Ristempa
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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 

 

Ristempa 6 mg solution for injection. 

 

 

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 (E420) 

Each pre-filled syringe contains less than 1 mmol (23 mg) sodium (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 

 

Ristempa 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 Ristempa is recommended for each chemotherapy cycle, 

given at least 24 hours after cytotoxic chemotherapy.   

 

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Method of administration 

 

Ristempa 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. 

 

Paediatric population 

 

The safety and efficacy of Ristempa 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 

 

No dose change is recommended in patients with renal impairment, including those with end stage 

renal disease. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients. 

 

4.4 Special warnings and precautions for use 

 

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 Ristempa have not been established in acute myeloid leukaemia; 

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 Ristempa 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 Ristempa administration in de novo AML patients aged  55 years with 

cytogenetics t(15;17) have not been established. 

 

The safety and efficacy of Ristempa 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. 

 

Pulmonary adverse events 

 

Uncommon (≥1/1,000 to < 1/100) 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 Ristempa should be discontinued at the discretion of the physician and the appropriate 

treatment given (see section 4.8). 

 

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Glomerulonephritis 

 

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 granulocyte-colony stimulating factor 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). 

 

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 Ristempa 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 

Ristempa 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 Ristempa.  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 Ristempa. Permanently discontinue Ristempa in patients with 

clinically significant hypersensitivity. Do not administer Ristempa 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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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.  
 

The safety and efficacy of Ristempa for the mobilisation of blood progenitor cells in patients or 

healthy donors has not been adequately evaluated.  

 

The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex), which may 

cause allergic reactions. 

 

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. 

 

Ristempa contains sorbitol.  Patients with rare hereditary problems of fructose intolerance should not 

take this medicine. 

 

Ristempa contains less than 1 mmol (23 mg) sodium per 6 mg dose, i.e. essentially ‘sodium-free’. 

 

In order to improve the traceability of granulocyte-colony stimulating factors (G-CSFs), the trade 

name of the administered product should be clearly recorded in the patient file. 

 

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‚ Ristempa 

should be administered at least 24 hours after administration of cytotoxic chemotherapy.  In clinical 

trials, Ristempa has been safely administered 14 days before chemotherapy. Concomitant use of 

Ristempa with any chemotherapy agent has not been evaluated in patients. In animal models 

concomitant administration of Ristempa 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 Ristempa 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 Ristempa 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). Ristempa is not recommended during 

pregnancy and in women of childbearing potential not using contraception. 

 

Women who become pregnant during Ristempa treatment are encouraged to enrol in Amgen’s 

Pregnancy Surveillance Programme. Contact details are provided in section 6 of the Package leaflet. 

 

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Breast-feeding 

 

There is insufficient information on the excretion of Ristempa / 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 Ristempa therapy taking into account the benefit of 

breast-feeding for the child and the benefit of therapy for the woman.   

 

Women who are breast-feeding during Ristempa treatment are encouraged to enrol in Amgen’s 

Lactation Surveillance programme. Contact details are provided in section 6 of the Package leaflet.  

 

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 

 

Ristempa 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 [≥ 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, angioedema, dyspnoea, erythaema, 

flushing, and hypotension occurred on initial or subsequent treatment with Ristempa (uncommon 

[≥ 1/1,000 to < 1/100]).  Serious allergic reactions, including anaphylaxis can occur in patients 

receiving Ristempa (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 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). 

 

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Tabulated summary of adverse reactions 

 

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 

seriousness. 

 
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 

  

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Acute Respiratory 

Distress 

Syndrome2; 

Pulmonary adverse 

reactions 

(interstitial 

pneumonia, 

pulmonary oedema, 

pulmonary 

infiltrates and 

pulmonary fibrosis) 

  

Gastrointestinal 

disorders 

Nausea1      

Skin and 

subcutaneous 

tissue disorders 

  Sweet’s syndrome 
(acute febrile 

dermatosis)1,2; 

Cutaneous 

vasculitis1,2 

  

Musculoskeletal 

and connective 

tissue disorders 

Bone pain  Musculoskeletal  
pain (myalgia, 

arthralgia, pain in 

extremity, back 

pain, musculo-

skeletal pain, neck 

pain) 

   

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 

  

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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) 

Renal and 

urinary 

disorders 

  Glomerulonephritis2   

1 See section “Description of selected adverse reactions” below. 
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 1576 patients receiving Ristempa in nine randomized 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 Ristempa. The 

mechanism of vasculitis in patients receiving Ristempa is unknown. 

