Grasustek

1 
 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 



2 
 

 This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Grasustek 6 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 6 mg of pegfilgrastim* in 0.6 ml solution for injection. The 
concentration is 10 mg/ml based on protein only**. 
 
*Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with 
polyethylene glycol (PEG). 
** The concentration is 20 mg/ml if the PEG moiety is included. 
 
The potency of this product should not be compared to the potency of another pegylated or non-
pegylated protein of the same therapeutic class. For more information, see section 5.1. 
 
Excipient(s) with known effect 
Each pre-filled syringe contains 30 mg sorbitol (E 420) (see section 4.4). 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Clear, colourless solution for injection. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients 
treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia 
and myelodysplastic syndromes). 
 
4.2 Posology and method of administration 
 
Pegfilgrastim therapy should be initiated and supervised by physicians experienced in oncology and/or 
haematology. 
 
Posology 
 
One 6 mg dose (a single pre-filled syringe) of pegfilgrastim is recommended for each chemotherapy 
cycle, given at least 24 hours after cytotoxic chemotherapy. 
 
Special populations 
 
Renal impairment 
 



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No dose adjustment is recommended in patients with renal impairment, including those with end-stage 
renal disease. 
 
Paediatric population 
 
The safety and efficacy of pegfilgrastim in children has not yet been established. Currently available 
data are described in sections 4.8, 5.1 and 5.2 but no dosing recommendations can be made. 
 
Method of administration 
 
Grasustek is injected subcutaneously. The injections should be given in the thigh, abdomen or upper 
arm.  
 
4.3 Contraindications 
 
Hypersensitivity to the active ingredient or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and batch number of 
the administered product should be clearly recorded. 
 
Limited clinical data suggest a comparable effect on time to recovery from severe neutropenia for 
pegfilgrastim to filgrastim in patients with de novo acute myeloid leukaemia (AML) (see section 5.1). 
However, the long-term effects of pegfilgrastim have not been established in AML; therefore, it 
should be used with caution in this patient population. 
 
Granulocyte-colony stimulating factor can promote growth of myeloid cells in vitro and similar effects 
may be seen on some non-myeloid cells in vitro. 
 
The safety and efficacy of pegfilgrastim have not been investigated in patients with myelodysplastic 
syndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it should 
not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast 
transformation of chronic myeloid leukaemia from AML. 
 
The safety and efficacy of pegfilgrastim administration in de novo AML patients aged < 55 years with 
cytogenetics t (15;17) have not been established. 
 
General 
 
The safety and efficacy of pegfilgrastim have not been investigated in patients receiving high-dose 
chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic 
chemotherapy beyond established dose regimens. 
 
Pulmonary adverse events 
 
Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF 
administration. Patients with a recent history of pulmonary infiltrates or pneumonia may be at higher 
risk (see section 4.8). 
 
The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological 
signs of pulmonary infiltrates, and deterioration in pulmonary function along with increased neutrophil 
count may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS). In such 
circumstances, pegfilgrastim should be discontinued at the discretion of the doctor and the appropriate 
treatment given (see section 4.8). 
 



4 
 

Glomerulonephritis 
 
Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally, 
events of glomerulonephritis resolved after dose reduction or discontinuation of filgrastim and 
pegfilgrastim. Urinalysis monitoring is recommended. 
 
Capillary leak syndrome 
 
Capillary leak syndrome has been reported after granulocyte-colony stimulating factor administration 
and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients 
who develop symptoms of capillary leak syndrome should be closely monitored and receive standard 
symptomatic treatment, which may include the need for intensive care (see section 4.8). 
 
Splenomegaly and splenic rupture 
 
Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal 
cases, have been reported following administration of pegfilgrastim (see section 4.8). Therefore, 
spleen size should be carefully monitored (e.g. clinical examination, ultrasound). A diagnosis of 
splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip 
pain. 
 
Thrombocytopenia and anaemia 
 
Treatment with pegfilgrastim alone does not preclude thrombocytopenia and anaemia because full 
dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of 
platelet count and haematocrit is recommended. Special care should be taken when administering 
single or combination chemotherapeutic medicinal products which are known to cause severe 
thrombocytopenia. 
 
Sickle cell anaemia 
 
Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell trait or 
sickle cell disease (see section 4.8). Therefore, doctors should use caution when prescribing 
pegfilgrastim in patients with sickle cell trait or sickle cell disease, should monitor appropriate clinical 
parameters and laboratory status and be attentive to the possible association of this medicinal product 
with splenic enlargement and vaso-occlusive crisis. 
 
Leucocytosis 
 
White blood cell (WBC) counts of 100 x 109/L or greater have been observed in less than 1 % of 
patients receiving pegfilgrastim. No adverse events directly attributable to this degree of leucocytosis 
have been reported. Such elevation in white blood cells is transient, typically seen 24 to 48 hours after 
administration and is consistent with the pharmacodynamic effects of this medicinal product. 
Consistent with the clinical effects and the potential for leucocytosis, a WBC count should be 
performed at regular intervals during therapy. If leukocyte counts exceed 50 x 109/L after the expected 
nadir, this medicinal product should be discontinued immediately. 
 
Hypersensitivity 
 
Hypersensitivity, including anaphylactic reactions, occurring during initial or subsequent treatment 
have been reported in patients treated with pegfilgrastim. Pegfilgrastim should be permanently 
discontinued in patients with clinically significant hypersensitivity. Pegfilgrastim should not be 
administered to patients with a history of hypersensitivity to pegfilgrastim or filgrastim. If a serious 
allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over 
several days. 



