Lonquex

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Lonquex 6 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 6 mg of lipegfilgrastim* in 0.6 ml solution. 
 
Each ml of solution for injection contains 10 mg of lipegfilgrastim. 
 
The active substance is a covalent conjugate of filgrastim** with methoxy polyethylene glycol (PEG) 
via a carbohydrate linker. 
 
*This is based on protein content only. The concentration is 20.9 mg/ml (i.e. 12.6 mg per pre-filled 
syringe) if the PEG moiety and the carbohydrate linker are included. 
 
**Filgrastim (recombinant methionyl human granulocyte-colony stimulating factor [G-CSF]) is 
produced in Escherichia coli cells by recombinant DNA technology. 
 
The potency of this medicinal product should not be compared to the potency of another pegylated or 
non-pegylated protein of the same therapeutic class. For more information, see section 5.1. 
 
Excipients with known effect 
 
Each pre-filled syringe contains 30 mg sorbitol. 
Sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in pre-filled syringe (injection) 
 
Clear, colourless solution 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Lonquex is indicated in adults for reduction in the duration of neutropenia and the incidence of febrile 
neutropenia in patients treated with cytotoxic chemotherapy for malignancy (with the exception of 
chronic myeloid leukaemia and myelodysplastic syndromes). 
 
4.2 Posology and method of administration 
 
Lonquex treatment should be initiated and supervised by physicians experienced in oncology or 
haematology. 
 
Posology 
 
One 6 mg dose of lipegfilgrastim (a single pre-filled syringe of Lonquex) is recommended for each 
chemotherapy cycle, given approximately 24 hours after cytotoxic chemotherapy. 
 



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Special populations 
 
Elderly patients 
In clinical studies with a limited number of elderly patients, there was no relevant age-related 
difference with regard to the efficacy or safety profiles of lipegfilgrastim. Therefore, no adjustment of 
the dose is necessary for elderly patients. 
 
Patients with renal impairment 
Currently available data are described in section 5.2, but no recommendation on a posology can be 
made. 
 
Patients with hepatic impairment 
Currently available data are described in section 5.2, but no recommendation on a posology can be 
made. 
 
Paediatric population 
The safety and efficacy of Lonquex in children and adolescents aged up to 17 years have not yet been 
established. Currently available data are described in sections 4.8, 5.1 and 5.2. 
 
Method of administration 
 
The solution is injected subcutaneously (SC). The injections should be given into the abdomen, upper 
arm or thigh. 
 
Self-administration of Lonquex should only be performed by patients who are well motivated, 
adequately trained and have access to expert advice. The first injection should be performed under 
direct medical supervision. 
 
For instructions on handling of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the trade name and batch number 
of the administered medicinal product should be clearly recorded in the patient file. 
 
General 
 
The safety and efficacy of Lonquex have not been investigated in patients receiving high dose 
chemotherapy. Lonquex should not be used to increase the dose of cytotoxic chemotherapy beyond 
established dose regimens. 
 
Allergic reactions and immunogenicity 
 
Patients who are hypersensitive to G-CSF or derivatives are also at risk of hypersensitivity reactions to 
lipegfilgrastim due to possible cross-reactivity. No lipegfilgrastim therapy should be commenced in 
these patients because of the risk of cross-reaction. 
 
Most biological medicinal products elicit some level of anti-drug antibody response. This antibody 
response can, in some cases, lead to undesirable effects or loss of efficacy. If a patient fails to respond 
to treatment, the patient should undergo further evaluation. 
 



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If a serious allergic reaction occurs, appropriate therapy with close patient follow-up over several days 
should be administered. 
 
Haematopoietic system 
 
Treatment with lipegfilgrastim does not preclude thrombocytopenia and anaemia caused by 
myelosuppressive chemotherapy. Lipegfilgrastim may also cause reversible thrombocytopenia (see 
section 4.8). Regular monitoring of the platelet count and haematocrit is recommended. Special care 
should be taken when administering single or combination chemotherapeutic medicinal products that 
are known to cause severe thrombocytopenia. 
 
Leukocytosis may occur (see section 4.8). No adverse events directly attributable to leukocytosis have 
been reported. Elevation in white blood cells (WBC) is consistent with the pharmacodynamic effects 
of lipegfilgrastim. A WBC count should be performed at regular intervals during therapy owing to the 
clinical effects of lipegfilgrastim and the potential for leukocytosis. If WBC counts exceed 50 x 109/l 
after the expected nadir, lipegfilgrastim should be discontinued immediately. 
 
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. 
 
Patients with myeloid leukaemia or myelodysplastic syndromes 
 
Granulocyte-colony stimulating factor can promote growth of myeloid cells and some non-myeloid 
cells in vitro. 
 
The safety and efficacy of Lonquex have not been investigated in patients with chronic myeloid 
leukaemia, myelodysplastic syndromes or secondary acute myeloid leukaemia; it should therefore 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. 
 
Splenic adverse reactions 
 
Generally asymptomatic cases of splenomegaly have been reported after administration of 
lipegfilgrastim (see section 4.8) and infrequent cases of splenic rupture, including fatal cases, have 
been reported after administration of G-CSF or derivatives (see section 4.8). Spleen size should 
therefore 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. 
 
Pulmonary adverse reactions 
 
Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after 
administration of lipegfilgrastim (see section 4.8). Patients with a recent history of pulmonary 
infiltrates or pneumonia may be at higher risk. 
 
The onset of pulmonary symptoms such as cough, fever and dyspnoea in association with radiological 
signs of pulmonary infiltrates and deterioration in pulmonary function together with an increased 
neutrophil count may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS) (see 
section 4.8). In such circumstances Lonquex should be discontinued at the discretion of the physician 
and appropriate treatment given. 
 