 

Injection site reactions, including injection site erythaema (uncommon (≥ 1/1000 to < 1/100)) as well 

as injection site pain (common events ≥ 1/100 to < 1/10) have occurred on initial or subsequent 

treatment with Ristempa. 

 

Common (≥ 1/100 to < 1/10) 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 Ristempa 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 medications 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 

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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 

 

Pharmacotherapeutic group: immunostimulants, colony stimulating factor; ATC Code:  L03AA13 

 

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.  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 to7 days, and a 30-40% incidence of febrile 

neutropenia. In one study (n = 157), which used a 6mg 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, 

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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 

 

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 

 

Study Day

0 3 6 9 12 15 18 21

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(n
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0.1

1

10

100

1000

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(c

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0.1

1

10

100

Pegfilgrastim Conc.

ANC

 
 

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 people 

 

Limited data indicate that the pharmacokinetics of pegfilgrastim in elderly subjects (> 65 years) is 

similar to that in adults.  

 

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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 

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).   

 

Ristempa may be exposed to room temperature (not above 30C) for a maximum single period of up 

to 72 hours.  Ristempa 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 Ristempa. 

 

Keep the container in the outer carton in order to protect from light.  

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6.5 Nature and contents of container 

 

Pre-filled syringe (Type I glass), with a rubber stopper and a stainless steel needle with or without an 

automatic needle guard.  

 

The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex) (see section 

4.4). 

 

Each pre-filled syringe contains 0.6 ml of solution for injection. Pack size of one pre-filled syringe, in 

either a blistered or non-blistered packaging.   

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Before administration, Ristempa 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. 

 

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

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/15/996/001 1 pack blistered syringe 

EU/1/15/996/002 1 pack unblistered syringe 

EU/1/15/996/003 1 pack blistered syringe with needle guard 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: April 2015 

 

 

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 

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13 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE 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 

 

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14 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers of the biological active substance 

 

Amgen Inc. 

One Amgen Center Drive 

Thousand Oaks 

CA 91320 

USA 

 

Amgen Manufacturing Limited 

P.O Box 4060 

Road 31 km. 24.6 

Juncos 

Puerto Rico 00777-4060 

USA 

 

Name and address of the manufacturers responsible for batch release 

 

Amgen Europe BV 

Minervum 7061 

NL-4817 ZK Breda 

The Netherlands 

 

Amgen Technology (Ireland) Unlimited Company 

Pottery Road 

Dun Laoghaire 

Co Dublin 

Ireland 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 

Characteristics, 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The marketing authorisation holder shall submit periodic safety update reports for this product in 

accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided 

for under Article 107c(7) of Directive 2001/83/EC and published on the European medicines 

web-portal. 

 

 

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15 
 

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. 

 

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

at the same time. 

 

 

 

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16 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

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17 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

OUTER CARTON FOR BLISTERED SYRINGE 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ristempa 6 mg solution for injection  

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: sodium acetate, sorbitol (E420), polysorbate 20, water for injections. See leaflet for further 

information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in a single use pre-filled syringe (0.6 ml).  

Solution for injection in a single use pre-filled syringe with automatic needle guard (0.6 ml). 

Pack size of one. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For subcutaneous use. 

Read the package leaflet before use. 

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

 

 

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 

 

 

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19 
 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Keep the container 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 

 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/15/996/001 1 pack 

EU/1/15/996/003 1 pack with needle guard 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ristempa 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER PACK WITH SYRINGE  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ristempa 6 mg injection 

Pegfilgrastim 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Amgen Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

BLISTERED SYRINGE LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Ristempa 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  

 

Amgen Europe B.V. 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

OUTER CARTON FOR UNBLISTERED SYRINGE 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ristempa 6 mg solution for injection  

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: sodium acetate, sorbitol (E420), polysorbate 20, water for injections. See leaflet for further 

information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in a single use pre-filled syringe (0.6 ml).  

Pack size of one. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For subcutaneous use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Avoid vigorous shaking.  

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Keep the container in the outer carton in order to protect from light. 

 

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23 
 

 

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 

 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/15/996/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ristempa 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

UNBLISTERED SYRINGE LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Ristempa 6 mg injection 

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  

 

Amgen Europe B.V. 

 

 

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25 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

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Package leaflet: Information for the user 
 

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

 

1. What Ristempa is and what it is used for 

 

Ristempa 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.  

