trastuzumab: package leaflet

Herceptin contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates their growth. When Herceptin binds to HER2 it stops the growth of such cells and causes them to die.
Your doctor may prescribe Herceptin for the treatment of breast and gastric cancer when:

You have early breast cancer, with high levels of a protein called HER2.

You have metastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapy medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful. It is also used in combination with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex hormones).

You have metastatic gastric cancer with high levels of HER2, when it is in combination with the other cancer medicines capecitabine or 5-flououracil and cisplatin.

Do not use Herceptin if:
 you are allergic to trastuzumab, 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 cancer or if you need oxygen treatment.
Warnings and precautions
Your doctor will closely supervise your therapy.

Heart checks
Treatment with Herceptin alone or with a taxane may affect the heart, especially if you have ever used an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer).
The effects may be moderate to severe and could cause death. Therefore, your heart function will be checked before, during (every three months) and after (up to two to five years) treatment with Herceptin. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your heart function may be checked more frequently (every six to eight weeks), you may receive treatment for heart failure or you may have to stop Herceptin treatment.
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), high blood pressure, taken any high blood pressure medicine or are currently taking any high blood pressure medicine.
 you have ever had or are currently using a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle and increase the risk of heart problems with Herceptin.
 you suffer from breathlessness, especially if you are currently using a taxane. Herceptin can cause breathing difficulties, especially when it is first given. This could be more serious if you are already breathless. Very rarely, patients with severe breathing difficulties before treatment have died when they were given Herceptin.
 you have ever had any other treatment for cancer.
If you receive Herceptin with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient information leaflets for these products.
Children and adolescents
Herceptin is not recommended for anyone under the age of 18 years.
Other medicines and Herceptin
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or may take any other medicines.
It may take up to 7 months for Herceptin to be removed from the body. Therefore you should tell your doctor, pharmacist or nurse that you have had Herceptin if you start any new medicine in the 7 months after stopping treatment.
Pregnancy and breast-feeding
 If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before taking this medicine.
 You should use effective contraception during treatment with Herceptin and for at least 7 months after treatment has ended.
 Your doctor will advise you of the risks and benefits of taking Herceptin during pregnancy. In rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby within the womb has been observed in pregnant women receiving Herceptin. This condition may be harmful to your baby in the womb and has been associated with the lungs not developing fully resulting in foetal death.
Do not breast-feed your baby during Herceptin therapy and for 7 months after the last dose of Herceptin as Herceptin may pass to your baby through your breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Herceptin may affect your ability to drive a car or operate machines.If during treatment you experience symptoms, such as dizziness, sleepiness, chills or fever, you should not drive or use machines until these symptoms disappear.
Herceptin contains polysorbate
Herceptin contains 0.6 mg of polysorbate 20 in each 150mg vial, which is equivalent to 0.083mg/mL (after reconstitution with 7.2mL sterile water for injection). Polysorbates may cause allergic reactions.
Tell your doctor if you have any known allergies.

Before starting the treatment your doctor will determine the amount of HER2 in your tumour. Only patients with a large amount of HER2 will be treated with Herceptin. Herceptin should only be given by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is right for you. The dose of Herceptin depends on your body weight.
Two different types (formulations) of Herceptin exist:
- one is given as an infusion into a vein (intravenous infusion)
- the other is given as an injection under the skin (subcutaneous injection).
It is important to check the product labels to ensure that the correct formulation is being given as prescribed. Herceptin intravenous formulation is not for subcutaneous use and should be given as an intravenous infusion only.
Your doctor may consider switching your Herceptin intravenous treatment to Herceptin subcutaneous treatment (and vice versa) if considered appropriate for you.
Herceptin intravenous formulation is given as an intravenous infusion (“drip”) directly into your veins.
The first dose of your treatment is given over 90 minutes and you will be observed by a health professional while it is being given in case you have any side effects. If the first dose is well tolerated the next doses may be given over 30 minutes (see section 2 under “Warnings and precautions”). The number of infusions you receive will depend on how you respond to the treatment. Your doctor will discuss this with you.
In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Herceptin (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
For early breast cancer, metastatic breast cancer and metastatic gastric cancer, Herceptin is given every 3 weeks. Herceptin may also be given once a week for metastatic breast cancer.
If you stop using Herceptin
Do not stop using this medicine without talking to your doctor first. All doses should be taken at the right time every week or every three weeks (depending on your dosing schedule). This helps your medicine work as well as it can.
It may take up to 7 months for Herceptin to be removed from your body. Therefore your doctor may decide to continue to check your heart functions, even after you finish treatment.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, Herceptin can cause side effects, although not everybody gets them. Some of these side effects may be serious and may lead to hospitalisation.

