Herzuma

Informazzjoni prinċipali

  • Isem kummerċjali:
  • Herzuma
  • Dominju tal-mediċina:
  • Bnedmin
  • Tip ta 'mediċina:
  • Droga allopatika

Dokumenti

Lokalizzazzjoni

  • Disponibbli fi:
  • Herzuma
    Unjoni Ewropea
  • Lingwa:
  • Ingliż

Informazzjoni terapewtika

  • Grupp terapewtiku:
  • Antineoplastic agents,
  • Żona terapewtika:
  • Stomach Neoplasms, Breast Neoplasms
  • Indikazzjonijiet terapewtiċi:
  • Breast cancerMetastatic breast cancerHerzuma is indicated for the treatment of adult patients with HER2 positive metastatic breast cancer (MBC):as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless patients are unsuitable for these treatments.in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable.in combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with trastuzumab.Early breast cance
  • Sommarju tal-prodott:
  • Revision: 6

Status

  • Sors:
  • EMA - European Medicines Agency
  • L-istatus ta 'awtorizzazzjoni:
  • Authorised
  • Numru ta 'awtorizzazzjoni:
  • EMEA/H/C/002575
  • Data ta 'l-awtorizzazzjoni:
  • 07-02-2018
  • Kodiċi EMEA:
  • EMEA/H/C/002575
  • L-aħħar aġġornament:
  • 25-09-2019

Rapport ta 'Valutazzjoni Pubblika

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Canary Wharf

London E14 5EU

United Kingdom

Telephone

+44 (0)20 3660 6000

Facsimile

+44 (0)20 3660 5555

Send a question via our website

www.ema.europa.eu/contact

An agency of the European Union

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

EMA/1108/2018

EMEA/H/C/002575

EPAR summary for the public

Herzuma

trastuzumab

This is a summary of the European public assessment report (EPAR) for Herzuma. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Herzuma.

For practical information about using Herzuma, patients should read the package leaflet or contact

their doctor or pharmacist.

What is Herzuma and what is it used for?

Herzuma is a cancer medicine used to treat the following conditions:

early breast cancer (when the cancer has spread within the breast or to the glands under the arm

but not to other parts of the body) after surgery, chemotherapy (medicines to treat cancer), and

radiotherapy (treatment with radiation) if applicable. It can also be used earlier in treatment, in

combination with chemotherapy. For tumours that are locally advanced (including those that are

inflammatory) or more than 2 cm wide, Herzuma is used before surgery in combination with

chemotherapy and then again after surgery on its own;

metastatic breast cancer (cancer that has spread to other parts of the body). It is used on its own

in patients in whom previous treatments have failed. It is also used in combination with other

cancer medicines: with paclitaxel or docetaxel, or with another class of medicines called aromatase

inhibitors;

metastatic gastric (stomach) cancer, in combination with cisplatin and either capecitabine or

fluorouracil (other cancer medicines).

Herzuma can only be used when the cancer has been shown to ‘overexpress HER2’: this means that

the cancer produces a protein called HER2 in large quantities on the surface of the tumour cells. HER2

is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers.

Herzuma

EMA/1108/2018

Page 2/3

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

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

medicine for Herzuma is Herceptin. For more information on biosimilar medicines, see here.

Herzuma contains the active substance trastuzumab.

How is Herzuma used?

Herzuma can only be obtained with a prescription and treatment should be started by a doctor who has

experience in the use of cancer medicines.

It is available as a powder used to make up a solution for adding to an infusion (drip) into a vein. The

infusion is given over 90 minutes every week or every three weeks for breast cancer, and every three

weeks for gastric cancer. For early breast cancer, treatment is given for a year or until the disease

comes back, and for metastatic breast or gastric cancer, treatment is continued for as long as it

remains effective. The recommended dose depends on the patient’s body weight, on the condition

being treated and on whether Herzuma is given weekly or three-weekly.

The infusion may be associated with allergic reactions, so the patient should be monitored during and

after the infusion. Patients who tolerate the first 90-minute infusion can receive subsequent infusions

over 30 minutes.

For further information, see the package leaflet.

How does Herzuma work?

The active substance in Herzuma, trastuzumab, is a monoclonal antibody (a type of protein) that has

been designed to recognise and attach to the HER2 protein. By attaching to HER2, trastuzumab

activates cells of the immune system, which then kill the tumour cells. Trastuzumab also stops HER2

producing signals that cause the tumour cells to grow.

What benefits of Herzuma have been shown in studies?

Laboratory studies comparing Herzuma with Herceptin have shown that the active substance in

Herzuma is highly similar to that in Herceptin in terms of structure, purity and biological activity.

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

body to giving Herceptin.