Vascular adverse reactions 
 
Capillary leak syndrome has been reported after administration of G-CSF or derivatives and is 
characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who 
develop symptoms of capillary leak syndrome should be closely monitored and receive standard 
symptomatic treatment, which may include a need for intensive care (see section 4.8). 



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Patients with sickle cell anaemia 
 
Sickle cell crisis has been associated with the use of G-CSF or derivatives in patients with sickle cell 
anaemia (see section 4.8). Physicians should therefore exercise caution when administering Lonquex 
in patients with sickle cell anaemia, monitor appropriate clinical parameters and laboratory results and 
be attentive to the possible association of lipegfilgrastim with splenic enlargement and vaso-occlusive 
crisis. 
 
Aortitis has been reported after G-CSF administration in healthy subjects and in cancer patients. The 
symptoms experienced included fever, abdominal pain, malaise, back pain and increased inflammatory 
markers (e.g. C-reactive protein and white blood cell count). In most cases aortitis was diagnosed by 
CT scan and generally resolved after withdrawal of G-CSF. See also section 4.8. 
 
Hypokalaemia 
 
Hypokalaemia may occur (see section 4.8). For patients with increased risk on hypokalaemia due to 
underling disease or co-medications, it is recommended to monitor the serum potassium level carefully 
and to substitute potassium if necessary. 
 
Glomerulonephritis 
 
Glomerulonephritis has been reported in patients receiving filgrastim, lenograstim or pegfilgrastim. 
Generally, events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim, 
lenograstim or pegfilgrastim. Urinalysis monitoring is recommended (see section 4.8). 
 
Excipients with known effect 
 
This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance 
should not use this medicinal product. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe, i.e. 
essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, Lonquex 
should be administered approximately 24 hours after administration of cytotoxic chemotherapy. 
Concomitant use of lipegfilgrastim with any chemotherapeutic medicinal product has not been 
evaluated in patients. In animal models, concomitant administration of G-CSF and 5-fluorouracil 
(5-FU) or other antimetabolites has been shown to potentiate myelosuppression. 
 
The safety and efficacy of Lonquex have not been evaluated in patients receiving chemotherapy 
associated with delayed myelosuppression, e.g. nitrosoureas. 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are very limited data (less than 300 pregnancy outcomes) on the use of lipegfilgrastim in 
pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). As a 
precautionary measure, it is preferable to avoid the use of Lonquex during pregnancy. 
 
Breast-feeding 



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It is unknown whether lipegfilgrastim/metabolites are excreted in human milk. A risk to the breast-fed 
child cannot be excluded. Breast-feeding should be discontinued during treatment with Lonquex. 
 
Fertility 
 
No data are available. Animal studies with G-CSF and derivatives do not indicate harmful effects with 
respect to fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Lonquex has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequent undesirable effects are musculoskeletal pain and nausea. 
 
Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported 
mostly in cancer patients undergoing chemotherapy after administration of G-CSF or derivatives (see 
section 4.4 and section 4.8). 
 
Tabulated list of adverse reactions 
 
The safety of lipegfilgrastim has been evaluated based on results from clinical studies including 
506 patients and 76 healthy volunteers treated at least once with lipegfilgrastim. 
 
The adverse reactions listed below in table 1 are classified according to system organ class. Frequency 
groupings are defined according to the following convention: very common (≥1/10), common (≥1/100 
to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not 
known (cannot be estimated from the available data). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 



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Table 1: Adverse reactions 
System organ class Frequency Adverse reaction 
Blood and lymphatic system 
disorders 

Common Thrombocytopenia* 
Uncommon Leukocytosis*, Splenomegaly* 

Immune system disorders Uncommon Hypersensitivity reactions* 
Metabolism and nutrition 
disorders 

Common Hypokalaemia* 

Nervous system disorders Common Headache 
Vascular disorders Not known Capillary leak syndrome* 

Aortitis*  
Respiratory, thoracic and 
mediastinal disorders 

Common Haemoptysis 
Uncommon Pulmonary adverse reactions*, 

Pulmonary Haemorrhage 
Gastrointestinal disorders Very common Nausea* 
Skin and subcutaneous tissue 
disorders 

Common Skin reactions* 
Uncommon Injection site reactions* 

Musculoskeletal and connective 
tissue disorders 

Very common Musculoskeletal pains* 

General disorders and 
administration site conditions 

Common Chest pain 

Investigations Uncommon Blood alkaline phosphatase 
increased*, Blood lactate 
dehydrogenase increased* 

*See section “Description of selected adverse reactions” below 
 
Description of selected adverse reactions 
 
Thrombocytopenia and leukocytosis have been reported (see section 4.4). 
 
Splenomegaly, generally asymptomatic, has been reported (see section 4.4). 
 
Hypersensitivity reactions such as allergic skin reactions, urticaria, angioedema and serious allergic 
reactions may occur. 
 
Hypokalaemia has been reported (see section 4.4). 
 
Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported (see section 4.4). 
These pulmonary adverse reactions may also include pulmonary oedema, pulmonary infiltrates, 
pulmonary fibrosis, respiratory failure or ARDS (see section 4.4).  
 
Nausea was very commonly observed in patients receiving chemotherapy. 
 
Skin reactions such as erythema and rash may occur. 
 
Injection site reactions such as injection site induration and injection site pain may occur. 
 
The most frequent adverse reactions include musculoskeletal pains such as bone pain and myalgia. 
Musculoskeletal pain is generally of mild to moderate severity, transient and can be controlled in most 
patients with standard analgesics. However cases of severe musculoskeletal pain (mainly bone pain 
and back pain) have been reported, including cases that led to hospitalisation. 
 
