Neulasta

1.

NAME OF THE MEDICINAL PRODUCT

Neulasta 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.

Excipients:

Excipients known to have a recognised action: sorbitol E420, sodium acetate (see section 4.4).

For a 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 patients treated

with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and

myelodysplastic syndromes).

4.2 Posology and method of administration

Neulasta therapy should be initiated and supervised by physicians experienced in oncology and/or

haematology.

One 6 mg dose (a single pre-filled syringe) of Neulasta is recommended for each chemotherapy cycle,

administered as a subcutaneous injection approximately 24 hours following cytotoxic chemotherapy.

Paediatric patients

The experience in children is limited (see section 4.8, 5.1 and 5.2).

Renal impairment

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

renal disease.

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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 Neulasta 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 Neulasta 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 Neulasta administration in de novo AML patients aged < 55 years with

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

The safety and efficacy of Neulasta have not been investigated in patients receiving high dose

chemotherapy.

Rare (≥ 1/10,000 to < 1/1,000) pulmonary adverse effects, 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.

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 Adult Respiratory Distress Syndrome (ARDS). In such

circumstances Neulasta should be discontinued at the discretion of the physician and the appropriate

treatment given.

Common (≥ 1/100 to < 1/10) but generally asymptomatic cases of splenomegaly and very rare

(< 1/10,000) cases of splenic rupture, including some fatal cases, have been reported following

administration of pegfilgrastim. 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.

Treatment with Neulasta 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.

Neulasta should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage

regimens.

Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell disease.

Therefore, physicians should exercise caution when administering Neulasta in patients with sickle cell

disease, should monitor appropriate clinical parameters and laboratory status and be attentive to the

possible association of Neulasta with splenic enlargement and vaso-occlusive crisis.

White blood cell counts of 100 x 10 9 /l or greater have been observed in less than 1% of patients

receiving Neulasta. 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 Neulasta.

3

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

donors has not been adequately evaluated.

The needle cover 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.

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

take this medicine.

Neulasta contains less than 1 mmol (23 mg) sodium per 6 mg dose, 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‚ Neulasta

should be administered approximately 24 hours after administration of cytotoxic chemotherapy. In

clinical studies, Neulasta has been safely administered 14 days before chemotherapy. Concomitant use

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

concomitant administration of Neulasta 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 studies.

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 Neulasta 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 studies have not

indicated an interaction of Neulasta with any other medicinal products.

4.6 Pregnancy and lactation

There are no adequate data from the use of pegfilgrastim in pregnant women. Studies in animals have

shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Neulasta should not be used during pregnancy unless clearly necessary.

There is no clinical experience with breast-feeding women, therefore Neulasta should not be

administered to women who are breast-feeding.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

In randomised clinical studies in patients with malignancy receiving Neulasta after cytotoxic

chemotherapy, most adverse events were caused by the underlying malignancy or cytotoxic

chemotherapy.

4

The most frequently reported and very common study-drug related undesirable effect was bone pain

Bone pain was generally of mild-to-moderate severity, transient and could be controlled in most

patients with standard analgesics.

Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea,

hypotension, injection site reactions, erythaema and flushing, occurring on initial or subsequent

treatment have been reported with Neulasta. In some cases, symptoms have recurred with rechallenge,

suggesting a causal relationship. If a serious allergic reaction occurs, appropriate therapy should be

administered, with close patient follow-up over several days. Pegfilgrastim should be permanently

discontinued in patients who experience a serious allergic reaction.

Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated

clinical effects, were common (≥ 1/100 to < 1/10); reversible, mild to moderate elevations in lactate

dehydrogenase, with no associated clinical effects, were very common (≥ 1/10) in patients receiving

Neulasta following cytotoxic chemotherapy. Nausea was observed in healthy volunteers and patients

receiving chemotherapy.

Common (≥ 1/100 to <1/10) but generally asymptomatic cases of splenomegaly and very rare cases of

splenic rupture, including some fatal cases, have been reported following administration of

pegfilgrastim (see section 4.4). Other commonly reported undesirable effects include pain, injection

site pain; chest pain (non-cardiac); headache; arthralgia; myalgia; back, limb, musculo-skeletal and

neck pain.

