Package leaflet: Information for the user

Herzuma 150 mg powder for concentrate for solution for infusion

trastuzumab
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
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.

Contents of this leaflet

What Herzuma is and what it is used for
What you need to know before you are given Herzuma
How Herzuma is given
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 bind to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is present in large amounts on the surface of certain tumour cells and stimulates their growth. When Herzuma binds to HER2, it blocks the growth of these cells and causes their death.

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

you have early-stage breast cancer with high levels of a protein called HER2.
you have metastatic breast cancer (breast cancer that has spread away from the primary tumour) with high levels of HER2. Herzuma may be prescribed in combination with the chemotherapeutic medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer, or it may be prescribed alone when other treatments have proven ineffective. It is also used in combination with medicines called aromatase inhibitors for the treatment of patients with high levels of HER2 and metastatic breast cancer with positive hormone receptors (cancer that is sensitive to female sex hormones).
you have metastatic gastric cancer with high levels of HER2, in combination with other anticancer medicines, capecitabine or 5-fluorouracil and cisplatin.

2. What you should know before being given Herzuma

Do not use Herzuma if:

you are allergic to trastuzumab, mouse proteins (murine proteins), or to any of the other ingredients of this medicine (listed in section 6).
you have severe breathing problems at rest due to tumour disease or require oxygen treatment.

Warnings and precautions
Your doctor will closely monitor you during treatment.
Heart checks
Treatment with Herzuma, either alone or in combination with a taxane, may have effects on the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two other types of medicines used to treat tumours). These effects may range from moderate to severe and can be fatal. Heart function will therefore be monitored before, during (every three months), and after (up to two to five years) treatment with Herzuma. If you develop signs of heart failure (i.e. the heart's inability to pump blood adequately), you may require more frequent monitoring of heart function (every six to eight weeks), may be given treatment for heart failure, or may need to discontinue treatment with Herzuma.
Speak to your doctor, pharmacist, or nurse before receiving Herzuma if:

you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, or if you have taken or are currently taking any medicine to treat high blood pressure.
you have taken or are currently taking a medicine called doxorubicin or epirubicin (medicines used to treat tumours). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems when taking trastuzumab.
you suffer from shortness of breath, particularly if you are currently receiving a taxane. Trastuzumab can cause difficulty in breathing, especially the first time it is administered. This may be more severe if you already have breathing difficulties. Very rarely, patients with severe breathing difficulties before treatment have died after receiving trastuzumab.
you have received other cancer treatments.

If you are receiving Herzuma in combination with any other medicine used to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflet of these medicines.
Children and adolescents
Herzuma is not recommended for patients under 18 years of age.
Other medicines and Herzuma
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
It may take up to 7 months for Herzuma to be eliminated from the body. Therefore, you must tell your doctor, pharmacist, or nurse that you have been given Herzuma if you start taking any new medicine within 7 months after stopping treatment.
Pregnancy

If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor, pharmacist, or nurse before taking this medicine.
You must use effective contraception during treatment with Herzuma and for at least 7 months after the end of treatment.
Your doctor will discuss with you the risks and benefits of taking Herzuma during pregnancy. In rare cases, women treated with Herzuma during pregnancy have experienced a reduction in the fluid (amniotic fluid) surrounding the developing baby in the womb. This condition may be harmful to the unborn baby and has been associated with incomplete lung development, which has led to fetal death.

Breastfeeding
Do not breastfeed during treatment with Herzuma and for 7 months after the last dose of Herzuma, as Herzuma may pass into breast milk.
Consult your doctor or pharmacist before taking any medicine.
Driving and using machines
Herzuma may affect your ability to drive or operate machinery. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, do not drive or operate machinery until these symptoms have resolved.
Sodium
Herzuma contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How Herzuma is administered