In addition, one main study involving 549 patients with early breast cancer that overexpressed HER2

showed that Herzuma was as effective as Herceptin. Patients were given either Herzuma or Herceptin

with other cancer medicines before surgery to remove the cancer, and then the same medicine on its

own every three weeks for 1 year. There were no relevant differences in the main measure of

effectiveness (absence of invasive cancer cells in the breast or in linked tissues called lymph nodes)

between the two products: this was seen in nearly 44% of those given Herzuma (118 of 271) and 47%

of those given Herceptin (131 of 278).

Because Herzuma is a biosimilar medicine, the studies on effectiveness and safety of trastuzumab

carried out with Herceptin do not all need to be repeated for Herzuma.

What are the risks associated with Herzuma?

The most common or serious side effects with Herzuma are heart problems, reactions related to the

Herzuma infusion, reduced levels of blood cells (especially white blood cells), infections and lung

problems.

Herzuma

EMA/1108/2018

Page 3/3

Herzuma can cause cardiotoxicity (harm to the heart), including heart failure (when the heart does not

work as well as it should). Care should be taken if it is given to patients who already have heart

problems or high blood pressure, and all patients need to be monitored during and after treatment to

check their heart.

Herzuma must not be used in people who are hypersensitive (allergic) to trastuzumab, mouse proteins

or to any of the other ingredients. It must not be used in patients who have serious breathing

problems because of advanced cancer, even when resting, or who need oxygen therapy.

For the full list of all side effects and restrictions with trastuzumab, see the package leaflet.

Why is Herzuma approved?

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

medicines, Herzuma has been shown to have a comparable quality, safety and effectiveness to

Herceptin.

Therefore, the Agency’s view was that, as for Herceptin, the benefit outweighs the identified risk and

Herzuma should be given marketing authorisation.

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

Herzuma?

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

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

package leaflet.

Other information about Herzuma

The European Commission granted a marketing authorisation valid throughout the European Union for

Herzuma on 9 February 2018.

The full EPAR for Herzuma can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Herzuma, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

This summary was last updated in 02-2018.

Fuljett ta 'Informazzjoni għall-Pazjent: prodott - kompożizzjoni, indikazzjonijiet, effetti sekondarji, dożaġġ, interazzjonijiet, reazzjonijiet avversi, tqala, treddigħ

B. PACKAGE LEAFLET

Package leaflet: Information for the user

Herzuma 150 mg powder for concentrate for solution for infusion

trastuzumab

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 or pharmacist.

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 Herzuma is and what it is used for

What you need to know before you use Herzuma

How to use Herzuma

Possible side effects

How to store Herzuma

Contents of the pack and other information

1.

What Herzuma is and what it is used for

Herzuma contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal

antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an

antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on

the surface of some cancer cells where it stimulates their growth. When Herzuma binds to HER2 it

stops the growth of such cells and causes them to die.

Your doctor may prescribe Herzuma for the treatment of breast and gastric cancer when:

you have early breast cancer, with high levels of a protein called HER2.

you have metastatic breast cancer (breast cancer that has spread beyond the original tumour)

with high levels of HER2. Herzuma may be prescribed in combination with the chemotherapy

medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be

prescribed alone if other treatments have proved unsuccessful. It is also used in combination

with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone

receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex

hormones).

you have metastatic gastric cancer with high levels of HER2, when it is in combination with the

other cancer medicines capecitabine or 5-fluorouracil and cisplatin.

2.

What you need to know before you use Herzuma

Do not take Herzuma if:

you are allergic to trastuzumab, to murine (mouse) proteins or any of the other ingredients of

this medicine (listed in section 6).

you have severe breathing problems at rest due to your cancer or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely supervise your therapy.

Heart checks

Treatment with Herzuma alone or with a taxane may affect the heart, especially if you have ever used

an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer). The

effects may be moderate to severe and could cause death. Therefore, your heart function will be

checked before, during (every three months) and after (up to two to five years) treatment with

Herzuma. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your

heart function may be checked more frequently (every six to eight weeks), you may receive treatment

for heart failure or you may have to stop Herzuma treatment.

Talk to your doctor, pharmacist or nurse before using Herzuma if:

you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high

blood pressure, taken any high blood pressure medicine or are currently taking any high blood

pressure medicine.

you have ever had or are currently using a medicine called doxorubicin or epirubicin (medicines

used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle

and increase the risk of heart problems with trastuzumab.

you suffer from breathlessness, especially if you are currently using a taxane. Trastuzumab can

cause breathing difficulties, especially when it is first given. This could be more serious if you

are already breathless. Very rarely, patients with severe breathing difficulties before treatment

have died when they were given trastuzumab.

you have ever had any other treatment for cancer.

If you receive Herzuma with any other medicine to treat cancer, such as paclitaxel, docetaxel, an

aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient

information leaflets for these products.

Children and adolescents

Herzuma is not recommended for anyone under the age of 18 years.