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Stevens-Johnson syndrome 
 
Stevens-Johnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in 
association with pegfilgrastim treatment. If the patient has developed SJS with the use of 
pegfilgrastim, treatment with pegfilgrastim must not be restarted in this patient at any time. 
 
Immunogenicity 
 
As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of 
antibodies against pegfilgrastim are generally low. Binding antibodies do occur as expected with all 
biologics; however, they have not been associated with neutralising activity at present. 
 
Aortitis 
 
Aortitis has been reported after G-CSF administration in healthy subjects and in cancer patients. The 
symptoms experienced included fever, abdominal pain, malaise, back pain and increased inflammatory 
markers (e.g. c-reactive protein and white blood cell count). In most cases aortitis was diagnosed by 
CT scan and generally resolved after discontinuation of GCSF. See also section 4.8. 
 
Other warnings 
 
The safety and efficacy of pegfilgrastim for the mobilisation of blood progenitor cells in patients or 
healthy donors has not been adequately evaluated. 
 
Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been 
associated with transient positive bone imaging findings. This should be considered when interpreting 
bone-imaging results. 
 
Excipients 
 
This medicinal product contains 30 mg sorbitol in each 6 mg dose which is equivalent to 50 mg/ml.  
This medicinal product contains less than 1 mmol sodium (23 mg) per 6 mg dose, i.e. it is essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ 
pegfilgrastim should be administered at least 24 hours after administration of cytotoxic chemotherapy. 
In clinical trials, pegfilgrastim has been safely administered 14 days before chemotherapy. 
Concomitant use of pegfilgrastim with any chemotherapy medicinal product has not been evaluated in 
patients. In animal models, concomitant administration of pegfilgrastim and 5-fluorouracil (5-FU) or 
other antimetabolites has been shown to potentiate myelosuppression.  
 
Possible interactions with other haematopoietic growth factors and cytokines have not been 
specifically investigated in clinical trials. 
 
The potential for interaction with lithium, which also promotes the release of neutrophils, has not been 
specifically investigated. There is no evidence that such an interaction would be harmful. 
 
The safety and efficacy of Grasustek have not been evaluated in patients receiving chemotherapy 
associated with delayed myelosuppression e.g., nitrosoureas. 
 
Specific interaction or metabolism studies have not been performed; however, clinical trials have not 
indicated an interaction of pegfilgrastim with any other medicinal products. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited data on the use of pegfilgrastim in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). Grasustek is not recommended during pregnancy and in 
women of childbearing potential not using contraception. 
 
Breast-feeding 
 
There is insufficient information on the excretion of pegfilgrastim / metabolites in breast milk. 
Therefore a risk for new-borns/infants cannot be ruled out. A decision must be made whether to 
discontinue breast-feeding or to discontinue/abstain from Grasustek therapy taking into account the 
benefit of breast-feeding for the child and the benefit of therapy for the mother. 
 
Fertility 
 
Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative 
weekly doses approximately 6 to 9 times higher than the recommended human dose (based on body 
surface area) (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Pegfilgrastim has no or a negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions were bone pain (very common [≥ 1/10]) and 
musculoskeletal pain (common). Bone pain was generally of mild to moderate severity, transient and 
could be controlled in most patients with standard analgesics. 
 
Hypersensitivity-type reactions, including skin rash, urticaria, angiooedema, dyspnoea, erythema, 
flushing, and hypotension occurred on initial or subsequent treatment with pegfilgrastim (uncommon 
[≥ 1/1,000 to < 1/100]). Serious allergic reactions, including anaphylaxis can occur in patients 
receiving pegfilgrastim (uncommon) (see section 4.4). 
 
Capillary Leak Syndrome, which can be life-threatening if treatment is delayed, has been reported as 
uncommon (≥ 1/1,000 to < 1/100) in cancer patients undergoing chemotherapy following 
administration of granulocyte colony-stimulating factors; see section 4.4 and section “Description of 
selected adverse reactions” below. 
 
Splenomegaly, generally asymptomatic, is uncommon. 
 
Splenic rupture including some fatal cases is uncommonly reported following administration of 
pegfilgrastim (see section 4.4). 
 
Uncommon pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema, 
pulmonary infiltrates and pulmonary fibrosis have been reported. Uncommonly, cases have resulted in 
respiratory failure or ARDS, which may be fatal (see section 4.4). 
 
Isolated cases of sickle cell crises have been reported in patients with sickle cell trait or sickle cell 
disease (uncommon in sickle cell patients) (see section 4.4). 
 
Tabulated list of adverse reactions 
 



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The data in the table below describe adverse reactions reported from clinical trials and spontaneous 
reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing 
severity. 
 