Reversible, mild to moderate elevations in alkaline phosphatase and lactate dehydrogenase may occur, 
with no associated clinical effects. Elevations in alkaline phosphatase and lactate dehydrogenase most 
likely originate from the increase in neutrophils. 
 



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Certain adverse reactions have not yet been observed with lipegfilgrastim, but are generally accepted 
as being attributable to G-CSF and derivatives: 
 
Blood and lymphatic system disorders 
- Splenic rupture including some fatal cases (see section 4.4) 
- Sickle cell crisis in patients with sickle cell anaemia (see section 4.4) 
 
Vascular disorders 
- Capillary leak syndrome 

Cases of capillary leak syndrome have been reported in postmarketing experience after 
administration of G-CSF or derivatives. These have generally occurred in patients suffering 
from advanced malignant diseases, having sepsis, taking multiple chemotherapy medicinal 
products or undergoing apheresis (see section 4.4). 

- Aortitis (see section 4.4) 
 
Skin and subcutaneous tissue disorders 
- Acute febrile neutrophilic dermatosis (Sweet’s syndrome) 
- Cutaneous vasculitis 
 
Renal and urinary disorders 
- Glomerulonephritis (see section 4.4) 
 
Paediatric population 
 
The experience in children is limited to a single-dose phase 1 study in 21 paediatric patients aged 2 to 
<18 years (see section 5.1), which did not indicate a difference in the safety profile of lipegfilgrastim 
in children compared to that in adults. Treatment-related adverse events were back pain, bone pain and 
increased neutrophil count (1 event each). 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no experience with overdose of lipegfilgrastim. In the case of overdose, WBC and platelet 
count should be performed regularly and spleen size should be carefully monitored (e.g. clinical 
examination, ultrasound). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, colony stimulating factors, ATC code: L03AA14 
 
Mechanism of action 
 
Lipegfilgrastim is a covalent conjugate of filgrastim with a single methoxy polyethylene glycol (PEG) 
molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and 
N-acetylgalactosamine. The average molecular mass is approximately 39 kDa of which the protein 
moiety constitutes approximately 48 %. Human G-CSF is a glycoprotein that regulates the production 
and release of functional neutrophils from the bone marrow. Filgrastim is an un-glycosylated 
recombinant methionyl human G-CSF. Lipegfilgrastim is a sustained duration form of filgrastim due 

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


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to decreased renal clearance. Lipegfilgrastim binds to human the G-CSF receptor like filgrastim and 
pegfilgrastim. 
 
Pharmacodynamic effects 
 
Lipegfilgrastim and filgrastim induced a marked increase in peripheral blood neutrophil counts within 
24 hours, with minor increases in monocytes and/or lymphocytes. These results suggest that the 
G-CSF moiety of lipegfilgrastim confers the expected activity of this growth factor: stimulation of 
proliferation of haematopoietic progenitor cells, differentiation into mature cells and release into the 
peripheral blood. This effect includes not only the neutrophil lineage but extends to other single 
lineage and multilineage progenitors and pluripotent haematopoietic stem cells. G-CSF also increases 
the antibacterial activities of neutrophils including the phagocytosis. 
 
Clinical efficacy and safety 
 
Once-per-cycle dosing of lipegfilgrastim was investigated in two pivotal randomised, double-blind 
clinical studies in patients undergoing myelosuppressive chemotherapy. 
 
The first pivotal (phase III) clinical study XM22-03 was an active-controlled study in 202 patients 
with stage II-IV breast cancer receiving up to 4 cycles of chemotherapy consisting of doxorubicin and 
docetaxel. Patients were randomised 1:1 to receive 6 mg lipegfilgrastim or 6 mg pegfilgrastim. The 
study showed non-inferiority of 6 mg lipegfilgrastim to 6 mg pegfilgrastim for the primary endpoint, 
duration of severe neutropenia (DSN) in the first cycle of chemotherapy (see table 2). 
 
Table 2: DSN, severe neutropenia (SN) and febrile neutropenia (FN) in cycle 1 of 
study XM22-03 (ITT) 

 Pegfilgrastim 6 mg 
(n = 101) 

Lipegfilgrastim 6 mg 
(n = 101) 

DSN 
Mean ± SD (d) 0.9 ± 0.9 0.7 ± 1.0 
Δ LS mean -0.186 
95 % CI -0.461 to 0.089 
SN 
Incidence (%) 51.5 43.6 
FN 
Incidence (%) 3.0 1.0 
ITT =  Intent-to-treat population (all randomised patients) 
SD  = standard deviation 
d = days 
CI = confidence interval 
Δ LS mean (least square mean difference lipegfilgrastim – pegfilgrastim) and CI out of multivariate 
Poisson regression analysis 
 
The second pivotal (phase III) clinical study XM22-04 was a placebo-controlled study in 375 patients 
with non-small cell lung cancer receiving up to 4 cycles of chemotherapy consisting of cisplatin and 
etoposide. Patients were randomised 2:1 to receive either 6 mg lipegfilgrastim or placebo. The results 
of the study are presented in table 3. When the main study was finalised, the incidence of death was 
7.2 % (placebo) and 12.5 % (6 mg lipegfilgrastim) although after the 360-day follow-up period the 
overall incidence of death was similar between placebo and lipegfilgrastim (44.8 % and 44.0 %; safety 
population). 
 