During a Herceptin infusion, chills, fever and other flu like symptoms may occur. These are very common (may affect more than 1 in 10 people). Other infusion-related symptoms are: feeling sick (nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disturbances (palpitations, heart fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these symptoms can be serious and some patients have died (see section 2 under “Warnings and precautions”).
These effects mainly occur with the first intravenous infusion (“drip” into your vein) and during the first few hours after the start of the infusion. They are usually temporary. You will be observed by a health care professional during the infusion and for at least six hours after the start of the first infusion and for two hours after the start of other infusions. If you develop a reaction, they will slow down or stop the infusion and may give you treatment to counteract the side effects. The infusion may be continued after the symptoms improve.
Occasionally, symptoms start later than six hours after the infusion begins. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then get worse later.
Serious side effects
Other side effects can occur at any time during treatment with Herceptin, not just related to an infusion. Tell a doctor or nurse straight away, if you notice any of the following side effects:

Heart problems can sometimes occur during treatment and occasionally after treatment has stopped and can be serious. They include weakening of the heart muscle possibly leading to heart failure, inflammation of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as breathlessness (including breathlessness at night), cough, fluid retention (swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see section 2.
Heart checks).
Your doctor will monitor your heart regularly during and after treatment but you should tell your doctor immediately if you notice any of the above symptoms.

Tumour lysis syndrome (a group of metabolic complications occurring after cancer treatment characterized by high blood levels of potassium and phosphate, and low blood levels of calcium).
Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion), heart problems (fluttering of the heart or a faster or slower heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet If you experience any of the above symptoms when your treatment with Herceptin has finished, you should see your doctor and tell them that you have previously been treated with Herceptin.
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 counts of red blood cells and white blood cells (which help fight infection) sometimes with fever  muscle pain  conjunctivitis  watery eyes

 nose bleeds
 runny nose
 hair loss
 tremor
 hot flush
 dizziness
 nail disorders
 weight loss
 loss of appetite
 inability to sleep (insomnia)
 altered taste
 low platelet count
 bruising
 numbness or tingling of the fingers and toes, which occasionally may extend to the rest of the limb  redness, swelling or sores in your mouth and/or throat  pain, swelling, redness or tingling of hands and/or feet  breathlessness  headache  cough  vomiting  nausea Common side effects of Herceptin: may affect up to 1 in 10 people  allergic reactions  throat infections  bladder and skin infections  inflammation of the breast  inflammation of the liver  kidney disorders  increased muscle tone or tension (hypertonia)  pain in the arms and/or legs  itchy rash  sleepiness (somnolence)  haemorrhoids  itchiness  dry mouth and skin  dry eyes  sweating  feeling weak and unwell  anxiety  depression  asthma  infection of lungs  lung disorders  back pain  neck pain  bone pain  acne

 leg cramps
Uncommon side effects of Herceptin: may affect up to 1 in 100 people:
 deafness
 bumpy rash
 wheezing
 inflammation or scarring of the lungs
Rare side effects of Herceptin: may affect up to 1 in 1000 people
 jaundice
 anaphylactic reactions
Other side effects that have been reported with Herceptin use: frequency cannot be estimated from the available data  abnormal or impaired blood clotting  high potassium levels  swelling or bleeding at the back of the eyes  shock  abnormal heart rhythm  respiratory distress  respiratory failure  acute accumulation of fluid in the lungs  acute narrowing of the airways  abnormally low oxygen levels in the blood  difficulty in breathing when lying flat  liver damage  swelling of the face, lips and throat  kidney failure  abnormally low levels of fluid around baby in womb  failure of the lungs of the baby to develop in the womb  abnormal development of the kidneys of the baby in the womb Some of the side-effects you experience may be due to your underlying cancer. If you receive Herceptin in combination with chemotherapy, some of them may also be due to the chemotherapy.
If you get any side effects, talk to your doctor, pharmacist or nurse.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Herceptin will be stored by the health 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 which is stated on the outer carton and on the vial label after EXP. The expiry date refers to the last day of that month.
The unopened vial should be stored in a refrigerator (2°C – 8°C).

Do not freeze the reconstituted solution.
Infusion solutions should be used immediately after dilution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user, and would not normally be longer than 24 hours at 2°C – 8°C.
Do not use Herceptin if you notice any particulate matter or discoloration prior to administration.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Herceptin contains

The active substance is trastuzumab. Each vial contains 150 mg trastuzumab that has to be dissolved in 7.2 mL of water for injection. The resulting solution contains approximately 21 mg/mL trastuzumab.

