PACKAGE LEAFLET: INFORMATION FOR THE USER

Herceptin 150 mg powder for concentrate for solution for infusion

trastuzumab
Please read all of 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, ask your doctor or pharmacist.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

What Herceptin is and what it is used for
What you need to know before being given Herceptin
How Herceptin is given
Possible side effects
How to store Herceptin
Contents of the pack and other information

1. What is Herceptin and what is it used for

Herceptin 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 Herceptin binds to HER2, it blocks the growth of these cells and causes their death.

Your doctor may prescribe Herceptin for the treatment of breast and gastric cancer if:

you have early-stage breast cancer with high levels of a protein called HER2.
you have metastatic breast cancer (breast cancer that has spread from the original tumour to distant sites) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapeutic agents 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 HER2 levels 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 Herceptin

Do not use Herceptin if:

you are allergic to trastuzumab, mouse (murine) proteins, or any of the excipients of this medicine (listed in section 6).
you have severe breathing difficulties at rest due to the tumour, or require oxygen therapy.

Warnings and precautions
Your doctor will closely monitor you during treatment.
Heart checks
Treatment with Herceptin, 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). The effects can range from moderate to severe and may be life-threatening. Your heart function will therefore be monitored before, during (every three months), and after (up to two to five years) treatment with Herceptin. 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 need treatment for heart failure, or may have to discontinue Herceptin treatment.
Talk to your doctor, pharmacist, or nurse before being given Herceptin 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 the heart muscle and increase the risk of heart problems when taking Herceptin.
you suffer from shortness of breath, particularly if you are currently receiving a taxane. Herceptin 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 Herceptin.
you have received other cancer treatments.

If you are receiving Herceptin 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 these medicines.
Children and adolescents
Herceptin is not recommended for patients under 18 years of age.
Other medicines and Herceptin
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 Herceptin to be eliminated from the body. Therefore, you must inform your doctor, pharmacist, or nurse that you have been given Herceptin 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, inform your doctor, pharmacist, or nurse before taking this medicine.
You must use effective contraception during treatment with Herceptin and for at least 7 months after the end of treatment.
Your doctor will discuss with you the risks and benefits of taking Herceptin during pregnancy. In rare cases, women treated with Herceptin during pregnancy have shown reduced levels of 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.

Breast-feeding
Do not breast-feed during treatment with Herceptin and for 7 months after receiving the last dose of Herceptin, as Herceptin may pass into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Herceptin may affect your ability to drive or use machines. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, do not drive or operate machinery until these symptoms resolve.

3. How Herceptin 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 Herceptin. Herceptin must be administered only
by a doctor or nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you. The dose of Herceptin depends on your body weight.
There are two different types (formulations) of Herceptin:

one is administered by intravenous infusion (intravenous infusion)
the other is administered by injection under the skin (subcutaneous injection). It is important to check the medicine label to ensure that the correct formulation is administered as prescribed. Intravenous formulation of Herceptin is not intended for subcutaneous administration and must be administered exclusively by intravenous infusion. Your doctor may consider switching from treatment with intravenous formulation of Herceptin to subcutaneous formulation of Herceptin (and vice versa), as appropriate for your condition.

The intravenous formulation of Herceptin is given as an intravenous infusion ("drip") directly into the veins. The first dose of treatment is administered over a period of 90 minutes, 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 period of 30 minutes (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 Herceptin (trastuzumab) and not another trastuzumab-containing medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early-stage breast cancer, metastatic breast cancer and metastatic gastric cancer, Herceptin is administered every 3 weeks. Herceptin may also be administered once weekly for the treatment of metastatic breast cancer.
If you interrupt treatment with Herceptin
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 administration schedule). This helps the medicine work as effectively as possible.
It may take up to 7 months for Herceptin 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 questions about how to use this medicine, consult your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, Herceptin can cause side effects, although not everyone gets them. Some of these side effects can be serious and may require hospitalisation.
During Herceptin 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, breathing difficulties, 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 may be severe, and some patients have died (see section 2 “Warnings and precautions”).
These effects occur mainly with the first intravenous infusion (“drip” into the vein) and during the first hours after the start of infusion. They are generally 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 experience 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 symptoms have improved.
Occasionally, symptoms begin more than six hours after the start of infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then worsen later.

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

Heart problems, which may sometimes be 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 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 calcium levels). Symptoms may include kidney problems (weakness, shortness of breath, fatigue, 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 Herceptin, you must see a doctor and inform them about your previous treatment with Herceptin.