MedDRA 
system organ class 

Adverse reactions 
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) 

Blood and 
lymphatic 
system disorders 

 Thrombocytopenia1; 
Leukocytosis1 
 

Sickle cell crisis2; 
Splenomegaly2; 
Splenic rupture2 

  

Immune system 
Disorders 

  Hypersensitivity 
reactions; 
Anaphylaxis 

  

Metabolism and 
nutrition 
disorders 

  Elevations in uric 
acid 

  

Nervous system 
Disorders 

Headache1 
 

    

Vascular 
Disorders 

  Capillary leak 
syndrome1 

Aortitis  

Respiratory, 
thoracic and 
mediastinal 
disorders 

  Acute Respiratory 
Distress 
Syndrome2; 
Pulmonary adverse 
reactions 
(interstitial 
pneumonia, 
pulmonary oedema, 
pulmonary 
infiltrates and 
pulmonary fibrosis) 
Haemoptysis 

Pulmonary 
haemorrhage 

 

Gastrointestinal 
disorders 

Nausea1     

Skin and 
subcutaneous 
tissue disorders 

  Sweet’s syndrome 
(acute febrile 
dermatosis)1,2; 
Cutaneous 
Vasculitis1,2 

Stevens-
Johnson 
syndrome 

 

Musculoskeletal 
and connective 
tissue disorders 

Bone pain 
 

Musculoskeletal 
pain (myalgia, 
arthralgia, pain in 
extremity, back pain, 
musculoskeletal 
pain, neck pain) 

   

Renal and urinary 
disorders 

  Glomerulonephritis2   

General 
disorders and 
administration 
site conditions 

 Injection site pain1  
Non-cardiac chest 
pain 

Injection site 
Reactions2 

  

Investigations   Elevations in lactate 
dehydrogenase and 
alkaline 
phosphatase1; 
Transient elevations 
in LFTs for ALT or 
AST1 

  

1 See section “Description of selected adverse reactions” below. 



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2 This adverse reaction was identified through post-marketing surveillance of pegfilgrastim but not observed in randomised, 
controlled clinical trials in adults. The frequency category was estimated from a statistical calculation based upon 1,576 
patients receiving pegfilgrastim in nine randomised clinical trials. 
 
Description of selected adverse reactions 
 
Uncommon cases of Sweet's syndrome have been reported, although in some cases underlying 
haematological malignancies may play a role. 
 
Uncommon events of cutaneous vasculitis have been reported in patients treated with pegfilgrastim. 
The mechanism of vasculitis in patients receiving pegfilgrastim is unknown. 
 
Injection site reactions, including injection-site erythema (uncommon) as well as injection-site pain 
(common events) have occurred during initial or subsequent treatment with pegfilgrastim. 
 
Common cases of leucocytosis (White Blood Count [WBC] > 100 x 109/l) have been reported (see 
section 4.4). 
 
Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated 
clinical effects, were uncommon; reversible, mild to moderate elevations in lactate dehydrogenase, 
with no associated clinical effects, were uncommon in patients receiving pegfilgrastim following 
cytotoxic chemotherapy. 
 
Nausea and headaches were very commonly observed in patients receiving chemotherapy. 
 
Uncommon elevations in liver function tests (LFTs) for ALT (alanine aminotransferase) or AST 
(aspartate aminotransferase), have been observed in patients after receiving pegfilgrastim following 
cytotoxic chemotherapy. These elevations are transient and return to baseline. 
 
Common cases of thrombocytopenia have been reported. 
 
Cases of capillary leak syndrome have been reported in the post marketing setting with granulocyte 
colony-stimulating factor use. These have generally occurred in patients with advanced malignant 
diseases, sepsis, taking multiple chemotherapy medicinal products or undergoing apheresis (see 
section 4.4). 
 
Paediatric population 
 
Experience in children is limited. A higher frequency of serious adverse reactions in younger children 
aged 0-5 years (92 %) has been observed compared to older children aged 6-11 and 12-21 years 
respectively (80 % and 67 %) and adults. The most common adverse reaction reported was bone pain 
(see section 5.1 and 5.2).  
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation 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 
 
Single doses of 300 μg/kg have been administered subcutaneously to a limited number of healthy 
volunteers and patients with non-small cell lung cancer without serious adverse reactions. The adverse 
events were similar to those in subjects receiving lower doses of pegfilgrastim. 
 
 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1. Pharmacodynamic properties 
 
Pharmacotherapeutic group: immunostimulants, colony stimulating factors; ATC Code: L03AA13. 
 
Grasustek is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
Human granulocyte colony stimulating factor (G-CSF) is a glycoprotein, which regulates the 
production and release of neutrophils from the bone marrow. Pegfilgrastim is a covalent conjugate of 
recombinant human G-CSF (r-metHuG-CSF) with a single 20 kd polyethylene glycol (PEG) molecule. 
Pegfilgrastim is a sustained duration form of filgrastim due to decreased renal clearance. Pegfilgrastim 
and filgrastim have been shown to have identical modes of action, causing a marked increase in 
peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/or 
lymphocytes. Similar to filgrastim, neutrophils produced in response to pegfilgrastim show normal or 
enhanced function as demonstrated by tests of chemotactic and phagocytic function. As with other 
haematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelial 
cells. G-CSF can promote growth of myeloid cells, including malignant cells, in vitro and similar 
effects may be seen on some non-myeloid cells in vitro. 
 
In two randomised, double-blind, pivotal studies in patients with high risk stage II-IV breast cancer 
undergoing myelosuppressive chemotherapy consisting of doxorubicin and docetaxel, use of 
pegfilgrastim, as a single once per cycle dose, reduced the duration of neutropenia and the incidence of 
febrile neutropenia similarly to that observed with daily administrations of filgrastim (a median of 
11 daily administrations). In the absence of growth factor support, this regimen has been reported to 
result in a mean duration of grade 4 neutropenia of 5 to7 days, and a 30-40 % incidence of febrile 
neutropenia. In one study (n = 157), which used a 6 mg fixed dose of pegfilgrastim the mean duration 
of grade 4  neutropenia for the pegfilgrastim group was 1.8 days compared with 1.6  days in the 
filgrastim group (difference 0.23 days, 95 % CI -0.15, 0.63). Over the entire study, the rate of febrile 
neutropenia was 13 % of pegfilgrastim-treated patients compared with 20 % of filgrastim-treated 
patients (difference 7 %, 95 % CI of-19 %, 5 %). In a second study (n = 310), which used a 
weight-adjusted dose (100  μg /kg), the mean duration of grade 4 neutropenia for the pegfilgrastim 
group was 1.7 days, compared with 1.8 days in the filgrastim group (difference 0.03 days, 95 % CI 
-0.36, 0.30).  
 