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Table 3: DSN, SN and FN in cycle 1 of study XM22-04 (ITT) 
 Placebo 

(n = 125) 
Lipegfilgrastim 6 mg 

(n = 250) 
FN 
Incidence (%) 5.6 2.4 
95 % CI 0.121 to 1.260 
p-value 0.1151 
DSN 
Mean ± SD (d) 2.3 ± 2.5 0.6 ± 1.1 
Δ LS mean -1.661 
95 % CI -2.089 to -1.232 
p-value < 0.0001 
SN 
Incidence (%) 59.2 32.1 
Odds ratio 0.325 
95 % CI 0.206 to 0.512 
p-value < 0.0001 
Δ LS mean (least square mean difference lipegfilgrastim – placebo), CI and p-value out of 
multivariate Poisson regression analysis 
Odds ratio (lipegfilgrastim / placebo), CI and p-value out of multivariate logistic regression analysis 
 
A post-authorisation safety study XM22-ONC-40041 was conducted to collect data of disease 
progression and mortality in patients with advanced squamous or non-squamous cell lung cancer 
receiving lipegfilgrastim in addition to the platinum-based chemotherapy. Increased risk of disease 
progression or death was not observed with lipegfilgrastim.  
 
Immunogenicity 
An analysis of anti-drug antibodies of 579 patients and healthy volunteers treated with lipegfilgrastim, 
188 patients and healthy volunteers treated with pegfilgrastim and 121 patients treated with placebo 
was performed. Drug-specific antibodies emerging after start of treatment were detected in 0.86 % of 
the subjects receiving lipegfilgrastim, in 1.06 % of the subjects receiving pegfilgrastim and in 1.65 % 
of the subjects receiving placebo. No neutralising antibodies against lipegfilgrastim were observed. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Lonquex in all subsets of the paediatric population in the treatment of chemotherapy-induced 
neutropenia and prevention of chemotherapy-induced febrile neutropenia (see section 4.2 for 
information on paediatric use). In a phase 1 study of 21 children aged between 2 and 16 years with 
Ewing family of tumours or rhabdomyosarcoma, lipegfilgrastim was administered as a single 
subcutaneous dose of 100 μg/kg (up to a maximum of 6 mg, which is the fixed dose for adults) 
24 hours after the end of the last chemotherapy treatment in week 1 of the regimen. The incidence of 
FN varied according to age (from 14.3 % to 71.4 %), with the highest frequency in the oldest age 
group. The use of three different chemotherapy regimens, with varying myelosuppressive effects and 
age distributions, complicated the comparison of efficacy across age groups (see section 4.2). 
 
5.2 Pharmacokinetic properties 
 
General 
 
Healthy volunteers 
In 3 studies (XM22-01, XM22-05, XM22-06) in healthy volunteers, the maximum blood 
concentration was reached after a median of 30 to 36 hours and the average terminal half-life ranged 
from approximately 32 to 62 hours after a single subcutaneous injection of 6 mg lipegfilgrastim. 
 



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After subcutaneous injection of 6 mg lipegfilgrastim at three different sites (upper arm, abdomen and 
thigh) in healthy volunteers, the bioavailability (peak concentration and area under the curve [AUC]) 
was lower after subcutaneous injection in the thigh compared to subcutaneous injection in the 
abdomen and in the upper arm. In this limited study XM22-06, bioavailability of lipegfilgrastim and 
observed differences among the injection sites were higher in male subjects compared to female 
subjects. Nevertheless, pharmacodynamic effects were similar and independent from gender and 
injection site. 
 
Metabolism 
 
Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes. 
Lipegfilgrastim is internalised by neutrophils (non-linear process), then degraded within the cell by 
endogenous proteolytic enzymes. The linear pathway is likely due to extracellular protein degradation 
by neutrophil elastase and other plasma proteases. 
 
Drug interactions 
In vitro data indicate that lipegfilgrastim is has little or no direct or immune system-mediated effects 
on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5 activity. Therefore, 
lipegfilgrastim is not likely to affect metabolism via human cytochrome P450 enzymes. 
 
Special populations 
 
Cancer patients 
In 2 studies (XM22-02 and XM22-03) in patients with breast cancer receiving chemotherapy 
consisting of doxorubicin and docetaxel, mean maximum blood concentrations of 227 and 262 ng/ml 
were reached after median times to maximum concentration (tmax) of 44 and 48 hours. The mean 
terminal half-lives were approximately 29 and 31 hours after a single subcutaneous injection of 6 mg 
lipegfilgrastim during the first cycle of chemotherapy. After a single subcutaneous injection of 6 mg 
lipegfilgrastim during the fourth cycle, the maximum blood concentrations were lower than observed 
in the first cycle (mean values 77 and 111 ng/ml) and were reached after median tmax of 8 hours. The 
mean terminal half-lives in the fourth cycle were approximately 39 and 42 hours. 
 
In a study (XM22-04) in patients with non-small cell lung cancer receiving chemotherapy consisting 
of cisplatin and etoposide, the mean maximum blood concentration of 317 ng/ml was reached after a 
median tmax of 24 hours and the mean terminal half-life was approximately 28 hours after a single 
subcutaneous injection of 6 mg lipegfilgrastim during the first cycle of chemotherapy. After a single 
subcutaneous injection of 6 mg lipegfilgrastim during the fourth cycle, the mean maximum blood 
concentration of 149 ng/ml was reached after a median tmax of 8 hours and the mean terminal half-life 
was approximately 34 hours. 
 
Lipegfilgrastim 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 lipegfilgrastim declines slowly during the chemotherapy-induced transient neutrophil 
nadir and rapidly at the following onset of neutrophil recovery (see figure 1). 
 



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Figure 1: Profile of median serum concentration of lipegfilgrastim and median ANC in 
chemotherapy-treated patients after a single 6 mg injection of lipegfilgrastim 
 
 

         
 
 
Patients with renal or hepatic impairment 
Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of lipegfilgrastim is not 
expected to be affected by renal or hepatic impairment. 
 