The other ingredient(s) are histidine hydrochloride monohydrate, histidine, α,α-trehalose dihydrate, polysorbate 20 (E432) (see section 2 “Herceptin contains polysorbate”).
What Herceptin looks like and contents of the pack
Herceptin is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass vial with a rubber stopper containing 150 mg of trastuzumab. The powder is a white to pale yellow pellet. Each carton contains 1 vial of powder.
Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien,
Luxembourg/Luxemburg
N.V. Roche S.A.
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
Latvija
Roche Latvija SIA
Tel: +371 - 67 039831
България
Рош България ЕООД
Тел: +359 2 474 5444
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111
Magyarország
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500
Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99
Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438050
Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140
Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00
Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739
Ελλάδα, Kύπρος
Roche (Hellas) A.E.
Ελλάδα
Τηλ: +30 210 61 66 100
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Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88
España
Roche Farma S.A.
Tel: +34 - 91 324 81 00
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Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
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Roche
Tél: +33 (0)1 47 61 40 00
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Roche România S.R.L.
Tel: +40 21 206 47 01
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Roche d.o.o.
Tel: + 385 1 47 22 333
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Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00
Ireland, Malta
Roche Products (Ireland) Ltd.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
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Roche Slovensko, s.r.o.
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Roche Pharmaceuticals A/S c/o Icepharma hf
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Sverige
Roche AB
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This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.
The following information is intended for medical or healthcare professionals only Herceptin IV is provided in sterile, preservative-free, non-pyrogenic, single use vials.
In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Herceptin (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
Always keep this medicine in the closed original pack at a temperature of 2ºC – 8 ºC in a refrigerator.
Appropriate aseptic technique should be used for reconstitution and dilution procedures. Care must be taken to ensure the sterility of prepared solutions. Since the medicinal product does not contain any anti-microbial preservative or bacteriostatic agents, aseptic technique must be observed.
A vial of Herceptin aseptically reconstituted with sterile water for injections (not supplied) is chemically and physically stable for 48 hours at 2ºC – 8 ºC after reconstitution and must not be frozen.
After aseptic dilution in polyvinylchloride, polyethylene or polypropylene bags containing sodium chloride 9 mg/mL (0.9 %) solution for injection, chemical and physical stability of Herceptin has been demonstrated for up to 30 days at 2 oC – 8oC, and 24 hours at temperatures not exceeding 30°C.
From a microbiological point of view, the reconstituted solution and Herceptin infusion solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user, and would not normally be longer than 24 hours at 2°C to 8°C, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.
Aseptic preparation, handling and storage:
Aseptic handling must be ensured when preparing the infusion. Preparation should be:
 performed under aseptic conditions by trained personnel in accordance with good practice rules especially with respect to the aseptic preparation of parenteral products.
 prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
followed by adequate storage of the prepared solution for intravenous infusion to ensure maintenance of the aseptic conditions Each vial of Herceptin is reconstituted with 7.2 mL of water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields a 7.4 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab. A volume overage of 4 % ensures that the labelled dose of 150 mg can be withdrawn from each vial.
Herceptin should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted Herceptin may result in problems with 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 in the vial containing the lyophilised Herceptin, directing the stream into the lyophilised cake.
2) Swirl vial gently to aid reconstitution. DO NOT SHAKE!
Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed for approximately 5 minutes. The reconstituted Herceptin results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.

Instructions for aseptic dilution of the reconstituted solution
Determine the volume of the solution required:
based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose of 2 mg trastuzumab/kg body weight:
Volume (mL) = Body weight (kg) x dose (4 mg/kg for loading or 2 mg/kg for maintenance) 21 (mg/mL, concentration of reconstituted solution) based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly dose of 6 mg trastuzumab/kg body weight:
Volume (mL) = Body weight (kg) x dose (8 mg/kg for loading or 6 mg/kg for maintenance) 21 (mg/mL, concentration of reconstituted solution) The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to a polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 mL of 0.9 % sodium chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to mix the solution in order to avoid foaming. Parenteral solutions should be inspected visually for particulates and discoloration prior to administration.

Herceptin contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates their growth. When Herceptin binds to HER2 it stops the growth of such cells and causes them to die.
Your doctor may prescribe Herceptin for the treatment of breast cancer when:

You have early breast cancer, with high levels of a protein called HER2.

You have metastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Herceptin may be prescribed in combination with the chemotherapy medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful. It is also used in combination with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex hormones).

Do not use Herceptin if:
 you are allergic to trastuzumab (the active substance of Herceptin), murine (mouse) proteins, or any of the other ingredients of this medicine (listed in section 6).
 you have severe breathing problems at rest due to your cancer or if you need oxygen treatment.
Warnings and precautions
Your doctor will closely supervise your therapy.
Heart checks
Treatment with Herceptin alone or with a taxane may affect the heart, especially if you have ever used an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer). The effects may be moderate to severe and could cause death. Therefore, your heart function will be checked before, during (every three months) and after (up to two to five years) treatment with Herceptin. If you develop any signs of heart failure (i.e. inadequate pumping of blood by the heart),