Before starting treatment, your doctor will determine the amount of HER2 in the tumour. Only patients with high levels of HER2 will be treated with Herzuma. Herzuma must be administered only by a doctor or a nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you. The dose of Herzuma depends on your body weight.
Herzuma is given as an intravenous infusion (“drip”) directly into the veins. The first dose of treatment is administered over a 90-minute period, and you will be monitored by a healthcare professional during administration in case you experience any adverse effects.
If the first dose is well tolerated, subsequent doses may be administered over a 30-minute period (see section 2 “Warnings and precautions”). The number of infusions you will receive depends on your response to treatment. Your doctor will discuss this with you.
To avoid medication errors, it is important to check the vial labels to ensure that the medicine being prepared and administered is Herzuma (trastuzumab) and not another trastuzumab-based medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Herzuma is administered every 3 weeks. Herzuma may also be administered once weekly for the treatment of metastatic breast cancer.
If you interrupt treatment with Herzuma
Do not stop taking this medicine without first talking to your doctor. All doses must be taken at the correct time, either weekly or every three weeks (depending on your treatment schedule). This helps the medicine work as effectively as possible.
It may take up to 7 months for Herzuma to be eliminated from the body. Therefore, your doctor may decide to continue monitoring your heart function even after treatment has ended.
If you have any questions about how to use this medicine, consult 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 can be serious and may require hospitalisation.
During infusion of Herzuma, reactions such as chills, fever and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people).
Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, difficulty breathing, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), facial or lip swelling, skin rashes and feeling of fatigue. Some of these symptoms can be serious and some patients have died (see section 2 “Warnings and precautions”).
These effects occur mainly during the first intravenous infusion (“drip” into the vein) and within the first hours after the start of the infusion. They are usually temporary. You will be monitored by a healthcare 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 subsequent infusions. If you have a reaction, the infusion will be slowed down or stopped and you may be given treatment to counteract the side effects. The infusion may be resumed once your symptoms have improved.
Occasionally, symptoms begin more than six hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes symptoms may improve and then worsen later.

Serious side effects
Other side effects may occur at any time during treatment with Herzuma, not only in relation to an infusion. Tell your doctor or nurse immediately if you notice any of the following side effects:

Heart problems, which may sometimes be potentially serious, can occur during treatment and occasionally after treatment has been stopped. These include weakening of the heart muscle which may lead to heart failure, inflammation of the lining of the heart, and heart rhythm disorders. These may cause symptoms such as shortness of breath (including at night), cough, fluid retention (swelling) in the legs or arms, and palpitations (rapid or irregular heartbeat) (see section 2 Cardiac monitoring).

Your doctor will monitor your heart regularly during and after treatment, but you must tell your doctor immediately if you notice any of the symptoms listed above.

Tumour lysis syndrome (a group of metabolic complications occurring after anti-tumour treatment, characterised by high levels of potassium and phosphate in the blood and low calcium levels in the blood). Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion), heart problems (rapid or slow heartbeat), seizures, vomiting or diarrhoea, and tingling around the mouth, hands or feet.

If you experience any of the above symptoms after completing treatment with Herzuma, you should see a doctor and inform them about your previous treatment with Herzuma.

Other very common side effects (may affect more than 1 in 10 people):

infections
diarrhoea
constipation
chest burning (dyspepsia)
fatigue
skin rash
chest pain
abdominal pain
joint pain
low red and white blood cell counts (which help fight infections), sometimes associated with fever
muscle pain
conjunctivitis
excessive tearing
nosebleeds
runny nose
hair loss
tremor
hot flushes
dizziness
nail problems
weight loss
loss of appetite
inability to sleep (insomnia)
altered taste
low platelet count
bruising
numbness or tingling in fingers and toes, which occasionally may extend to the rest of the limb
redness, swelling or blisters in the mouth and/or throat
pain, swelling, redness or numbness in the hands and/or feet
shortness of breath
headache
cough
vomiting
nausea

Other common side effects (may affect up to 1 in 10 people):

allergic reactions • dry mouth and dry skin
throat infections • dry eyes
bladder and skin infections • sweating
sinus inflammation • fatigue and malaise
liver inflammation • anxiety
kidney disorders • depression
increased muscle tone or tension • asthma (hypertonia) • lung infection
pain in arms and/or legs • lung disorders
itchy skin rash • back pain
drowsiness • neck pain
haemorrhoids • bone pain
itching • acne
leg cramps

Other uncommon side effects (may affect up to 1 in 100 people):

deafness
skin rash with wheals
wheezing
inflammation or scarring in the lungs (fibrosis)

Other rare side effects (may affect up to 1 in 1000 people):

jaundice
anaphylactic reactions

Other side effects with unknown frequency (frequency cannot be estimated from the available data):

blood clotting abnormalities or alterations
high potassium levels
swelling or bleeding behind the eyes
shock
abnormal heart rhythm
respiratory distress
respiratory failure
acute accumulation of fluid in the lungs
acute narrowing of the airways
abnormally low levels of oxygen in the blood
difficulty breathing when lying down
liver damage
swelling of the face, lips and throat
kidney failure
abnormally low levels of amniotic fluid around the unborn child
inadequate development of the unborn child’s lungs
abnormal development of the unborn child’s kidneys

Some of the side effects that occur may be due to the carcinoma. If you are receiving Herzuma in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.
If you experience any side effect, talk to your doctor, pharmacist or nurse.

