HERCEPTIN 150 mg Concentrate For Infusion Solution

Зміст інструкції

1. Herceptin 150 mg powder for concentrate for solution for infusion
   1. What is Herceptin and what it is used for
   2. What you need to know before you are given Herceptin
   3. How Herceptin is administered
   4. Possible side effects
   5. How to store Herceptin
   6. Contents of the pack and other information
2. Herceptin 600 mg injectable solution in vial
   1. What is Herceptin and what it is used for
   2. What you need to know before you are given Herceptin
   3. How Herceptin is administered
   4. Possible side effects
   5. How to store Herceptin
   6. Contents of the pack and other information

Herceptin 150 mg powder for concentrate for solution for infusion

trastuzumab

Read this leaflet carefully before you use 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 or pharmacist.
• If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Herceptin is and what it is used for
• 2. What you need to know before you are given Herceptin
• 3. How Herceptin is administered
• 4. Possible side effects
• 5. How to store Herceptin
• 6. Contents of the pack and other information

1. What is Herceptin 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 large quantities on the surface of some cancer 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 primary tumor) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapeutic drugs paclitaxel or docetaxel as a first treatment for metastatic breast cancer, or it may be prescribed alone where other treatments have proven ineffective. It is also used in association with drugs called aromatase inhibitors for the treatment of patients with high levels of HER2 and metastatic breast cancer with hormone receptors positive (cancer that is sensitive to the presence of female sex hormones).
• you have metastatic gastric cancer with high levels of HER2, in combination with other anticancer drugs capecitabine or 5-fluorouracil and cisplatin.

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

Do not use Herceptin if:

• you are allergic to trastuzumab, murine (mouse) proteins, or any of the excipients of this medicine (listed in section 6).
• you have severe breathing problems at rest due to the cancer or if you need oxygen treatment.

Warnings and precautions
The doctor will carefully monitor you during therapy.

Heart checks
Treatment with Herceptin given alone or with a taxane can have effects on the heart,
especially if you have previously used an anthracycline (taxanes and anthracyclines are two other types of medicines
used to treat cancer). The effects can range from moderate to severe and can be fatal. Cardiac function will therefore be monitored before, during (every three months) and after (up to
two-five years) treatment with Herceptin. If you develop signs of heart failure (i.e.
the inadequate pumping of blood by the heart), you may undergo more
frequent checks of cardiac function (every six to eight weeks), you may receive treatment for
heart failure or you may need to stop treatment with Herceptin.

Talk to your doctor, pharmacist or nurse before you are given Herceptin
if:

• you have had heart failure, coronary heart disease, heart valve disease (heart murmurs), high blood pressure, 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 cancer). These medicines (or any other anthracycline) can damage the heart muscle and increase the risk of heart problems with the use of Herceptin.
• you suffer from shortness of breath, especially if you are currently taking a taxane. Herceptin can cause difficulty breathing, especially the first time it is given. This may be more severe if you already suffer from shortness of breath. Very rarely, patients with severe difficulty breathing before treatment have died when they received Herceptin.
• you have received other cancer treatments.

If you receive treatment with Herceptin in combination with any other medicine used to treat
tumours, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or

Children and adolescents
Herceptin is not recommended for use in children 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
tell your doctor, pharmacist or nurse that you have been given Herceptin if you
start taking any new medicines within 7 months of stopping therapy.

Pregnancy

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

Breastfeeding
Do not breastfeed during the period of taking Herceptin and for 7 months after the administration
of the last dose of Herceptin as Herceptin can pass into the baby through breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Herceptin can have effects on the ability to drive and operate machines. If you develop symptoms such as dizziness, drowsiness, chills or fever during
treatment, do not drive or
operate machines until these symptoms disappear.

