PELGRAZ 6mg injection solution in pre-filled syringe medication leaflet

Pelgraz 6 mg solution for injection in pre-filled syringe

Pelgraz 6 mg solution for injection in pre-filled injector

Pelgraz 6 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 6 mg of pegfilgrastim* in 0.6 mL solution for injection. Theconcentration is 10 mg/mL based on protein only**.

Pelgraz 6 mg solution for injection in pre-filled injector

Each pre-filled injector contains 6 mg of pegfilgrastim* in 0.6 mL solution for injection. Theconcentration is 10 mg/mL based on protein only**.

* Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation withpolyethylene glycol (PEG).

** The concentration is 20 mg/mL if the PEG moiety is included.

The potency of this medicinal product should not be compared to the potency of another pegylated ornon-pegylated protein of the same therapeutic class. For more information, see section 5.1.

Each pre-filled syringe or pre-filled injector contains 30 mg sorbitol (E420).

For the full list of excipients, see section 6.1.

Solution for injection.

Clear, colourless solution for injection.

Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patientstreated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemiaand myelodysplastic syndromes).

Pelgraz therapy should be initiated and supervised by physicians experienced in oncology and/orhaematology.

One 6 mg dose (a single pre-filled syringe or pre-filled injector) of Pelgraz is recommended for eachchemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy.

The safety and efficacy of Pelgraz in children and adolescents has not yet been established. Currentlyavailable data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can bemade.

No dose change is recommended in patients with renal impairment, including those with end-stagerenal disease.

Pelgraz is for subcutaneous use. The injections should be given subcutaneously into the thigh,abdomen or upper arm.

For instructions on handling of the medicinal product before administration, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

In order to improve the traceability of biological medicinal products, the trade name of theadministered product should be clearly recorded.

Acute myeloid leukaemia (AML)

Limited clinical data suggest a comparable effect on time to recovery of severe neutropenia forpegfilgrastim to filgrastim in patients with de novo AML (see section 5.1). However, the long-termeffects of pegfilgrastim have not been established in AML; therefore, it should be used with caution inthis patient population.

G-CSF can promote growth of myeloid cells in vitro and similar effects may be seen on some non-myeloid cells in vitro.

The safety and efficacy of pegfilgrastim have not been investigated in patients with myelodysplasticsyndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it shouldnot be used in such patients. Particular care should be taken to distinguish the diagnosis of blasttransformation of chronic myeloid leukaemia from AML.

The safety and efficacy of pegfilgrastim administration in de novo AML patients aged < 55 years withcytogenetics t(15;17) have not been established.

The safety and efficacy of pegfilgrastim have not been investigated in patients receiving high dosechemotherapy. This medicinal product should not be used to increase the dose of cytotoxicchemotherapy beyond established dose regimens.

Pulmonary adverse reactions

Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSFadministration. Patients with a recent history of pulmonary infiltrates or pneumonia may be at higherrisk (see section 4.8).

The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiologicalsigns of pulmonary infiltrates, and deterioration in pulmonary function along with increased neutrophilcount may be preliminary signs of acute respiratory distress syndrome (ARDS). In such circumstancespegfilgrastim should be discontinued at the discretion of the physician and the appropriate treatmentgiven (see section 4.8).

Glomerulonephritis

Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally,events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim andpegfilgrastim. Urinalysis monitoring is recommended.

Capillary leak syndrome has been reported after G-CSF administration and is characterised byhypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms ofcapillary 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

Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatalcases, 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 ofsplenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tippain.

Thrombocytopenia and anaemia

Treatment with pegfilgrastim alone does not preclude thrombocytopenia and anaemia because fulldose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring ofplatelet count and haematocrit is recommended. Special care should be taken when administeringsingle or combination chemotherapeutic medicinal products which are known to cause severethrombocytopenia.