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex 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 stated on the outer carton and on the label of the
vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Infusion solutions should be used immediately after dilution. Do not use
Herzuma if you notice any particles or change in colour before administration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Herzuma contains

The active substance is trastuzumab. Each vial contains 150 mg of trastuzumab to be dissolved in 7.2 ml of water for injections. The resulting solution contains approximately 21 mg/ml of trastuzumab.
The other components are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Description of the appearance of Herzuma and contents of the pack
Herzuma is a powder for concentrate for solution for infusion. It is supplied in a glass vial sealed 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.
Váci út 1-3. WestEnd Office Building B tower
1062 Budapest
Hungary

Manufacturer
Millmount Healthcare Ltd.
Block 7
City North Business Campus
Stamullen, Co. Meath K32 YD60
Ireland
Nuvisan GmbH
Wegenerstraße 13,
89231 Neu Ulm,
Germany
Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France
Kymos S.L.
Ronda Can Fatjó 7B
(Parc Tecnològic del Vallès)
Cerdanyola del Vallès,
08290 Barcelona,
Spain
Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: + 32 1528 7418 Tel.: +36 1 231 0493
[email protected]

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Tel.: +36 1 231 0493 Tél/Tel: + 32 1528 7418
[email protected]

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Hungary Kft. Mint Health Ltd.
Tel: +36 1 231 0493 Tel: +356 2093 9800
[email protected]

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected] [email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel: +36 1 231 0493
[email protected] [email protected]

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
ΒΙΑΝΕΞ Α.Ε. Celltrion Healthcare Hungary Kft.
Τηλ: +30 210 8009111 - 120 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS PharmaKERN Portugal - Produtos Farmacêuticos,
Tél.: +33 (0)1 71 25 27 00 Sociedade Unipessoal, Lda.
Tel: +351 214 200 290

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel: +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22
[email protected]

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel: +36 1 231 0493
[email protected]

Italia Suomi/Finland
Celltrion Healthcare Italy S.R.L. Celltrion Healthcare Finland Oy.
Tel: +39 0247 927040 Puh/Tel: +358 29 170 7755
[email protected] [email protected]

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Healthcare Hungary Kft.
Τηλ: +357 22741741 Tel: +36 1 231 0493
[email protected]

Latvija United Kingdom (Northern Ireland)
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Ireland Limited
Tālr.: +36 1 231 0493 Tel: +353 1 223 4026
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

The following information is intended exclusively for physicians or healthcare professionals

To prevent administration errors and to ensure that the drug being prepared and administered is Herzuma (trastuzumab) and not another trastuzumab-containing product (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is essential to check the vial label.
Always store the medicinal product in its original closed packaging at 2°C - 8°C in a refrigerator.
Adhere to appropriate aseptic techniques during reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. The medicinal product does not contain antimicrobial preservatives or bacteriostatic agents; therefore, aseptic techniques must be employed.
A Herzuma vial reconstituted aseptically with sterile water for injections (not supplied) remains chemically and physically stable for 7 days at 2°C - 8°C after reconstitution and must not be frozen.
After aseptic dilution in polyvinyl chloride, polyethylene, or polypropylene bags containing 9 mg/mL (0.9%) sodium chloride injection solution, the chemical and physical stability of Herzuma has been demonstrated for up to 30 days at temperatures between 2°C and 8°C and for 24 hours at temperatures not exceeding 30°C.
From a microbiological standpoint, the reconstituted solution and the Herzuma infusion solution should be used immediately. If the product is not used immediately, the duration and storage conditions before and during use are under the responsibility of the user and should normally not exceed 24 hours at temperatures between 2°C and 8°C, unless reconstitution and dilution were performed under controlled and validated aseptic conditions.