 

Ristempa 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 Ristempa 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 Ristempa 

 

Do not use Ristempa 

 

 if you are allergic to pegfilgrastim, filgrastim, E. coli derived proteins, or any of the other 
ingredients of this medicine. 

 

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Warnings and precautions 

 

Talk to your doctor, pharmacist or nurse before using Ristempa: 

 

 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 

 have an allergy to latex. The needle cap on the pre-filled syringe contains a derivative of latex 
and may cause severe allergic reactions 

 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. 

 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. 

 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. 

 

Your doctor will check your blood and urine regularly as Ristempa can harm the tiny filters inside 

your kidneys (glomerulonephritis). 

 

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 Ristempa, 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 Ristempa 

 

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.  Ristempa has not been tested in 

pregnant women.  It is important to tell your doctor if you: 

 are pregnant; 

 think you may be pregnant; or 

 are planning to have a baby. 
 

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If you become pregnant during Ristempa treatment, please inform your doctor. You may be 

encouraged to enrol in Amgen’s Pregnancy Surveillance programme.  Local representative contact 

details are provided in section 6 of this leaflet. 

 

Unless your doctor directs you otherwise, you must stop breast feeding if you use Ristempa.  

 

If you are nursing during Ristempa treatment, you may be encouraged to enrol in Amgen’s Lactation 

Surveillance programme. Local representative contact details are provided in section 6 of this leaflet. 

 

Driving and using machines 
 

Ristempa has no or negligible effect on the ability to drive or use machines. 

 

Ristempa contains sorbitol (E420) and sodium acetate 

 

Ristempa contains sorbitol (a type of sugar). If you have been told by your doctor that you have an 

intolerance to some sugars, contact your doctor before taking this medicinal product. 

 

This medicinal product contains less than 1 mmol (23 mg) sodium per 6 mg dose, i.e. essentially 

‘sodium-free’ 

 

 

3. How to use Ristempa 

 

Ristempa is for use in adults aged 18 and over.  

 

Always take Ristempa exactly as your doctor has told you.  You should check with your doctor or 

pharmacist if you are unsure.  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. 

 

Do not shake Ristempa vigorously as this may affect its activity. 

 

Injecting Ristempa yourself 

 

Your doctor may decide that it would be more convenient for you to inject Ristempa 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 Ristempa, please read the section at the end of 

this leaflet. 

 

If you use more Ristempa than you should 

 

If you use more Ristempa than you should contact your doctor, pharmacist or nurse.  

 

If you forget to inject Ristempa 

 

If you have forgotten a dose of Ristempa, 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. 

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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. 
 

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. 
 

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 Ristempa 

 

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).   

 

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You may take Ristempa 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.  Ristempa 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 Ristempa 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 Ristempa looks like and contents of the pack 

Ristempa is a clear, colourless solution for injection in a pre-filled syringe (6 mg/0.6 ml).  

 

Each pack contains 1 pre-filled syringe of type I glass with an attached stainless steel needle and 

needle cap.  The syringes are provided either with or without a blister wrapping.   

 

Marketing Authorisation Holder and Manufacturer: 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

Marketing Authorisation Holder: 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

Manufacturer: 

Amgen Technology (Ireland) Unlimited Company 

Pottery Road 

Dun Laoghaire 

Co Dublin 

Ireland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder. 

 

België/Belgique/Belgien 

s.a. Amgen n.v. 

Tel/Tél: +32 (0)2 7752711 

 

Lietuva 

Amgen Switzerland AG Vilniaus filialas 

Tel: +370 5 219 7474 

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България 

Амджен България ЕООД 

Тел.: +359 (0)2 424 7440 

Luxembourg/Luxemburg 

s.a. Amgen  

Belgique/Belgien 
Tel/Tél: +32 (0)2 7752711 

 

Česká republika 

Amgen s.r.o. 

Tel: +420 221 773 500 

Magyarország 

Amgen Kft. 

Tel.: +36 1 35 44 700 

Danmark 
Amgen filial af Amgen AB, Sverige 

Tlf: +45 39617500 

 

Malta 

Amgen B.V. 

The Netherlands 

Tel: +31 (0)76 5732500 

 

Deutschland 
AMGEN GmbH  

Tel.: +49 89 1490960  

 

Nederland 
Amgen B.V. 

Tel: +31 (0)76 5732500 

 

Eesti 

Amgen Switzerland AG Vilniaus filialas 

Tel: +372 5125 501 

Norge 

Amgen AB 

Tel: +47 23308000 

 

Ελλάδα 

Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε.  