Other medicines and Herzuma

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or may take any other

medicines.

It may take up to 7 months for Herzuma to be removed from the body. Therefore you should tell your

doctor, pharmacist or nurse that you have had Herzuma if you start any new medicine in the 7 months

after stopping treatment.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor,

pharmacist or nurse for advice before taking this medicine.

You should use effective contraception during treatment with Herzuma and for at least 7 months

after treatment has ended.

Your doctor will advise you of the risks and benefits of taking Herzuma during pregnancy. In

rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby

within the womb has been observed in pregnant women receiving Herzuma. This condition may

be harmful to your baby in the womb and has been associated with the lungs not developing

fully resulting in foetal death.

Breast-feeding

Do not breast-feed your baby during Herzuma therapy and for 7 months after the last dose of Herzuma

as Herzuma may pass to your baby through your breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Herzuma may affect your ability to drive a car or operate machines. If during treatment you

experience symptoms, such as chills or fever, you should not drive or use machines until these

symptoms disappear.

3.

How to use Herzuma

Before starting the treatment your doctor will determine the amount of HER2 in your tumour. Only

patients with a large amount of HER2 will be treated with Herzuma. Herzuma should only be given by

a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is right for

you

. The

dose of Herzuma depends on your body weight.

Herzuma is given as an intravenous infusion (“drip”) directly into your veins. The first dose of your

treatment is given over 90 minutes and you will be observed by a health professional while it is being

given in case you have any side effects. If the first dose is well tolerated the next doses may be given

over 30 minutes (see section 2 under “Warnings and precautions”). The number of infusions you

receive will depend on how you respond to the treatment. Your doctor will discuss this with you.

In order to prevent medication errors it is important to check the vial labels to ensure that the medicine

being prepared and given is Herzuma (trastuzumab) and not trastuzumab emtansine.

For early breast cancer, metastatic breast cancer and metastatic gastric cancer, Herzuma is given every

3 weeks. Herzuma may also be given once a week for metastatic breast cancer.

If you stop using Herzuma

Do not stop using this medicine without talking to your doctor first. All doses should be taken at the

right time every week or every three weeks (depending on your dosing schedule). This helps your

medicine work as well as it can.

It may take up to 7 months for Herzuma to be removed from your body. Therefore your doctor may

decide to continue to check your heart functions, even after you finish treatment.

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. Some of

these side effects may be serious and may lead to hospitalisation.

During a Herzuma infusion, chills, fever and other flu like symptoms may occur. These are very

common (may affect more than 1 in 10 people). Other infusion-related symptoms are: feeling sick

(nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing

difficulties, wheezing, high or low blood pressure, heart rhythm disturbances (palpitations, heart

fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these

symptoms can be serious and some patients have died (see section 2 under “Warnings and

precautions”).

These effects mainly occur with the first intravenous infusion (“drip” into your vein) and during the

first few hours after the start of the infusion. They are usually temporary. You will be observed by a

health care professional during the infusion and for at least six hours after the start of the first infusion

and for two hours after the start of other infusions. If you develop a reaction, they will slow down or

stop the infusion and may give you treatment to counteract the side effects. The infusion may be

continued after the symptoms improve.

Occasionally, symptoms start later than six hours after the infusion begins. If this happens to you,

contact your doctor immediately. Sometimes, symptoms may improve and then get worse later.

Serious side effects

Other side effects can occur at any time during treatment with Herzuma, not just related to an infusion.

Tell a doctor or nurse straight away, if you notice any of the following side effects:

Heart problems can sometimes occur during treatment and occasionally after treatment has

stopped and can be serious. They include weakening of the heart muscle possibly leading to heart

failure, inflammation of the lining around the heart and heart rhythm disturbances. This can lead

to symptoms such as breathlessness (including breathlessness at night), cough, fluid retention

(swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see 2. Heart

checks).

Your doctor will monitor your heart regularly during and after treatment but you should tell your

doctor immediately if you notice any of the above symptoms.

Tumour lysis syndrome (a group of metabolic complications occurring after cancer treatment

characterized by high blood levels of potassium and phosphate, and low blood levels of calcium).

Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion),

heart problems (fluttering of the heart or a faster or slower heartbeat), seizures, vomiting or

diarrhoea and tingling in the mouth, hands or feet

If you experience any of the above symptoms when your treatment with Herzuma has finished, you

should see your doctor and tell them that you have previously been treated with Herzuma.