Aseptic preparation, handling, and storage
Aseptic handling of the medicinal product must be ensured during infusion preparation.
The preparation must:

Be carried out under aseptic conditions by trained personnel in accordance with good manufacturing practices, particularly observing aseptic techniques for parenteral medicinal product preparation.
Be performed within laminar airflow hoods or in biologically safe environments, adopting standard precautions for safe handling of intravenous agents.
Be followed by appropriate storage of the intravenous infusion solution to ensure maintenance of aseptic conditions.

Each Herzuma vial is reconstituted with 7.2 mL of sterile water for injections (not supplied). Avoid using other solvents for reconstitution. This yields 7.4 mL of single-dose solution containing approximately 21 mg/mL of trastuzumab. A 4% overfill ensures accurate withdrawal of the intended 150 mg dose from the vial.
Herzuma must be handled carefully during the reconstitution process. Excessive foaming during reconstitution or agitation of the reconstituted Herzuma solution may result in difficulties in accurately withdrawing the required amount of Herzuma from the vial.

Instructions for aseptic reconstitution

Using a sterile syringe, slowly inject 7.2 mL of sterile water for injections into the vial containing lyophilized Herzuma, directing the stream onto the lyophilized powder.
Gently rotate the vial to facilitate reconstitution. DO NOT SHAKE!
Slight foaming during reconstitution is not unusual. Allow the vial to stand undisturbed in an upright position for approximately 5 minutes. Once reconstituted, Herzuma appears as a clear, particle-free solution, colorless to pale yellow.

Instructions for aseptic dilution of the reconstituted solution
Determine the volume of solution required:

Based on a loading dose of 4 mg of trastuzumab/kg body weight, or a subsequent weekly maintenance dose of 2 mg of trastuzumab/kg body weight:

Volume (mL) = Body Weight (kg) x Dose ( 4 mg/kg for loading dose or 2 mg/kg for maintenance dose)
21 (mg/mL, concentration of reconstituted solution)

Based on a loading dose of 8 mg of trastuzumab/kg body weight, or a subsequent dose of 6 mg of trastuzumab/kg body weight every 3 weeks:

Volume (mL) = Body Weight (kg) x Dose ( 8 mg/kg for loading dose or 6 mg/kg for maintenance dose)
21 (mg/mL, concentration of reconstituted solution)

Withdraw the required volume of solution from the vial using a sterile needle and syringe and transfer it into an infusion bag made of polyvinyl chloride, polyethylene, or polypropylene containing 250 mL of 9 mg/mL (0.9%) sodium chloride injection solution. Do not use solutions containing glucose. The bag should be gently inverted to mix the solution, avoiding foaming. Parenteral solutions should be visually inspected for particulate matter and discoloration prior to administration.

Package leaflet: information for the user

Herzuma 420 mg powder for concentrate for solution for infusion

trastuzumab
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What Herzuma is and what it is used for
What you need to know before Herzuma is administered to you
How Herzuma is administered
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 bind to specific proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is present in large amounts on the surface of certain tumour cells and stimulates their growth. When Herzuma binds to HER2, it blocks the growth of these cells and causes their death.

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

You have early-stage breast cancer with high levels of a protein called HER2.
You have metastatic breast cancer (breast cancer that has spread away from the primary tumour) with high levels of HER2. Herzuma may be prescribed in combination with the chemotherapeutic medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer, or it may be prescribed alone when other treatments have proven ineffective. It is also used in combination with medicines called aromatase inhibitors for the treatment of patients with high levels of HER2 and metastatic breast cancer that is hormone receptor-positive (cancer that is sensitive to female sex hormones).
You have metastatic gastric cancer with high levels of HER2, in combination with other anticancer medicines, capecitabine or 5-fluorouracil and cisplatin.

2. What you should know before being given Herzuma

Do not use Herzuma if:

you are allergic to trastuzumab, mouse proteins (murine), or to any of the other ingredients of this medicine (listed in section 6).
you have severe respiratory problems at rest due to tumour disease or require oxygen therapy.