Myelodysplastic syndrome and acute myeloid leukaemia in breast and lung cancer patients

In the post-marketing observational study setting, pegfilgrastim in conjunction with chemotherapyand/or radiotherapy has been associated with development of myelodysplastic syndrome (MDS) andacute myeloid leukaemia (AML) in breast and lung cancer patients (see section 4.8). Monitor breastand lung cancer patients for signs and symptoms of MDS/AML.

Sickle cell anaemia

Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell trait orsickle cell disease (see section 4.8). Therefore, physicians should use caution when prescribingpegfilgrastim in patients with sickle cell trait or sickle cell disease, should monitor appropriate clinicalparameters and laboratory status and be attentive to the possible association of this medicinal productwith splenic enlargement and vaso-occlusive crisis.

Leukocytosis

White blood cell (WBC) counts of 100 × 109/L or greater have been observed in less than 1% ofpatients receiving pegfilgrastim. No adverse reactions directly attributable to this degree ofleukocytosis have been reported. Such elevation in WBCs is transient, typically seen 24 to 48 hoursafter administration and is consistent with the pharmacodynamic effects of this medicinal product.

Consistent with the clinical effects and the potential for leukocytosis, a WBC count should beperformed at regular intervals during therapy. If leukocyte counts exceed 50 × 109/L after the expectednadir, this medicinal product should be discontinued immediately.

Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment havebeen reported in patients treated with pegfilgrastim. Permanently discontinue pegfilgrastim in patientswith clinically significant hypersensitivity. Do not administer pegfilgrastim to patients with a historyof hypersensitivity to pegfilgrastim or filgrastim. If a serious allergic reaction occurs, appropriatetherapy should be administered, with close patient follow-up over several days.

Stevens-Johnson syndrome (SJS)

SJS, which can be life-threatening or fatal, has been reported rarely in association with pegfilgrastimtreatment. If the patient has developed SJS with the use of pegfilgrastim, treatment with pegfilgrastimmust not be restarted in this patient at any time.

As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation ofantibodies against pegfilgrastim is generally low. Binding antibodies do occur as expected with allbiologics; however, they have not been associated with neutralising activity at present.

Aortitis

Aortitis has been reported after filgrastim or pegfilgrastim administration in healthy subjects and incancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain andincreased inflammatory markers (e.g. C-reactive protein and WBC count). In most cases aortitis wasdiagnosed by CT scan and generally resolved after withdrawal of filgrastim or pegfilgrastim. See alsosection 4.8.

Mobilisation of PBPC

The safety and efficacy of Pelgraz for the mobilisation of blood progenitor cells in patients or healthydonors has not been adequately evaluated.

Other special precautions

Increased haematopoietic activity of the bone marrow in response to growth factor therapy has beenassociated with transient positive bone-imaging findings. This should be considered when interpretingbone-imaging results.

All patients

The needle cover of the pre-filled syringe contains dry natural rubber (a derivative of latex), whichmay cause allergic reactions.

Sorbitol

The additive effect of concomitantly administered products containing sorbitol (or fructose) anddietary intake of sorbitol (or fructose) should be taken into account.

This medicinal product contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to sayessentially ‘sodium-free’.

Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚pegfilgrastim should be administered at least 24 hours after administration of cytotoxic chemotherapy.

In clinical trials, pegfilgrastim has been safely administered 14 days before chemotherapy.

Concomitant use of Pelgraz with any chemotherapeutic medicinal product has not been evaluated inpatients. In animal models concomitant administration of pegfilgrastim and 5-fluorouracil (5-FU) orother antimetabolites has been shown to potentiate myelosuppression.

Possible interactions with other haematopoietic growth factors and cytokines have not beenspecifically investigated in clinical trials.

The potential for interaction with lithium, which also promotes the release of neutrophils, has not beenspecifically investigated. There is no evidence that such an interaction would be harmful.

The safety and efficacy of Pelgraz have not been evaluated in patients receiving chemotherapyassociated with delayed myelosuppression e.g. nitrosoureas.