Elderly patients 
Limited patient data indicate that the pharmacokinetics of lipegfilgrastim in elderly patients 
(65 - 74 years) is similar to that in younger patients. No pharmacokinetic data are available in patients 
≥ 75 years. 
 
Paediatric population 
In a phase 1 study (see section 5.1), using a 10 mg/ml solution for subcutaneous injection specifically 
developed for the paediatric studies, the mean maximum blood concentrations (Cmax) were 243 ng/ml 
in the 2 to <6-year group, 255 ng/ml in the 6 to <12-year group and 224 ng/ml in the 12 to <18-year 
group after a single subcutaneous injection of 100 μg/kg (maximum 6 mg) lipegfilgrastim with the 
first cycle of chemotherapy. The maximum blood concentrations were reached after a median time 
(tmax) of 23.9 hours, 30.0 hours and 95.8 hours, respectively. See section 4.2. 
 
Overweight patients 
A trend towards a decrease in lipegfilgrastim exposure was observed with increase in weight. This 
may result in lowered pharmacodynamic responses in heavy patients (> 95 kg). Consequent decrease 
in efficacy in these patients cannot be excluded on current data. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeated dose toxicity and local tolerance. 
 
In a study of toxicity to reproduction and development in rabbits, an increased incidence of 
post-implantation loss and abortion has been observed at high doses of lipegfilgrastim, likely owing to 

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an exaggerated pharmacodynamic effect specific for rabbits. There is no evidence that lipegfilgrastim 
is teratogenic. These findings are consistent with results from G-CSF and derivatives. Published 
information on G-CSF and derivatives reveal no evidence of adverse effects on fertility and 
embryo-foetal development in rats or pre-/postnatal effects other than those related to maternal 
toxicity as well. There is evidence that filgrastim and pegfilgrastim may be transported at low levels 
over the placenta in rats, although no information is available for lipegfilgrastim. The relevance of 
these findings for humans is not known. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glacial acetic acid 
Sodium hydroxide (for pH-adjustment) 
Sorbitol (E420) 
Polysorbate 20 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
 
Do not freeze. 
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Lonquex may be removed from the refrigerator and stored below 25°C for a maximum single period 
of up to 3 days. Once removed from the refrigerator, the medicinal product must be used within this 
period or disposed of. 
 
6.5 Nature and contents of container 
 
Pre-filled syringe (type I glass) with a plunger stopper [poly(ethylene-co-tetrafluoroethylene)-coated 
bromobutyl rubber] and a fixed injection needle (stainless steel, 29G [0.34 mm] or 27G [0.4 mm] x 
0.5 inch [12.7 mm]). 
 
Each pre-filled syringe contains 0.6 ml of solution. 
 
Pack sizes of 1 pre-filled syringe with or without safety device (which prevents needle stick injury and 
re-use). 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The solution should be visually inspected before use. Only clear, colourless solutions without particles 
should be used. 



14 

 
The solution should be allowed to reach a comfortable temperature (15°C - 25°C) for injection. 
 
Vigorous shaking should be avoided. Excessive shaking may aggregate lipegfilgrastim, rendering it 
biologically inactive. 
 
Lonquex does not contain any preservative. In view of the possible risk of microbial contamination, 
Lonquex syringes are for single use only. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/856/001 
EU/1/13/856/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 25 July 2013. 
Date of latest renewal: 08 May 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

  



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ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURERS 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 

 



16 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Teva Biotech GmbH 
Dornierstraße 10 
D-89079 Ulm 
Germany 
 
Name and address of the manufacturers responsible for batch release 
 
Teva Biotech GmbH 
Dornierstraße 10 
D-89079 Ulm 
Germany 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5 
NL-2031 GA Haarlem 
The Netherlands 
 
Merckle GmbH, 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
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, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
● Periodic safety update reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
● Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 



17 

● 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. 

 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lonquex 6 mg solution for injection in pre-filled syringe 
lipegfilgrastim 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 6 mg lipegfilgrastim in 0.6 ml solution. Each ml of solution contains 
10 mg lipegfilgrastim. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20 and water for 
injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
 
1 pre-filled syringe of 0.6 ml solution 
1 pre-filled syringe of 0.6 ml solution with safety device 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
 
Avoid vigorous shaking. 
 
Read the package leaflet before use. 
 
Only for the pre-filled syringe with safety device: 
Important: read the package leaflet before handling syringe. 
 
Subcutaneous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



21 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
 
Do not freeze. 
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/856/001 1 pre-filled syringe with safety device 
EU/1/13/856/002 1 pre-filled syringe 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Lonquex 6 mg 
 
 



22 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Lonquex 6 mg injection 
lipegfilgrastim 
 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.6 ml 
 
 
6. OTHER 
 

  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



25 

Package leaflet: Information for the user 
 

Lonquex 6 mg solution for injection in pre-filled syringe 
 

lipegfilgrastim 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Lonquex is and what it is used for 
2. What you need to know before you use Lonquex 
3. How to use Lonquex 
4. Possible side effects 
5. How to store Lonquex 
6. Contents of the pack and other information 
 
 
1. What Lonquex is and what it is used for 
 
What Lonquex is 
Lonquex contains the active substance lipegfilgrastim. Lipegfilgrastim is a long-acting modified 
protein produced by biotechnology in bacteria called Escherichia coli. It belongs to a group of proteins 
called cytokines and is similar to a natural protein (granulocyte-colony stimulating factor [G-CSF]) 
produced by your own body. 
 