Rare (≥ 1/10,000 to < 1/1,000) pulmonary adverse effects including interstitial pneumonia, pulmonary

oedema, pulmonary infiltrates and pulmonary fibrosis have been reported. Some of the reported cases

have resulted in respiratory failure or Adult Respiratory Distress Syndrome (ARDS), which may be

fatal (see section 4.4)

Rare (≥ 1/10,000 to < 1/1,000) cases of thrombocytopenia and leukocytosis have been reported.

Rare (≥ 1/10,000 to < 1/1,000) cases of Sweet’s syndrome have been reported, although in some cases

underlying haematological malignancies may play a role.

Very rare (< 1/10,000) events of cutaneous vasculitis have been reported in patients treated with

Neulasta. The mechanism of vasculitis in patients receiving Neulasta is unknown.

Very rare (< 1/10,000) 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.

Isolated cases of sickle cell crises have been reported in patients with sickle cell disease (see section

4.4).

Paediatric Patients

A higher frequency of serious adverse events 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 study medicinal product reaction was bone pain (see section 5.1 and

5.2).

4.9 Overdose

There is no experience with overdose of Neulasta in humans.

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5.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Cytokines, 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 micrograms/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/m 2 every 3 weeks for

4 cycles). Nine hundred and twenty eight patients were randomised to receive either a single dose of

pegfilgrastim or placebo approximately 24 hours (Day 2) after chemotherapy in each cycle. The

incidence of febrile neutropenia was lower for patients randomised to receive pegfilgrastim compared

with placebo (1% versus 17%, p<0.001). The incidence of hospitalisations and IV anti-infective use

associated with a clinical diagnosis of febrile neutropenia was lower in the pegfilgrastim group

compared with placebo (1% versus 14%, p<0.001; and 2% versus 10%, p<0.001)

A small (n = 83), Phase II, randomised, double-blind study in patients receiving chemotherapy for de

novo acute myeloid leukaemia compared pegfilgrastim (single dose of 6 mg) with filgrastim,

administered during induction chemotherapy. Median time to recovery from severe neutropenia was

estimated as 22 days in both treatment groups. Long term outcome was not studied (see section 4.4).

In a phase II (n = 37) multicentre, randomised, open-label study of paediatric sarcoma patients

receiving 100 μg/kg pegfilgrastim following cycle 1 of vincristine, doxorubicin and cyclophosphamide

(VAdriaC/IE) chemotherapy, a longer duration of severe neutropenia (neutrophils < 0.5 x 10 9 ) 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).

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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

1000

100

Pegfilgrastim Conc.

ANC

100

10

1

0.1

0

3

6

9

12

15

18

21

Study Day

Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of pegfilgrastim is not

expected to be affected by renal or hepatic impairment. In a 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.

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

similar to that in adults.

Paediatric patients

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.

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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 low subcutaneous doses. In rat studies, it was shown that pegfilgrastim may cross the placenta.

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

30 months.

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

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

72 hours. Neulasta 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 Neulasta.

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

6.5 Nature and contents of container

0.6 ml of solution for injection in a pre-filled syringe (Type I glass), with a rubber stopper, and with a

stainless steel needle. Pack size of one, in either blistered, with or without an automatic needle guard

or non-blistered packaging. Single use only.

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

section 4.4).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Before administration, Neulasta 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.

8

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/1/02/227/001 1 pack blistered syringe

EU/1/02/227/002 1 pack unblistered syringe

EU/1/02/227/004 1 pack blistered syringe with needle guard

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 August 2002

Date of last renewal: 16 July 2007

10. DATE OF REVISION OF THE TEXT

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

Agency (EMEA) U http://www.emea.europa.eu/ U .

9

ANNEX II

A.

MANUFACTURER OF THE BIOLOGICAL ACTIVE

SUBSTANCE AND MANUFACTURING

AUTHORISATION HOLDER RESPONSIBLE FOR BATCH

RELEASE

B.