Very common side effects of Herceptin: may affect more than 1 in 10 people

infections
diarrhoea
constipation
heartburn (dyspepsia)
fatigue
skin rash
chest pain
abdominal pain
joint pain
low red and white blood cell counts (white blood cells 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 hands and/or feet
shortness of breath
headache
cough
vomiting
nausea

Common side effects of Herceptin: may affect up to 1 in 10 people

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

Uncommon side effects of Herceptin: may affect up to 1 in 100 people

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

Rare side effects of Herceptin: may affect up to 1 in 1,000 people

jaundice
anaphylactic reactions

Other side effects reported with the use of Herceptin: frequency cannot be estimated from the available data

blood clotting abnormalities or changes
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 baby
inadequate lung development in the unborn baby
abnormal kidney development in the unborn baby

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

Reporting of side effects
If you experience 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 referred to in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Herceptin

Herceptin must be stored by healthcare professionals at the hospital or clinic.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the vial after "Exp." The expiry date refers to the last day of that month.
Store the vial in a refrigerator (2 °C - 8 °C) prior to reconstitution.
Do not freeze the reconstituted solution.
Infusion solutions should be used immediately after dilution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C.
Do not use Herceptin 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 Herceptin contains

The active substance is trastuzumab. Each vial contains 150 mg of trastuzumab, which must 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 monohydrochloride monohydrate, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Description of the appearance of Herceptin and contents of the pack
Herceptin is a powder for concentrate for solution for intravenous infusion 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 pack contains 1 vial of powder.
Marketing Authorization Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
N.V. Roche S.A. UAB “Roche Lietuva”
Tél/Tel: +32 (0) 2 525 82 11 Tel: +370 5 2546799
България Luxembourg/Luxemburg
Рош България ЕООД (See/siehe Belgique/Belgien)
Тел: +359 2 474 5444
Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 1 279 4500
Danmark Malta
Roche Pharmaceuticals A/S (See Ireland)
Tlf: +45 - 36 39 99 99
Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050
Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 - 6 177 380 Tlf: +47 - 22 78 90 00
Ελλάδα Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Τηλ: +30 210 61 66 100 Tel: +43 (0) 1 27739
España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88
France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0)1 47 61 40 00 Tel: +351 - 21 425 70 00
Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: + 385 1 47 22 333 Tel: +40 21 206 47 01
Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00
Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000
Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500
Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200
Latvija United Kingdom (Northern Ireland)
Roche Latvija SIA Roche Products (Ireland) Ltd.
Tel: +371 - 67 039831 Tel: +44 (0) 1707 366000

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 European Medicines Agency website.

The following information is intended exclusively for physicians or healthcare professionals

Herceptin intravenous is supplied in sterile, single-use vials that are preservative-free and pyrogen-free.
To prevent medication administration errors and to ensure that the drug being prepared and administered is Herceptin (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is important to check the vial label.
Store the medicinal product in its original closed packaging at a temperature of 2°C–8°C in the refrigerator.
Follow appropriate aseptic techniques for reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. The medicinal product contains no antimicrobial preservatives or bacteriostatic agents; therefore, aseptic techniques must be used.
A Herceptin vial reconstituted aseptically with sterile water for injection (not supplied) remains chemically and physically stable for 48 hours at 2°C–8°C after reconstitution and must not be frozen.
After aseptic dilution into polyvinylchloride, polyethylene, or polypropylene infusion bags containing 9 mg/mL (0.9%) sodium chloride injection solution, the chemical stability and physical stability of Herceptin have been demonstrated for up to 30 days at 2°C–8°C and for 24 hours at temperatures not exceeding 30°C.
From a microbiological standpoint, the reconstituted solution and Herceptin infusion solution should be used immediately. If the product is not used immediately, the duration and conditions of storage prior to and during use are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

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

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

Follow appropriate aseptic techniques. Each vial of Herceptin is reconstituted with 7.2 mL of water for injection (not supplied). Avoid using other solvents for reconstitution. This yields 7.4 mL of solution for a single dose, containing approximately 21 mg/mL of trastuzumab. A 4% overfill ensures that the intended dose of 150 mg can be withdrawn from the vial.
Herceptin must be handled carefully during the reconstitution process.
Excessive foaming during reconstitution or agitation of the reconstituted Herceptin solution may result in difficulties in accurately withdrawing the intended amount of Herceptin from the vial.