3. How Herceptin is administered

Before starting treatment, the doctor will determine the amount of HER2 in the tumor. Only patients with high levels of HER2 will be treated with Herceptin. Herceptin must be administered only by a doctor or a nurse. The doctor will prescribe the dose and treatment schedule suitable for you. The dose of Herceptin depends on your body weight.
There are two different types (formulations) of Herceptin:

• one is administered by infusion into a vein (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. Herceptin intravenous formulation is not intended for subcutaneous administration and must be administered only by intravenous infusion. The doctor may consider switching from treatment with Herceptin intravenous formulation to treatment with Herceptin subcutaneous formulation (and vice versa), if appropriate for your condition.

Herceptin intravenous formulation is administered 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 side 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 will depend on your response to treatment. The doctor will discuss this with you.
In order 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 medicine containing trastuzumab (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 can also be administered once a week for the treatment of metastatic breast cancer.

If you stop taking Herceptin
Do not stop taking this medicine without first talking to your doctor. All doses must be taken at the right time every week or every three weeks (depending on your dosing schedule). This helps the medicine to work best.
It may take up to 7 months for Herceptin to be eliminated from the body. Therefore, the doctor may decide to continue to monitor cardiac function even after you have finished treatment.
If you have any doubts about using this medicine, ask your doctor, pharmacist or nurse

4. Possible side effects

Like all medicines, Herceptin can cause side effects, although not everybody gets them.
Some of these side effects can be serious and may require hospitalisation.
During the 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 symptoms related to the infusion are: nausea, vomiting, pain, increased muscle tension and
tremors, headache, dizziness, difficulty breathing, high or low blood pressure, heart rhythm disorders (palpitations, fast or irregular heartbeat), swelling of the face or lips,
skin rashes and feeling tired. Some of these symptoms can be serious 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 few hours after the start of the infusion. They are generally temporary. You will be kept
under observation by a healthcare professional during the infusion and for at least six hours after the start of the
first infusion and for two hours from the start of the other 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 continued after the symptoms have improved.
Occasionally, symptoms start 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 Herceptin,
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 can be potentially serious, may sometimes occur during treatment and, occasionally, after it has stopped. These include weakening of the heart muscle which can lead to heart failure, inflammation of the lining of the heart and heart rhythm disorders. These can cause symptoms such as shortness of breath (including at night), cough, fluid retention (swelling) in the legs or arms and palpitations (fast or irregular heartbeat) (see section 2 Heart monitoring).

The 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 that occur after cancer 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 (fast or slow heartbeat), seizures, vomiting or diarrhoea and tingling around the mouth, hands or feet.

If you experience any of the above symptoms after you have finished treatment with Herceptin,
you should see your doctor and tell 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 counts of red blood cells and white blood cells (which help to 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
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling of the fingers and toes, which can occasionally spread to the rest of the limb • redness, swelling or blisters in the mouth and/or throat
• pain, swelling, redness or numbness of 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 skin
• throat infections • dry eyes
• bladder and skin infections • sweating
• tiredness and weakness
• breast inflammation • anxiety
• liver inflammation • depression
• kidney problems
• increased muscle tone or tension (hypertonia)
• asthma
• lung infection
• pain in the arms and/or legs • lung disorders
• itchy skin rash • back pain
• sleepiness • neck pain
• haemorrhoids • bone pain
• itching • acne
• leg cramps Uncommon side effects of Herceptin:may affect up to 1 in 100
• hearing loss
• skin rash with blisters
• wheezing
• inflammation or scarring in the lungs (fibrosis)

Rare side effects of Herceptin: may affect up to 1 in 1000:

• jaundice
• anaphylactic reactions

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

• blood clotting abnormalities
• high potassium levels
• swelling or bleeding behind the eyes
• shock
• irregular heartbeat
• respiratory distress
• respiratory failure
• acute fluid accumulation 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 fluid around the baby in the womb
• insufficient development of the baby's lungs in the womb
• abnormal development of the baby's kidneys in the womb

Some of the side effects that occur may be due to the cancer. If you receive
Herceptin in combination with chemotherapy, some of these side effects may also be
due to the chemotherapy.
If you get any side effects, tell your doctor, pharmacist or nurse.

Reporting of side effects
If you get any side effects, see your doctor, pharmacist or nurse. You can also report side effects directly
through 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

Herceptin must be stored by healthcare professionals in the hospital or care facility.