your heart function may be checked more frequently (every six to eight weeks), you may receive treatment for heart failure or you may have to stop Herceptin treatment.
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), high blood pressure, taken any high blood pressure medicine or are currently taking any high blood pressure medicine.
 you have ever had or are currently using a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle and increase the risk of heart problems with Herceptin.
 you suffer from breathlessness, especially if you are currently using a taxane. Herceptin can cause breathing difficulties, especially when it is first given. This could be more serious if you are already breathless. Very rarely, patients with severe breathing difficulties before treatment have died when they were given Herceptin.
 you have ever had any other treatment for cancer.
If you receive Herceptin with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, carboplatin or cisplatin you should also read the patient information leaflets for these products.
Children and adolescents
Herceptin is not recommended for anyone under the age of 18 years.
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 removed from the body. Therefore you should tell your doctor, pharmacist or nurse that you have had Herceptin if you start any new medicine in the 7 months after stopping treatment.
Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are planning to have a baby, you must tell your doctor, pharmacist or nurse before taking this medicine.

You should use effective contraception during treatment with Herceptin and for at least 7 months after treatment has ended.
Your doctor will advise you of the risks and benefits of taking Herceptin during pregnancy. In rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby within the womb has been observed in pregnant women receiving Herceptin. This condition may be harmful to your baby in the womb and has been associated with the lungs not developing fully resulting in foetal death.
Do not breast-feed your baby during Herceptin therapy and for 7 months after the last dose of Herceptin as Herceptin may pass to your baby through your 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 a car or operate machines. If during treatment, you experience symptoms, such as dizziness, sleepiness, chills or fever, you should not drive or use machines until these symptoms disappear.
Herceptin contains sodium
Herceptin contains less than 1 mmol of sodium (23 mg) per dose, that is to say essentially sodium-free.

Herceptin contains polysorbate
Herceptin contains 2.0 mg of polysorbate 20 in each 600mg/5mL vial, which is equivalent to 0.4mg/mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Before starting the treatment your doctor will determine the amount of HER2 in your tumour. Only patients with a large amount of HER2 will be treated with Herceptin. Herceptin should only be given by a doctor or nurse.
Two different types (formulations) of Herceptin exist:
 one is given as an infusion into a vein (intravenous infusion)
 the other is given as an injection under the skin (subcutaneous injection).
It is important to check the product labels to ensure that the correct formulation is being given as prescribed. Herceptin subcutaneous fixed dose formulation is not for intravenous use and should be given as a subcutaneous injection only.
Your doctor may consider switching your Herceptin intravenous treatment to Herceptin subcutaneous treatment (and vice versa) if considered appropriate for you.
In order to prevent medication errors it is also important to check the vial labels to ensure that the medicine being prepared and given is Herceptin (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
The recommended dose is 600 mg. Herceptin is given as a subcutaneous injection (under the skin) over 2 to 5 minutes every three weeks.
The injection site should be alternated between the left and right thigh. New injections should be given at least 2.5 cm away from an old site. No injection should be given into areas where the skin is red, bruised, tender or hard.
If other medicines for subcutaneous use are used during the treatment course with Herceptin, a different injection site should be used.
Herceptin should not be mixed or diluted with other products.
If you stop using Herceptin
Do not stop using this medicine without talking to your doctor first. All doses should be taken at the right time every three weeks. This helps your medicine work as well as it can.
It may take up to 7 months for Herceptin to be removed from your body. Therefore your doctor may decide to continue to check your heart functions, even after you finish treatment.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these side effects may be serious and may lead to hospitalisation.
During treatment with Herceptin, chills, fever and other flu like symptoms may occur. These are very common (may affect more than 1 in 10 people). Other symptoms are: feeling sick (nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disturbances (palpitations, heart fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these symptoms can be serious and some patients have died (see the section “Warnings and precautions”).

Your doctor or nurse will check for side effects during the administration and for 30 minutes after the first administration and for 15 minutes after other administrations.
Serious side effects
Other side effects can occur at any time during treatment with Herceptin. Tell a doctor or nurse straight away, if you notice any of the following side effects:

Heart problems can sometimes occur during treatment and occasionally after treatment has stopped and can be serious. They include weakening of the heart muscle possibly leading to heart failure, inflammation of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as breathlessness (including breathlessness at night), cough, fluid retention (swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see section 2.
Heart checks).
Your doctor will monitor your heart regularly during and after treatment but you should tell your doctor immediately if you notice any of the above symptoms.