Τηλ.: +30 210 3447000 
 

Österreich 
Amgen GmbH  

Tel: +43 (0)1 50 217  

 

España 
Amgen S.A.  

Tel: +34 93 600 18 60  

 

Polska 

Amgen Biotechnologia Sp. z o.o. 

Tel.: +48 22 581 3000 

France 

Amgen S.A.S.  

Tél: +33 (0)9 69 363 363  

Portugal 

Amgen Biofarmacêutica, Lda. 

Tel: +351 21 4220550 

 

Hrvatska 

Amgen d.o.o. 

Tel: +385 (1) 562 57 20 

România 

Amgen România SRL 

Tel: +4021 527 3000 

 

Ireland 

Amgen Limited 

United Kingdom 

Tel: +44 (0)1223 420305 

 

Slovenija 

AMGEN zdravila d.o.o. 

Tel: +386 (0)1 585 1767 

 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Amgen Slovakia s.r.o. 

Tel: +421 33 321 13 22 

 

Italia 

Amgen S.r.l. 

Tel: +39 02 6241121 

Suomi/Finland 

Amgen AB, sivuliike Suomessa/Amgen AB, filial 

i Finland 

Puh/Tel: +358 (0)9 54900500 

 

Kύπρος 

Papaellinas & Co Ltd 

Τηλ.: +357 22741 741 

Sverige 

Amgen AB  

Tel: +46 (0)8 6951100 

 

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32 
 

Latvija 

Amgen Switzerland AG Rīgas filiāle 

Tel: +371 292 84807 

 

United Kingdom 

Amgen Limited 

Tel: +44 (0)1223 420305 

 

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 

 

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

 

Instructions for injecting with the Ristempa pre-filled syringe 
 

This section contains information on how to give yourself an injection of Ristempa.  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, 

pharmacist for assistance. 

 

How do you, or the person injecting you, use Ristempa pre-filled syringe? 

 

You will need to give yourself the injection into the tissue just under the skin.  This is known as a 

subcutaneous injection. 

 

Equipment that you need 

 

To give yourself a subcutaneous injection you will need:  

 

 a pre-filled syringe of Ristempa; and 

 alcohol wipes or similar. 
 

What should I do before I give myself a subcutaneous injection of Ristempa? 

 

1. Remove from the refrigerator. 
 

2. Do not shake the pre-filled syringe. 
 

3. Do not remove the cap from the syringe until you are ready to inject. 
 

4. Check the expiry date on the pre-filled syringe label (EXP).  Do not use it if the date has passed 
the last day of the month shown. 

 

5. Check the appearance of Ristempa.  It must be a clear and colourless liquid.  If there are 
particles in it, you must not use it. 

 

6. For a more comfortable injection, let the pre-filled syringe stand for 30 minutes to reach room 
temperature or hold the pre-filled syringe gently in your hand for a few minutes.  Do not warm 

Ristempa in any other way (for example, do not warm it in a microwave or in hot water). 

 

7. Wash your hands thoroughly. 

 

8. Find a comfortable, well-lit, clean surface and put all the equipment you need within reach. 

 

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33 
 

How do I prepare my Ristempa injection? 

 

Before you inject Ristempa you must do the following: 

 

1. Hold the syringe barrel and gently take the cap from the needle 
without twisting.  Pull straight as shown in pictures 1 and 2.  Do 

not touch the needle or push the plunger. 

 

 

 

2. You may notice a small air bubble in the pre-filled syringe. You do not have to remove the air 
bubble before injecting. Injecting the solution with the air bubble is harmless. 

 

3. You can now use the pre-filled syringe. 

 

Where should I give my injection? 

 

 

The most suitable places to inject yourself are: 

 the top of your thighs; and 

 the abdomen, except for the area around the navel. 
If someone else is injecting you, they can also use the back of your arms. 

 

How do I give my injection? 

 

1. Clean your skin by using an alcohol wipe. 

 
2. Pinch (without squeezing) the skin using your thumb and forefinger. Insert the needle into the 

skin. 

 
3. Push the plunger down with a slow constant pressure. Push the plunger all the way down as far 

as it will go to inject all the liquid. 

 

4. After injecting the liquid, remove the needle and let go of your skin. 
 

5. If you notice a spot of blood at the injection site dab with a cotton ball or tissues.  Do not rub the 
injection site.  If needed, you may cover the injection site with a plaster. 