The overall rate of febrile neutropenia was 9 % of patients treated with pegfilgrastim and 18 % of 
patients treated with filgrastim (difference 9 %, 95 % CI of-16.8 %,-1.1 %). 
 
In a placebo-controlled, double blind study in patients with breast cancer the effect of pegfilgrastim on 
the incidence of febrile neutropenia was evaluated following administration of a chemotherapy 
regimen associated with a febrile neutropenia rate of 10-20 % (docetaxel 100 mg/m2 every 3 weeks for 
4 cycles). Nine hundred and twenty-eight patients were randomised to receive either a single dose of 
pegfilgrastim or placebo approximately 24 hours (day 2) after chemotherapy in each cycle. The 
incidence of febrile neutropenia was lower for patients randomised to receive pegfilgrastim compared 
with placebo (1% versus 17 %, p < 0.001). The incidence of hospitalisations and intravenous 
anti-infective use associated with a clinical diagnosis of febrile neutropenia was lower in the 
pegfilgrastim group compared with placebo (1 % versus 14 %, p < 0.001; and 2 % versus 10 %, p < 
0.001). 
 
A small (n = 83), Phase II, randomised, double-blind study in patients receiving chemotherapy for de 
novo acute myeloid leukaemia compared pegfilgrastim (single dose of 6 mg) with filgrastim, 
administered during induction chemotherapy. Median time to recovery from severe neutropenia was 
estimated as 22 days in both treatment groups. Long-term outcome was not studied (see section 4.4). 
 
In a phase II (n = 37) multicentre, randomised, open-label study of paediatric sarcoma patients 
receiving 100 μg/kg pegfilgrastim following cycle 1 of vincristine, doxorubicin and cyclophosphamide 

http://www.ema.europa.eu/


10 
 

(VAdriaC/IE) chemotherapy, a longer duration of severe neutropenia (neutrophils < 0.5 x 109) was 
observed in younger children aged 0-5 years (8.9 days) compared to older children aged 6-11 years 
and 12-21 years (6 days and 3.7 days, respectively) and adults. Additionally, a higher incidence of 
febrile neutropenia was observed in younger children aged 0-5 years (75 %) compared to older 
children aged 6-11 years and 12-21 years (70 % and 33 %, respectively) and adults (see sections 4.8 
and 5.2). 
 
5.2. Pharmacokinetic properties 
 
After a single subcutaneous dose of pegfilgrastim, the peak serum concentration of pegfilgrastim 
occurs at 16 to 120 hours after dosing and serum concentrations of pegfilgrastim are maintained 
during the period of neutropenia after myelosuppressive chemotherapy. The elimination of 
pegfilgrastim is non-linear with respect to dose; serum clearance of pegfilgrastim decreases with 
increasing dose. Pegfilgrastim appears to be mainly eliminated by neutrophil mediated clearance, 
which becomes saturated at higher doses. Consistent with a self-regulating clearance mechanism, the 
serum concentration of pegfilgrastim declines rapidly at the onset of neutrophil recovery (see figure 
1). 
 

Figure 1. Profile of median pegfilgrastim serum concentration and absolute neutrophil count 
(ANC) in chemotherapy treated patients after a single 6 mg injection 

 

 
Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of pegfilgrastim is not 
expected to be affected by renal or hepatic impairment. In an open label, single dose study (n = 31) 
various stages of renal impairment, including end-stage renal disease, had no impact on the 
pharmacokinetics of pegfilgrastim. 
 
Elderly 
 
Limited data suggest that the pharmacokinetics of pegfilgrastim in elderly subjects (> 65 years) is 
similar to that in adults. 
 
Paediatric population 
 
The pharmacokinetics of pegfilgrastim were studied in 37 paediatric patients with sarcoma, who 
received 100 μg/kg pegfilgrastim after the completion of VAdriaC/IE chemotherapy. The youngest 
age group (0-5 years) had a higher mean exposure to pegfilgrastim (AUC) (± Standard Deviation) 



11 
 

(47.9 ± 22.5 μg·hr/ml) than older children aged 6-11 years and 12-21 years (22.0 ± 13.1 μg·hr/ml and 
29.3 ± 23.2 μg·hr/ml, respectively) (see section 5.1). With the exception of the youngest age group 
(0 5 years), the mean AUC in paediatric subjects appeared similar to that for adult patients with 
high-risk stage II-IV breast cancer and receiving 100 μg/kg pegfilgrastim after the completion of 
doxorubicin/docetaxel (see sections 4.8 and 5.1). 
 
5.3. Preclinical safety data 
 
Preclinical data from conventional studies of repeated dose toxicity revealed the expected 
pharmacological effects including increases in leukocyte count, myeloid hyperplasia in bone marrow, 
extramedullary haematopoiesis and splenic enlargement. 
 
