remove the empty cartridge and discard it properly. 

 
 
 
 

2. Press the white reset button. 
 

3. Turn the black dose knob counter-clockwise back to its starting position until it 
no longer turns. (See illustration.) Then turn the dose knob clockwise until the first 
click position is reached (approximately 1/4 turn). This ensures that the plunger 
push rod is reset to the starting position. If this is not done when the dosage knob is 
first pushed in, NutropinAq will be wasted or the cartridge may crack. 

 
4. Insert cartridge into the cartridge holder, then screw the cartridge holder back 
onto the pen. (Be careful not to touch the rubber seal.) 

 
 
 
 

5. Remove the paper seal from a new needle assembly and screw it onto the cartridge holder. 
 

6. Carefully remove both protective caps from the needle by pulling gently. Do not throw the larger 
cap away as it will be used later for proper needle removal and disposal. 

 
7. Holding the pen with the needle pointing upward, gently tap the cartridge holder 



45  

to move any air bubbles to the top. While still holding the pen in the upright 
position, push in the black dose knob until it clicks into position. You should see a 
drop of solution appear. 
Be patient. If the medicine does not appear within a few seconds, you may need 
to push the reset button again. 

 
8. If no drop of medicine appears, push the white reset button again. Now turn the 
black dose knob clockwise (See illustration) by one click (0.1mg). If you 
accidentally turn it too far, go back one click (0.1 mg). 

 
 
 

9. While still holding the pen in the upright position, push in the black dose knob again and watch 
the needle tip for a drop of medicine to appear. Repeat steps 8 and 9 until it appears. 

 
10. Press the white reset button. 

 
11. Set the required dose by turning the black dose knob. If you cannot dial the full 
dose, either start a new cartridge (as described in Part I), or inject the partial dose. 
Then, start a new cartridge (as described in Part I) to administer the remaining 
portion of your medication. Your doctor or nurse will advise you on the procedure 
for administering the last dose in the cartridge. 

 
Prepare the injection site by wiping with an antiseptic impregnated swab. Injection sites 
include the upper arms, abdomen, and upper thighs. Change the injection sites to avoid 
discomfort. Even if you develop a preference for one site, you still should rotate the injection 
site. 

 

   Upper Arm 
 

   Abdomen 
 
 

    Thigh 
 
 

12. If you are using the passive shield (or no shield) proceed to step 13. If you are 
using the active shield, slide the shield onto the pen and push the 2 black lock 
knobs on the needle shield toward the tip. 

 
 
 
13. Set the tip of the pen on the prepared injection site and press the needle into the skin by pushing 
the pen downward until the shield is totally depressed. Your doctor or nurse will show you how to do 



46  

this. Now you are ready to administer the dose. Press down on the black dose knob. Wait 5 seconds 
after the button is pushed, then withdraw the pen from the skin. A drop of blood may appear. Put a 
plaster on the injection site if you wish. 

 
14. Pull the needle shield off the pen (if you have used one) and place the larger needle cap on a flat 
surface. Slide the needle in to pick it up and push the cap completely down over the needle. Twist off 
the needle and discard it properly. Your doctor or nurse will tell you how to dispose of the items you 
have used for the injection. Always store your disposal container out of the reach of children. 

 
15. Attach the pen cap and return it to its case with the black dose knob pressed in. You should 
always store the pen in a refrigerator. Do not remove cartridge between injections. DO NOT 
FREEZE. 

 
For subsequent injections with the NutropinAq Pen, attach a new needle, push the white reset 
button and dial your dose. 
 
 
Part II: Storage and Maintenance 
 
Follow these tips to ensure proper care of your NutropinAq Pen: 
 

• Always keep your NutropinAq Pen and cartridge refrigerated and protected from light when 
not in use. 

• You may remove the pen and cartridge from the refrigerator up to 45 minutes prior to use. 
• Do not let your NutropinAq Pen and/or cartridge freeze. Contact your doctor or nurse for 

a replacement if either the pen or cartridge does not work. 
• Avoid excessive temperatures.  The solution in the cartridge is stable for up to 28 days 

after first use when stored at 2 - 8°C. 
• If your pen requires cleaning, do not place under water. Use a damp cloth to wipe away dirt. 

Do not use alcohol. 
• When priming a new cartridge, you may need to repeat Part I, steps 8 and 9 up to a total of 

6 times (0.6 mg) to remove air bubbles. Small bubbles may remain and will not affect the dose. 
• The pen should contain the NutropinAq that is being used. Do not remove cartridge 

between injections. 
• The NutropinAq cartridge may be used for up to 28 days. 
• Do not store the NutropinAq Pen with needle attached. 

 
 
Part III: Needles for the NutropinAq Pen 
 
Your doctor or nurse will recommend a needle that is appropriate for you. Always use the needles 
recommended. 
 