• 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 pack and on the vial label after ”Expiry /EXP”. The expiry date refers to the last day of that month.
• Store the vial in a refrigerator (2 ° C - 8 ° C) before opening.
• Do not freeze the reconstituted solution.
• Infusion solutions must be used immediately after dilution. If not used immediately, the storage times and conditions before 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 colour change before administration.
• Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack 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 ingredients are L-histidine hydrochloride 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 that is supplied in a
glass vial sealed with a rubber stopper containing 150 mg of trastuzumab. The powder is a
pellet ranging in colour from white to pale yellow. Each pack contains 1 vial of powder.

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 on this medicine, 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

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

България
Рош България ЕООД
Тел: +359 2 474 5444

Luxembourg/Luxemburg
(Voir/siehe Belgique/Belgien)

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

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

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

Malta
(See Ireland)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Latvija
Roche Latvija SIA
Tel: +371 - 67 039831

United Kingdom (Northern Ireland)
Roche Products (Ireland) Ltd.
Tel: +44 (0) 1707 366000
More detailed information on this medicine is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/
This leaflet is available in all official 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
Herceptin intravenous is supplied in sterile, preservative-free, apyrogenic single-dose vials.
In order to avoid errors in drug administration 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.
Always store the medicine in the original packaging closed at a temperature of 2°C - 8°C in a
refrigerator.
Follow appropriate aseptic techniques for reconstitution and dilution. Take care to ensure the sterility
of prepared solutions. The medicine does not contain antimicrobial or bacteriostatic preservatives,
therefore aseptic techniques must be adopted.
A vial of Herceptin aseptically reconstituted with sterile water for injections (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 in polyvinyl chloride, polyethylene or polypropylene bags containing 9 mg/ml
(0.9%) sodium chloride solution for injection, the chemical and physical stability of Herceptin has
been demonstrated for up to 30 days at a temperature between 2 °C and 8 °C and 24 hours at a
temperature not exceeding 30°C.
From a microbiological point of view, the reconstituted solution and the Herceptin infusion solution
must be used immediately. If the product is not used immediately, the period and conditions of
storage before and during use are the responsibility of the user, and should not normally exceed 24
hours at a temperature between 2°C and 8°C, unless the dilution has been carried out under
controlled and validated aseptic conditions.
Aseptic preparation, handling and storage:
Aseptic handling of the medicine must be ensured during the preparation of the infusion.
Preparation should:

• Be carried out under aseptic conditions by trained personnel in accordance with good manufacturing
  practice, in particular with respect to aseptic techniques for preparing parenteral medicines.
• Be carried out inside laminar flow hoods or inside biologically safe environments, adopting standard
  precautions for the safe handling of intravenous agents.
• Be followed by adequate storage of the intravenous infusion solution, ensuring the maintenance of
  aseptic conditions.

Follow appropriate aseptic techniques. Each vial of Herceptin is reconstituted with 7.2 ml of water
for injections (not supplied). Avoid the use of other solvents for reconstitution. This yields 7.4 ml of
solution per single dose, containing approximately 21 mg/ml of trastuzumab. An excess volume of
4% ensures aspiration of the programmed dose of 150 mg from the vial.
Herceptin must be handled with care during the reconstitution process.
Excessive foaming caused during reconstitution or shaking of the reconstituted Herceptin solution may
cause problems in terms of the amount of Herceptin that can be withdrawn from the vial.
Instructions for aseptic reconstitution:

• 1) Using a sterile syringe, slowly inject 7.2 ml of water for injections into the vial containing the
  lyophilized Herceptin, directing the jet towards the lyophilized substance.
• 2) Slowly rotate the vial to facilitate reconstitution. DO NOT SHAKE!