 

6. Do not use any Ristempa that is left in the syringe. 

 

Remember  

 

Only use each syringe for one injection.  If you have any problems, please ask your doctor or nurse for 

help and advice. 

 

Disposing of used syringes 

 

 Do not put the cap back on used needles. 
 

 Keep used syringes out of the sight and reach of children. 
 

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 The used syringe should be disposed of in accordance with local requirements.  Ask your 
pharmacist how to dispose of medicines no longer required. These measures will help to protect 

the environment. 

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Package leaflet: Information for the user 
 

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

 

1. What Ristempa is and what it is used for 

 

Ristempa 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.  

 

Ristempa 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 Ristempa 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 Ristempa 

 

Do not use Ristempa 

 

 if you are allergic to pegfilgrastim, filgrastim, E. coli derived proteins, or any of the other 
ingredients of this medicine. 

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36 
 

 

Warnings and precautions 

 

Talk to your doctor, pharmacist or nurse before using Ristempa: 

 

 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 

 have an allergy to latex. The needle cap on the pre-filled syringe contains a derivative of latex 
and may cause severe allergic reactions 

 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. 

 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. 

 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. 

 

Your doctor will check your blood and urine regularly as Ristempa can harm the tiny filters inside 

your kidneys (glomerulonephritis). 

 

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 Ristempa, 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 Ristempa 

 

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.  Ristempa has not been tested in 

pregnant women.  It is important to tell your doctor if you: 

 are pregnant; 

 think you may be pregnant; or 

 are planning to have a baby. 

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37 
 

 

If you become pregnant during Ristempa treatment, please inform your doctor. You may be 

encouraged to enrol in Amgen’s Pregnancy Surveillance programme.  Local representative contact 

details are provided in section 6 of this leaflet. 

 

Unless your doctor directs you otherwise, you must stop breast feeding if you use Ristempa.  

 

If you are nursing during Ristempa treatment, you may be encouraged to enrol in Amgen’s Lactation 

Surveillance programme. Local representative contact details are provided in section 6 of this leaflet. 

 

Driving and using machines 
 

Ristempa has no or negligible effect on the ability to drive or use machines. 

 

Ristempa contains sorbitol (E420) and sodium acetate 

 

Ristempa contains sorbitol (a type of sugar). If you have been told by your doctor that you have an 

intolerance to some sugars, contact your doctor before taking this medicinal product.  

  

This medicinal product contains less than 1 mmol (23 mg) sodium per 6 mg dose, i.e. essentially 

‘sodium-free’ 

 

 

3. How to use Ristempa 

 

Ristempa is for use in adults aged 18 and over.  

 

Always take Ristempa exactly as your doctor has told you.  You should check with your doctor or 

pharmacist if you are unsure.  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. 

 

Do not shake Ristempa vigorously as this may affect its activity. 

 

Injecting Ristempa yourself 

 

Your doctor may decide that it would be more convenient for you to inject Ristempa 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 Ristempa, please read the section at the end of 

this leaflet. 

 

If you use more Ristempa than you should 

 

If you use more Ristempa than you should contact your doctor, pharmacist or nurse.  

 

If you forget to inject Ristempa 

 

If you have forgotten a dose of Ristempa, 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. 

 

 

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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.  

 

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. 
 

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. 
 

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 Ristempa 

 

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).   

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39 
 

 

You may take Ristempa 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.  Ristempa 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 Ristempa 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 Ristempa looks like and contents of the pack 

Ristempa is a clear, colourless solution for injection in a pre-filled syringe (6 mg/0.6 ml).  

 

Each pack contains 1 pre-filled syringe of type I glass with an attached stainless steel needle and 

needle cap. The syringes are provided with an automatic needle guard.    

 

Marketing Authorisation Holder and Manufacturer: 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

Marketing Authorisation Holder: 

Amgen Europe B.V. 

Minervum 7061 

4817 ZK Breda 

The Netherlands 

 

Manufacturer: 

Amgen Technology (Ireland) Unlimited Company 

Pottery Road 

Dun Laoghaire 

Co Dublin 

Ireland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder. 

 

België/Belgique/Belgien 

s.a. Amgen n.v. 

Tel/Tél: +32 (0)2 7752711 

 

Lietuva 

Amgen Switzerland AG Vilniaus filialas 

Tel: +370 5 219 7474 

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България 

Амджен България ЕООД 

Тел.: +359 (0)2 424 7440 

Luxembourg/Luxemburg 

s.a. Amgen  

Belgique/Belgien 

Tel/Tél: +32 (0)2 7752711 

 

Česká republika 

Amgen s.r.o. 