Tumour lysis syndrome (a group of metabolic complications occurring after cancer treatment characterized by high blood levels of potassium and phosphate, and low blood levels of calcium).
Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion), heart problems (fluttering of the heart or a faster or slower heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet If you experience any of the above symptoms when your treatment with Herceptin has finished, you should see your doctor and tell them that you have previously been treated with Herceptin.
Two different types (formulations) of Herceptin exist:
 one is given as an infusion into a vein over 30 to 90 minutes
 the other is given as a subcutaneous injection over 2 to 5 minutes.
In the clinical study comparing these two formulations, infections and cardiac events leading to hospitalisation were more frequent with the subcutaneous formulation. There were also more local reactions at the site of injection and more increases in blood pressure. 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 counts of red blood cells and white blood cells (which help fight infection) sometimes with fever  muscle pain  conjunctivitis  watery eyes  nose bleeds  runny nose  hair loss  tremor  hot flush  dizziness

 nail disorders
 weight loss
 loss of appetite
 inability to sleep (insomnia)
 altered taste
 low platelet count
 bruising
 numbness or tingling of the fingers and toes, which occasionally may extend to the rest of the limb  redness, swelling or sores in your mouth and/or throat  pain, swelling, redness or tingling of hands and/or feet  breathlessness  headache  cough  vomiting  nausea Common side effects of Herceptin: may affect up to 1 in 10 people  allergic reactions  throat infections  bladder and skin infections  inflammation of the breast  inflammation of the liver  kidney disorders  increased muscle tone or tension (hypertonia)  pain in the arms and/or legs  itchy rash  sleepiness (somnolence)  haemorrhoids  itchiness  dry mouth and skin  dry eyes  sweating  feeling weak and unwell  anxiety  depression  asthma  infection of lungs  lung disorders  back pain  neck pain  bone pain  acne  leg cramps Uncommon side effects of Herceptin: may affect up to 1 in 100 people  deafness  bumpy rash  wheezing  inflammation or scarring of the lungs

Rare side effects of Herceptin: may affect up to 1 in 1,000 people
 jaundice
 anaphylactic reactions
Other side effects that have been reported with Herceptin use: frequency cannot be estimated from the available data  abnormal or impaired blood clotting  high potassium levels  swelling or bleeding at the back of the eyes  shock  abnormal heart rhythm  respiratory distress  respiratory failure  acute accumulation of fluid in the lungs  acute narrowing of the airways  abnormally low oxygen levels in the blood  difficulty in breathing when lying flat  liver damage  swelling of the face, lips and throat  kidney failure  abnormally low levels of fluid around baby in womb  failure of the lungs of the baby to develop in the womb  abnormal development of the kidneys of the baby in the womb Some of the side effects you experience may be due to your underlying breast cancer. If you receive Herceptin in combination with chemotherapy, some of them may also be due to the chemotherapy.
If you get any side effects, talk to your doctor, pharmacist or nurse.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton and on the vial label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Keep the vial in the outer carton to protect from light.
Do not freeze.
Upon opening of the vial, the solution should be used immediately.
Do not use this medicine if you notice any particulate matter or discoloration prior to administration.

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Herceptin contains

The active substance is trastuzumab. One vial of 5 mL contains 600 mg of trastuzumab.

The other ingredients are recombinant human hyaluronidase (rHuPH20), histidine hydrochloride monohydrate, histidine, α,α-trehalose dihydrate, methionine, polysorbate 20 (E432), water for injections (see section 2 “Herceptin contains polysorbate”).
What Herceptin looks like and contents of the pack
Herceptin is a solution for injection that is supplied in a glass vial with a butyl rubber stopper containing 5 mL (600 mg) of trastuzumab. The solution is clear to opalescent and colourless to yellowish.
Each carton 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 any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien,
Luxembourg/Luxemburg
N.V. Roche S.A.
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
Latvija
Roche Latvija SIA
Tel: +371 - 67 039831
България
Рош България ЕООД
Тел: +359 2 474 5444
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799
Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111
Magyarország
Roche (Magyarország) Kft.
Tel: +36 -1 279 4500
Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99
Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438050

Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140
Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00
Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739
Ελλάδα, Kύπρος
Roche (Hellas) A.E.
Ελλάδα
Τηλ: +30 210 61 66 100
Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88
España
Roche Farma S.A.
Tel: +34 - 91 324 81 00
Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
France
Roche
Tél: +33 (0)1 47 61 40 00
România
Roche România S.R.L.
Tel: +40 21 206 47 01
Hrvatska
Roche d.o.o.
Tel: + 385 1 47 22 333
Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00
Ireland, Malta
Roche Products (Ireland) Ltd.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201
Ísland
Roche Pharmaceuticals A/S c/o Icepharma hf
Sími: +354 540 8000
Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500
Italia
Roche S.p.A.
Tel: +39 - 039 2471
Sverige
Roche AB
Tel: +46 (0) 8 726 1200
This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

Tuznue contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates their growth. When Tuznue binds to HER2 it stops the growth of such cells and causes them to die.

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

• you have early breast cancer, with high levels of a protein called HER2
• you have metastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Tuznue may be prescribed in combination with the chemotherapy medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful. It is also used in combination with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex hormones).
• you have metastatic gastric cancer with high levels of HER2, when it is in combination with the other cancer medicines capecitabine or 5-fluorouracil and cisplatin.

