Udenyca

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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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 
 
UDENYCA 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 content only**. 
 
*The active substance is a covalent conjugate of filgrastim produced in Escherichia coli cells by 
recombinant DNA technology with polyethylene glycol (PEG). 
** The concentration is 20 mg/ml if the PEG moiety is included. 
 
The potency of this medicinal 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 with known effect 
Each pre--filled syringe contains 30 mg sorbitol  
 
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. 
 
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 recommendation on a posology can be made. 
 
Patients with renal impairment 



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No dose change is recommended in patients with renal impairment, including those with end stage 
renal disease. 
 
Method of administration  
Pegfilgrastim is injected subcutaneously. The injections should be given into the thigh, abdomen or 
upper arm. For instructions on handling of the medicinal product before administration, see section 
6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
4.4 Special warnings and precautions for use 
 
In order to improve the traceability of biological medicinal products, the trade name of the 
administered product should be clearly recorded. 
 
Limited clinical data suggest a comparable effect on time to recovery of severe neutropenia for 
pegfilgrastim to filgrastim in patients with de novo acute myeloid leukaemia (see section 5.1). 
However, the long-term effects of pegfilgrastim have not been established in acute myeloid leukaemia; 
therefore, it should be used with caution in this patient population. 
 
G-CSF 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 Acute Myeloid Leukaemia 
(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 acute myeloid leukaemia.  
 
The safety and efficacy of pegfilgrastim administration in de novo AML patients aged < 55 years with 
cytogenetics t(15;17) have not been established. 
 
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 dosage regimens. 
 
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. 
 
Pulmonary adverse reactions 
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 physician and the 
appropriate treatment given (see section 4.8). 
 
Glomerulonephritis 



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Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally, 
events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim and 
pegfilgrastim. Urinalysis monitoring is recommended. 
 
Capillary leak syndrome  
Capillary leak syndrome has been reported after G-CSF administration and is characterised by 
hypotension, hypoalbuminaemia, oedema and hemoconcentration. Patients who develop symptoms of 
capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, 
which may include a need for intensive care (see section 4.8). 
 
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 withdrawal of G-CSF (see also section 4.8). 
 
Splenomegaly and splenic rupture 
Uncommon but generally asymptomatic cases of splenomegaly and uncommon 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 agents 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, physicians 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 medicine with 
splenic enlargement and vaso-occlusive crisis. 
 
Leukocytosis  
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 leukocytosis 
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 medicine. Consistent with 
the clinical effects and the potential for leukocytosis, a WBC count should be performed at regular 
intervals during therapy. If leukocyte counts exceed 50 x 109/l after the expected nadir, this medicine 
should be discontinued immediately. 
 
Hypersensitivity 
Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have 
been reported in patients treated with pegfilgrastim. Permanently discontinue pegfilgrastim in patients 
with clinically significant hypersensitivity. Do not administer pegfilgrastim 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 is generally low. Binding antibodies do occur as expected with all 
biologics; however, they have not been associated with neutralising activity at present.  
 
Pegfilgrastim contains sorbitol. Patients with hereditary fructose intolerance (HFI) should not take/be 
given this medicinal product. 
 
Pegfilgrastim contains less than 1 mmol (23 mg) sodium per 6 mg dose, that is to say, 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 agent 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 pegfilgrastim 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.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no or limited amount of data from the use of pegfilgrastim in pregnant women. Studies in 
animals have shown reproductive toxicity (see section 5.3). UDENYCA 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 human milk, a risk 
to the newborns/infants cannot be excluded. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from UDENYCA therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman.  
 
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 



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UDENYCA has no or 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) 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, angioedema, dyspnoea, erythaema, 
flushing, and hypotension occurred on initial or subsequent treatment with pegfilgrastim (uncommon). 
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 in cancer patients undergoing chemotherapy following administration of G-CSFs; see 
section 4.4 and section “Description of selected adverse reactions” below. 
 
Aortitis [rare frequency] (see section 4.4). 
 
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 Acute Respiratory Distress Syndrome (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 
The data in the table below describe adverse reactions reported from clinical trials and spontaneous 
reporting. The adverse reactions are ranked under heading of frequency using the following 
convention: 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) and not known (cannot be estimated from the available 
data). Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 



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MedDRA  
system organ class 

Adverse reactions 
Very common  Common  Uncommon  Rare  Very rare  

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 

 Aortitis2   

Respiratory, 
thoracic and 
mediastinal 
disorders 

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

Pulmonary 
haemorrhage2  
 

  

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, 
musculo-skeletal 
pain, neck pain)  

      

Renal and urinary 
disorders 

    Glomerulonephritis2     

General disorders 
and administrative 
site conditions 

  Injection site pain1 
Non-cardiac chest 
pain 

Injection site 
reactions2 

    

Investigations     Elevations in lactate 
dehydrogenase and 
alkaline 
phosphatase1;  
Transient elevations 
in LFT's 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 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 erythaema (uncommon) as well as injection site pain 
(common) have occurred on initial or subsequent treatment with pegfilgrastim. 
 
