Ziextenzo

Main information

  • Trade name:
  • Ziextenzo
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Ziextenzo
    European Union
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • Immunostimulants,
  • Therapeutic area:
  • Neutropenia
  • Therapeutic indications:
  • Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).,

Status

  • Source:
  • EMA - European Medicines Agency
  • Authorization status:
  • Authorised
  • Authorization number:
  • EMEA/H/C/004802
  • Authorization date:
  • 21-11-2018
  • EMEA code:
  • EMEA/H/C/004802
  • Last update:
  • 25-03-2019

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© European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged.

EMA/653854/2018

EMEA/H/C/004802

Ziextenzo (pegfilgrastim)

An overview of Ziextenzo and why it is authorised in the EU

What is Ziextenzo and what is it used for?

Ziextenzo is a medicine used in cancer patients to help with neutropenia (low levels of neutrophils, a

type of white blood cell), which is a common side effect of cancer treatment and can leave patients

vulnerable to infections.

It is given specifically to reduce the duration of neutropenia and prevent febrile neutropenia (when

neutropenia is accompanied by fever).

Ziextenzo is not intended for use in patients with the blood cancer chronic myeloid leukaemia or with

myelodysplastic syndromes (conditions in which large numbers of abnormal blood cells are produced,

which can develop into leukaemia).

Ziextenzo is a ‘biosimilar medicine’. This means that Ziextenzo is highly similar to another biological

medicine (the ‘reference medicine’) that is already authorised in the EU. The reference medicine for

Ziextenzo is Neulasta. For more information on biosimilar medicines, see here

How is Ziextenzo used?

Ziextenzo can only be obtained with a prescription and treatment should be started and supervised by

a doctor who has experience in the treatment of cancer or blood disorders. It is available as a prefilled

syringe containing a solution for injection under the skin. Ziextenzo is given as a single dose of 6 mg

injected under the skin at least 24 hours after the end of each cycle of chemotherapy (treatment with

cancer medicines). Patients can inject themselves if they have been trained appropriately.

For more information about using Ziextenzo, see the package leaflet or contact your doctor or

pharmacist.

How does Ziextenzo work?

The active substance in Ziextenzo, pegfilgrastim, is a form of filgrastim, which is very similar to a

human protein called granulocyte-colony-stimulating factor (G-CSF). Filgrastim works by encouraging

Ziextenzo (pegfilgrastim)

EMA/653854/2018

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the bone marrow to produce more white blood cells, increasing white blood cell counts and so treating

neutropenia.

Filgrastim has been available in other medicines in the European Union (EU) for a number of years. In

Ziextenzo, filgrastim has been ‘pegylated’ (attached to a chemical called polyethylene glycol). This

slows down the removal of filgrastim from the body, allowing the medicine to be given less often.

What benefits of Ziextenzo have been shown in studies?

Laboratory studies comparing Ziextenzo with Neulasta have shown that the active substance in

Ziextenzo is highly similar to that in Neulasta in terms of structure, purity and biological activity.

Studies have also shown that giving Ziextenzo produces similar levels of the active substance in the

body to giving Neulasta.

In addition, two studies involving 624 patients who had chemotherapy before or after surgery for

breast cancer showed that Ziextenzo was as effective as Neulasta in reducing the duration of

neutropenia. Neutropenia lasted 1 day on average with both medicines.

Because Ziextenzo is a biosimilar medicine, the studies on effectiveness and safety of pegfilgrastim

carried out with Neulasta do not all need to be repeated for Ziextenzo.

What are the risks associated with Ziextenzo?

The safety of Ziextenzo has been evaluated, and on the basis of all the studies carried out the side

effects of the medicine are considered to be comparable to those of the reference medicine Neulasta.

The most common side effect with Ziextenzo (which may affect more than 1 in 10 people) is pain in

the bones. Pain in muscles is also common. For the full list of side effects and restrictions with

Ziextenzo, see the package leaflet.

Why is Ziextenzo authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar

medicines, Ziextenzo has a highly similar structure, purity and biological activity to Neulasta and is

distributed in the body in the same way. In addition, studies in breast cancer patients undergoing

chemotherapy have shown that the effectiveness of Ziextenzo is equivalent to that of Neulasta in

reducing the duration of neutropenia.

All these data were considered sufficient to conclude that Ziextenzo will behave in the same way as

Neulasta in terms of effectiveness and safety in its authorised uses. Therefore, the Agency’s view was

that, as for Neulasta, the benefit of Ziextenzo outweighs the identified risk and it can be authorised for

use in the EU.