What Lonquex is used for 
Your doctor has prescribed Lonquex for you in order to reduce the duration of a condition called 
neutropenia (low white blood cell count) and the occurrence of febrile neutropenia (low white blood 
cell count with a fever). These can be caused by the use of cytotoxic chemotherapy (medicines that 
destroy rapidly-growing cells). 
 
How Lonquex works 
Lipegfilgrastim stimulates the bone marrow (the tissue where new blood cells are made) to produce 
more white blood 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. 
 
 
2. What you need to know before you use Lonquex 
 
Do not use Lonquex: 
• if you are allergic to lipegfilgrastim or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse BEFORE using Lonquex 
• if you get left upper abdominal pain or pain at the tip of your shoulder. It could be a 

consequence of a spleen disorder (see section4 “Possible side effects”). 



26 

• if you have a cough, fever and difficulty breathing. It could be a consequence of a pulmonary 
disorder (see section4 “Possible side effects”). 

• if you have sickle cell anaemia, which is an inherited disease characterised by sickle-shaped red 
blood cells. 

• if you have previously experienced allergic reactions to other medicines like this one (e.g. 
filgrastim, lenograstim or pegfilgrastim of the group of G-CSFs). There could be a risk of 
reacting to Lonquex too. 

 
Your doctor will carry out regular blood tests in order to monitor various blood components and their 
levels. Your doctor will also check your urine regularly as other medicines similar to this one (e.g. 
other granulocyte colony stimulating factors such as filgrastim, lenograstim or pegfilgrastim) can 
possibly harm the tiny filters inside your kidneys (glomerulonephritis; see section “4. Possible side 
effects”). 
 
Inflammation of the aorta (the large blood vessel which transports blood from the heart to the body) 
has been reported rarely with other medicines like this one (e.g. filgrastim, lenograstim or 
pegfilgrastim of the group of G-CSFs). The symptoms can include fever, abdominal pain, malaise, 
back pain and increased inflammatory markers. Tell your doctor if you experience these symptoms. 
 
Children and adolescents 
Do not give this medicine to children and adolescents under 18 years of age because there is only 
limited experience in children to show that this medicine is safe and works in this age group. 
 
Other medicines and Lonquex 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
You will normally inject your dose of Lonquex approximately 24 hours after your last dose of 
chemotherapy at the end of each chemotherapy cycle. 
 
Pregnancy and breast-feeding 
Lonquex 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, as the doctor may decide that you should 
not use this medicine. 
 
It is unknown whether the active substance in this medicine passes into the breast milk. You should 
therefore interrupt breast-feeding during treatment.. 
 
Driving and using machines 
Lonquex has no or negligible influence on your ability to drive and use machines. 
 
Lonquex contains sorbitol and sodium 
This medicine contains 30 mg sorbitol in each pre-filled syringe. 
 
This medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say 
essentially ‘sodium-free’. 
 
 
3. How to use Lonquex 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
What the recommended dose is 
The recommended dose is one pre-filled syringe (6 mg lipegfilgrastim) once per chemotherapy cycle. 
 



27 

When to use Lonquex 
This medicine should be given approximately 24 hours after your last dose of chemotherapy at the end 
of each chemotherapy cycle. 
 
How are the injections given? 
This medicine is given as an injection using a pre-filled syringe. The injection is given into the tissue 
just under the skin (subcutaneous injection). 
 
Your doctor may suggest that you learn how to inject yourself with this medicine. Your doctor or 
nurse will give you instructions on how to do this. Do not attempt to give Lonquex to yourself without 
this training. Information required for using the pre-filled syringe can be found under “Information for 
injecting yourself”. Proper treatment of your disease, however, requires close and constant 
co-operation with your doctor. 
 
Information for injecting yourself 
 
This section contains information on how to give yourself an injection of Lonquex under the skin. It is 
important that you do not try to give yourself the injection unless you have received special training 
from your doctor or nurse. If you are not sure about giving yourself the injection or you have any 
questions, please ask your doctor or nurse for help. 
 
How Lonquex is used 
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 an injection into the tissue under the skin you will need: 
• a pre-filled syringe of Lonquex, 
• an alcohol wipe, 
• a piece of gauze bandage or a sterile gauze swab, 
• a puncture-proof container (plastic container provided by the hospital or pharmacy) so you can 

dispose of used syringes safely. 
 
What you should do before your injection 
1. Take the medicine out of the refrigerator. 
2. Open the blister and take the pre-filled syringe out of the blister. Do not pick up the pre-filled 

syringe by the plunger or needle cover. 
3. 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. 
4. Check the appearance of Lonquex. It must be a clear and colourless liquid. If there are particles 

in it or if it is cloudy, you must not use it. 
5. Do not shake Lonquex vigorously as this may affect its activity. 
6. For a more comfortable injection, let the pre-filled syringe stand for 30 minutes to reach room 

temperature (not above 25°C) or hold the pre-filled syringe gently in your hand for a few 
minutes. Do not warm Lonquex in any other way (for example, do not warm it in a microwave 
or in hot water). 

7. Do not remove the needle cover from the syringe until you are ready to inject. 
8. Find a comfortable, well-lit place. Put everything you need within easy reach (the Lonquex 

pre-filled syringe, an alcohol wipe, a piece of gauze bandage or a sterile gauze swab and the 
puncture-proof container). 

9. Wash your hands thoroughly. 
 
How to prepare for your injection 
Before you give yourself a Lonquex injection, you must do the following: 
1. Hold the syringe and gently remove the cover from the needle without twisting. Pull straight as 

shown in pictures 1 and 2. Do not touch the needle or push the plunger. 