Specific interaction or metabolism studies have not been performed, however, clinical trials have notindicated an interaction of pegfilgrastim with any other medicinal products.

There are no or limited amount of data from the use of pegfilgrastim in pregnant women. Studies inanimals have shown reproductive toxicity (see section 5.3). Pegfilgrastim is not recommended duringpregnancy and in women of childbearing potential not using contraception.

There is insufficient information on the excretion of pegfilgrastim/metabolites in human milk, a risk tothe newborns/infants cannot be excluded. A decision must be made whether to discontinuebreast-feeding or to discontinue/abstain from pegfilgrastim therapy taking into account the benefit ofbreast-feeding for the child and the benefit of therapy for the woman.

Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulativeweekly doses approximately 6 to 9 times higher than the recommended human dose (based on bodysurface area) (see section 5.3).

Pegfilgrastim has no or negligible influence on the ability to drive and use machines.

The most frequently reported adverse reactions were bone pain (very common [≥ 1/10]) andmusculoskeletal pain (common [≥ 1/100 to < 1/10]). Bone pain was generally of mild to moderateseverity, transient and could be controlled in most patients with standard analgesics.

Hypersensitivity-type reactions, including skin rash, urticaria, angioedema, dyspnoea, erythaema,flushing, and hypotension occurred on initial or subsequent treatment with pegfilgrastim (uncommon[≥ 1/1 000 to < 1/100]). Serious allergic reactions, including anaphylaxis can occur in patientsreceiving pegfilgrastim (uncommon) (see section 4.4).

Capillary Leak Syndrome, which can be life-threatening if treatment is delayed, has been reported asuncommon (≥ 1/1 000 to < 1/100) in cancer patients undergoing chemotherapy followingadministration of G-CSFs; 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 ofpegfilgrastim (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 inrespiratory failure or ARDS, which may be fatal (see section 4.4).

Isolated cases of sickle cell crises have been reported in patients with sickle cell trait or sickle celldisease (uncommon in sickle cell patients) (see section 4.4).

The data in the table below describe adverse reactions reported from clinical trials and spontaneousreporting. Within each frequency grouping, adverse reactions are presented in order of decreasingseriousness.

MedDRA Adverse reactionssystem organ Very common Common Uncommon Rare Very rareclass (≥ 1/10) (≥ 1/100 to (≥ 1/1,000 to (≥ 1/10,00 (< 1/10,00< 1/10) < 1/100) 0 to 0)< 1/1,000)

Neoplasms Myelodysplasticbenign, syndrome1malignant and Acute myeloidunspecified(incl cysts and leukaemia1polyps)

Blood and Thrombocytopeni Sickle celllymphatic a1 anaemia withsystem Leukocytosis1 crisis2disorders Splenomegaly2

Splenic rupture2

Immune Hypersensitivitysystem reactions;disorders Anaphylaxis

Metabolism Elevations in uricand nutrition aciddisorders

Nervous Headache1systemdisorders

Vascular Capillary leak Aortitisdisorders syndrome1

Respiratory, Acute Pulmonarythoracic and Respiratory haemorrhamediastinal Distress gedisorders Syndrome2;

Pulmonaryadverse reactions(interstitialpneumonia,pulmonaryoedema,pulmonaryinfiltrates andpulmonaryfibrosis)

Haemoptysis

Gastrointestin Nausea1al disorders

Skin and Sweet’s Stevens-subcutaneous syndrome (acute Johnsontissue febrile syndromedisorders neutrophilicdermatosis)1,2

Cutaneousvasculitis1,2

Musculoskelet Bone pain Musculoskeletalal and pain (myalgia,connective arthralgia, pain intissue extremity, backdisorders pain, musculo-skeletal pain,neck pain)

Renal and Glomerulonephriturinary is2disorders

General Injection site Injection sitedisorders and pain1 reactions2administrative Non-cardiac chestsite conditions pain

Investigations Elevations inlactatedehydrogenaseand alkalinephosphatase1

Transientelevations in

LFTs for ALT or

AST11 See section “Description of selected adverse reactions” below.