What measures are being taken to ensure the safe and effective use of

Ziextenzo?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Ziextenzo have been included in the summary of product characteristics and the

package leaflet.

As for all medicines, data on the use of Ziextenzo are continuously monitored. Side effects reported

with Ziextenzo are carefully evaluated and any necessary action taken to protect patients.

Ziextenzo (pegfilgrastim)

EMA/653854/2018

Page 3/3

Other information about Ziextenzo

Ziextenzo received a marketing authorisation valid throughout the EU on 22 November 2018.

Further information on Ziextenzo can be found on the Agency’s website:

https://www.ema.europa.eu/en/medicines/human/EPAR/ziextenzo

This overview was last updated in 11-2018.

Patient Information leaflet: composition, indications, side effects, dosage, interactions, adverse reactions, pregnancy, lactation

B. PACKAGE LEAFLET

Package leaflet: Information for the user

Ziextenzo 6 mg solution for injection in pre-filled syringe

pegfilgrastim

▼This medicine is subject to additional monitoring. This will allow quick identification of new safety

information. You can help by reporting any side effects you may get. See the end of section 4 for how to

report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important

information for you.

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

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

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

even if their symptoms of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What Ziextenzo is and what it is used for

What you need to know before you use Ziextenzo

How to use Ziextenzo

Possible side effects

How to store Ziextenzo

Contents of the pack and other information

1.

What Ziextenzo is and what it is used for

Ziextenzo 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.

Ziextenzo 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 Ziextenzo to encourage your bone marrow (part of the bone which makes

blood cells) to produce more white blood cells that help your body fight infection.

2.

What you need to know before you use Ziextenzo

Do not use Ziextenzo

if you are allergic to pegfilgrastim, filgrastim

,

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 Ziextenzo:

if you experience an allergic reaction including weakness, drop in blood pressure, difficulty

breathing, swelling of the face (anaphylaxis), redness and flushing, skin rash and areas of the skin

that itch.

if you experience a cough, fever and difficulty breathing. This can be a sign of Acute Respiratory

Distress Syndrome (ARDS).

if you have any of the following or combination of the following side effects:

swelling or puffiness, which may be associated with passing water less frequently,

difficulty breathing, abdominal swelling and feeling of fullness, and a general feeling of

tiredness

These could be symptoms of condition called “Capillary Leak Syndrome” which causes blood to

leak from the small blood vessels into your body. See section 4.

if you get left upper abdominal pain or pain at the tip of your shoulder. This may be a sign of a

problem with your spleen (splenomegaly).

if you have recently had a serious lung infection (pneumonia), fluid in the lungs (pulmonary

oedema), inflammation of the lungs (interstitial lung disease) or an abnormal chest x-ray (lung

infiltration).

if you are aware of any altered blood cell counts (e.g. increase in white blood cells or anaemia) or

decreased blood platelet counts, which reduces the ability of your blood to clot

(thrombocytopenia). Your doctor may want to monitor you more closely.

if you have sickle cell anaemia. Your doctor may monitor your condition more closely.

if you have sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face,

lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing these

could be signs of a severe allergic reaction.

Inflammation of the aorta (the large blood vessel which transports blood from the heart to the

body) has been reported rarely in cancer patients and healthy donors. The symptoms can include

fever, abdominal pain, malaise, back pain and increased inflammatory markers. Tell your doctor

if you experience these symptoms.

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

your kidneys (glomerulonephritis).

You should talk to your doctor about your risks of developing cancers of the blood. If you develop or

are likely to develop cancers of the blood, you should not use Ziextenzo, unless instructed by your

doctor.

Loss of response to pegfilgrastim

If you experience a loss of response or failure to maintain a response with pegfilgrastim treatment, your

doctor will investigate the reasons why, including whether you have developed antibodies which

neutralise pegfilgrastim’s activity.

Other medicines and Ziextenzo

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Pregnancy and breast-feeding

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

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

are pregnant;

think you may be pregnant; or

are planning to have a baby.

If you become pregnant during Ziextenzo treatment, please inform your doctor.

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

Driving and using machines

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

Ziextenzo contains sorbitol (E420) and sodium

This medicine contains 30 mg sorbitol in each pre-filed syringe which is equivalent to 50 mg / mL.

This medicine contains less than 1 mmol (23 mg) sodium per 6 mg dose, that is to say essentially

‘sodium-free’.