Instructions for aseptic reconstitution:

Using a sterile syringe, slowly inject 7.2 mL of water for injection into the vial containing lyophilized Herceptin, directing the stream onto the lyophilized material.
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, Herceptin appears as a clear, colorless to pale yellow solution, free from visible particles.

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) × 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) × 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 add it to an infusion bag made of polyvinylchloride, polyethylene, or polypropylene containing 250 mL of 0.9% sodium chloride solution. Do not use 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 particulate matter and discoloration prior to administration.

PATIENT INFORMATION LEAFLET: INFORMATION FOR THE USER

Herceptin 600 mg solution for injection in vial

trastuzumab
Please read this leaflet carefully before using this medicine as 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 experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Herceptin is and what it is used for
What you need to know before being given Herceptin
How Herceptin is administered
Possible side effects
How to store Herceptin
Contents of the pack and other information

1. What Herceptin is and what it is used for

Herceptin 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 high amounts on the surface of certain tumor cells and stimulates their growth.
When Herceptin binds to HER2, it blocks the growth of these cells and causes their death.
Your doctor may prescribe Herceptin for the treatment of breast cancer if:

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 tumor) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapeutic agents 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 drugs 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).

2. What you need to know before you are given Herceptin

Do not use Herceptin if:

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

Warnings and precautions
Your doctor will monitor you closely during treatment.
Heart checks
Treatment with Herceptin, 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 could lead to death.
Therefore, your heart function will be checked before, during (every three months), and after (up to two to five years)
treatment with Herceptin. If you develop signs of heart failure (the heart's inability to pump blood effectively), you may
require more frequent heart function monitoring (every six to eight weeks), may receive treatment for heart failure,
or may need to stop taking Herceptin.
Talk to your doctor, pharmacist, or nurse before you are given Herceptin if:

you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), or 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 Herceptin.
you suffer from shortness of breath, particularly if you are currently receiving a taxane. Herceptin can cause difficulty breathing, especially the first time it is administered. This may be more serious if you already have breathing difficulties. Very rarely, patients with severe breathing difficulties before treatment have died after receiving Herceptin.
you have received other cancer treatments.

If you are receiving Herceptin in combination with another anticancer medicine such as
paclitaxel, docetaxel, an aromatase inhibitor, carboplatin, or cisplatin, you should also read the package leaflet of these medicines.
Children and adolescents
Herceptin is not recommended for patients under 18 years of age.
Other medicines and Herceptin
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 Herceptin to be eliminated from the body. Therefore, you must inform your doctor,
pharmacist, or nurse that you have been given Herceptin if you start any new treatment within 7 months after stopping therapy.
Pregnancy

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

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

3. How Herceptin is administered

Before starting treatment, your doctor will determine the amount of HER2 present in the tumour. Only
patients with high levels of HER2 will be treated with Herceptin. Herceptin must be
administered exclusively by a doctor or nurse.
There are two different types (formulations) of Herceptin:

one is administered as an intravenous infusion (intravenous infusion)
the other is administered as an injection under the skin (subcutaneous injection). It is important to check the product label to ensure that the correct formulation is administered as prescribed. The fixed-dose subcutaneous formulation of Herceptin is not intended for intravenous administration and must be administered exclusively by subcutaneous injection.

Your doctor may consider switching from treatment with the intravenous formulation of Herceptin to
treatment with the subcutaneous formulation (and vice versa), if appropriate for your
condition.
To avoid medication errors, it is important to check the vial labels to ensure that
the medicine being prepared and administered is Herceptin (trastuzumab) and not another
trastuzumab-containing medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
The recommended dose is 600 mg. Herceptin is administered by subcutaneous injection (under the
skin) over 2–5 minutes every three weeks.
The injection site should be alternated between the left and right thigh. New injections should
be administered at least 2.5 cm away from the previous injection site. Do not administer
injections into areas where the skin is red, bruised, tender, or hardened.
If you are taking other subcutaneously administered medicines during treatment with Herceptin,
those injections should be given at a different site.
Herceptin must not be mixed or diluted with other products.
If you interrupt treatment with Herceptin
Do not stop using this medicine without first discussing it with your doctor. Take all your
doses regularly every three weeks. This helps the medicine work most effectively.
It may take up to 7 months for Herceptin to be eliminated from your 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 treatment with Herceptin, chills, fever and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people). Other symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), swelling of the face or lips, skin rashes and feeling of tiredness. Some of these symptoms may be severe and some patients have died (see section “Warnings and precautions”).
During administration, for 30 minutes after the first dose and for 15 minutes after subsequent doses, your doctor or nurse will monitor you for the occurrence of side effects.