Needles from other countries may not fit on your NutropinAq Pen. If you travel outside the European 
Union, make sure you take enough needles for the duration of your stay. 
 
 
Part IV: Commonly Asked Questions 
 
Q: Do I need to change the needle every time I use my NutropinAq Pen? 
A: Yes. A new needle should be used for every injection. The needle is only sterile on the first use. 
 
Q: Where should I store my NutropinAq Pen? 
A: Your NutropinAq Pen should be stored in the case, inside a refrigerator when a cartridge is 
inserted. When travelling, place your pen case in a cooler. DO NOT FREEZE. 
 
Q: Why do I keep my medication in the refrigerator? 



47  

A: To maintain its strength. 
 
Q: Can I store my NutropinAq Pen in the freezer? 
A: No. Freezing will damage the pen and medicine. 
 
Q: How long can I keep my NutropinAq Pen and cartridge outside the refrigerator? 
A: We recommend no longer than one hour. Your doctor or nurse will advise you regarding pen 
storage. 
 
Q: What is the maximum dose the NutropinAq Pen can deliver in one injection? 
A: The NutropinAq Pen can give a minimum dose of 0.1 mg up to a maximum dose of 4.0 mg (40 
clicks). If you attempt to dose more than 4 mg at a time, the medicine will either be forced out of the 
needle and wasted or excess pressure will be placed upon the cartridge and it may crack. 
 
Q: Is it possible to turn the black dose knob back if I click too many times? 
A: Yes. You can turn the black dose knob backwards until the correct number appears in the LCD. 
 
Q: What should I do if there is not enough solution left in the cartridge for my next dose? 
A: Your doctor or nurse will advise you what to do for the last dose in the cartridge. 
 
Q: Why do I have to rewind the black dose knob on my NutropinAq Pen every time I replace the 
cartridge? 
A: This ensures that the plunger push rod completely resets itself back to the starting position. If this 
is not done, liquid will come out of the needle when a new cartridge is placed into the pen. 
 
Q: Can I use my NutropinAq Pen without the shields? 
A: Yes. Your NutropinAq Pen works without shields. The shields are optional to help you administer 
your injection. 
 
Q: What should I do if I drop my NutropinAq Pen? 
A: If you drop the NutropinAq Pen, check to see if the cartridge is damaged. You should also check the 
pen to see that the black dose knob is moving up and down properly and that the LCD counter is working. 
If your cartridge or pen is damaged, ask your doctor or nurse for a replacement. 
 
Q: How long can I use my NutropinAq Pen? 
A: The NutropinAq Pen is designed to last 24 months from the time you first use your pen. 
 
Q: What does a blinking “bt‟ mean in the LCD? 
A: The battery in your NutropinAq Pen is losing its charge. Please contact your doctor or nurse for a 
replacement pen. Batteries typically last 24 months and have a 4-week life from the time the „bt‟ first 
starts blinking. 
 
Q: How do I replace my NutropinAq Pen? 
A: Contact your doctor or nurse if you need a replacement part or if you need to replace your entire 
pen. 
 
For more information, please contact the local representative. Your local representative and the 
manufacturer for the NutropinAq Pen device are the same as for the medicinal product detailed overleaf. 
Please see section 6 overleaf for contact details. 
 
Manufacturer: IPSEN PHARMA BIOTECH S.A.S., Parc d’Activités du Plateau de Signes, CD no 
402, 83870 Signes, France 
 
This leaflet was last approved in <{MM/YYYY}> 
 
CE 0459 
 



48  

 
NutropininAq is a registered trademark of Genentech, Inc.  



49  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 

OF THE MARKETING AUTHORISATION(S) 
 



50  

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for somatropin, the scientific 
conclusions of CHMP are as follows:  
 
All products: 
 
Based on available literature, higher doses of growth hormone are generally required during the 
initiation and maintenance phases of treatment in women with an intact hypothalamic-pituitary-
gonadal axis and on oral oestrogens. Therefore, in order to achieve an equivalent clinical and 
biochemical response compared to men dose adjustments may need to be considered by the 
prescriber in female patients. 
 
Omnitrope (MAH: Sandoz), Zomacton and associated names (MAH: Ferring), Norditropin and 
associated names (MAH: Novo Nordisk), Genotropin and associated names (MAH: Pfizer) 
 
Based on available literature, hypothalamic-pituitary-adrenal axis can be affected and needs to be re-
assessed during growth hormone therapy in growth hormone deficient patients, who were previously 
not found to be deficient in this axis. If necessary, glucocorticoid replacement should be initiated. In 
addition, patients already receiving glucocorticoid replacement therapy may need to have the dose of 
their replacement therapy adjusted, after somatropin treatment is initiated.  
 
The CHMP agrees with the scientific conclusions made by the PRAC. 

 
 

Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for somatropin the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing somatropin is unchanged subject to the proposed 
changes to the product information 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)