2 This adverse reaction was identified through post-marketing surveillance but not observed inrandomised, controlled clinical trials in adults. The frequency category was estimated from a statisticalcalculation based upon 1,576 patients receiving pegfilgrastim in nine randomised clinical trials.

Uncommon cases of Sweet’s syndrome have been reported, although in some cases underlyinghaematological malignancies may play a role.

Uncommon events of cutaneous vasculitis have been reported in patients treated with pegfilgrastim.

The mechanism of vasculitis in patients receiving pegfilgrastim is unknown.

Injection site reactions, including injection site erythaema (uncommon) as well as injection site pain(common events) have occurred on initial or subsequent treatment with pegfilgrastim.

Common cases of leukocytosis (WBC > 100 × 109/L) have been reported (see section 4.4).

Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associatedclinical effects, were uncommon; reversible, mild to moderate elevations in lactate dehydrogenase,with no associated clinical effects, were uncommon in patients receiving pegfilgrastim followingcytotoxic chemotherapy.

Nausea and headaches were very commonly observed in patients receiving chemotherapy.

Uncommon elevations in liver function tests (LFTs) for alanine aminotransferase (ALT) or aspartateaminotransferase (AST), have been observed in patients after receiving pegfilgrastim followingcytotoxic chemotherapy. These elevations are transient and return to baseline.

An increased risk of MDS/AML following treatment with Pelgraz in conjunction with chemotherapyand/or radiotherapy has been observed in an epidemiological study in breast and lung cancer patients(see section 4.4).

Common cases of thrombocytopenia have been reported.

Cases of capillary leak syndrome have been reported in the post-marketing setting with G-CSF use.

These have generally occurred in patients with advanced malignant diseases, sepsis, taking multiplechemotherapy medicinal products or undergoing apheresis (see section 4.4).

The experience in children is limited. A higher frequency of serious adverse reactions in youngerchildren aged 0-5 years (92%) has been observed compared to older children aged 6-11 and 12-21years respectively (80% and 67%) and adults. The most common adverse reaction reported was bonepain (see sections 5.1 and 5.2).

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Single doses of 300 mcg/kg have been administered subcutaneously to a limited number of healthyvolunteers and patients with non-small cell lung cancer without serious adverse reactions. The adversereactions were similar to those in subjects receiving lower doses of pegfilgrastim.

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

Pelgraz is a biosimilar medicinal product. Detailed information is available on the website of the

European Medicines Agency http://www.ema.europa.eu.

Human granulocyte-colony stimulating factor (G-CSF) is a glycoprotein, which regulates theproduction and release of neutrophils from the bone marrow. Pegfilgrastim is a covalent conjugate ofrecombinant human G-CSF (r-metHuG-CSF) with a single 20 kd Poly Ethylene Glycol molecule.