Serious side effects
Other serious side effects may occur at any time during treatment with Herceptin.
Tell your doctor or nurse immediately if you notice any of the following side effects:

During treatment, and occasionally after its completion, potentially serious heart problems may sometimes occur. 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 inform your doctor immediately if you notice any of the above symptoms.

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 Herceptin, you must see a doctor and inform them about your previous treatment with Herceptin.
There are two different types (formulations) of Herceptin:

one to be administered by intravenous infusion over 30–90 minutes
the other to be administered by subcutaneous injection over 2–5 minutes. In a clinical study comparing these two formulations, infections and cardiac events leading to hospitalisation were more frequent with the subcutaneous formulation. In addition, there were more local injection site reactions and increases in blood pressure. Other side effects were found to be similar.

Very common side effects of Herceptin: may affect more than 1 in 10 people:

infections
diarrhoea
constipation
heartburn (dyspepsia)
fatigue
skin rashes
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 of the hands and feet, 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

Common side effects of Herceptin: may affect up to 1 in 10 people

allergic reactions • dry mouth and dry skin
throat infections • dry eyes
bladder and skin infections • sweating
fatigue and malaise
breast inflammation • anxiety
liver inflammation • depression
kidney disorders
increased muscle tone or tension • spasticity • 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

Uncommon side effects of Herceptin: may affect up to 1 in 100 people:

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

Rare side effects of Herceptin: may affect up to 1 in 1,000 people:

jaundice
anaphylactic reactions

Other side effects reported with the use of Herceptin: frequency cannot be estimated from the available data

abnormal or insufficient blood clotting
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 breast cancer. If you are receiving Herceptin in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.

If you experience any of the side effects, consult 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 Herceptin

Keep out of the sight and reach of children.
Do not use this medicinal product after the expiry date which is stated on the carton and on the label
of the vial after “Exp. /EXP”. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Keep the vial in the outer carton to protect it from light.
Do not freeze.
Once the vial has been opened, the solution should be used immediately.
Do not use this medicinal product if you notice any particles or change in colour before
administration.
Do not dispose of any medicinal product via wastewater. Ask your pharmacist how to dispose of
medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Herceptin contains

The active substance is trastuzumab. A 5 ml vial contains 600 mg of trastuzumab.
The other ingredients are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine monohydrochloride monohydrate, α,α-trehalose dihydrate, L-methionine, polysorbate 20, water for injections.

Description of the appearance of Herceptin and contents of the pack

Herceptin is an injectable solution supplied in a glass vial with a butyl rubber stopper containing 5 ml (600 mg) of trastuzumab. The solution ranges from clear to opalescent and from colourless to yellowish.
Each pack contains one vial.

Marketing Authorisation Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

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

België/Belgique/Belgien
N.V. Roche S.A.
Tél/Tel: +32 (0) 2 525 82 11

България
Рош България ЕООД
Тел: +359 2 474 5444

Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111

Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99

Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140

Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380

Ελλάδα
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

España
Roche Farma S.A.
Tel: +34 - 91 324 81 00

France
Roche
Tél: +33 (0)1 47 61 40 00

Hrvatska
Roche d.o.o.
Tel: + 385 1 47 22 333

Ireland
Roche Products (Ireland) Ltd.
Tel: +353 (0) 1 469 0700

Ísland
Roche Pharmaceuticals A/S
c/o Icepharma hf
Sími: +354 540 8000

Italia
Roche S.p.A.
Tel: +39 - 039 2471

Kύπρος
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100

Latvija
Roche Latvija SIA
Tel: +371 - 67 039831

Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

Luxembourg/Luxemburg
(See Belgium)

Magyarország
Roche (Magyarország) Kft.
Tel: +36 1 279 4500

Malta
(See Ireland)

Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438050

Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00

Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739

Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88

Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00

România
Roche România S.R.L.
Tel: +40 21 206 47 01

Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00

Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201

Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500

Sverige
Roche AB
Tel: +46 (0) 8 726 1200

United Kingdom (Northern Ireland)
Roche Products (Ireland) Ltd.
Tel: +44 (0) 1707 366000

Other sources of information