3.

How to use Ziextenzo

Ziextenzo is for use in adults aged 18 and over.

Always use Ziextenzo exactly as your doctor has told you. You should check with your doctor or

pharmacist if you are unsure. The usual dose is one 6 mg subcutaneous injection (injection under your

skin) using a pre-filled syringe and it should be given at least 24 hours after your last dose of

chemotherapy at the end of each chemotherapy cycle.

Injecting Ziextenzo yourself

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

this leaflet.

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

If you use more Ziextenzo than you should

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

If you forget to inject Ziextenzo

If you are injecting yourself and have forgotten a dose of Ziextenzo, you should contact your doctor to

discuss when you should inject the next dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4.

Possible side effects

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

Please tell your doctor immediately if you have any of the following or combination of the following

side effects:

swelling or puffiness, which may be associated with passing water less frequently, difficulty

breathing, abdominal swelling and feeling of fullness, and a general feeling of tiredness. These

symptoms generally develop in a rapid fashion.

These could be symptoms of an uncommon (may affect up to 1 in 100 people) condition called

“Capillary Leak Syndrome” which causes blood to leak from the small blood vessels into your body and

needs urgent medical attention.

Very common side effects

(may affect more than 1 in 10 people):

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

nausea and headaches.

Common side effects

(may affect up to 1 in 10 people):

pain at the site of injection.

general aches and pains in the joints and muscles.

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

white blood cell count may become high for a short period of time. Your platelet count may

become low which might result in bruising.

Uncommon side effects

(may affect up to 1 in 100 people):

allergic-type reactions, including redness and flushing, skin rash, and raised areas of the skin that

itch.

serious allergic reactions, including anaphylaxis (weakness, drop in blood pressure, difficulty

breathing, swelling of the face).

increased spleen size.

spleen rupture. Some cases of splenic rupture were fatal. It is important that you contact your

doctor immediately if you experience pain in the upper left side of the abdomen or left shoulder

pain since this may relate to a problem with your spleen.

breathing problems. If you have a cough, fever and difficulty breathing please tell your doctor.

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

and neck with fever) has occurred but other factors may play a role.

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

damage to the tiny filters inside your kidneys (glomerulonephritis).

redness at the site of injection.

coughing up blood (haemoptysis)

Rare side effects

(may affect up to 1 in 1,000 people):

inflammation of the aorta (the large blood vessel which transports blood from the heart to the

body), see section 2.

bleeding from the lung (pulmonary haemorrhage)

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 Ziextenzo

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the syringe label after

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

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

You may take Ziextenzo out of the refrigerator and keep it at room temperature (not above 25 °C) for no

longer than 72 hours. Once a syringe has been removed from the refrigerator and has reached room

temperature (not above 25 °C) it must either be used within 72 hours or disposed of.

Do not freeze. Ziextenzo may be used if it is accidentally frozen for a single period of less than 24

hours.

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

Do not use this medicine if you notice it is cloudy or there are particles in it.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help to protect the environment.

6.

Contents of the pack and other information

What Ziextenzo contains

The active substance is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in

0.6 mL of solution.

The other ingredients are glacial acetic acid, sorbitol (E420), polysorbate 20, sodium hydroxide

and water for injections. See section 2 “Ziextenzo contains sorbitol (E420) and sodium”.

What Ziextenzo looks like and contents of the pack

Ziextenzo is a clear, colourless to slightly yellowish solution for injection in a pre-filled syringe

(6 mg/0.6 mL).

Each pack contains 1 glass pre-filled syringe with a rubber plunger stopper, a plunger rod, an attached

stainless steel needle and needle cap. The syringes are provided with an automatic needle guard.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Manufacturer

Sandoz GmbH

Biochemiestr. 10

6336 Langkampfen

Austria

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

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

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

Instructions for use of Ziextenzo pre-filled syringe

To help avoid possible infections and to ensure that you use the medicine correctly, it is important that

you follow these instructions.

Read ALL the way through these instructions before injecting. It is important not to try to inject yourself

until you have been trained by your doctor, nurse or pharmacist. The carton contains the pre-filled

syringe individually sealed in a plastic blister.

Your Ziextenzo pre-filled syringe with needle guard

After the medicine has been injected, the needle guard will be activated to cover the needle. The needle

guard is intended to protect healthcare professionals, caregivers and patients from accidental needle

sticks after the injection.

