Trazimera

Package leaflet: Information for the user

Trazimera 150 mg powder for concentrate for solution for infusion, 420 mg powder for concentrate for solution for infusion

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Trazimera is and what it is used for

Trazimera contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies bind to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is present in large amounts on the surface of certain tumour cells and stimulates their growth. When Trazimera binds to HER2, it blocks the growth of these cells and causes their death.

Your doctor may prescribe Trazimera 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 away from the primary tumour) with high levels of HER2. Trazimera 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 when other treatments have proven ineffective. It is also used in combination with medicines called aromatase inhibitors for the treatment of patients with high HER2 levels and metastatic hormone receptor-positive breast cancer (cancer that is sensitive to female sex hormones).
• You have metastatic gastric cancer with high levels of HER2, in combination with other anticancer medicines capecitabine or 5-fluorouracil and cisplatin.

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

Do not use Trazimera if

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

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

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

If you are receiving Trazimera in combination with any other medicine used to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflet for these medicines.
Children and adolescents
Trazimera is not recommended for patients under 18 years of age.
Other medicines and Trazimera
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
It may take up to 7 months for Trazimera to be eliminated from the body. Therefore, you must inform your doctor, pharmacist, or nurse that you have been given Trazimera if you start taking any new medicine within 7 months after stopping treatment.
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, inform your doctor,
pharmacist, or nurse before taking this medicine.
You must use effective contraception during treatment with Trazimera and for
at least 7 months after the end of treatment.
Your doctor will discuss with you the risks and benefits of taking Trazimera
during pregnancy. In rare cases, a reduced amount of fluid (amniotic fluid) surrounding the developing baby in the womb has been observed in pregnant women treated with Trazimera. This condition could be harmful to the unborn baby and has been associated with incomplete lung development, which has led to fetal death.
Breast-feeding
Do not breast-feed during treatment with Trazimera and for 7 months after the last dose of Trazimera, as Trazimera may pass into breast milk and harm the baby.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Trazimera may affect your ability to drive or use machines. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, you should not drive or operate machinery until these symptoms resolve.

3. How Trazimera is administered

Before starting treatment, your doctor will determine the amount of HER2 in the tumour. Only
patients with high levels of HER2 will be treated with Trazimera. Trazimera must be administered only
by a doctor or nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you.
The dose of Trazimera depends on your body weight.
The intravenous formulation of Trazimera is not intended for subcutaneous administration and must
be administered exclusively by intravenous infusion.
The intravenous formulation of Trazimera is given as an intravenous infusion (“drip”) directly into the
veins. The first dose of treatment is administered over a period of 90 minutes, and you will be monitored
by a healthcare professional during administration in case you experience any adverse effects. If the
first dose is well tolerated, subsequent doses may be administered over a period of 30 minutes (see
section 2 “Warnings and precautions”). The number of infusions you will receive depends on your
response to treatment. Your doctor will discuss this with you.
To prevent medication errors, it is important to check the vial labels to ensure that the medicine being
prepared and administered is Trazimera (trastuzumab) and not another trastuzumab-containing
medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Trazimera
is administered every 3 weeks. Trazimera may also be administered once weekly for the treatment of
metastatic breast cancer.
If you interrupt treatment with Trazimera
Do not stop taking this medicine without first talking to your doctor. All doses must be taken at the
correct time, either weekly or every three weeks (depending on your dosing schedule). This helps the
medicine work as effectively as possible.
It may take up to 7 months for Trazimera to be eliminated from your body. Therefore, your doctor may
decide to continue monitoring your heart function even after treatment has ended.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

During infusion of Trazimera, reactions such as chills, fever and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people).

Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), facial or lip swelling, skin rashes and feeling tired. Some of these symptoms may 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 starting the infusion. They are usually temporary. You will be monitored by a healthcare professional during the infusion and for at least six hours after the start of the first infusion, and for two hours after the start of subsequent infusions. If you have a reaction, the infusion will be slowed down or stopped, and you may be given treatment to counteract the side effects. The infusion may be resumed once your symptoms have improved.

Occasionally, symptoms begin more than six hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes symptoms may improve and then worsen later.

Serious side effects

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

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

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

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

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

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

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

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

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

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

• deafness
• skin rash with hives
• wheezing
• inflammation or scarring in the lungs

Rare (may affect up to 1 in 1,000 people):
jaundice
anaphylactic reactions

Not known (frequency cannot be estimated from available data):
blood clotting abnormalities or changes

• high potassium levels
• swelling or bleeding behind the eyes
• shock
• abnormal heart rhythm
• respiratory distress
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low levels of oxygen in the blood
• difficulty breathing when lying down
• liver damage
• swelling of the face, lips and throat
• kidney failure
• abnormally low levels of fluid around the baby in the womb
• inadequate 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 carcinoma. If you are receiving Trazimera in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.

If you experience any of the side effects, tell your doctor, pharmacist or nurse.

Reporting of side effects

If you get any side effects, including ones not listed in this leaflet, talk to 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 Trazimera

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial after “Exp.” The expiry date refers to the last day of that month.
Store in a refrigerator (2°C–8°C).
Keep in the original packaging to protect from light.
Unopened vials of Trazimera may be stored at temperatures up to 30°C for a single period not exceeding 3 months. After removal from the refrigerator, Trazimera must not be returned to refrigerated storage. Discard them at the end of this 3-month period or by the expiry date stated on the vial, whichever comes first. Record the “discard by” date in the designated space on the carton.
Infusion solutions should be used immediately after dilution. Do not use Trazimera if you notice any particles or changes in colour before administration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Trazimera contains
The active substance is trastuzumab. One vial contains either:
150 mg of trastuzumab to be dissolved in 7.2 mL of sterile water for injections, or
420 mg of trastuzumab to be dissolved in 20 mL of sterile water for injections.
The resulting solution contains approximately 21 mg/mL of trastuzumab.
The other components are L-histidine hydrochloride monohydrate, L-histidine, sucrose, polysorbate
20 (E 432).