Very common side effects

(may affect more than 1 in 10 people):

infections

diarrhoea

constipation

heartburn (dyspepsia)

fatigue

skin rashes

chest pain

abdominal pain

joint pain

low counts of red blood cells and white blood cells (which help fight infection) sometimes with

fever

muscle pain

conjunctivitis

watery eyes

nose bleeds

runny nose

hair loss

tremor

hot flush

dizziness

nail disorders

weight loss

loss of appetite

inability to sleep (insomnia)

altered taste

low platelet count

bruising

numbness or tingling of the fingers and toes

redness, swelling or sores in your mouth and/or throat

pain, swelling, redness or tingling of hands and/or feet

breathlessness

headache

cough

vomiting

nausea

Common side effects

(may affect up to 1 in 10 people):

allergic reactions

dry mouth and skin

throat infections

dry eyes

bladder and skin infections

sweating

shingles

feeling weak and unwell

inflammation of the breast

anxiety

inflammation of the liver

depression

kidney disorders

abnormal thinking

increased muscle tone or tension

(hypertonia)

asthma

infection of lungs

pain in the arms and/or legs

lung disorders

itchy rash

back pain

sleepiness (somnolence)

neck pain

haemorrhoids

bone pain

itchiness

acne

leg cramps

Uncommon side effects

(may affect up to 1 in 100 people):

deafness

bumpy rash

blood infection

Rare side effects

(may affect up to 1 in 1000 people):

muscle weakness

jaundice

inflammation or scarring of the lungs

Other side effects that have been reported with Herzuma use

(frequency cannot be estimated from

the available data):

abnormal or impaired blood clotting

anaphylactic reactions

high potassium levels

swelling of the brain

swelling or bleeding at the back of the eyes

shock

swelling of the lining of the heart

slow heart rate

abnormal heart rhythm

respiratory distress

respiratory failure

acute accumulation of fluid in the lungs

acute narrowing of the airways

abnormally low oxygen levels in the blood

difficulty in breathing when lying flat

liver damage/failure

swelling of the face, lips and throat

kidney failure

abnormally low levels of fluid around baby in womb

failure of the lungs of the baby to develop in the womb

abnormal development of the kidneys of the baby in the womb

Some of the side effects you experience may be due to your underlying cancer. If you receive

Herzuma in combination with chemotherapy, some of them may also be due to the chemotherapy.

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

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 Herzuma

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

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

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

Store in a refrigerator (2ºC - 8ºC).

Infusion solutions should be used immediately after dilution. Do not use Herzuma if you notice any

particulate matter or discoloration prior to administration.

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

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

6.

Contents of the pack and other information

What Herzuma contains

The active substance is trastuzumab. Each vial contains 150 mg trastuzumab that has to be

dissolved in 7.2 mL of water for injection. The resulting solution contains approximately

21 mg/mL trastuzumab.

The other ingredients are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate,

polysorbate 20.

What Herzuma looks like and contents of the pack

Herzuma is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass

vial with a rubber stopper containing 150 mg of trastuzumab. The powder is a white to pale yellow

pellet. Each carton contains 1 vial of powder.

Marketing Authorisation Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B torony

Hungary

Manufacturer

Biotec Services International Ltd.

Biotec House

Central Park

Western Avenue

Bridgend Industrial Estate

Bridgend, CF31 3RT

United Kingdom

Millmount Healthcare Ltd.

Block 7

City North Business Campus

Stamullen, Co. Meath K32 YD60

Ireland

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

Authorisation Holder:

België/Belgique/Belgien

Mundipharma CVA

Tél/Tel: + 32 15 45 1180

Lietuva

EGIS PHARMACEUTICALS PLC atstovybė

Tel.: +370 5 231 4658

България

EGIS Bulgaria EOOD

Teл.: + 359 2 987 6040

Luxembourg/Luxemburg

Mundipharma CVA

Tél/Tel: + 32 15 45 1180

Česká republika

EGIS Praha, spol. s r.o

Tel: + 420 227 129 111

Magyarország

Egis Gyógyszergyár Zrt.

Tel.: + 36 1 803 5555

Danmark

Orion Pharma A/S

Tlf: + 45 86 14 00 00

Malta

Medical Logistics Ltd.

Tel: +356 2755 9990

Deutschland

Mundipharma GmbH

Tel: +49 (0) 69 506029 000

Nederland

Mundipharma Pharmaceuticals B.V

Tel: + 31 33 450 8270

Eesti

Orion Pharma Eesti OÜ

Norge

Orion Pharma AS

Tel: + 372 6 644 550

Tlf: + 47 40 00 42 10

España

Kern Pharma, S.L.

Tel: +34 93 700 2525

Ö sterreich

Astro-Pharma GmbH

Tel: +43 1 97 99 860

Ελλάδα

ΒΙΑΝΕΞ Α.Ε.

Τηλ: +30 210 8009111 - 120

Polska

EGIS Polska Sp. z o.o.

Tel.: + 48 22 417 9200

France

Laboratoires Biogaran

Tél.: +33 (0) 800 970 109

Portugal

PharmaKERN Portugal - Produtos

Farmacêuticos, Sociedade Unipessoal, Lda.