Common cases of leukocytosis (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 G-CSF 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 
The 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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Pharmacotherapeutic group: immunostimulants, colony stimulating factor; ATC Code: L03AA13 
 
Human 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-met-Hu-G-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. Similarly 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 to 7 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 IV 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 
(VAdriaC/IE) chemotherapy, a longer duration of severe neutropenia (neutrophils < 0.5 x 109) was 
observed in younger children aged 0-5 yrs (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 yrs (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 
 



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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 indicate 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) 
(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 from pregnant rats given pegfilgrastim 
subcutaneously, but in rabbits pegfilgrastim has been shown to cause embryo/foetal toxicity (embryo 



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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 trihydrate (for pH adjustment) 
Acetic acid (for pH adjustment) 
Sorbitol (E420) 
Polysorbate 20 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products, particularly with sodium 
chloride solutions.  
 
6.3 Shelf life 
 
2 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
 
UDENYCA may be exposed to room temperature (not above 30°C) for a maximum single period of 
up to 72 hours. When left at room temperature for more than 72 hours it 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 pegfilgrastim. 
 
Keep the container in the outer carton in order to protect from light.  
 
6.5 Nature and contents of container 
 
Pre-filled syringe, with a coated bromobutyl rubber stopper and a stainless steel needle with automatic 
needle guard.  
 
Each pre-filled syringe contains 0.6 ml of solution for injection.  
 
Pack size: Each carton contains 1 pre-filled syringe with an automatic needle guard blistered in a 
plastic tray. 
 
6.6 Special precautions for disposal and other handling 
 
Before administration, pegfilgrastim solution should be inspected visually 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. 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ERA Consulting GmbH 
Lange Strasse 70 
29664 Walsrode 
Germany. 
Tel: +49 (0) 5161 9890 0 
Fax: +49 (0) 5161 9890 18 
E-mail: EUAgent@eraconsulting.com 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1303/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 September 2018 
 
 
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 OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER 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 OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
KBI Biopharma, Inc. 
2500 Central Avenue 
Boulder 
Colorado 
80301 
UNITED STATES 
 
Name and address of the manufacturer responsible for batch release 
 
Millmount Healthcare Limited  
Block 7, City North Business Campus, 
Stamullen Co. Meath, K32 YD60 
Ireland 
 
 
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 
 
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 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 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
UDENYCA 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 solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium acetate, sorbitol (E420), polysorbate 20, water for injections. See leaflet for further 
information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe (0.6 ml).  
 
1 single-use pre-filled syringe with automatic needle guard. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Important: read the package leaflet before use/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 
 
Store in a refrigerator.  



18 

Do not freeze.  
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ERA Consulting GmbH 
Lange Strasse 70 
29664 Walsrode 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1303/001  
 
 
13. BATCH NUMBER 
 

Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 

 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
UDENYCA 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
2D barcode carrying the unique identifier will be included.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
 



19 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 

UDENYCA 6 mg solution for injection in pre-filled syringe 
pegfilgrastim 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
ERA Consulting GmbH 
Lange Strasse 70 
29664 Walsrode 
Germany 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

 

  
 



20 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
UDENYCA 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 
 
ERA, GmbH - Germany 
 
 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



22 

Package leaflet: Information for the user 
 

UDENYCA 6 mg solution for injection in 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 UDENYCA is and what it is used for  
2. What you need to know before you use UDENYCA  
3. How to use UDENYCA  
4. Possible side effects  
5. How to store UDENYCA 
6. Contents of the pack and other information 
 
 
1. What UDENYCA is and what it is used for 
 
UDENYCA contains the active substance pegfilgrastim. Pegfilgrastim is a protein produced by 
biotechnology in bacteria called E. coli followed by conjugation with polyethylene glycol (PEG) It 
belongs to a group of proteins called cytokines. The protein part is very similar to a natural protein 
produced by your own body. 
 
The medicinal product is used to reduce the duration of low white blood cell count (neutropenia) and 
the occurrence of low white blood cell count with a fever (febrile neutropenia) 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 UDENYCA 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 UDENYCA 
 
Do not use UDENYCA 
- if you are allergic to pegfilgrastim, filgrastim, or any of the other ingredients of this medicine.  
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using UDENYCA if you: 



23 

• experience an allergic reaction including weakness, drop in blood pressure, difficulty breathing, 
swelling of the face (anaphylaxis), redness and flushing, skin rash and itchy skin 

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

• 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. 