What you additionally need for

your injection:

Alcohol swab.

Cotton ball or gauze.

Sharps disposal container.

Important safety information

Caution: Keep the pre-filled syringe out of the sight and reach of children.

Do not open the carton until you are ready to use the pre-filled syringe.

Do not use the pre-filled syringe if the seal of the blister is broken, as it may not be safe for you to

use.

Never leave the pre-filled syringe unattended where others might tamper with it.

Do not shake the pre-filled syringe.

Be careful not to touch the needle guard wings before use. By touching them, the needle guard

may be activated too early.

Do not remove the needle cap until just before you give the injection.

The pre-filled syringe cannot be re-used. Dispose of the used pre-filled syringe immediately after

use in a sharps container.

Storage of the Ziextenzo pre-filled syringe

Store the blistered pre-filled syringe in its carton to protect it from light.

Store in the refrigerator between 2 °C and 8 °C.

Do not freeze

Prior to use‚ remove the pre-filled syringe from the refrigerator and allow Ziextenzo to reach

room temperature (up to a maximum of 25 °C) for approximately 15-30 minutes.

Do not use

the pre-filled syringe after the expiry date which is stated on the carton or syringe

label. If it has expired, return the entire pack to the pharmacy.

The injection site

The injection site is the place on the body where you are

going to use the pre-filled syringe.

The recommended site is the front of your thighs. You

may also use the lower abdomen, but

not

the area

5 centimetres around the navel (belly button).

Choose a different site each time you give yourself an

injection.

Do not inject into areas where the skin is tender,

bruised, red, scaly or hard. Avoid areas with scars or

stretch marks.

If a caregiver is giving you the injection, the outer upper

arms may also be used.

Preparing the Ziextenzo pre-filled syringe ready for use

Take the carton containing the blistered pre-filled syringe out of the refrigerator and leave it

unopened

for approximately 15-30 minutes so that it reaches room temperature.

When you are ready to use the pre-filled syringe, open the blister and wash your hands thoroughly

with soap and water.

Clean the injection site with an alcohol swab.

Remove the pre-filled syringe from the blister.

Check to ensure the plastic transparent needle

guard is situated over the barrel of the glass syringe. If the transparent needle guard is covering

the needle cap (as shown below) the syringe has been activated, DO NOT use this syringe and

take a new syringe. The figure below shows a ready to use syringe.

Inspect the pre-filled syringe. The liquid should be clear. Its colour may vary from colourless to

slightly yellowish. You may see a small air bubble in the liquid. This is normal.

Do not use

pre-filled syringe if any other particulates and/or discolouration are observed.

Do not use

if the syringe is broken or activated. Return the Ziextenzo pre-filled syringe and the

package to your pharmacy.

Device ACTIVATED – DO NOT USE

In this configuration the needle guard is

ACTIVATED – DO NOT USE the pre-filled syringe

Device READY TO BE USED

In this configuration the needle guard is NOT

ACTIVATED and the pre-filled syringe is ready for

use

How to use the Ziextenzo pre-filled syringe

1

Carefully pull the needle cap straight off. You may

see a drop of liquid at the end of the needle. This

is normal.

2

Gently pinch the skin at the injection site and insert

the needle as shown. Push the needle all the way in

to ensure that the medicine can be fully

administered.

3

Holding the pre-filled syringe as shown,

slowly

depress

the plunger

as

far as it will go

so that the plunger head

is completely between the needle guard wings.

Keep the plunger pressed fully down while you hold the

syringe in place for 5 seconds.

4

Keep the plunger fully

depressed

while you carefully

pull the needle straight out from the injection site and

let it go off your skin.

5

Slowly release the plunger and allow the syringe needle

guard to automatically cover the exposed needle.

There may be a small amount of blood at the injection

site. You can press a cotton ball or gauze onto the

injection site and hold it for 10 seconds. Do not rub the

injection site. You may cover the injection site with a

small adhesive bandage, if needed.

6

Healthcare providers only

The trade name of the administered product

should be clearly recorded in the patient file.

Remove and save the pre-filled syringe label.

Turn the plunger to move the label into a position

where you can remove the syringe label.

Disposal instructions

Dispose of the used syringe in a sharps container

(closable, puncture resistant container).

Do not throw away any medicines via wastewater or

household waste. Ask your doctor or pharmacist how to

throw away medicines you no longer use. These

measures will help protect the environment. Any unused

product or waste material should be disposed of in

accordance with local requirements.