28 

2. You may notice small air bubbles in the pre-filled syringe. If there are air bubbles present, 
gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. With 
the syringe pointing upwards, expel all air from the syringe by pushing the plunger slowly 
upwards. 

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

1 2 
 
Where your injection should be given 
The most suitable places to inject yourself are: 
• the top of your thighs, 
• the abdomen (see grey areas in picture 3) avoiding the skin directly surrounding the navel. 
 
If someone else is injecting you, they can also use the back and side of your upper arms (see grey 
areas in pictures 4 and 5). 
 

3 
 

4 5 
 
How you should inject yourself 
1. Disinfect the injection site on the skin by using an alcohol wipe and pinch the skin between your 

thumb and forefinger, without squeezing it (see picture 6). 
2. Put the needle fully into the skin as shown by your doctor or nurse. The angle between the 

syringe and skin should not be too narrow (at least 45°, see picture 7). 



29 

3. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood 
in the syringe, remove the needle and re-insert it in another place. 

4. Inject the liquid into the tissue slowly and evenly, always keeping your skin pinched. 
5. After injecting the liquid, remove the needle and let go of your skin. 
6. Press the injection site with a piece of gauze bandage or a sterile gauze swab for several 

seconds. 
7. Only use each syringe for one injection. Do not use any Lonquex that is left in the syringe. 
 

6 7 
 
Remember 
If you have any problems, please ask your doctor or nurse for help and advice. 
 
Disposing of used syringes 
• Do not put the cover back on used needles. 
• Put used syringes into the puncture-proof container and keep this container out of the sight and 

reach of children. 
• Dispose of the full puncture-proof container as instructed by your doctor, pharmacist or nurse. 
• Never put the syringes that you have used into your normal household rubbish bin. 
 
Information for injecting yourself 
 
This section contains information on how to give yourself an injection of Lonquex under the skin. It is 
important that you do not try to give yourself the injection unless you have received special training 
from your doctor or nurse. If you are not sure about giving yourself the injection or you have any 
questions, please ask your doctor or nurse for help. 
 
How Lonquex is used 
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 an injection into the tissue under the skin you will need: 
• a pre-filled syringe of Lonquex, 
• an alcohol wipe, 
• a piece of gauze bandage or a sterile gauze swab. 
 
What you should do before your injection 
1. Take the medicine out of the refrigerator. 
2. Open the blister and take the pre-filled syringe out of the blister (see picture 1). Do not pick up 

the pre-filled syringe by the plunger or needle cover. This could damage the safety device. 
3. 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. 
4. Check the appearance of Lonquex. It must be a clear and colourless liquid. If there are particles 

in it or if it is cloudy, you must not use it. 
5. Do not shake Lonquex vigorously as this may affect its activity.  



30 

6. For a more comfortable injection, let the pre-filled syringe stand for 30 minutes to reach room 
temperature (not above 25°C) or hold the pre-filled syringe gently in your hand for a few 
minutes. Do not warm Lonquex in any other way (for example, do not warm it in a microwave 
or in hot water). 

7. Do not remove the needle cover from the syringe until you are ready to inject. 
8. Find a comfortable, well-lit place. Put everything you need within easy reach (the Lonquex 

pre-filled syringe, an alcohol wipe and a piece of gauze bandage or a sterile gauze swab). 
9. Wash your hands thoroughly. 
 

1 
How to prepare for your injection 
Before you give yourself a Lonquex injection, you must do the following: 
1. Hold the syringe and gently remove the cover from the needle without twisting. Pull straight as 

shown in pictures 2 and 3. Do not touch the needle or push the plunger. 
2. You may notice small air bubbles in the pre-filled syringe. If there are air bubbles present, 

gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. With 
the syringe pointing upwards, expel all air from the syringe by pushing the plunger slowly 
upwards. 

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

 2 3 
 
Where your injection should be given 
The most suitable places to inject yourself are: 
• the top of your thighs, 
• the abdomen (see grey areas in picture 4) avoiding the skin directly surrounding the navel. 
 
If someone else is injecting you, they can also use the back and side of your upper arms (see grey 
areas in pictures 5 and 6). 
 



31 

4 

5 6 
 
How you should inject yourself 
1. Disinfect the injection site on the skin by using an alcohol wipe and pinch the skin between your 

thumb and forefinger, without squeezing it (see picture 7). 
2. Put the needle fully into the skin as shown by your doctor or nurse. The angle between the 

syringe and skin should not be too narrow (at least 45°, see picture 8). 
3. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood 

in the syringe, remove the needle and re-insert it in another place. 
4. Inject the liquid into the tissue slowly and evenly, always keeping your skin pinched (see 

picture 9). 
5. Push the plunger as far as it will go to inject all the liquid. While the plunger is still pressed all 

the way down, remove the needle from the skin (see picture 10). Then release the plunger. The 
safety device will be activated immediately. The entire needle and syringe will be drawn back 
automatically and covered so that you cannot prick yourself (see picture 11). 

6. Press the injection site with a piece of gauze bandage or a sterile gauze swab for several 
seconds. 

7. Each pre-filled syringe is for single use only. 
 

7 



32 

8 9 

10 11 
 
Remember 
If you have any problems, please ask your doctor or nurse for help and advice. 
 
If you use more Lonquex than you should 
If you use more Lonquex than you should, talk to your doctor. 
 
If you forget to use Lonquex 
If you have missed an injection, 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. 
 
Most serious side effects 
 
• Allergic reactions such as skin rash, raised itchy areas of skin and serious allergic reactions with 

weakness, drop in blood pressure, difficulty breathing and swelling of the face have been 
reported uncommonly (may affect up to 1 in 100 people). If you think you are having this type 
of reaction, you must stop your Lonquex injection and get medical help immediately. 