Warnings and precautions
Your doctor will closely monitor you during treatment.
Heart checks
Treatment with Herzuma, whether given alone or in combination with a taxane, may affect the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two other types of medicines used to treat tumours). These effects may range from moderate to severe and can be fatal. Heart function will therefore be monitored before, during (every three months), and after (up to two to five years) treatment with Herzuma. If you develop signs of heart failure (i.e. the heart's inability to pump blood adequately), you may require more frequent heart function monitoring (every six to eight weeks), may be given treatment for heart failure, or may need to discontinue treatment with Herzuma.
Talk to your doctor, pharmacist, or nurse before receiving Herzuma if:

you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, or if you have taken or are currently taking any medicine for high blood pressure.
you have taken or are currently taking a medicine called doxorubicin or epirubicin (medicines used to treat tumours). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems when taking trastuzumab.
you suffer from shortness of breath, particularly if you are currently receiving a taxane. Trastuzumab can cause breathing difficulties, especially the first time it is administered. This may be more severe if you already have breathing problems. Very rarely, patients with severe breathing difficulties before treatment have died after receiving trastuzumab.
you have received other cancer treatments.

If you are receiving Herzuma in combination with any other cancer medicine, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflet for those medicines.
Children and adolescents
Herzuma is not recommended for patients under 18 years of age.
Other medicines and Herzuma
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
It may take up to 7 months for Herzuma to be eliminated from your body. Therefore, you must inform your doctor, pharmacist, or nurse that you have been given Herzuma if you start taking any new medicine within 7 months after stopping treatment.
Pregnancy

If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor, pharmacist, or nurse before taking this medicine.
You must use effective contraception during treatment with Herzuma and for at least 7 months after the end of treatment.
Your doctor will discuss with you the risks and benefits of taking Herzuma during pregnancy. In rare cases, a reduction in the fluid (amniotic fluid) surrounding the developing baby in the womb has been observed in pregnant women treated with Herzuma. This condition may be harmful to the unborn baby and has been associated with incomplete lung development, which has led to fetal death.

Breast-feeding
Do not breast-feed during treatment with Herzuma and for 7 months after the last dose of Herzuma, as trastuzumab may pass into breast milk.
Consult your doctor or pharmacist before taking any medicine.
Driving and using machines
Herzuma may affect your ability to drive or use machinery. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, do not drive or operate machinery until these symptoms resolve.
Sodium
Herzuma contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How Herzuma is administered

Before starting treatment, your doctor will determine the amount of HER2 in the tumour. Only
patients with high levels of HER2 will be treated with Herzuma. Herzuma must be administered
only by a doctor or a nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you. The dose of Herzuma depends on your body weight.
Herzuma is given as an intravenous infusion (“drip”) directly into the veins. The first dose of treatment
is administered over a 90-minute period, and you will be monitored by a healthcare professional during
administration in case you experience any adverse effects.
If the first dose is well tolerated, subsequent doses may be administered over a 30-minute period (see
section 2 “Warnings and precautions”). The number of infusions you will receive depends on your
response to treatment. Your doctor will discuss this with you.
To avoid medication errors, it is important to check the vial labels to ensure that the medicine being
prepared and administered is Herzuma (trastuzumab) and not another trastuzumab-containing
medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Herzuma
is administered every 3 weeks. Herzuma may also be administered once weekly for the treatment of
metastatic breast cancer.
If you interrupt treatment with Herzuma
Do not stop taking this medicine without first discussing it with your doctor. All doses must be taken
at the correct time, either weekly or every three weeks (depending on your treatment schedule). This
helps the medicine work as effectively as possible.
It may take up to 7 months for Herzuma to be eliminated from the body. Therefore, your doctor may
decide to continue monitoring heart function even after treatment has ended.
If you have any doubts about how to use this medicine, consult 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 can be serious and may require hospitalisation.
During Herzuma infusion, reactions such as chills, fever and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people).
Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, difficulty breathing, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), facial or lip swelling, skin rashes and feeling of fatigue. Some of these symptoms can be serious, and some patients have died (see section 2 “Warnings and precautions”).
These effects occur mainly during the first intravenous infusion (“drip” into the vein) and during the first few hours after the start of the infusion. They are usually temporary. You will be monitored by a healthcare 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 subsequent infusions. If you have a reaction, the infusion will be slowed down or stopped, and you may be given treatment to counteract the side effects. The infusion may be resumed once your symptoms have improved.
Occasionally, symptoms begin more than six hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then worsen later.