Do not use Tuznue if

• you are allergic to trastuzumab, 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 cancer or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely supervise your therapy.

Heart checks

Treatment with Tuznue alone or with a taxane may affect the heart, especially if you have ever used an anthracycline (taxanes or anthracyclines are two kinds of medicine used to treat cancer). The effects may be moderate to severe and could cause death. Therefore, your heart function will be checked before, during (every three months) and after (up to two to five years) treatment with Tuznue. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your heart function may be checked more frequently (every six to eight weeks), you may receive treatment for heart failure or you may have to stop Tuznue treatment.

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

• you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, taken any high blood pressure medicine or are currently taking any high blood pressure medicine.
• you have ever had or are currently using a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle and increase the risk of heart problems with Tuznue.
• you suffer from breathlessness, especially if you are currently using a taxane. Tuznue can cause breathing difficulties, especially when it is first given. This could be more serious if you are already breathless. Very rarely, patients with severe breathing difficulties before treatment have died when they were given Tuznue.
• you have ever had any other treatment for cancer.

If you receive Tuznue with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin you should also read the patient information leaflets for these products.

Children and adolescents

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

Other medicines and Tuznue

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

It may take up to 7 months for Tuznue to be removed from the body. Therefore, you should tell your doctor, pharmacist or nurse that you have had Tuznue if you start any new medicine in the 7 months after stopping treatment.

Pregnancy and breast feeding

• If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before taking this medicine.
• You should use effective contraception during treatment with Tuznue and for at least 7 months after treatment has ended.
• Your doctor will advise you of the risks and benefits of taking Tuznue during pregnancy. In rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby within the womb has been observed in pregnant women receiving trastuzumab. This condition may be harmful to your baby in the womb and has been associated with the lungs not developing fully

resulting in foetal death.

Do not breast-feed your baby during Tuznue therapy and for 7 months after the last dose of Tuznue as Tuznue may pass to your baby through your breast milk.

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

Driving and using machines

Tuznue may affect your ability to drive a car or operate machines. If during treatment you experience symptoms, such as dizziness, sleepiness, chills or fever, you should not drive or use machines until these symptoms disappear.

Tuznue contains polysorbate
Tuznue contains 0.6 mg of polysorbate 20 in each 150 mg vial, which is equivalent to 0.083 mg/mL (after reconstitution with 7.2 mL sterile water for injection). Polysorbates may cause allergic reactions.
Tell your doctor if you have any known allergies.

Tuznue contains 1.7 mg of polysorbate 20 in each 420 mg vial, which is equivalent to 0.085 mg/mL (after reconstitution with 20 mL sterile water for injection). Polysorbates may cause allergic reactions.
Tell your doctor if you have any known allergies.

Before starting the treatment, your doctor will determine the amount of HER2 in your tumour. Only patients with a large amount of HER2 will be treated with Tuznue. This medicine should only be given by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen that is right for you. The dose of Tuznue depends on your body weight.

Tuznue is given as an infusion into a vein (intravenous infusion, “drip”). This intravenous formulation is not for subcutaneous use and should be given as an intravenous infusion only.

The first dose of your treatment is given over 90 minutes and you will be observed by a health professional while it is being given in case you have any side effects (see section 2 under “Warnings and precautions”). If the first dose is well tolerated the next doses may be given over 30 minutes. The number of infusions you receive will depend on how you will respond to the treatment. Your doctor will discuss this with you.

In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Tuznue (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

Tuznue is given every 3 weeks for early breast cancer, metastatic breast cancer and metastatic gastric cancer. This medicine may also be given once a week for metastatic breast cancer.

If you stop using Tuznue

Do not stop using this medicine without talking to your doctor first. All doses should be taken at the right time every week or every three weeks (depending on your dosing schedule). This helps your medicine work as well as it can.

It may take up to 7 months for this medicine to be removed from your body. Therefore, your doctor may decide to continue to check your heart functions, even after you finish treatment.

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

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these side effects may be serious and may lead to hospitalisation.

During infusion of Tuznue, chills, fever and other flu like symptoms may occur. These are very common (may affect more than 1 in 10 people). Other infusion-related symptoms are: feeling sick (nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disturbances (palpitations, heart fluttering or irregular heart beat), swelling of the face and lips, rash and feeling tired. Some of these symptoms can be serious and some patients have died (see section 2 under “Warnings and precautions”).

These effects mainly occur with the first intravenous infusion (“drip” into your vein) and during the first few hours after the start of the infusion. They are usually temporary. You will be observed by a healthcare professional during the infusion and for at least 6 hours after the start of the first infusion and for 2 hours after the start of other infusions. If you develop a reaction, they will slow down or stop the infusion and may give you treatment to counteract the side effects. The infusion may be continued after the symptoms improve.