• 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) 

• 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) 

• 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 

• have sickle cell anaemia. Your doctor may monitor your condition more closely 
• 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 these symptoms 
 

Your doctor will check your blood and urine regularly as UDENYCA can harm the tiny filters inside 
your kidneys (glomerulonephritis).  
 
Severe skin reactions (Stevens-Johnson syndrome) have been reported with the use of UDENYCA. 
Stop using UDENYCA 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 UDENYCA, unless instructed by your 
doctor. 
 
Loss of response to pegfilgrastim 
If you experience a loss of response or decrease in 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 UDENYCA 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. UDENYCA has not been tested 
in pregnant women. It is important to tell your doctor if you: 
• are pregnant 
• think you may be pregnant 
• are planning to have a baby 
 
If you become pregnant during UDENYCA treatment, please inform your doctor. 
 
Unless your doctor directs you otherwise, you must stop breast-feeding if you use UDENYCA. 



24 

 
Driving and using machines 
UDENYCA has no or negligible effect on the ability to drive or use machines. 
 
UDENYCA contains sorbitol (E420) and sodium acetate  
UDENYCA contains sorbitol (a type of sugar). Sorbitol is a source of fructose. If your doctor has told 
you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with 
hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down 
fructose, talk to your doctor before you (or your child) take or receive this medicine. 
This medicine contains less than 1 mmol (23 mg) sodium per 6 mg dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use UDENYCA 
 
UDENYCA is for use in adults aged 18 and over. 
 
Always take UDENYCA exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are unsure.  
 
Dose 
The usual dose is one 6 mg subcutaneous injection (injection under your skin) using a pre-filled 
syringe. It should be given at least 24 hours after your last dose of chemotherapy, at the end of each 
chemotherapy cycle. 
 
Do not shake UDENYCA vigorously as this may affect its activity.  
 
Injecting UDENYCA yourself 
Your doctor may decide that it would be more convenient for you to inject UDENYCA 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 UDENYCA, please read the section at the end 
of this leaflet. 
 
If you use more UDENYCA than you should 
If you use more UDENYCA than you should contact your doctor, pharmacist or nurse. 
 
If you forget to inject UDENYCA 
If you have forgotten a dose of UDENYCA, you should 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 can cause 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. 

 



25 

These could be symptoms of an uncommon 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 

 
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. 
• inflammation of the blood vessels in the skin (cutaneous vasculitis) 
• 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 people) 
• 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 UDENYCA 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 UDENYCA 
 
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). 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


26 

You may take UDENYCA out of the refrigerator and keep it at room temperature (not above 30°C) for 
no longer than 72 hours. Once a syringe has been removed from the refrigerator and has reached room 
temperature (not above 30°C) it must either be used within 72 hours or disposed of. 
 
Do not freeze. UDENYCA may be used if it is accidentally frozen for a single period of less than 
24 hours. 
 
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 UDENYCA 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 acetic acid and sodium acetate (for pH adjustment), sorbitol (E420), 

polysorbate 20 and water for injections. See section 2.  
 
What UDENYCA looks like and contents of the pack 
UDENYCA is a clear, colourless solution for injection in a 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 guard. 
 
 
Marketing Authorisation Holder 
 
ERA Consulting GmbH  
Lange Strasse 70  
29664 Walsrode  
Germany  
Tel: +49 (0) 5161 9890 0  
Fax: +49 (0) 5161 9890 18 

 

E-mail: EUAgent@eraconsulting.com  
 
 
Manufacturer 
 
Millmount Healthcare Limited  
Block 7, City North Business Campus, 
Stamullen Co. Meath, K32 YD60 
Ireland 
 
 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
--------------------------------------------------------------------------------------------------------------------------- 



27 

 
Instructions for use 

 
This section contains information on how to give yourself an injection of UDENYCA. It is important 
that you do not try to give yourself the injection unless you have received training from your doctor, 
nurse or pharmacist. If you have questions about how to inject, please ask your doctor, nurse or 
pharmacist for assistance. 
About this pre-filled syringe with automatic needle guard 

 
• It is important that you read the instructions before using the syringe so you understand how to 

administer the injection. 
• This medicine comes as a one-time use pre-filled safety syringe that contains a single dose. The 

syringe should be disposed of after giving the injection. 
• The syringe has an automatic needle guard that covers the needle after administering the medicine 

and designed to prevent needle stick injury 
 
 

 
Before use 

  
After use 

 
Storage information 
 
• Store the pre-filled syringes in the refrigerator between 2° to 8° C in its original carton.  



28 

  
DO NOT freeze or shake the pre-filled syringe. If frozen, thaw in the refrigerator before 
administration.  Discard syringe if frozen more than once. 
 

• Store the pre-filled syringe in its original carton to protect from light until you are ready to use it.  
 