• Increased spleen size has been reported uncommonly  and cases of splenic ruptures have been 
reported with other medicines similar to Lonquex. Some cases of splenic rupture were fatal. It is 
important to 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. 

• Cough, fever and difficult or painful breathing can be signs of uncommon  serious pulmonary 
side effects, such as pneumonia and acute respiratory distress syndrome, which may be fatal. If 
you have a fever or any of these symptoms, it is important to contact your doctor immediately.  

• It is important to contact your doctor immediately if you have any of the following symptoms: 
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. 



33 

These could be symptoms of a condition reported with frequency not known (cannot be 
estimated from the available data), called “capillary leak syndrome”, which causes blood to leak 
from the small blood vessels into your body and needs urgent medical attention. 

 
Other side effects 
 
Very common (may affect more than 1 in 10 people) 
• Musculoskeletal pains such as bone pain and pain in the joints, muscles, limbs, chest, neck or 

back. Tell your doctor if you experience severe musculoskeletal pain. 
• Nausea. 
 
Common (may affect up to 1 in 10 people) 
• Reduction in blood platelets, which increases risk of bleeding or bruising. 
• Headache. 
• Skin reactions, such as redness or rash. 
• Low blood levels of potassium, which can cause muscle weakness, twitching or abnormal heart 

rhythm. 
• Chest pain. 
• Coughing up blood. 
 
Uncommon (may affect up to 1 in 100 people) 
• Rise in white blood cells. 
• Local reactions at the injection site, such as pain or hardening. 
• Some changes may occur in your blood, but these will be detected by routine blood tests. 
• Bleeding from the lung. 
 
Not known (frequency cannot be estimated from the available data): 
• Inflammation of the aorta (the large blood vessel which transports blood from the heart to the 

body), see section 2. 
 
Side effects that have been seen with similar medicines, but not yet with Lonquex 
• Sickle cell crises in patients with sickle cell anaemia. 
• Plum-coloured raised painful sores on the limbs and sometimes the face and neck with fever 

(Sweet’s syndrome). 
• Inflammation of the blood vessels in the skin. 
• Damage to the tiny filters inside your kidneys (glomerulonephritis; see section 2 under 

“Warnings and precautions”). 
 
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 Lonquex 
 
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 outer carton and on the label of 
the pre-filled syringe after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C – 8 °C). 
 
Do not freeze. 
 
Keep the pre-filled syringe in the outer carton, in order to protect from light. 



34 

 
Lonquex may be removed from the refrigerator and stored below 25°C for a maximum single period 
of up to 3 days. Once removed from the refrigerator, the medicine must be used within this period or 
disposed of. 
 
Do not use this medicine if you notice that it is cloudy or there are particles in it. 
 
Do not throw away this medicine via wastewater or household waste. Dispose of this medicine as 
instructed by your doctor, pharmacist or nurse. 
 
 
6. Contents of the pack and other information 
 
What Lonquex contains 
• The active substance is lipegfilgrastim. Each pre-filled syringe contains 6 mg lipegfilgrastim. 

Each ml solution contains 10 mg lipegfilgrastim. 
• The other ingredients (excipients) are glacial acetic acid, sodium hydroxide , sorbitol (E420), 

polysorbate 20 and water for injections. 
 
What Lonquex looks like and contents of the pack 
Lonquex is a solution for injection (injection) in pre-filled syringe with a fixed injection needle in a 
blister. Lonquex is a clear and colourless solution. Each pre-filled syringe contains 0.6 ml solution. 
 
Each pack contains 1 pre-filled syringe with or without safety device. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
Netherlands 
 
Manufacturer 
Teva Biotech GmbH 
Dornierstraße 10 
89079 Ulm 
Germany 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
Merckle GmbH, 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG 
Tél/Tel: +32 3 820 73 73 
 

Lietuva 
UAB "Sicor Biotech" 
Tel: +370 5 266 0203 
 

България Luxembourg/Luxemburg 



35 

Актавис ЕАД 
Teл: +359 2 489 95 85 
 

Teva Pharma Belgium N.V./S.A./AG, 
Belgique/Belgien 
Tél/Tel: +32 3 820 73 73 
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o. 
Tel: +420 251 007 111 
 

Magyarország 
Teva Gyógyszergyár Zrt. 
Tel.: +36 1 288 64 00 
 

Danmark 
Teva Denmark A/S 
Tlf: +45 44 98 55 11 
 

Malta 
Teva Pharmaceuticals Ireland, L-Irlanda 
Tel: +353 51 321740 
 

Deutschland 
TEVA GmbH 
Tel: +49 731 402 08 
 

Nederland 
Teva Nederland B.V. 
Tel: +31 800 0228 400 
 

Eesti 
UAB "Sicor Biotech" Eesti filiaal 
Tel: +372 661 0801 
 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 211 880 5000 
 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97 007 
 

España 
Teva Pharma, S.L.U. 
Tel: +34 91 387 32 80 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 
 

France 
Teva Santé 
Tél: +33 1 55 91 78 00 
 

Portugal 
Teva Pharma - Produtos Farmacêuticos, Lda 
Tel: +351 21 476 75 50 
 

Hrvatska 
Pliva Hrvatska d.o.o. 
Tel: +385 1 37 20 000 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321740 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
TEVA Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 57 26 79 11 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 02 89 17 98 1 
 

Suomi/Finland 
Teva Finland 
Puh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε., Ελλάδα 
Τηλ: +30 211 880 5000 
 

Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 
 

Latvija 
UAB Sicor Biotech filiāle Latvijā 
Tel: +371 673 23 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977 628500 
 

 



36 

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

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

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS 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