There were no adverse effects observed in offspring of pregnant rats given pegfilgrastim 
subcutaneously, but in rabbits pegfilgrastim has been shown to cause embryo/foetal toxicity (embryo 
loss) at cumulative doses approximately 4 times the recommended human dose, which were not seen 
when pregnant rabbits were exposed to the recommended human dose. In rat studies, it was shown that 
pegfilgrastim may cross the placenta. Studies in rats indicated that reproductive performance, fertility, 
oestrous cycling, days between pairing and coitus, and intrauterine survival were unaffected by 
pegfilgrastim given subcutaneously. The relevance of these findings for humans is not known. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1. List of excipients 
 
Sodium acetate * 
Sorbitol (E420) 
Polysorbate 20  
Water for injections 
 
*Sodium acetate is formed by titrating glacial acetic acid with sodium hydroxide.  
 
6.2. Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products, particularly with sodium 
chloride solutions. 
 
6.3. Shelf life 
 
3 years.  
 
6.4. Special precautions for storage 
 
Store in a refrigerator (2 °C-8 °C). 
 
Grasustek may be exposed to room temperature (not above 30 °C) for a maximum single period of up 
to 72 hours. Grasustek left at room temperature for more than 72 hours should be discarded. 
 
Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours 
does not adversely affect the stability of Grasustek. 
 
Keep the container in the outer carton to protect from light.  
 
6.5. Nature and contents of container 
 
Pre-filled syringe (Type I glass), with a (butyl) rubber stopper and a stainless-steel needle with 
automatic needle guard. The needle has flexible, rigid needle shield.  



12 
 

 
Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 ml of solution for injection. 
 
Pack size of one pre-filled syringe with automatic needle guard (0.6 ml) and supplied in a dispensing 
pack containing one syringe. 
 
6.6. Special precautions for disposal and other handling 
 
Before administration, Grasustek solution should be visually inspected for particulate matter. Only a 
solution that is clear and colourless should be injected.  
 
Excessive shaking may aggregate pegfilgrastim, rendering it biologically inactive.  
 
Allow the pre-filled syringe to reach room temperature before injecting. 
 
Any unused product or waste material should be disposed of in accordance with local requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Juta Pharma GmbH,  
Gutenbergstr. 13,  
24941 Flensburg, 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1375/001  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 June 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

http://www.ema.europa.eu/


13 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
                                                                      

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 

 



14 
 

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

 
Name and address of the manufacturer(s) of the biological active substance(s)  
 
USV Private Limited 
D-115, TTC Industrial Area, Shirvane 
Navi Mumbai - 400706,  
Maharashtra,  
India 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Juta Pharma GmbH  
Gutenbergstr. 13  
24941 Flensburg 
Germany 
 
 
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  
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs 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 marketing authorisation holder (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 a significant change to the benefit/risk profile 
or as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 



15 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III  
 

LABELLING AND PACKAGE LEAFLET 



16 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



17 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR BLISTERED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Grasustek 6 mg solution for injection in pre-filled syringe 
pegfilgrastim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 ml (10 mg/ml) solution for injection. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sorbitol (E420), polysorbate 20, sodium acetate, water for injection. 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe  
 
1 pre-filled syringe with automatic needle guard (0.6 ml). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only.  
Read the package leaflet before use. 
Important: Read the package leaflet before handling the pre-filled syringe. 
For subcutaneous 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 
 
Avoid vigorous shaking. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



18 
 

Store in a refrigerator. 
Do not freeze. 
Keep the container in the outer carton to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Juta Pharma GmbH,  
Gutenbergstr. 13,  
24941 Flensburg,  
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1375/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Grasustek 6 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 
 



19 
 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTER WITH 
 
SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Grasustek 6 mg solution for injection in pre-filled syringe 
pegfilgrastim 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Juta Pharma GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

 
Important: read the package leaflet before handling the pre-filled syringe. 
 
 
 
 
 
 
 



20 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING 
UNITS 
 
BLISTERED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Grasustek 6 mg 
pegfilgrastim 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.6 ml 
 
 
6. OTHER 
 
Juta Pharma GmbH 
 
 
 
 
 
 
 
 



21 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



22 
 

 
Package leaflet: Information for the user 

 
Grasustek 6 mg solution for injection in a pre-filled syringe 

pegfilgrastim 
 

 This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects 
 
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, pharmacist or nurse.  
• 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Grasustek is and what it is used for 
2. What you need to know before you use Grasustek 
3. How to use Grasustek 
4. Possible side effects 
5. How to store Grasustek 
6. Contents of the pack and other information 
 
 
1. What Grasustek is and what it is used for 
 
Grasustek is for use in adults aged 18 and over. 
 
Grasustek contains the active substance pegfilgrastim. Pegfilgrastim is a protein produced by 
biotechnology in bacteria called E. coli. It belongs to a group of proteins called cytokines and is very 
similar to a natural protein (granulocyte-colony stimulating factor) produced by your own body. 
 
Grasustek is used to reduce the duration of neutropenia (low white blood cell count) and the 
occurrence of febrile neutropenia (low white blood cell count with a fever) which can be caused by the 
use of cytotoxic chemotherapy (medicines that destroy rapidly growing cells). White blood cells are 
important as they help your body fight infection. These cells are very sensitive to the effects of 
chemotherapy which can cause the number of these cells in your body to decrease. If white blood cells 
fall to a low level, there may not be enough left in the body to fight bacteria and you may have an 
increased risk of infection. 
 
Your doctor has given you Grasustek to encourage your bone marrow (part of the bone which makes 
blood cells) to produce more white blood cells that help your body fight infection. 
 