DO NOT use the pre-filled syringe if it has been left out at room temperature for more than 
72 hours. 
DO NOT shake the pre-filled syringe. If shaken vigorously, the solution may appear foamy and 
should not be used. 
DO NOT use this medicine if you are: 
- Allergic to pegfilgrastim or any of its ingredients.  

 
Prepare the injection 
 
1  Remove carton from refrigerator and check expiry date. 
 
A: Remove the carton from the refrigerator and check the expiry date printed on the carton. (see 
Figure  1). 
DO NOT use if the expiry date has passed. The expiry date refers to the last day of that month. 

Pegfilgrastim 

Pegfilgrastim 



29 

 
     FIGURE 1 
 
B: Open the carton and remove the sealed syringe tray (see Figure 2). 

 
     FIGURE 2 
 
2  Allow medicine to reach room temperature and gather supplies. 
 
A: Place the sealed syringe tray on a flat, clean surface and allow it to sit at room temperature for at 
least 30 minutes (see Figure 3).  

   FIGURE 3 
 
DO NOT attempt to warm up the syringe in any other way, such as a microwave, hot water, or direct 
sunlight. 
 
B: Gather the following supplies (see Figure 4). 
 

    FIGURE 4 
 
3  Wash your hands and remove syringe from tray. 
 
A: Wash your hands with soap and warm water (see Figure  5). 
 

EXP: 01/2016  

Pegfilgrastim 



30 

 
   FIGURE 5 
 
B: Remove the syringe from the sealed tray as follows: peel the cover off the tray, remove the syringe 
by grasping the middle of the syringe body (see Figure 6) 
DO NOT handle the syringe by the plunger, plunger head, or needle cap. 

 
     FIGURE 6 

 
4  Inspect the syringe and solution. 
 
Check the solution through the inspection window. The solution should be clear and colourless. It is 
normal to see one or more air bubbles in the syringe. Removal of the air is not needed (see Figure 7). 
 
 
 

 
 
 
 
 
 
 

    FIGURE 7 
 
DO NOT use if the solution appears discoloured or cloudy. 
DO NOT use if the solution contains lumps, flakes, or particles. 
DO NOT use the syringe if it appears used or damaged. 

 
Select and clean the injection site 
 
5  Select the injection site. 
The recommended injection sites for a subcutaneous injection are the:  
• Abdomen (except for a two-inch area surrounding the navel) 
• Thighs 
• Back of Arms 
• Buttocks 

Pegfilgrastim 



31 

(see Figure 8) 

     FIGURE 8 
 
 
DO NOT inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard. 
 
6  Clean the injection site. 
Clean the injection site with an alcohol swab (see Figure 9). 

    FIGURE 9 
 

 
Inject the dose 
 
7  Remove needle cap. 
Pull the needle cap straight off (see Figure 10). 
 
 
 

 

     FIGURE 10 
 
DO NOT recap the syringe. 
DO NOT use the pre-filled syringe if it has been dropped with the needle cap removed. 
 
 
8  Position fingers. 
Grasp the body of the syringe like a dart (just under the finger grips) with your thumb and index 
fingers (see Figure 11). 



32 

   FIGURE 11 
 

 
DO NOT touch the plunger or grasp the syringe above the finger grips. 
 
 
9  Pinch the skin and insert the needle. 
 
A: Use your free hand to gently pinch the skin around the injection site (see Figure  12). 

    FIGURE 12 
 
B: Insert the needle into the pinched area of the skin at a 45 to 90 degree angle (see Figure 13)  
 
 

 
    FIGURE 13 
 
DO NOT touch the plunger head while inserting the needle into the skin. 
 
C: After fully inserting the needle, release the pinched skin and use your free hand to stabilise the 
bottom of the syringe. 
Then move your other hand into injection position with your thumb on the plunger head (see 
Figure 14). 



33 

    FIGURE 14 
 
10  Push plunger head down to deliver dose. 
 
A: Using your thumb, slowly and steadily push the plunger head down until it will go no further. This 
will ensure you have received the full dose (see Figure 15). 

     FIGURE 15 
 
B: While the needle is still inserted, slowly move your thumb back, allowing the plunger to rise. This 
will retract the needle and secure it inside the syringe body. Then remove the syringe from the 
injection site (see Figure 16). 

     FIGURE 16 
 
C: If you see drops of blood at the injection site, treat by pressing a cotton ball or gauze to the site as 
needed 
 
11  Dispose of syringe and treat injection site. 
 
Immediately after injecting, discard the used syringe into a sharps disposal container (see Figure 17). 
 



34 

FIGURE 17 
 
DO NOT throw away loose needles and syringes in your household waste. 
  



35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

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

 
 
 
 
 



36 

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 OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER 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)