CONDITIONS OF THE MARKETING AUTHORISATION

10

3B

4B

A

MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND

MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH

RELEASE

Name and address of the manufacturer 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 manufacturer responsible for batch release

Amgen Europe BV

Minervum 7061

NL-4817 ZK Breda

The Netherlands

B

CONDITIONS OF THE MARKETING AUTHORISATION

•

CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON

THE MARKETING AUTHORISATION HOLDER

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

Characteristics, 4.2).

•

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

EFFECTIVE USE OF THE MEDICINAL PRODUCT

Not applicable.

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ANNEX III

LABELLING AND PACKAGE LEAFLET

12

A. LABELLING

13

1B

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BLISTERED SYRINGE OUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCT

Neulasta 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.

Excipients known to have a recognised action: sorbitol (E420), sodium acetate.

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.

6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7.

OTHER SPECIAL WARNING(S), IF NECESSARY

Avoid vigorous shaking.

8.

EXPIRY DATE

EXP

14

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/1/02/227/001 1 pack

EU/1/02/227/004 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

Neulasta

15

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER PACK WITH SYRINGE

1.

NAME OF THE MEDICINAL PRODUCT

Neulasta 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

16

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

BLISTERED SYRINGE LABEL

1.

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

Neulasta 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.

17

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

UNBLISTERED SYRINGE OUTER CARTON

1.

NAME OF THE MEDICINAL PRODUCT

Neulasta 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.

Excipients known to have a recognised action: sorbitol (E420), sodium acetate.

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 REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7.

OTHER SPECIAL WARNING(S), IF NECESSARY

Avoid vigorous shaking.

8.

EXPIRY DATE

EXP

18

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/1/02/227/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16.

INFORMATION IN BRAILLE

Neulasta

19

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

UNBLISTERED SYRINGE LABEL

1.

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

Neulasta 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.

20

B. PACKAGE LEAFLET

21

2B

PACKAGE LEAFLET: INFORMATION FOR THE USER

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

pegfilgrastim

Read all of this leaflet carefully before you start using this medicine.

-

Keep this leaflet. You may need to read it again.

-

If you have any further questions, ask your doctor or pharmacist.

-

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even

if their symptoms are the same as yours.

-

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,

please tell your doctor or pharmacist.

In this leaflet

1. What Neulasta is and what it is used for

2. Before you use Neulasta

3. How to use Neulasta

4. Possible side effects

5. How to store Neulasta

6. Further information

1.

WHAT NEULASTA IS AND WHAT IT IS USED FOR

Neulasta 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 Neulasta 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.

BEFORE YOU USE NEULASTA

Do not use Neulasta

•

if you are hypersensitive (allergic) to pegfilgrastim, filgrastim, E. coli derived proteins, or any

of the other ingredients of Neulasta.

Take special care with Neulasta

Please tell your doctor:

•

if you experience a cough, fever and difficulty breathing;

•

if you have sickle cell anaemia;

•

if you get left upper abdominal pain or pain at the tip of your shoulder;

•

if you have an allergy to latex. The needle cover on the pre-filled syringe contains a derivative

of latex and may cause severe allergic reactions.

22

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,

including medicines obtained without a prescription.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. Neulasta has not been tested in

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

•

are pregnant;

•

think you may be pregnant; or

•

plan to become pregnant.

You must stop breast feeding if you use Neulasta.

Driving and using machines

The effect of Neulasta on the ability to drive or use machines is not known.

Important information about some of the ingredients of Neulasta

Neulasta 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 Neulasta. Neulasta is essentially

sodium-free.

3.

HOW TO USE NEULASTA

Neulasta is for use in adults aged 18 and over.

Always take Neulasta 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 approximately 24 hours after your last dose of

chemotherapy at the end of each chemotherapy cycle.

Do not shake Neulasta vigorously as this may affect its activity

Injecting Neulasta yourself

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

this leaflet.

If you use more Neulasta than you should

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

23

If you forget to inject Neulasta

If you have forgotten a dose of Neulasta, you should contact your doctor to discuss when you should

inject the next dose.

4.

POSSIBLE SIDE EFFECTS

Like all medicines, Neulasta can cause side effects, although not everybody gets them.