Slight foaming during reconstitution is not unusual. Allow the vial to rest in an upright position for
approximately 5 minutes. Once reconstituted, Herceptin appears as a clear solution, from colourless to
pale yellow, with a complete absence of visible particles.
Instructions for aseptic dilution of the reconstituted solution
Determine the volume of solution needed:

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

Volume(ml) = Body Weight(kg) x dose( 4mg/kg for the loading dose or 2mg/kg for the maintenance dose)

21(mg/ml, concentration of reconstituted solution)

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

Volume(ml) = Body Weight(kg) x dose( 8mg/kg for the loading dose or 6mg/kg for the maintenance dose)

21(mg/ml, concentration of reconstituted solution)
Withdraw the required amount of solution from the vial using a sterile needle and syringe and add it to
a polyvinyl chloride, polyethylene or polypropylene infusion bag containing 250 ml of 0.9% sodium
chloride solution. Do not use solutions containing glucose. The bag should be gently inverted to mix
the solution to avoid foaming. Parenteral solutions must be visually inspected for the presence of any
particles or colour change before administration.

Herceptin 600 mg injectable solution in vial

trastuzumab

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:

• 1. What Herceptin is and what it is used for
• 2. What you need to know before Herceptin is administered to you
• 3. How Herceptin is administered
• 4. Possible side effects
• 5. How to store Herceptin
• 6. Contents of the pack and other information

1. What is Herceptin 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 large quantities on the surface of some cancer 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 from the primary tumor) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapeutic drugs paclitaxel or docetaxel as a first-line treatment for metastatic breast cancer, or it may be prescribed alone where 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 with hormone receptors positive (cancer that is sensitive to the presence of 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 ingredient of 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 the cancer or if you need oxygen treatment.

Warnings and precautions
The doctor will carefully monitor you during therapy.

Heart checks
Treatment with Herceptin given alone or with a taxane can have effects on the heart,
especially if you have already used an anthracycline (taxanes and anthracyclines are two other types of medicines
used to treat cancer). The effects can range from moderate to severe and could
cause death. Therefore, your heart function will be checked before, during (every three months) and
after (up to two-five years) treatment with Herceptin. If you develop signs of heart failure (the heart's inability to pump blood), you may undergo more
frequent heart function checks (every six-eight weeks), you may receive treatment for
heart failure or you may have to stop taking Herceptin.

Talk to your doctor, pharmacist or nurse before you are given Herceptin
if:

• you have had heart failure, coronary heart disease, heart valve disease (heart murmurs) or high blood pressure, 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 cancer). 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, especially if you are currently taking a taxane. Herceptin can cause difficulty breathing, especially the first time it is given. This may be more serious if you already suffer from shortness of breath. Very rarely, patients with severe difficulty breathing before treatment have died when they received Herceptin;
• you have received other cancer treatments.

If you receive treatment with 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 in 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 should
tell your doctor, pharmacist or nurse that you have been given Herceptin if you
start taking any new treatment within 7 months of stopping therapy.

Pregnancy

• If you are pregnant, suspect you are pregnant or are planning to become pregnant, tell your doctor, pharmacist or nurse before taking this medicine.
• You must use effective contraceptive measures during treatment with Herceptin and for at least 7 months after the end of treatment. The doctor will discuss with you the risks and benefits of taking Herceptin during pregnancy. In rare cases, a reduction in the amount of fluid (amniotic fluid) surrounding the developing baby in the womb has been observed in pregnant women treated with Herceptin. This condition could harm the baby in the womb and has been associated with incomplete lung maturation that has caused fetal death.

Breast-feeding
Do not breast-feed during treatment with Herceptin and for 7 months after the administration
of the last dose of Herceptin, as Herceptin can pass into breast milk.
Ask your doctor, pharmacist or nurse before taking any medicine.

Driving and using machines
Herceptin 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 use machines until these symptoms disappear.

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, the doctor will determine the amount of HER2 present in the tumor. Only patients with large amounts of HER2 will be treated with Herceptin. Herceptin must be administered exclusively by a doctor or a nurse.
There are two different types (formulations) of Herceptin:

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

The doctor may consider switching from Herceptin intravenous formulation treatment to Herceptin subcutaneous formulation treatment (and vice versa), if appropriate for your condition.
In order to avoid medication errors, it is important to check the vial labels to ensure that the medicine you are preparing and administering is Herceptin (trastuzumab) and not another medicine based on trastuzumab (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
The recommended dose is 600 mg. Herceptin is administered via subcutaneous injection (under the skin) in 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 in areas where the skin is red, bruised, sensitive or hardened.
If you are taking other medications for subcutaneous use during treatment with Herceptin, the injection of these latter should be done at another site.
Herceptin must not be mixed or diluted with other products.