Tel: +351 214 200 290

Hrvatska

Oktal Pharma d.o.o.

Tel: +385 1 6595 777

România

Egis Pharmaceuticals PLC Romania

Tel: + 40 21 412 0017

Ireland

Mundipharma Pharmaceuticals Limited

Tel: +353 1 2063800

Slovenija

OPH Oktal Pharma d.o.o.

Tel.: +386 1 519 29 22

Ísland

Vistor hf.

Sími: +354 535 7000

Slovenská republika

EGIS SLOVAKIA spol. s r.o

Tel: +421 2 3240 9422

Italia

Mundipharma Pharmaceuticals Srl

Tel: +39 02 31 82 88 1

Suomi/Finland

Orion Pharma

Puh/Tel: + 358 10 4261

Κύπρος

C.A. Papaellinas Ltd

Τηλ: +357 22741741

Sverige

Orion Pharma AB

Tel: + 46 8 623 64 40

Latvija

EGIS Pharmaceuticals PLC pārstāvniecība

Latvijā

Tālr.: +371 67613859

United Kingdom

NAPP Pharmaceuticals Ltd.

Tel: +44 (0) 1223 424444

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.

The following information is intended for medical or healthcare professionals only

Always keep this medicine in the closed original pack at a temperature of 2ºC - 8ºC in a refrigerator. A

vial of Herzuma reconstituted with water for injections (not supplied) is stable for 7 days at 2ºC - 8ºC

after reconstitution and must not be frozen.

Appropriate aseptic technique should be used. Each vial of Herzuma is reconstituted with 7.2 mL of

water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields

a 7.4 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab. A volume

overage of 4% ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Herzuma should be carefully handled during reconstitution. Causing excessive foaming during

reconstitution or shaking the reconstituted Herzuma may result in problems with the amount of

Herzuma that can be withdrawn from the vial.

Instructions for reconstitution and dilution:

1) Using a sterile syringe, slowly inject 7.2 mL of water for injections in the vial containing the

lyophilised Herzuma, directing the stream into the lyophilised cake.

2) Swirl vial gently to aid reconstitution. DO NOT SHAKE!

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed

for approximately 5 minutes. The reconstituted Herzuma results in a colourless to pale yellow

transparent solution and should be essentially free of visible particulates.

Determine the volume of the solution required:

based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose

of 2 mg trastuzumab/kg body weight:

Volume

(mL) =

Body weight

(kg) x

dose

4

mg/kg for loading or

2

mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly

dose of 6 mg trastuzumab/kg body weight:

Volume

(mL) =

Body weight

(kg) x

dose

8

mg/kg for loading or

6

mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial and added to a

polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 mL of 0.9% sodium

chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to

mix the solution in order to avoid foaming. Parenteral solutions should be inspected visually for

particulates and discoloration prior to administration. Once the infusion is prepared it should be

administered immediately. If diluted aseptically, it may be stored for 24 hours (do not store above

30ºC).

Package leaflet: Information for the user

Herzuma 420 mg powder for concentrate for solution for infusion

trastuzumab

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 or pharmacist.

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 Herzuma is and what it is used for

What you need to know before you use Herzuma

How to use Herzuma

Possible side effects

How to store Herzuma

Contents of the pack and other information

1.

What Herzuma is and what it is used for

Herzuma contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal

antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an

antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on

the surface of some cancer cells where it stimulates their growth. When Herzuma binds to HER2 it

stops the growth of such cells and causes them to die.

Your doctor may prescribe Herzuma for the treatment of breast and gastric cancer when:

you have early breast cancer, with high levels of a protein called HER2.

you have metastatic breast cancer (breast cancer that has spread beyond the original tumour)

with high levels of HER2. Herzuma may be prescribed in combination with the chemotherapy

medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be

prescribed alone if other treatments have proved unsuccessful. It is also used in combination

with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone

receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex

hormones).

you have metastatic gastric cancer with high levels of HER2, when it is in combination with the

other cancer medicines capecitabine or 5-fluorouracil and cisplatin.

2.

What you need to know before you use Herzuma

Do not take Herzuma if:

you are allergic to trastuzumab, to murine (mouse) proteins or any of the other ingredients of

this medicine (listed in section 6).

you have severe breathing problems at rest due to your cancer or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely supervise your therapy.

Heart checks

Treatment with Herzuma alone or with a taxane may affect the heart, especially if you have ever used

an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer). The

effects may be moderate to severe and could cause death. Therefore, your heart function will be

checked before, during (every three months) and after (up to two to five years) treatment with

Herzuma. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your

heart function may be checked more frequently (every six to eight weeks), you may receive treatment

for heart failure or you may have to stop Herzuma treatment.