A very common side effect (likely to occur in more than 1 in 10 patients) is bone pain. Your doctor

will tell you what you can take to ease the bone pain.

Common side effects (likely to occur in fewer than 1 in 10 patients) include; pain and redness at the

site of the injection, headaches, and general aches and pains in the joints, muscles, chest, limbs, neck

or back. An uncommon side effect (likely to occur in fewer than 1 in 100 patients) is nausea.

Allergic-type reactions to Neulasta, including redness and flushing, skin rash, raised areas of the skin

that itch and anaphylaxis (weakness, drop in blood pressure, difficulty breathing, swelling of the face),

have rarely (likely to occur in fewer than 1 in 1,000 patients) been reported.

Increased spleen size and very rare cases (likely to occur in fewer than 1 in 10,000 patients) of spleen

rupture have been reported after the use of Neulasta. 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.

Rare (likely to occur in fewer than 1 in 1,000 patients) cases of breathing problems have been reported

after taking G-CSFs. If you have a cough, fever and difficulty breathing please tell your doctor.

Some changes may occur in your blood, but these will be detected by routine blood tests. Your

platelet count may become low which might result in bruising. Your white blood cell count may

become high for a short period of time.

Sweet’s syndrome (plum-coloured, raised, painful lesions on the limbs and sometimes the face and

neck with fever) has occurred rarely (likely to occur in fewer than 1 in 1,000 patients) but other factors

may play a role.

Very rarely (likely to occur in fewer than 1 in 10,000 patients) cutaneous vasculitis (inflammation of

the blood vessels in the skin) has occurred in patients receiving Neulasta.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please

tell your doctor or pharmacist.

5.

HOW TO STORE NEULASTA

Keep out of the reach and sight of children.

Do not use Neulasta after the expiry date which is stated on the box and on the syringe label (EXP).

The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

You may take Neulasta 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.

24

Do not freeze. Neulasta 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 Neulasta if you notice it is cloudy or there are particles in it.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to

dispose of medicines no longer required. These measures will help to protect the environment.

6.

FURTHER INFORMATION

What Neulasta contains

Neulasta 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.

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.

What Neulasta looks like and contents of the pack

Neulasta is a solution for injection in a pre-filled syringe (6 mg/0.6 ml).

Each pack contains 1 pre-filled syringe. The syringes are provided either with or without a blister

wrapping. It is a clear, colourless liquid.

Marketing Authorisation Holder and Manufacturer:

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands

Further information

If you want more 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

Luxembourg/Luxemburg

s.a. Amgen

Belgique/Belgien

Tel/Tél: +32 (0)2 7752711

България

Амджен България ЕООД

Тел: +359 (0) 2 805 7020

Magyarország

Amgen Kft.

Tel: +36 1 35 44 700

25

Česká republika

Amgen s.r.o

Tel: +420 2 21 773 500

Malta

Amgen B.V.

The Netherlands

Tel: +31 (0) 76 5732500

Danmark

Amgen filial af Amgen AB, Sverige

Tlf: +45 39617500

Nederland

Amgen B.V.

Tel: +31 (0) 76 5732500

Deutschland

AMGEN GmbH

Tel: +49 (0)89 1490960

Norge

Amgen AB

Tel: +47 23308000

Eesti

Amgen Switzerland AG Eesti filiaal

Tel: +372 5125 501

Österreich

Amgen GmbH

Tel: +43 (0) 1 50 217

Ελλάδα

Genesis Pharma S.A.

Τηλ: +30 210 8771500

Polska

Amgen Sp. z o.o.

Tel: +48 22 581 3000

España

Amgen S.A.

Tel: +34 93 600 19 00

Portugal

AMGEN Biofarmacêutica, Lda.

Tel: +351 21 4220550

France

Amgen S.A.S

Tél: +33 (0)1 40 88 27 00

România

Amgen România SRL

Tel: +4021 527 3000

Ireland

Amgen Limited

United Kingdom

Tel: +44 (0)1223 420305

Suomi/Finland

Amgen AB, sivuliike Suomessa/Amgen AB, filial

i Finland

Puh/Tel: +358 (0)9 54900500

Ísland

Vistor hf.