If you stop taking Herceptin
Do not stop using this medicine without first talking to your doctor. Take all your doses regularly every three weeks. This helps the medicine to work best.
It may take up to 7 months for Herceptin to be eliminated from your body.
Therefore, the doctor may decide to continue monitoring cardiac function even after you have finished treatment.
If you have any doubts about the use of this medicine, please contact your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience 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,
difficulty breathing, high or low blood pressure, irregular heartbeat (palpitations, fast or irregular
heartbeat), swelling of the face or lips, skin rashes and feeling tired. Some of these symptoms can be serious and some patients have died (see
section “Warnings and precautions”).
During administration, for 30 minutes after the first administration and for 15 minutes after
other administrations, the doctor or nurse will monitor for the onset of side effects.

Serious side effects
Other 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 it has ended, heart problems may occur which could be serious. These include weakening of the heart muscle which can lead to heart failure, inflammation of the lining of the heart and irregular heartbeat. These can cause symptoms such as shortness of breath (even at night), cough, fluid retention (swelling) in the legs or arms and palpitations (fast or irregular heartbeat) (see section 2 Heart monitoring).

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

• Tumour lysis syndrome (a group of metabolic complications that occur after cancer 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 (fast or slow heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet.

If you experience any of the above symptoms after you have finished treatment with Herceptin,
you should see your doctor and tell them about your previous treatment with Herceptin.
There are two different types (formulations) of Herceptin:

• one to be administered by infusion into a vein 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 heart events leading to hospitalisation were more frequent with the subcutaneous formulation. In addition, a greater number of local reactions at the injection site and increases in blood pressure were observed. Other side effects were 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 blood cell 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
• difficulty sleeping (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 skin
• throat infections • dry eyes
• bladder and skin infections • sweating
• fatigue and malaise
• breast inflammation • anxiety
• liver inflammation • depression
• kidney problems
• increased muscle tone or tension (hypertonia)
• asthma
• lung infection
• arm and/or leg pain • 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:

• hearing loss
• skin rash with blisters
• wheezing
• inflammation or scarring in the lungs (fibrosis)

Rare side effects of Herceptin: may affect up to 1 in 1000:

• • jaundice
• anaphylactic reactions

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

• abnormal blood clotting or insufficient clotting
• high levels of potassium
• swelling or bleeding behind the eyes
• shock
• abnormal heart rhythm
• respiratory distress
• acute 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 fluid around the baby in the womb
• insufficient development of the baby's lungs in the womb
• abnormal development of the baby's kidneys in the womb Some of the side effects that occur may be due to breast cancer. If you receive 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, contact your doctor, pharmacist or
nurse.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or
nurse. You can also report side effects directly through 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 sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the
vial label after “Expiry /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 must be used immediately.
Do not use this medicine if you notice any particles or a change in colour before
administration.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Herceptin contains

• The active substance is trastuzumab. One 5 ml vial contains 600 mg of trastuzumab.
• The other ingredients are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine monohydrate hydrochloride, α,α-trehalose dihydrate, L-methionine, polysorbate 20, water for injections. Description of Herceptin and contents of the pack

Herceptin is an injectable solution that is supplied in a glass vial with a butyl rubber stopper
containing 5 ml (600 mg) of trastuzumab. The solution is from clear to opalescent, from colourless to
pale yellow.
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 on this medicinal product, 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

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

България
Рош България ЕООД
Тел: +359 2 474 5444

Luxembourg/Luxemburg
(Voir/siehe Belgique/Belgien)

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

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

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

Malta
(See Ireland)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Latvija
Roche Latvija SIA
Tel: +371 - 67 039831

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

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.