Tel: +420 221 773 500 

Magyarország 

Amgen Kft. 

Tel.: +36 1 35 44 700 

Danmark 

Amgen filial af Amgen AB, Sverige 

Tlf: +45 39617500 

 

Malta 

Amgen B.V. 

The Netherlands 

Tel: +31 (0)76 5732500 

 

Deutschland 

AMGEN GmbH  

Tel.: +49 89 1490960  

 

Nederland 
Amgen B.V. 

Tel: +31 (0)76 5732500 

 

Eesti 

Amgen Switzerland AG Vilniaus filialas 

Tel: +372 5125 501 

Norge 

Amgen AB 

Tel: +47 23308000 

 

Ελλάδα 

Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε.  

Τηλ.: +30 210 3447000 

 

Österreich 
Amgen GmbH  

Tel: +43 (0)1 50 217  

 

España 
Amgen S.A.  

Tel: +34 93 600 18 60  

 

Polska 

Amgen Biotechnologia Sp. z o.o. 

Tel.: +48 22 581 3000 

France 

Amgen S.A.S.  

Tél: +33 (0)9 69 363 363  

Portugal 

Amgen Biofarmacêutica, Lda. 

Tel: +351 21 4220550 

 

Hrvatska 

Amgen d.o.o. 

Tel: +385 (1) 562 57 20 

România 

Amgen România SRL 

Tel: +4021 527 3000 

 

Ireland 

Amgen Limited 

United Kingdom 

Tel: +44 (0)1223 420305 

 

Slovenija 

AMGEN zdravila d.o.o. 

Tel: +386 (0)1 585 1767 

 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Amgen Slovakia s.r.o. 

Tel: +421 33 321 13 22 

 

Italia 

Amgen S.r.l. 

Tel: +39 02 6241121 

Suomi/Finland 

Amgen AB, sivuliike Suomessa/Amgen AB, filial 

i Finland 

Puh/Tel: +358 (0)9 54900500 

 

Kύπρος 

Papaellinas & Co Ltd 

Τηλ.: +357 22741 741 

Sverige 

Amgen AB  

Tel: +46 (0)8 6951100 

 

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Latvija 

Amgen Switzerland AG Rīgas filiāle 

Tel: +371 292 84807 

 

United Kingdom 

Amgen Limited 

Tel: +44 (0)1223 420305 

 

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 

 

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

 

Instructions for use: 

 

Guide to parts 

Before use After use 

Plunger 

 

Finger grips 

 

Syringe label 

Syringe barrel 

Syringe safety guard 

 

Needle safety spring 

 

Grey needle cap on 

 

  

 

Used plunger 

Syringe label 

Used syringe barrel 

Used needle 

Used needle safety 

spring 

Grey needle cap off 

 

 

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42 
 

Important 

Before you use a Ristempa 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. 

  Ristempa is given as an injection into the tissue just under the skin (subcutaneous injection). 

  Tell your doctor if you have an allergy to latex. The needle cap on the pre-filled syringe 
contains a derivative of latex and may cause severe allergic reactions. 

 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 Open the tray, peeling away the cover. Grab the pre-filled syringe safety guard to remove the 

pre-filled syringe from the tray. 

 

Grab here 

For safety reasons: 

 Do not grasp the plunger. 

 Do not grasp the grey needle cap. 

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C Inspect the medicine and pre-filled syringe. 

 Medicine 

 

 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. 

 

Upper arm 

 

Belly 

Upper 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. 

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B Carefully pull the grey needle cap straight out and away from your body. 

 

 

C Pinch your injection site to create a firm surface. 

 

 It is important to keep the skin pinched when injecting. 

 

Step 3: Inject 

A Hold the pinch. INSERT the needle into skin. 

 

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B PUSH the plunger with slow and constant pressure until you feel or hear a “snap”.  Push all 

the way down through the snap. 

 

 “SNAP”  

 

 

 It is important to push down through the “snap” to deliver your full dose. 

 

C RELEASE your thumb. Then LIFT the syringe off skin. 

 

After releasing the plunger, the pre-filled syringe safety guard will safely cover the injection needle. 

 Do not put the grey needle cap back on used pre-filled syringes. 

 
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Healthcare professionals only  

The trade name of the administered product should be clearly recorded in the patient file. 

Remove and save the pre-filled syringe label. 