Pegfilgrastim is a sustained duration form of filgrastim due to decreased renal clearance. Pegfilgrastimand filgrastim have been shown to have identical modes of action, causing a marked increase inperipheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/orlymphocytes. Similarly to filgrastim, neutrophils produced in response to pegfilgrastim show normalor enhanced function as demonstrated by tests of chemotactic and phagocytic function. As with otherhaematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelialcells. G-CSF can promote growth of myeloid cells, including malignant cells, in vitro and similareffects 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 cancerundergoing myelosuppressive chemotherapy consisting of doxorubicin and docetaxel, use ofpegfilgrastim, as a single once per cycle dose, reduced the duration of neutropenia and the incidence offebrile neutropenia similarly to that observed with daily administrations of filgrastim (a median of 11daily administrations). In the absence of growth factor support, this regimen has been reported to resultin a mean duration of grade 4 neutropenia of 5 to7 days, and a 30-40% incidence of febrileneutropenia. In one study (n = 157), which used a 6 mg fixed dose of pegfilgrastim the mean durationof grade 4 neutropenia for the pegfilgrastim group was 1.8 days compared with 1.6 days in thefilgrastim group (difference 0.23 days, 95% CI -0.15, 0.63). Over the entire study, the rate of febrileneutropenia was 13% of pegfilgrastim-treated patients compared with 20% of filgrastim-treatedpatients (difference 7%, 95% CI of -19%, 5%). In a second study (n = 310), which used a weightadjusted dose (100 mcg/kg), the mean duration of grade 4 neutropenia for the pegfilgrastim group was1.7 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% ofpatients 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 onthe incidence of febrile neutropenia was evaluated following administration of a chemotherapyregimen associated with a febrile neutropenia rate of 10-20% (docetaxel 100 mg/m2 every 3 weeks for4 cycles). Nine hundred and twenty eight-patients were randomised to receive either a single dose ofpegfilgrastim or placebo approximately 24 hours (day 2) after chemotherapy in each cycle. Theincidence of febrile neutropenia was lower for patients randomised to receive pegfilgrastim comparedwith placebo (1% versus 17%, p < 0.001). The incidence of hospitalisations and intravenous anti-infective use associated with a clinical diagnosis of febrile neutropenia was lower in the pegfilgrastimgroup 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 denovo AML compared pegfilgrastim (single dose of 6 mg) with filgrastim, administered duringinduction chemotherapy. Median time to recovery from severe neutropenia was estimated as 22 daysin 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 patientsreceiving 100 mcg/kg pegfilgrastim following cycle 1 of vincristine, doxorubicin andcyclophosphamide (VAdriaC/IE) chemotherapy, a longer duration of severe neutropenia (neutrophils< 0.5 × 109/L) was observed in younger children aged 0-5 years (8.9 days) compared to older childrenaged 6-11 years and 12-21 years (6 days and 3.7 days, respectively) and adults. Additionally a higherincidence of febrile neutropenia was observed in younger children aged 0-5 years (75%) compared toolder children aged 6-11 years and 12-21 years (70% and 33%, respectively) and adults (see sections4.8 and 5.2).

After a single subcutaneous dose of pegfilgrastim, the peak serum concentration of pegfilgrastimoccurs at 16 to 120 hours after dosing and serum concentrations of pegfilgrastim are maintained duringthe period of neutropenia after myelosuppressive chemotherapy. The elimination of pegfilgrastim isnon-linear with respect to dose; serum clearance of pegfilgrastim decreases with increasing dose.

Pegfilgrastim appears to be mainly eliminated by neutrophil-mediated clearance, which becomessaturated at higher doses. Consistent with a self-regulating clearance mechanism, the serumconcentration of pegfilgrastim declines rapidly at the onset of neutrophil recovery (see figure 1).

Figure 1. Profile of median pegfilgrastim serum concentration and Absolute Neutrophil Count(ANC) in chemotherapy treated patients after a single 6 mg injection

Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of pegfilgrastim is notexpected 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 thepharmacokinetics of pegfilgrastim.

Limited data indicate that the pharmacokinetics of pegfilgrastim in elderly subjects (> 65 years) issimilar to that in adults.

The pharmacokinetics of pegfilgrastim were studied in 37 paediatric patients with sarcoma, whoreceived 100 mcg/kg pegfilgrastim after the completion of VAdriaC/IE chemotherapy. The youngestage group (0-5 years) had a higher mean exposure to pegfilgrastim (AUC) (± Standard Deviation)(47.9 ± 22.5 mcg·hr/ml) than older children aged 6-11 years and 12-21 years (22.0 ± 13.1 mcg·hr/mLand 29.3 ± 23.2 mcg·hr/mL, respectively) (see section 5.1). With the exception of the youngest agegroup (0-5 years), the mean AUC in paediatric subjects appeared similar to that for adult patients withhigh-risk stage II-IV breast cancer and receiving 100 mcg/kg pegfilgrastim after the completion ofdoxorubicin/docetaxel (see sections 4.8 and 5.1).