Occasionally, symptoms start later than six hours after the infusion begins. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then get worse later.

Serious side effects

Other side effects can occur at any time during treatment with this medicine, not just related to an infusion. Tell a doctor or nurse straight away, if you notice any of the following side effects:

- Heart problems can sometimes occur during treatment and occasionally after treatment has stopped and can be serious. They include weakening of the heart muscle possibly leading to heart failure, inflammation of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as breathlessness (including breathlessness at night), cough, fluid retention (swelling) in the legs or arms, palpitations (heart fluttering or irregular heart beat) (see section 2.
Heart checks).

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

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

If you experience any of the above symptoms when your treatment has finished, you should see your doctor and tell them that you have previously been treated with Tuznue.

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

• infections
• diarrhoea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rashes
• chest pain

• abdominal pain
• joint pain
• low counts of red blood cells and white blood cells (which help fight infection) sometimes with fever
• muscle pain
• conjunctivitis
• watery eyes
• nose bleeds
• runny nose
• hair loss
• tremor
• hot flush
• dizziness
• nail disorders
• weight loss
• loss of appetite
• inability to sleep (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling of the fingers and toes, which occasionally may extend to the rest of the limb
• redness, swelling or sores in your mouth and/or throat
• pain, swelling, redness or tingling of hands and/or feet
• breathlessness
• headache
• cough
• vomiting
• nausea

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

• allergic reactions
• throat infections
• bladder and skin infections
• inflammation of the breast
• inflammation of the liver
• kidney disorders
• increased muscle tone or tension (hypertonia)
• pain in the arms and/or legs
• itchy rash
• sleepiness (somnolence)
• haemorrhoids
• itchiness
• dry mouth and skin
• dry eyes
• sweating
• feeling weak and unwell
• anxiety
• depression
• asthma
• infection of lungs
• lung disorders
• back pain

• neck pain
• bone pain
• acne
• leg cramps

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

• deafness
• bumpy rash
• wheezing
• inflammation or scarring of the lungs

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

• jaundice
• anaphylactic reactions

Other side effects that have been reported (frequency cannot be estimated from the available data):

• abnormal or impaired blood clotting
• high potassium levels
• swelling or bleeding at the back of the eyes
• shock
• abnormal heart rhythm
• respiratory distress
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low oxygen levels in the blood
• difficulty in breathing when lying flat
• liver damage
• swelling of the face, lips and throat
• kidney failure
• abnormally low levels of fluid around baby in womb
• failure of lungs of the baby to develop in the womb
• abnormal development of the kidneys of the baby in the womb

Some of the side effects you experience may be due to your underlying cancer. If you receive Tuznue in combination with chemotherapy, some of them may also be due to the chemotherapy.

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

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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

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

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

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

Infusion solutions should be used immediately after dilution. Do not use this medicine if you notice any particulate matter or discolouration prior to administration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Tuznue contains

- The active substance is trastuzumab. Each vial contains either:
• 150 mg trastuzumab that has to be dissolved in 7.2 mL of sterile water for injections, or • 420 mg trastuzumab that has to be dissolved in 20 mL of sterile water for injections.
The resulting solution contains approximately 21 mg/mL trastuzumab.

• The other ingredient(s) are histidine hydrochloride monohydrate, histidine, α, α-trehalose dihydrate and polysorbate 20 (E432). (see section 2 “Tuznue contains polysorbate”)

What Tuznue looks like and contents of the pack

Tuznue is a powder for concentrate for solution for infusion, which is supplied in a glass vial with a rubber stopper containing either 150 mg or 420 mg of trastuzumab. The powder is a white to pale yellow cake.

Each carton contains 1 vial of powder.

Marketing Authorisation Holder

Prestige Biopharma Belgium BVBA
Terhulpensesteenweg 449
3090 Overijse, Belgium

Manufacturer(s)

Laboratorio Reig Jofre, S.A.
Gran Capitán, 10, Sant Joan Despí,
08970 Barcelona, Spain

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

België/Belgique/Belgien
Teva Pharma Belgium N.V./S.A./AG
Tél/Tel: +32 38207373

Lietuva
UAB Teva Baltics
Tel: +370 52660203

България
Тева Фарма ЕАД
Teл.: +359 24899585

Luxembourg/Luxemburg
Teva Pharma Belgium N.V./S.A./AG
Tél/Tel: +32 38207373

Česká republika
Teva Pharmaceuticals CR, s.r.o.
Tel: +420 251007111
Magyarország
Teva Gyógyszergyár Zrt.
Tel.: +36 12886400

Danmark
Teva Denmark A/S
Tlf.: +45 44985511

Malta
TEVA HELLAS Α.Ε.
il-Greċja
Tel: +30 2118805000

Deutschland ratiopharm GmbH
Tel: +49 (0) 73140202
Nederland
Teva Nederland B.V.
Tel: +31 8000228400