 
2. What you need to know before you use Grasustek 
 
Do not use Grasustek 
• if you are allergic to pegfilgrastim, filgrastim, E. coli derived proteins, or any of the other 

ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before using Grasustek: 



23 
 

 
• if you experience an allergic reaction including weakness, drop in blood pressure, difficulty   

breathing, swelling of the face (anaphylaxis), redness and flushing, skin rash and areas of the 
skin that itch 

• if you experience a cough, fever and difficulty breathing. This can be a sign of Acute 
Respiratory Distress Syndrome (ARDS) 

• if you have any of the following or combination of the following side effects: 
­ swelling or puffiness, which may be associated with passing water less frequently, 

difficulty breathing, abdominal swelling and feeling of fullness, and a general feeling of 
tiredness. These could be symptoms of condition called “Capillary Leak Syndrome” 
which causes blood to leak from the small blood vessels into your body (see section 4). 

• If you get left upper abdominal pain or pain at the tip of your shoulder. This may be a sign of a 
problem with your spleen (splenomegaly) 

• If you have recently had a serious lung infection (pneumonia), fluid in the lungs (pulmonary 
oedema), inflammation of the lungs (interstitial lung disease) or an abnormal chest x-ray (lung 
infiltration) 

• If you are aware of any altered blood cell counts (e.g. increase in white blood cells or anaemia) 
or decreased blood platelet counts, which reduces the ability of your blood to clot 
(thrombocytopenia). Your doctor may want to monitor you more closely 

• If you have sickle cell anaemia. Your doctor may monitor your condition more closely. 
• if you have sudden signs of allergy such as rash, itching or hives on the skin, swelling of the 

face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing. 
These could be signs of a severe allergic reaction. 

• Inflammation of the aorta (the large blood vessel which transports blood from the heart to the 
body) has been reported rarely in cancer patients and healthy donors. The symptoms can include 
fever, abdominal pain, malaise, back pain and increased inflammatory markers. Tell your doctor 
if you experience those symptoms. 

 
Your doctor will check your blood and urine regularly as Grasustek can harm the tiny filters inside 
your kidneys (glomerulonephritis). 
 
Severe skin reactions (Stevens-Johnson syndrome) have been reported with the use of Grasustek. Stop 
using Grasustek and seek medical attention immediately if you notice any of the symptoms described 
in section 4. 
 
You should talk to your doctor about your risks of developing cancers of the blood. If you develop or 
are likely to develop cancers of the blood, you should not use Grasustek, unless instructed by your 
doctor. 
 
Loss of response to pegfilgrastim 
If you experience a loss of response or failure to maintain a response with pegfilgrastim treatment, 
your doctor will investigate the reasons why, including whether you have developed antibodies which 
neutralise pegfilgrastim’s activity. 
 
Other medicines and Grasustek 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy, breast-feeding and fertility 
Ask your doctor or pharmacist for advice before taking any medicine. Grasustek has not been tested in 
pregnant women. It is important to tell your doctor if you: 
• are pregnant or breast-feeding 
• think you may be pregnant or 
• are planning to have a baby  
 
If you become pregnant during Grasustek treatment, please inform your doctor. 



24 
 

 
Unless your doctor directs you otherwise, you must stop breast-feeding if you use Grasustek. 
 
Driving and using machines 
Grasustek has no or a negligible effect on the ability to drive or use machines. 
 
Grasustek contains sorbitol (E420) and sodium 
This medicine contains 30 mg sorbitol in each 6 mg dose, which is equivalent to 50 mg/ml  
This medicine contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Grasustek 
 
Always use Grasustek exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. The usual dose is one 6 mg subcutaneous injection (injection under your skin) using 
a pre-filled syringe and it should be given at least 24 hours after your last dose of chemotherapy at the 
end of each chemotherapy cycle. 
 
Injecting Grasustek yourself 
Your doctor may decide that it would be more convenient for you to inject Grasustek yourself. Your 
doctor or nurse will show you how to inject yourself. Do not try to inject yourself if you have not been 
trained.  
 
For further instructions on how to inject yourself with Grasustek, please read the section at the end of 
this leaflet. 
 
Do not shake Grasustek vigorously as this may affect its activity. 
 
If you use more Grasustek than you should 
If you use more Grasustek than you should contact your doctor, pharmacist or nurse. 
 
If you forget to inject Grasustek 
If you have forgotten a dose of Grasustek, contact your doctor to discuss when you should inject the 
next dose. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine may have side effects, although not everybody gets them. 
 
Please tell your doctor immediately if you have any of the following or combination of the following 
side effects: 
• swelling or puffiness, which may be associated with passing water less frequently, difficulty 

breathing, abdominal swelling and feeling of fullness, and a general feeling of tiredness. These 
symptoms generally develop in a rapid fashion. 

 
These could be symptoms of an uncommon (may affect up to 1 in 100 people) condition called 
“Capillary Leak Syndrome”, which causes blood to leak from the small blood vessels into your 
body and needs urgent medical attention. 
 
Very common side effects (may affect more than 1 in 10 people) 
• bone pain. Your doctor will tell you what you can take to ease the bone pain.  
• nausea and headaches. 
 



25 
 

Common side effects (may affect up to 1 in 10 people) 
• pain at the site of injection.  
• general aches and pains in the joints and muscles.  
• some changes may occur in your blood, but these will be detected by routine blood tests. Your 

white blood cell count may become high for a short period of time. Your platelet count may 
become low which might result in bruising. 