Talk to your doctor, pharmacist or nurse before using Herzuma if:

you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high

blood pressure, taken any high blood pressure medicine or are currently taking any high blood

pressure medicine.

you have ever had or are currently using a medicine called doxorubicin or epirubicin (medicines

used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle

and increase the risk of heart problems with trastuzumab.

you suffer from breathlessness, especially if you are currently using a taxane. Trastuzumab can

cause breathing difficulties, especially when it is first given. This could be more serious if you

are already breathless. Very rarely, patients with severe breathing difficulties before treatment

have died when they were given trastuzumab.

you have ever had any other treatment for cancer.

If you receive Herzuma with any other medicine to treat cancer, such as paclitaxel, docetaxel, an

aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient

information leaflets for these products.

Children and adolescents

Herzuma is not recommended for anyone under the age of 18 years.

Other medicines and Herzuma

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or may take any other

medicines.

It may take up to 7 months for Herzuma to be removed from the body. Therefore you should tell your

doctor, pharmacist or nurse that you have had Herzuma if you start any new medicine in the 7 months

after stopping treatment.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor,

pharmacist or nurse for advice before taking this medicine.

You should use effective contraception during treatment with Herzuma and for at least 7 months

after treatment has ended.

Your doctor will advise you of the risks and benefits of taking Herzuma during pregnancy. In

rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby

within the womb has been observed in pregnant women receiving Herzuma. This condition may

be harmful to your baby in the womb and has been associated with the lungs not developing

fully resulting in foetal death.

Breast-feeding

Do not breast-feed your baby during Herzuma therapy and for 7 months after the last dose of Herzuma

as Herzuma may pass to your baby through your breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Herzuma may affect your ability to drive a car or operate machines. If during treatment you

experience symptoms, such as chills or fever, you should not drive or use machines until these

symptoms disappear.

3.

How to use Herzuma

Before starting the treatment your doctor will determine the amount of HER2 in your tumour. Only

patients with a large amount of HER2 will be treated with Herzuma. Herzuma should only be given by

a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is right for

you

. The

dose of Herzuma depends on your body weight.

Herzuma is given as an intravenous infusion (“drip”) directly into your veins. The first dose of your

treatment is given over 90 minutes and you will be observed by a health professional while it is being

given in case you have any side effects. If the first dose is well tolerated the next doses may be given

over 30 minutes (see section 2 under “Warnings and precautions”). The number of infusions you

receive will depend on how you respond to the treatment. Your doctor will discuss this with you.

In order to prevent medication errors it is important to check the vial labels to ensure that the medicine

being prepared and given is Herzuma (trastuzumab) and not trastuzumab emtansine.

For early breast cancer, metastatic breast cancer and metastatic gastric cancer, Herzuma is given every

3 weeks. Herzuma may also be given once a week for metastatic breast cancer.

If you stop using Herzuma

Do not stop using this medicine without talking to your doctor first. All doses should be taken at the

right time every week or every three weeks (depending on your dosing schedule). This helps your

medicine work as well as it can.

It may take up to 7 months for Herzuma to be removed from your body. Therefore your doctor may

decide to continue to check your heart functions, even after you finish treatment.

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. Some of

these side effects may be serious and may lead to hospitalisation.

During a Herzuma infusion, chills, fever and other flu like symptoms may occur. These are very

common (may affect more than 1 in 10 people). Other infusion-related symptoms are: feeling sick

(nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing

difficulties, wheezing, high or low blood pressure, heart rhythm disturbances (palpitations, heart

fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these

symptoms can be serious and some patients have died (see section 2 under “Warnings and

precautions”).

These effects mainly occur with the first intravenous infusion (“drip” into your vein) and during the

first few hours after the start of the infusion. They are usually temporary. You will be observed by a

health care professional during the infusion and for at least six hours after the start of the first infusion

and for two hours after the start of other infusions. If you develop a reaction, they will slow down or

stop the infusion and may give you treatment to counteract the side effects. The infusion may be

continued after the symptoms improve.

Occasionally, symptoms start later than six hours after the infusion begins. If this happens to you,

contact your doctor immediately. Sometimes, symptoms may improve and then get worse later.

Serious side effects

Other side effects can occur at any time during treatment with Herzuma, not just related to an infusion.

Tell a doctor or nurse straight away, if you notice any of the following side effects:

Heart problems can sometimes occur during treatment and occasionally after treatment has

stopped and can be serious. They include weakening of the heart muscle possibly leading to heart

failure, inflammation of the lining around the heart and heart rhythm disturbances. This can lead

to symptoms such as breathlessness (including breathlessness at night), cough, fluid retention

(swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see 2. Heart

checks).

Your doctor will monitor your heart regularly during and after treatment but you should tell your

doctor immediately if you notice any of the above symptoms.

Tumour lysis syndrome (a group of metabolic complications occurring after cancer treatment

characterized by high blood levels of potassium and phosphate, and low blood levels of calcium).

Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion),

heart problems (fluttering of the heart or a faster or slower heartbeat), seizures, vomiting or

diarrhoea and tingling in the mouth, hands or feet

If you experience any of the above symptoms when your treatment with Herzuma has finished, you

should see your doctor and tell them that you have previously been treated with Herzuma.

Very common side effects

(may affect more than 1 in 10 people):

infections

diarrhoea

constipation

heartburn (dyspepsia)

fatigue

skin rashes

chest pain

abdominal pain

joint pain

low counts of red blood cells and white blood cells (which help fight infection) sometimes with

fever

muscle pain

conjunctivitis

watery eyes

nose bleeds

runny nose

hair loss

tremor

hot flush

dizziness

nail disorders

weight loss

loss of appetite

inability to sleep (insomnia)

altered taste

low platelet count

bruising

numbness or tingling of the fingers and toes

redness, swelling or sores in your mouth and/or throat

pain, swelling, redness or tingling of hands and/or feet

breathlessness

headache

cough

vomiting

nausea

Common side effects

(may affect up to 1 in 10 people):

allergic reactions

dry mouth and skin

throat infections

dry eyes

bladder and skin infections

sweating

shingles

feeling weak and unwell

inflammation of the breast

anxiety

inflammation of the liver

depression

kidney disorders

abnormal thinking

increased muscle tone or tension

(hypertonia)

asthma

infection of lungs

pain in the arms and/or legs

lung disorders

itchy rash

back pain

sleepiness (somnolence)

neck pain

haemorrhoids

bone pain

itchiness

acne

leg cramps

Uncommon side effects

(may affect up to 1 in 100 people):

deafness

bumpy rash

blood infection

Rare side effects

(may affect up to 1 in 1000 people):

muscle weakness

jaundice

inflammation or scarring of the lungs

Other side effects that have been reported with Herzuma use

(frequency cannot be estimated from

the available data):

abnormal or impaired blood clotting

anaphylactic reactions

high potassium levels

swelling of the brain

swelling or bleeding at the back of the eyes

shock

swelling of the lining of the heart

slow heart rate

abnormal heart rhythm

respiratory distress

respiratory failure

acute accumulation of fluid in the lungs

acute narrowing of the airways

abnormally low oxygen levels in the blood

difficulty in breathing when lying flat

liver damage/failure

swelling of the face, lips and throat

kidney failure

abnormally low levels of fluid around baby in womb

failure of the lungs of the baby to develop in the womb

abnormal development of the kidneys of the baby in the womb

Some of the side effects you experience may be due to your underlying cancer. If you receive

Herzuma in combination with chemotherapy, some of them may also be due to the chemotherapy.

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

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 Herzuma

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

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

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

Store in a refrigerator (2ºC - 8ºC).

Infusion solutions should be used immediately after dilution. Do not use Herzuma if you notice any

particulate matter or discoloration prior to administration.

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

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

6.

Contents of the pack and other information

What Herzuma contains

The active substance is trastuzumab. Each vial contains 420 mg trastuzumab that has to be

dissolved in 20 mL of water for injection. The resulting solution contains approximately

21 mg/mL trastuzumab.

The other ingredients are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate,

polysorbate 20.

What Herzuma looks like and contents of the pack

Herzuma is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass

vial with a rubber stopper containing 420 mg of trastuzumab. The powder is a white to pale yellow

pellet. Each carton contains 1 vial of powder.

Marketing Authorisation Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B torony

Hungary

Manufacturer

Biotec Services International Ltd.

Biotec House

Central Park

Western Avenue

Bridgend Industrial Estate

Bridgend, CF31 3RT

United Kingdom

Millmount Healthcare Ltd.

Block 7

City North Business Campus

Stamullen, Co. Meath K32 YD60

Ireland

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

Authorisation Holder:

België/Belgique/Belgien

Mundipharma CVA

Tél/Tel: + 32 15 45 1180

Lietuva

EGIS PHARMACEUTICALS PLC atstovybė

Tel.: +370 5 231 4658

България

EGIS Bulgaria EOOD

Teл.: + 359 2 987 6040

Luxembourg/Luxemburg

Mundipharma CVA

Tél/Tel: + 32 15 45 1180

Česká republika

EGIS Praha, spol. s r.o

Tel: + 420 227 129 111

Magyarország

Egis Gyógyszergyár Zrt.

Tel.: + 36 1 803 5555

Danmark

Orion Pharma A/S

Tlf: + 45 86 14 00 00

Malta

Medical Logistics Ltd.

Tel: +356 2755 9990

Deutschland

Mundipharma GmbH

Tel: +49 (0) 69 506029 000

Nederland

Mundipharma Pharmaceuticals B.V

Tel: + 31 33 450 8270

Eesti

Orion Pharma Eesti OÜ

Norge

Orion Pharma AS

Tel: + 372 6 644 550

Tlf: + 47 40 00 42 10

España

Kern Pharma, S.L.