Serious side effects
Other side effects may occur at any time during treatment with Herzuma, not only in connection with an infusion. Inform your doctor or nurse immediately if you notice any of the following side effects:

Heart problems, which may sometimes be potentially serious, can occur during treatment and occasionally after treatment has been stopped. These include weakening of the heart muscle which may lead to heart failure, inflammation of the lining of the heart, and disturbances in heart rhythm. These may cause symptoms such as shortness of breath (including at night), cough, fluid retention (swelling) in the legs or arms, and palpitations (rapid or irregular heartbeat) (see section 2 Heart monitoring).

Your doctor will monitor your heart regularly during and after treatment, but you must inform your doctor immediately if you notice any of the symptoms listed above.

Tumour lysis syndrome (a group of metabolic complications occurring after anti-tumour treatment, characterised by high levels of potassium and phosphate in the blood and low levels of calcium in the blood). Symptoms may include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (rapid or slow heartbeat), seizures, vomiting or diarrhoea, and tingling around the mouth, hands or feet.

If you experience any of the above symptoms after completing treatment with Herzuma, you must see a doctor and inform them about your previous treatment with Herzuma.

Other very common side effects (may affect more than 1 in 10 people):

infections
diarrhoea
constipation
chest burning (dyspepsia)
fatigue
skin rash
chest pain
abdominal pain
joint pain
low red and white blood cell counts (which help fight infections), sometimes associated with fever
muscle pain
conjunctivitis
excessive tearing
nosebleeds
runny nose
hair loss
tremor
hot flushes
dizziness
nail problems
weight loss
loss of appetite
inability to sleep (insomnia)
altered taste
low platelet count
bruising
numbness or tingling in the fingers and toes, which occasionally may extend to the rest of the limb
redness, swelling or blisters in the mouth and/or throat
pain, swelling, redness or numbness in the hands and/or feet
shortness of breath
headache
cough
vomiting
nausea

Other common side effects (may affect up to 1 in 10 people):

allergic reactions • dry mouth and dry skin
throat infections • dry eyes
bladder and skin infections • sweating
sinus inflammation • fatigue and malaise
liver inflammation • anxiety
kidney disorders • depression
increased muscle tone or tension • asthma (hypertonia) • lung infection
pain in arms and/or legs • lung disorders
itchy skin rash • back pain
drowsiness • neck pain
haemorrhoids • bone pain
itching • acne
leg cramps

Other uncommon side effects (may affect up to 1 in 100 people):

deafness
skin rash with hives
wheezing
inflammation or scarring in the lungs (fibrosis)

Other rare side effects (may affect up to 1 in 1000 people):

jaundice
anaphylactic reactions

Other side effects with unknown frequency (frequency cannot be estimated from the available data):

blood coagulation abnormalities or alterations
high potassium levels
swelling or bleeding behind the eyes
shock
abnormal heart rhythm
respiratory distress
respiratory failure
acute accumulation of fluid in the lungs
acute narrowing of the airways
abnormally low levels of oxygen in the blood
difficulty breathing when lying down
liver damage
swelling of the face, lips and throat
kidney failure
abnormally low levels of amniotic fluid around the unborn child
insufficient lung development in the unborn child
abnormal kidney development in the unborn child

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex 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 stated on the outer carton and on the label
of the vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Infusion solutions should be used immediately after dilution. Do not use
Herzuma if you notice any particles or change in colour before administration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Herzuma contains

The active substance is trastuzumab. Each vial contains 420 mg of trastuzumab, which must be dissolved in 20 ml of water for injections. The resulting solution contains approximately 21 mg/ml of trastuzumab.
The other components are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Description of the appearance of Herzuma and contents of the pack
Herzuma is a powder for concentrate for solution. It is supplied in a glass vial sealed 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 Authorization Holder
Celltrion Healthcare Hungary Kft.
Váci út 1-3. WestEnd Office Building B tower
1062 Budapest
Hungary

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: +32 1528 7418 Tel.: +36 1 231 0493
[email protected]

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Tel.: +36 1 231 0493 Tél/Tel: +32 1528 7418
[email protected]

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Hungary Kft. Mint Health Ltd.
Tel: +36 1 231 0493 Tel: +356 2093 9800
[email protected]

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel: +49 (0)30 346494150 Tel: +31 20 888 7300
[email protected] [email protected]