Preclinical data from conventional studies of repeated dose toxicity revealed the expectedpharmacological 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 pegfilgrastimsubcutaneously, but in rabbits pegfilgrastim has been shown to cause embryo/foetal toxicity (embryoloss) at cumulative doses approximately 4 times the recommended human dose, which were not seenwhen pregnant rabbits were exposed to the recommended human dose. In rat studies, it was shown thatpegfilgrastim may cross the placenta. Studies in rats indicated that reproductive performance, fertility,oestrous cycling, days between pairing and coitus, and intrauterine survival were unaffected bypegfilgrastim given subcutaneously. The relevance of these findings for humans is not known.

Sodium acetate*

Sorbitol (E420)

Polysorbate 20

Water for injections

*Sodium acetate is formed by titrating glacial acetic acid with sodium hydroxide.

This medicinal product must not be mixed with other medicinal products, particularly with sodiumchloride solutions.

3 years.

Store in a refrigerator (2 °C - 8 °C).

Pelgraz may be exposed to room temperature (not above 25 °C ± 2 °C) for a maximum single periodof up to 15 days. Pelgraz left at room temperature for more than 15 days should be discarded.

Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hoursdoes not adversely affect the stability of Pelgraz.

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

Pelgraz 6 mg solution for injection in pre-filled syringe

Pre-filled syringe (type I glass) with a permanently attached stainless steel injection needle, with aneedle safety guard.

The needle cover of the pre-filled syringe contains dry natural rubber (see section 4.4).

Each pre-filled syringe contains 0.6 mL of solution for injection. Pack size of one pre-filled syringewith one alcohol swab, in a blistered packaging.

Pelgraz 6 mg solution for injection in pre-filled injector

Pre-filled injector containing a pre-filled syringe (type I glass) with a permanently attached stainlesssteel injection needle. The pre-filled syringe is externally equipped with the device for self-administration (pre-filled injector).

The needle cover of the pre-filled syringe contains dry natural rubber (see section 4.4).

Each pre-filled syringe injector contains 0.6 mL of solution for injection. Pack size of one pre-filledinjector with one alcohol swab, in a blistered packaging.

Pelgraz 6 mg solution for injection in pre-filled syringe

Before use, Pelgraz solution should be inspected visually for particulate matter. Only a solution that isclear and colourless should be injected.

Excessive shaking may aggregate pegfilgrastim, rendering it biologically inactive.

Allow the pre -filled syringe to reach room temperature for 30 minutes before injecting.

Using the pre filled syringe with a needle safety guard

The needle safety guard covers the needle after injection to prevent needle stick injury. This does notaffect normal operation of the syringe. Depress the plunger rod and push firmly at the end of theinjection to ensure that syringe emptying is completed. Hold the skin securely until the injection iscompleted. Keep the syringe still and slowly lift your thumb from the plunger rod head. The plungerrod will move up with your thumb and the spring retracts the needle from the site, into the Needlesafety guard.

Do not use a pre-filled syringe if it has been dropped on a hard surface.

Pelgraz 6 mg solution for injection in pre-filled injector

Before use, Pelgraz solution should be inspected visually for particulate matter. Only a solution that isclear and colourless should be injected.

Excessive shaking may aggregate pegfilgrastim, rendering it biologically inactive.

Allow the pre-filled injector to reach room temperature for 30 minutes before injecting.

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

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,08039 Barcelona,

Spain

EU/1/18/1313/001

EU/1/18/1313/002

Date of first authorisation: 21st September 2018

Date of latest renewal: 23rd June 2023

Detailed information on this medicinal product is available on the website of the European Medicines

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