Eesti
UAB Teva Baltics Eesti filiaal
Tel: +372 6610801

Norge
Teva Norway AS
Tlf: +47 66775590

Ελλάδα
TEVA HELLAS Α.Ε.
Τηλ: +30 2118805000

Österreich ratiopharm Arzneimittel Vertriebs-GmbH
Tel: +43 1970070

España
Teva Pharma, S.L.U.
Tel: +34 913873280
Polska
Teva Pharmaceuticals Polska Sp. z o.o.
Tel.: +48 223459300

France
Teva Santé
Tél: +33 155917800

Portugal
Teva Pharma - Produtos Farmacêuticos, Lda.
Tel: +351 214767550

Hrvatska
Pliva Hrvatska d.o.o.
Tel: +385 13720000

România
Teva Pharmaceuticals S.R.L.
Tel: +40 212306524

Ireland
Teva Pharmaceuticals Ireland
Tel: +44 2075407117

Slovenija
Pliva Ljubljana d.o.o.
Tel: +386 15890390

Ísland
Teva Pharma Iceland ehf.
Sími: +354 5503300

Slovenská republika
TEVA Pharmaceuticals Slovakia s.r.o.
Tel: +421 257267911

Italia
Teva Italia S.r.l.
Tel: +39 028917981

Suomi/Finland
Teva Finland Oy
Puh/Tel: +358 201805900

Κύπρος
TEVA HELLAS Α.Ε.
Ελλάδα
Τηλ: +30 2118805000

Sverige
Teva Sweden AB
Tel: +46 42121100

Latvija
UAB Teva Baltics filiāle Latvijā
Tel: +371 67323666

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu.

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

The following information is intended for healthcare professionals only:

Tuznue IV is provided in sterile, preservative-free, non-pyrogenic, single use vials.

In order to prevent medication errors it is important to check the vial labels to ensure that the medicine being prepared and given is Tuznue (trastuzumab) and not another trastuzumab-containing product (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicine in the closed original pack in a refrigerator at a temperature of 2 °C – 8 °C.

A vial of Tuznue reconstituted with water for injections (not supplied) is stable for 48 hours at 2 °C – 8 °C after reconstitution and must not be frozen.

From a microbiological point of view, the reconstituted solution and Tuznue infusion solution should be used immediately. The product is not intended to be stored after reconstitution and dilution unless this has taken place under controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Appropriate aseptic technique should be used for reconstitution and dilution procedures. Care must be taken to ensure sterility of prepared solutions. Since the medicinal product does not contain any anti- microbial preservative or bacteriostatic agents, aseptic technique must be observed.

Aseptic preparation, handling and storage:

Aseptic handling must be ensured when preparing the infusion. Preparation should be:

• performed by trained personnel in accordance with good practice rules especially with respect to the aseptic preparation of parenteral products.
• prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared solution for intravenous infusion to ensure maintenance of the aseptic conditions.

Tuznue should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted Tuznue may result in problems with the amount of Tuznue that can be withdrawn from each vial.

Tuznue 150 mg powder for concentrate for solution for infusion

Appropriate aseptic technique should be used. Each 150 mg vial of Tuznue is reconstituted with 7.2 mL of sterile water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields a 7.4 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab. A volume overage of 4% ensures that the labelled dose of 150 mg can be withdrawn from each vial.

Tuznue 420 mg powder for concentrate for solution for infusion

Appropriate aseptic technique should be used. Each 420 mg vial of Tuznue is reconstituted with 20 mL of sterile water for injections (not supplied). Use of other reconstitution solvents should be avoided. This yields a 21 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab. A volume overage of 4.8% ensures that the labelled dose of 420 mg can be withdrawn from each vial.

Tuznue vial

Volume of sterile water for injections

Final concentration
150 mg vial
+
7.2 mL
=
21 mg/mL
420 mg vial
+
20 mL
=
21 mg/mL

Instructions for reconstitution:

1)
Using a sterile syringe, slowly inject the appropriate volume (as noted above) of sterile water for injection (not supplied) in the vial containing the lyophilised Tuznue, directing the stream into the lyophilised cake.

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

Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed for approximately 5 minutes. The reconstituted Tuznue results in a clear, colourless to pale yellow transparent solution and should be essentially free of visible particulates.

Instructions for aseptic dilution of the reconstituted solution:

Determine the volume of the solution required:

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

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

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

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

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to a polypropylene infusion bag containing 250 mL of 0.9% sodium chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to mix the solution in order to avoid foaming. Parenteral solutions should be inspected visually for particulates and discolouration prior to administration. Once the infusion is prepared it should be administered immediately. If diluted aseptically, it may be stored for 24 hours (do not store above 30 °C).