 
Uncommon side effects (may affect up to 1 in 100 people) 
• allergic-type reactions, including redness and flushing, skin rash, and raised areas of the skin 

that itch.  
• serious allergic reactions, including anaphylaxis (weakness, drop in blood pressure, difficulty 

breathing, swelling of the face).  
• increased spleen size.  
• spleen rupture. Some cases of splenic rupture were fatal. It is important that you contact your 

doctor immediately if you experience pain in the upper left side of the abdomen or left shoulder 
pain since this may relate to a problem with your spleen.  

• breathing problems. If you have a cough, fever and difficulty breathing please tell your doctor.  
• Sweet’s syndrome (plum-coloured, raised, painful lesions on the limbs and sometimes the face 

and neck with fever) has occurred but other factors may play a role.  
• cutaneous vasculitis (inflammation of the blood vessels in the skin).  
• damage to the tiny filters inside your kidneys (glomerulonephritis).  
• redness at the site of injection. 
• coughing up blood (haemoptysis) 

 
Rare side effects (may affect up to 1 in 1,000) 
• Inflammation of the aorta (the large blood vessel which transports blood from the heart to the 

body), see section 2. 
• bleeding from the lung (pulmonary haemorrhage)  
• Stevens-Johnson syndrome, which can appear as reddish target-like or circular patches often 

with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes 
and can be preceded by fever and flu-like symptoms. Stop using Grasustek if you develop these 
symptoms and contact your doctor or seek medical attention immediately. See also section 2. 
 

Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Grasustek 
 
Keep this medicine out of the sight and reach of children.  
 
Do not use this medicine after the expiry date which is stated on the carton and on the syringe label 
after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C-8°C). 
 
You may take Grasustek out of the refrigerator and keep it at room temperature (not above 30 °C) for 
no longer than 3 days. Once a syringe has been removed from the refrigerator and has reached room 
temperature (not above 30 °C) it must either be used within 3 days or disposed of.  
 
Do not freeze. Grasustek may be used if it is accidentally frozen for a single period of less than 
24 hours.  
 



26 
 

Keep the container in the outer carton in order to protect from light. 
 
Do not use this medicine if you notice it is cloudy or there are particles in it.  
 
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. 
 
 
6. Contents of the pack and other information 
 
What Grasustek contains 
− The active substance is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in 

0.6 ml of solution. 
− The other ingredients are sodium acetate, sorbitol (E420), polysorbate 20 and water for 

injections (see section 2). 
 
What Grasustek looks like and contents of the pack 
Grasustek is a clear, colourless solution for injection in pre-filled syringe (6 mg/0.6 ml). 
 
Each pack contains 1 glass pre-filled syringe with an attached stainless-steel needle and needle cap. 
The syringes are provided with an automatic needle safety guard. 
 
Marketing Authorisation Holder 
Juta Pharma GmbH,  
Gutenbergstr. 13,  
24941Flensburg, 
Germany 
 
Manufacturer 
Juta Pharma GmbH,  
Gutenbergstr. 13,  
24941 Flensburg, 
Germany 
 
 
For any information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder:  
 
Ελλάδα 
RAFARM A.E.B.E 
Κορίνθου 12, Ν. Ψυχικό, Ελλάδα 
τηλ 210 6776550-1 

България 
Алвоген Фарма България ЕООД 
бул. България 86А, ет. 1, София 1680, 
България 
+359 2 441 7136 
 

Hrvatska  
Alvogen d.o.o. 
Av. V. Holjevca 40 , 10000 Zagreb, Hrvatska 
Tel:+385 1 6641 830 

Ísland  
Alvogen ehf. 
Sæmundargötu 15-19, 101 Reykjavík, Ísland 
Tel: +354 522 2900 
 

Magyarország 
Aramis Pharma Kft 
1095 Mester u. 28 Budapest  
Hungary 
Tel:+36-1-299-1051 

Polska 
Alvogen Pharma Sp. Z o.o. 
Ul Kniaźnina 4a lok 7 
01-607 Warsaw, Poland 
Tel: + 48 22 460 92 00 
 



27 

România 
Alvogen Romania SRL 
44B, Theodor Pallady Blvd. 
3rd district, 032266 
Bucharest, Romania 
Tel: +40 21 318 0377 

Česká republika 
EGIS Praha, spol. s r.o., 
Praha1-Staré Město,Ovocný trh 1096/8, PSČ 
11000 
Tel: +420 227 129 111 

Eesti 
Apteegikaubanduse Hulgimüük OÜ (Auxilia 
Pharma) 
Karamelli 6, 11317 Tallinn 
Tel: +372 605 0005 

Italia 
medac Pharma S.r.l. 
Via Viggiano 90, 00178 Rome 
Italien 
Tel: +39 06 51 59 121 

Suomi/Finland 
medac GmbH 
Hirsalantie 11 
02420 Jorvas 
Finland 
Tel: +358 10 420 4000 

Österreich 
Vertrieb 
G.L.Pharma GmbH 
Schlossplatz 1, 8502 Lannach, 
Osterreich
Tel: +43 3136 82577

Slovenská republika 
EGIS Slovakia spol. s r.o., 
Prievozská 4D, 821 09 Bratislava 
Tel: +421 2 32409422 

Deutschland 
medac GmbH 
Theaterstr. 6 
22880 Wedel, Deutschland Tel: 
+49 4103 / 8006-777 

France 
medac SAS 
23 rue Pierre Gilles de Gennes 
69007 Lyon 
Frankreich 
Tel: +33 4 37 66 14 70 

Sverige, Danmark, Norge 
medac GmbH 
Malmöhusvägen 1 
211 18 Malmö 
Schweden 
Tel: +46 0340 64 54 70 

This leaflet was last revised in {MM/YYYY} 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu

http://www.ema.europa.eu/


28 
 

 
--------------------------------------------------------------------------------------------------------------------- 

Instructions for use: 
 

Guide to parts 
Syringe before administration 

 

Caution: Avoid contact with the plunger and needle during the preparation of the syringe, The safety 
device is normally activated by pressure from the plunger on the syringe. 