 

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

 

Step 4: Finish 

A Discard the used pre-filled syringe and other supplies in a sharps disposal container. 

 

Medicines should be disposed of in accordance with local requirements. Ask your pharmacist how to 

dispose of medicines no longer required. These measures will help to 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 into 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. 

 

 

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Separate additional insert: 

 

Front – Ristempa reference guide: 

 

E
N

G
L

IS
H

 

Reference Guide – Read all instructions found in the carton before use 

1 2 3 Side 1 

Grab here 

 

Upper 

arm 

 

Belly 

 

Upper 

thigh 

 

Turn over to 

continue… 

Open tray, peeling away 

cover. Grab pre-filled 

syringe safety guard to 

remove pre-filled syringe 

from tray. 

Wash hands thoroughly. 

Prepare and clean your 

injection site. 

Carefully pull grey 

needle cap straight out 

and away from your 

body. 

 

Back- Ristempa reference guide: 

 

 E
N

G
L

IS
H

 

4 5 6 7 Side 2 

 

 

 “SNAP”  

 

 

 
 

Read other 

side first 

Pinch and hold the 

skin. INSERT 

needle into skin. 

PUSH plunger with 

slow and constant 

pressure until you feel 

or hear a “snap”.  Push 

all the way down 

through the snap. 

RELEASE your 

thumb. Then LIFT 

syringe off skin. 

Discard used 

pre-filled 

syringe and 

other supplies 

in a sharps 

disposal 

container. 

 