Tel: +34 93 700 2525

Ö sterreich

Astro-Pharma GmbH

Tel: +43 1 97 99 860

Ελλάδα

ΒΙΑΝΕΞ Α.Ε.

Τηλ: +30 210 8009111 - 120

Polska

EGIS Polska Sp. z o.o.

Tel.: + 48 22 417 9200

France

Laboratoires Biogaran

Tél.: +33 (0) 800 970 109

Portugal

PharmaKERN Portugal - Produtos

Farmacêuticos, Sociedade Unipessoal, Lda.

Tel: +351 214 200 290

Hrvatska

Oktal Pharma d.o.o.

Tel: +385 1 6595 777

România

Egis Pharmaceuticals PLC Romania

Tel: + 40 21 412 0017

Ireland

Mundipharma Pharmaceuticals Limited

Tel: +353 1 2063800

Slovenija

OPH Oktal Pharma d.o.o.

Tel.: +386 1 519 29 22

Ísland

Vistor hf.

Sími: +354 535 7000

Slovenská republika

EGIS SLOVAKIA spol. s r.o

Tel: +421 2 3240 9422

Italia

Mundipharma Pharmaceuticals Srl

Tel: +39 02 31 82 88 1

Suomi/Finland

Orion Pharma

Puh/Tel: + 358 10 4261

Κύπρος

C.A. Papaellinas Ltd

Τηλ: +357 22741741

Sverige

Orion Pharma AB

Tel: + 46 8 623 64 40

Latvija

EGIS Pharmaceuticals PLC pārstāvniecība

Latvijā

Tālr.: +371 67613859

United Kingdom

NAPP Pharmaceuticals Ltd.

Tel: +44 (0) 1223 424444

This leaflet was last revised in <

MM/YYYY

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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.

The following information is intended for medical or healthcare professionals only

Always keep this medicine in the closed original pack at a temperature of 2ºC - 8ºC in a refrigerator. A

vial of Herzuma reconstituted with water for injections (not supplied) is stable for 7 days at 2ºC - 8ºC

after reconstitution and must not be frozen.

Appropriate aseptic technique should be used. Each vial of Herzuma is reconstituted with 20 mL of

water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields

a 21 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab. A volume

overage of 4% ensures that the labelled dose of 420 mg can be withdrawn from each vial.

Herzuma should be carefully handled during reconstitution. Causing excessive foaming during

reconstitution or shaking the reconstituted Herzuma may result in problems with the amount of

Herzuma that can be withdrawn from the vial.

Instructions for reconstitution and dilution:

1) Using a sterile syringe, slowly inject 20 mL of water for injections in the vial containing the

lyophilised Herzuma, directing the stream into the lyophilised cake.

2) Swirl vial gently to aid reconstitution. DO NOT SHAKE!

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed

for approximately 5 minutes. The reconstituted Herzuma results in a colourless to pale yellow

transparent solution and should be essentially free of visible particulates.

Determine the volume of the solution required:

based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose

of 2 mg trastuzumab/kg body weight:

Volume

(mL) =

Body weight

(kg) x

dose

4

mg/kg for loading or

2

mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly

dose of 6 mg trastuzumab/kg body weight:

Volume

(mL) =

Body weight

(kg) x

dose

8

mg/kg for loading or

6

mg/kg for maintenance)

21

(mg/mL, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial and added to a

polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 mL of 0.9% sodium

chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to

mix the solution in order to avoid foaming. Parenteral solutions should be inspected visually for

particulates and discoloration prior to administration. Once the infusion is prepared it should be

administered immediately. If diluted aseptically, it may be stored for 24 hours (do not store above

30ºC).

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS

OF THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for trastuzumab, the scientific

conclusions of CHMP are as follows:

Although the number of cases identified by a search of the safety database and meeting the Cairo-

Bishop criteria for diagnosis was low, it is endorsed that a contributing factor of trastuzumab to

tumour lysis syndrome (TLS) could not be excluded. Although there are some limitations when

using Cairo-Bishop criteria for diagnosis leading to underestimation of the number of cases, the

update of the Product Information to include TLS with a frequency unknown is endorsed, because

trastuzumab is a potent mediator of antibody-dependent cell-mediated cytotoxicity (ADCC).

Therefore, from the mechanism of action there is evidence that trastuzumab can cause tumour lysis

syndrome. One case of tumour lysis syndrome with trastuzumab administration as monotherapy

lends further support.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for trastuzumab the CHMP is of the opinion that the

benefit-risk balance of the medicinal product(s) containing trastuzumab is unchanged subject to the

proposed changes to the product information

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.