Syringe after administration 
(Guard is released and covers the needle) 

 

 



29 
 

 
 
Important 
Before you use a Grasustek pre-filled syringe with automatic needle guard, read this important 
information: 
• It is important that you do not try to give yourself the injection unless you have received 

training from your doctor or healthcare provider. 
• Grasustek is given as an injection into the tissue just under the skin (subcutaneous use). 

     Do not remove the grey needle cap from the pre-filled syringe until you are ready to  
         inject.  

     Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-  
         filled syringe and call your doctor or healthcare provider. 

     Do not attempt to activate the pre-filled syringe prior to injection.  
     Do not attempt to remove the clear pre-filled syringe safety guard from the pre-filled  

         syringe.  
     Do not attempt to remove the peelable label on the pre-filled syringe barrel before  

         administering your injection.  
Call your doctor or healthcare provider if you have any questions. 
 
 Step 1: Prepare 
A.  Remove the pre-filled syringe tray from the package and gather the supplies needed for 

your injection: alcohol wipes, a cotton ball or gauze pad, a plaster and a sharps disposal 
container (not included). 

For a more comfortable injection, leave the pre-filled syringe at room temperature for about 30 
minutes before injecting. Wash your hands thoroughly with soap and water.  
 
On a clean, well-lit work surface, place the new pre-filled syringe and the other supplies. 

    Do not try to warm the syringe by using a heat source such as hot water or microwave. 
    Do not leave the pre-filled syringe exposed to direct sunlight. 
    Do not shake the pre-filled syringe. 

Keep pre-filled syringes out of the sight and reach of children.  
B.  Warning/Precaution: Check to ensure there is no loose fragment or fluid inside the pack. 

In case of doubt DO NOT open this pack and take another pack instead.  
Open the blister by peeling back the top layer all the way off the blister  
as shown. 

 
C.  Warning/Precaution: DO NOT lift the product by the plunger or needle cover. 

Remove the pre-filled syringe from blister as shown. 
 



30 
 

 
 

D.  Inspect the medicine content through the viewing window of the pre-filled syringe. 
 

   Do not use the pre-filled syringe if: 
• The medicine is cloudy or there are particles in it. It must be a clear and colourless liquid.  
• Any part appears cracked or broken.  
• The grey needle cap is missing or not securely attached.  
• The expiry date printed on the label has passed the last day of the month shown.  

In all cases, call your doctor or healthcare provider.  
 

Step 2: Get ready 
A.  Wash your hands thoroughly. Prepare and clean your injection site. 

 
You can use: 
• Upper part of your thigh 
• Belly, except for a 5 cm (2-inch) area right around your belly button.  
• Outer area of upper arm (only if someone else is giving you the injection).  
Clean the injection site with an alcohol wipe. Let your skin dry. 

    Do not touch the injection site before injecting.  
        
       Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into 
areas      
      with scars or stretch marks.  

 



31 
 

B.  Warning/Precaution: DO NOT twist the needle cover or touch the needle or plunger. 
Pull the needle cover straight off as shown and handle the guard to avoid injuries or bending 
the needle. 

 
 
C.  Pinch your injection site to create a firm surface. 

 
 

               It is important to keep the skin pinched when injecting. 
 

Step 3: Inject 
A.  INSERT the needle into skin.  

Push the plunger while grasping the finger flanges.  
Push the plunger all the way down as far as it will go to inject all of the solution. 

 
       Do not touch the injection site before injecting.  

 
B.  The entire dose has to be administered to trigger the guard. 



32 
 

 
 
 
 
 
 
C.  After the injection is complete, one of the below alternatives can be followed: 

-Remove the needle from the injection site and release the plunger until the entire needle is 
covered by the guard. 
-Release the plunger until the needle is covered and then remove the syringe from the injection 
site 

 
 
          Warning/Precaution: If the guard is not activated or only partially activated, discard the syringe 

without replacing the needle cover. 
 
 



33 
 

Healthcare professionals only 
The trade name of the medicine should be clearly recorded in the patient file. 

 

 
Turn the plunger to move the label into a position where you can remove the syringe label. 

 
Step 4: Finish 

A.  Dispose of the used medicine immediately in a Sharps container or as instructed by your 
healthcare provider. 
 

 
 
Medicines should be disposed of in accordance with local requirements. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.Keep 
the syringe and sharps disposal container out of sight and reach of children. 

    Do not reuse the pre-filled syringe. 
    Do not recycle pre-filled syringes or throw them away via household waste. 

B.  Examine the injection site. 
If there is blood, press a cotton ball or gauze pad on your injection site. Do not rub the injection site. 
Apply a plaster if needed.  
 
 
 



34 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 



35 
 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for pegfilgrastim, the scientific 
conclusions of the CHMP are as follows: 
 
Three reported cases show a causal relationship between the adverse drug reaction (ADR) Stevens-
Johnson syndrome and pegfilgrastim. The number of cases is small, but because of the seriousness of 
the ADR, the PRAC recommends that the Product Information should be updated accordingly. 
 
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 pegfilgrastim the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing pegfilgrastim 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