 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE 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
{'Title': '1. what ristempa is and what it is used for', 'Section_Content': 'ristempa 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. ristempa 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 ristempa 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.', 'Entity_Recognition': [{'Text': 'ristempa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 2, 'BeginOffset': 0, 'EndOffset': 8, 'Score': 0.39626339077949524, 'Text': 'ristempa', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'the active substance pegfilgrastim', 'Type': 'TREATMENT', 'BeginOffset': 18, 'EndOffset': 52}, {'Id': 4, 'BeginOffset': 54, 'EndOffset': 67, 'Score': 0.9674230217933655, 'Text': 'pegfilgrastim', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'a protein', 'Type': 'PROBLEM', 'BeginOffset': 71, 'EndOffset': 80}, {'Text': 'bacteria', 'Type': 'PROBLEM', 'BeginOffset': 110, 'EndOffset': 118}, {'Text': 'e. coli', 'Type': 'PROBLEM', 'BeginOffset': 126, 'EndOffset': 133}, {'Text': 'ristempa', 'Type': 'TREATMENT', 'BeginOffset': 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'RelationshipType': 'TEST_VALUE', 'Id': 19, 'BeginOffset': 801, 'EndOffset': 804, 'Text': 'low', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Traits': []}]}, {'Text': 'fight bacteria', 'Type': 'PROBLEM', 'BeginOffset': 855, 'EndOffset': 869}, {'Id': 10, 'BeginOffset': 908, 'EndOffset': 917, 'Score': 0.9830145835876465, 'Text': 'infection', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.7955683469772339}]}, {'Text': 'your bone marrow', 'Type': 'PROBLEM', 'BeginOffset': 967, 'EndOffset': 983}, {'Id': 1, 'BeginOffset': 997, 'EndOffset': 1001, 'Score': 0.773561954498291, 'Text': 'bone', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 21, 'BeginOffset': 1014, 'EndOffset': 1025, 'Score': 0.31136077642440796, 'Text': 'blood cells', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Type': 'TREATMENT_NAME', 'Traits': []}, {'Text': 'white blood cells', 'Type': 'TREATMENT', 'BeginOffset': 1043, 'EndOffset': 1060}, {'Text': 'your body 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{'Title': '2. what you need to know before you use ristempa', 'Section_Content': 'do not use ristempa if you are allergic to pegfilgrastim, filgrastim, e. coli derived proteins, or any of the other ingredients of this medicine. warnings and precautions talk to your doctor, pharmacist or nurse before using ristempa: 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 have an allergy to latex. the needle cap on the pre-filled syringe contains a derivative of latex and may cause severe allergic reactions 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. 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. 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. your doctor will check your blood and urine regularly as ristempa can harm the tiny filters inside your kidneys (glomerulonephritis). 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 ristempa, 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 ristempa 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. ristempa has not been tested in pregnant women. it is important to tell your doctor if you: are pregnant; think you may be pregnant; or are planning to have a baby. if you become pregnant during ristempa treatment, please inform your doctor. you may be encouraged to enrol in amgen\'s pregnancy surveillance programme. local representative contact details are provided in section 6 of this leaflet. unless your doctor directs you otherwise, you must stop breast feeding if you use ristempa. if you are nursing during ristempa treatment, you may be encouraged to enrol in amgen\'s lactation surveillance programme. local representative contact details are provided in section 6 of this leaflet. driving and using machines ristempa has no or negligible effect on the ability to drive or use machines. ristempa contains sorbitol (e420) and sodium acetate ristempa contains sorbitol (a type of sugar). if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. this 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{'Title': '3. how to use ristempa', 'Section_Content': 'ristempa is for use in adults aged 18 and over. always take ristempa exactly as your doctor has told you. you should check with your doctor or pharmacist if you are unsure. 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. do not shake ristempa vigorously as this may affect its activity. injecting ristempa yourself your doctor may decide that it would be more convenient for you to inject ristempa 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 ristempa, please read the section at the end of this leaflet. if you use more ristempa than you should if you use more ristempa than you should contact your doctor, pharmacist or nurse. if you forget to inject ristempa if you have forgotten a dose of ristempa, 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.', 'Entity_Recognition': [{'Text': 'ristempa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': '18', 'Type': 'NUMBER', 'BeginOffset': 35, 'EndOffset': 37}, {'Text': '6', 'Type': 'NUMBER', 'BeginOffset': 195, 'EndOffset': 196}, {'Id': 0, 'BeginOffset': 245, 'EndOffset': 249, 'Score': 0.9429337978363037, 'Text': 'skin', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': 'a pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 257, 'EndOffset': 277}, {'Text': '24', 'Type': 'NUMBER', 'BeginOffset': 310, 'EndOffset': 312}, {'Id': 4, 'BeginOffset': 343, 'EndOffset': 355, 'Score': 0.8552512526512146, 'Text': 'chemotherapy', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Type': 'TREATMENT_NAME', 'Traits': []}, {'Text': 'each chemotherapy cycle', 'Type': 'TREATMENT', 'BeginOffset': 370, 'EndOffset': 393}, {'Id': 3, 'BeginOffset': 1008, 'EndOffset': 1016, 'Score': 0.3472854495048523, 'Text': 'ristempa', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 1145, 'EndOffset': 1158}]}
{'Title': '4. possible side effects', 'Section_Content': '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. 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. 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. 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.', 'Entity_Recognition': [{'Text': 'ristempa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, {'Id': 20, 'BeginOffset': 44, 'EndOffset': 56, 'Score': 0.9616335034370422, 'Text': 'side effects', 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{'Title': '5. how to store ristempa', 'Section_Content': '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 (2c 8c). you may take ristempa out of the refrigerator and keep it at room temperature (not above 30c) for no longer than 3 days. once a syringe has been removed from the refrigerator and has reached room temperature (not above 30c) it must either be used within 3 days or disposed of. do not freeze. ristempa 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.', 'Entity_Recognition': [{'Text': 'ristempa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': '3', 'Type': 'NUMBER', 'BeginOffset': 372, 'EndOffset': 373}, {'Text': 'a syringe', 'Type': 'TREATMENT', 'BeginOffset': 385, 'EndOffset': 394}, {'Text': '3', 'Type': 'NUMBER', 'BeginOffset': 513, 'EndOffset': 514}, {'Text': 'ristempa', 'Type': 'TREATMENT', 'BeginOffset': 551, 'EndOffset': 559}, {'Text': '24', 'Type': 'NUMBER', 'BeginOffset': 634, 'EndOffset': 636}, {'Text': 'the outer carton', 'Type': 'TREATMENT', 'BeginOffset': 666, 'EndOffset': 682}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 726, 'EndOffset': 739}, {'Text': 'cloudy', 'Type': 'PROBLEM', 'BeginOffset': 760, 'EndOffset': 766}, {'Text': 'these measures', 'Type': 'TREATMENT', 'BeginOffset': 931, 'EndOffset': 945}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what ristempa 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 ristempa looks like and contents of the pack ristempa is a clear, colourless solution for injection in a pre-filled syringe (6 mg/0.6 ml). each pack contains 1 pre-filled syringe of type i glass with an attached stainless steel needle and needle cap. the syringes are provided either with or without a blister wrapping.', 'Entity_Recognition': [{'Text': 'ristempa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 49, 'EndOffset': 62, 'Score': 0.9864599704742432, 'Text': 'pegfilgrastim', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.4043585956096649, 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