Description of the appearance of Trazimera and contents of the pack
Trazimera is a powder for concentrate for solution for infusion supplied in a glass vial sealed with a rubber stopper containing 150 mg or 420 mg of trastuzumab. The powder is a white tablet. Each pack contains 1 vial of powder.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien K ύπρος
Luxembourg/Luxemburg Pfizer Ελλάς A.E. (Cyprus Branch)
Pfizer NV/SA T  : +357 22817690
Tél/Tel: +32 (0)2 554 62 11

Česká republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420 283 004 111 Tel.: +36 1 488 37 00

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf.: +45 44 20 11 00 Tel: + 356 2134 4610

Deutschland Nederland
PFIZER PHARMA GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл.: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
Pfizer Ελλάς A.E. Pfizer Polska Sp. z o.o.
Τηλ: +30 210 6785800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Tel: +34 91 490 99 00 Tel: +351 21 423 5500

France România
Pfizer Pfizer Romania S.R.L
Tél: + 33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL
Tel: +385 1 3908 777 Pfizer, podružnica za svetovanje s področja
farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská republika
Pfizer Healthcare Ireland Unlimited Pfizer Luxembourg SARL, organizačná zložka
Company Tel: +421 2 3355 5500
Tel: +1800 633 363 (toll free)
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel: +370 5 251 4000

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

The following information is intended exclusively for physicians or healthcare professionals

Trazimera for intravenous use is supplied in sterile, single-use vials that are preservative-free and pyrogen-free.
To prevent medication administration errors and to ensure that the drug being prepared and administered is Trazimera (trastuzumab) and not another trastuzumab-containing product (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is important to verify the vial label.
Store the medicinal product in its original closed packaging in a refrigerator at 2°C - 8°C.
Unopened vials of Trazimera may be stored at temperatures up to 30°C for a single maximum period of 3 months. After removal from the refrigerator, Trazimera must not be returned to refrigerated storage. Dispose of the vials at the end of this 3-month period or by the expiration date indicated on the vial, whichever occurs first. Record the “discard by” date in the designated space on the packaging.
After aseptic dilution in 9 mg/mL (0.9%) sodium chloride injection solution, Trazimera infusion solutions remain physically and chemically stable for up to 30 days when stored at 2°C - 8°C and for 24 hours at temperatures not exceeding 30°C.
From a microbiological standpoint, the reconstituted solution and the infusion solution of Trazimera should be used immediately. If the product is not used immediately, the storage period and conditions before and during use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C, unless reconstitution and dilution have been performed under controlled, validated aseptic conditions.
Follow appropriate aseptic techniques during reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. The medicinal product does not contain antimicrobial preservatives or bacteriostatic agents; therefore, aseptic techniques must be employed.

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

• Be performed under aseptic conditions by trained personnel in accordance with good manufacturing practices, particularly respecting aseptic techniques for parenteral medicinal product preparation.
• Be followed by appropriate storage of the infusion solution to maintain aseptic conditions.

If the prepared solution is to be stored for more than 24 hours before use, the reconstitution and dilution procedures must be carried out within laminar flow hoods or in biologically safe environments, applying standard precautions for the safe handling of intravenous agents.
A Trazimera vial aseptically reconstituted with water for injection (not supplied) remains chemically and physically stable for 48 hours at 2°C - 8°C after reconstitution and must not be frozen.

Trazimera 150 mg powder for concentrate for solution for infusion
Follow appropriate aseptic techniques. Each 150 mg Trazimera vial is reconstituted with 7.2 mL of sterile water for injection (not supplied). Avoid using other solvents for reconstitution. This yields 7.4 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. A 4% overfill ensures withdrawal of the intended dose of 150 mg from the vial.

Trazimera 420 mg powder for concentrate for solution for infusion
Follow appropriate aseptic techniques. Each 420 mg Trazimera vial is reconstituted with 20 mL of sterile water for injection (not supplied). Avoid using other solvents for reconstitution. This yields 20.6 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. A 5% overfill ensures withdrawal of the intended dose of 420 mg from the vial.

Trazimera must be handled carefully during the reconstitution process.
Excessive foaming occurring during reconstitution or agitation of the reconstituted Trazimera solution may result in difficulties in withdrawing the expected amount of Trazimera from the vial.

Aseptic reconstitution instructions:

1. Using a sterile syringe, slowly inject the appropriate volume (as indicated above) of sterile water for injections into the vial containing the Trazimera lyophilized powder.
2. Gently rotate the vial to facilitate reconstitution. DO NOT SHAKE!
   Slight foaming during reconstitution is not unusual. Allow the vial to stand undisturbed in an upright position for approximately 5 minutes. Once reconstituted, Trazimera appears as a clear, colourless to light brownish-yellow solution, free from visible particles.

Determine the volume of solution required:
Based on a loading dose of 4 mg of trastuzumab/kg body weight, or a subsequent weekly maintenance dose of 2 mg of trastuzumab/kg body weight:
Volume (mL) = Body Weight (kg) x dose ( 4mg /kg for loading dose or 2mg /kg for maintenance dose)
21 (mg/mL, concentration of reconstituted solution)

Based on a loading dose of 8 mg of trastuzumab/kg body weight, or a subsequent dose of 6 mg of trastuzumab/kg body weight every 3 weeks:
Volume (mL) = Body Weight (kg) x dose ( 8mg /kg for loading dose or 6mg /kg for maintenance dose)
21 (mg/mL, concentration of reconstituted solution)

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