Sími: +354 535 7000

Slovenská republika

Amgen Switzerland AG Slovakia

Tel: +421 33 321 13 22

Italia

Amgen Dompé S.p.A.

Tel: +39 02 6241121

Slovenija

AMGEN zdravila d.o.o.

Tel: +386 1 585 1767

Kύπρος

Genesis Pharma (Cyprus) Ltd

Τηλ: +357 22 76 99 46

Sverige

Amgen AB

Tel: +46 (0)8 6951100

Latvija

Amgen Switzerland AG Rīgas filiāle

Tel: +371 29284 807

United Kingdom

Amgen Limited

Tel: +44 (0)1223 420305

Lietuva

Amgen Switzerland AG Vilniaus filialas

Tel: +370 6983 6600

26

This leaflet was last approved in.

Detailed information on this medicine is available on the European Medicines Agency (EMEA) web

site: U http://www.emea.europa.eu/ U

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

Instructions for injecting with the Neulasta pre-filled syringe

This section contains information on how to give yourself an injection of Neulasta. 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 Neulasta 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 Neulasta; and

•

alcohol wipes or similar.

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

1. Remove from the refrigerator.

2. Do not shake the pre-filled syringe.

3. Do not remove the cover 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 Neulasta. 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

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

7.

Wash your hands thoroughly U .

8.

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

How do I prepare my Neulasta injection?

Before you inject Neulasta you must do the following:

1. Hold the syringe barrel and gently take 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.

27

U

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. Disinfect your skin by using an alcohol wipe and pinch the skin between your thumb and

forefinger, without squeezing it.

2. Put the needle fully into the skin as shown by your nurse or doctor.

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 slowly and evenly, always keeping your skin pinched.

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

6. If you notice a spot of blood at the injection site dab away with a cotton ball or tissues. Do not

rub the injection site. If needed, you may cover the injection site with a bandage.

7.

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

Remember

If you have any problems, please do not be afraid to ask your doctor or nurse for help and advice.

Disposing of used syringes

•

Do not put the cover back on used needles.

•

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

•

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.

28

PACKAGE LEAFLET: INFORMATION FOR THE USER

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

pegfilgrastim

Read all of this leaflet carefully before you start using this medicine.

-

Keep this leaflet. You may need to read it again.

-

If you have any further questions, ask your doctor or pharmacist.

-

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even

if their symptoms are the same as yours.

-

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,

please tell your doctor or pharmacist.

In this leaflet

1. What Neulasta is and what it is used for

2. Before you use Neulasta

3. How to use Neulasta

4. Possible side effects

5. How to store Neulasta

6. Further information

1.

WHAT NEULASTA IS AND WHAT IT IS USED FOR

Neulasta 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 Neulasta 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.

BEFORE YOU USE NEULASTA

Do not use Neulasta

•

if you are hypersensitive (allergic) to pegfilgrastim, filgrastim, E. coli derived proteins, or any

of the other ingredients of Neulasta.

Take special care with Neulasta

Please tell your doctor:

•

if you experience a cough, fever and difficulty breathing;

•

if you have sickle cell anaemia;

•

if you get left upper abdominal pain or pain at the tip of your shoulder;

•

if you have an allergy to latex. The needle cover on the pre-filled syringe contains a derivative

of latex and may cause severe allergic reactions.

29

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,

including medicines obtained without a prescription.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. Neulasta has not been tested in

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

•

are pregnant;

•

think you may be pregnant; or

•

plan to become pregnant.

You must stop breast feeding if you use Neulasta.

Driving and using machines

The effect of Neulasta on the ability to drive or use machines is not known.

Important information about some of the ingredients of Neulasta

Neulasta 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 Neulasta. Neulasta is essentially

sodium-free.

3.

HOW TO USE NEULASTA

Neulasta is for use in adults aged 18 and over.

Always take Neulasta 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 approximately 24 hours after your last dose of

chemotherapy at the end of each chemotherapy cycle.

Do not shake Neulasta vigorously as this may affect its activity

Injecting Neulasta yourself

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

this leaflet.

If you use more Neulasta than you should

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

30