Trazimera 420 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Trazimera 150 mg powder for concentrate for solution for infusion

Trazimera 420 mg powder for concentrate for solution for infusion

trastuzumab

Read the entire 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 experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Trazimera is and what it is used for
2. What you need to know before using Trazimera
3. How to use Trazimera
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 specifically recognize 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 certain cancer cells and stimulates the growth of these cells. When Trazimera binds to HER2, the growth of these cells is inhibited, leading to their death.

Your doctor may prescribe Trazimera for the treatment of breast or gastric cancer when:

• you have early breast cancer with high levels of a protein called HER2.

• you have metastatic breast cancer (breast cancer in which the original tumour has spread) 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 if other treatments have not been successful. It is also used in combination with other medicines called aromatase inhibitors in patients with high HER2 levels and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to female sex hormones).

• you have metastatic gastric cancer with high levels of HER2, and it is used in combination with other anticancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before using 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 breathing problems at rest due to your tumor or require oxygen therapy.

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac evaluations

Treatment with Trazimera alone or in combination with a taxane may affect the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two types of medicines used to treat cancer). The effects can range from moderate to severe and may result in death. Therefore, your cardiac function must be evaluated before, during (every three months), and after (up to two to five years) treatment with Trazimera. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your heart function will be monitored more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to discontinue treatment with Trazimera.

Consult your doctor, pharmacist, or nurse before receiving Trazimera if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmur), high blood pressure, have taken any medicine for high blood pressure, or are currently taking any medicine for high blood pressure;

• you have previously received or are currently receiving a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems when treated with Trazimera;

• you feel short of breath, especially if you are currently receiving a taxane. Trazimera can cause difficulty breathing, particularly when administered for the first time. This could be more serious if you already have shortness of breath. In very rare cases, patients with severe breathing difficulties before treatment have died after receiving Trazimera;

• you have previously received any other cancer treatment.

If you are receiving Trazimera together with any other cancer treatment, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflets 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 need to take any other medicines.

It may take up to 7 months for Trazimera to be completely eliminated from the body. Therefore, if you plan to take any new medicine within 7 months after stopping treatment, you must inform your doctor, pharmacist, or nurse that you have been treated with Trazimera.

Pregnancy

• If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before using this medicine.

• You must use an effective method of contraception during treatment with Trazimera and for at least 7 months after completing treatment.

• Your doctor will explain the risks and benefits of using Trazimera during pregnancy. In rare cases, a reduced amount of fluid surrounding the developing baby in the womb (amniotic fluid) has been observed in pregnant women who received Trazimera. This may be harmful to the unborn baby and has been associated with underdeveloped lungs, resulting in fetal death.

Breastfeeding

You must not breastfeed during treatment with Trazimera and for 7 months after the last dose of Trazimera, as Trazimera may pass into your breast milk and harm your baby.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Trazimera may affect your ability to drive or operate machinery. If you experience symptoms during treatment such as dizziness, drowsiness, chills, or fever, you should not drive or use machines until these symptoms resolve.

3. How to use Trazimera

Before starting treatment with Trazimera, your doctor will determine the amount of HER2 in your tumor. 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 a dose and treatment regimen 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 only intravenously.

The intravenous formulation of Trazimera is given as an intravenous infusion ("drip") directly into a vein. The first dose of your treatment will be administered over approximately 90 minutes, and you will be monitored by a healthcare professional during administration for any adverse reactions. If the initial dose is well tolerated, subsequent doses may be given over 30 minutes (see section 2 "Warnings and precautions"). The number of infusions you receive will depend on your response to treatment. Your doctor will inform you about this.

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 product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

For early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Trazimera is administered every 3 weeks. Trazimera may also be administered once weekly for metastatic breast cancer.

If you interrupt treatment with Trazimera

Do not interrupt treatment with this medicine without first speaking to your doctor. All doses should be taken at the correct time, either weekly or every three weeks (depending on your dosing schedule). This helps ensure your medicine works properly.

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 you have completed treatment.

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

4. Possible adverse effects

Like all medicines, Trazimera can produce adverse effects, although not everyone will experience them. Some of these adverse effects may be serious and require hospitalization.

During administration of a Trazimera infusion, chills, fever, and other flu-like symptoms may occur. This is very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: feeling unwell (nausea), vomiting, pain, increased muscle tension and agitation, headache, dizziness, breathing difficulties, decreased or increased blood pressure, changes in heart rhythm (palpitations, arrhythmias, or irregular heartbeat), swelling of the face and lips, rash, and feeling tired. Some of these symptoms may be severe, and in some patients they have been fatal (see section 2, "Warnings and precautions").

These effects occur mainly during the first intravenous infusion ("drip" into a vein) and within the first hours after the start of the infusion. They are usually transient. A healthcare professional will monitor you during the infusion and for at least six hours after the start of the first infusion, and for two hours after the start of each subsequent infusion. If you have a reaction, the infusion may be administered more slowly or stopped, and you may be given treatment to counteract the adverse effects. The infusion may continue once your symptoms have improved.

Occasionally, symptoms begin more than 6 hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then worsen again later.

Serious adverse effects

Other adverse effects may occur at any time during treatment with Trazimera, not only related to the infusion. Inform your doctor or nurse if you experience any of the following adverse effects:

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

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

• Tumor lysis syndrome (a group of metabolic complications that occur after cancer treatment and are characterized by high levels of potassium and phosphate in the blood and low levels of calcium in the blood). Symptoms may include kidney problems (weakness, shorterness of breath, fatigue, and confusion), heart problems (heart palpitations or a faster or slower heartbeat), seizures, vomiting or diarrhea, and tingling around the mouth, hands, or feet.

If you experience any of these symptoms after your treatment with Trazimera has ended, you must consult your doctor and inform them that you have previously been treated with Trazimera.

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rash (cutaneous rash)
• chest pain
• abdominal pain
• joint pain
• low red and white blood cell counts (which help fight infection), sometimes with fever
• muscle pain
• conjunctivitis
• tearing
• nosebleeds
• nasal discharge
• hair loss
• tremor
• hot flushes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• taste disturbances
• low platelet count
• bruising
• numbness or tingling in the fingers and toes, which may occasionally spread to the rest of the limb
• redness, swelling, or ulcers in the mouth and/or throat
• pain, swelling, redness, or tingling in the hands and/or feet
• difficulty breathing
• headache
• cough
• vomiting
• nausea

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

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

• deafness
• skin rash with blisters
• wheezing (whistling breath)
• lung inflammation/scarring

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

• jaundice
• anaphylactic reactions

Frequency not known (cannot be estimated from available data):

• abnormal blood clotting or failure to clot
• high levels of potassium
• inflammation or bleeding at the back of the eyes
• shock
• abnormal heart rhythm
• difficulty breathing
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low levels of oxygen in the blood
• difficulty breathing while lying down
• liver damage
• swelling of the face, lips, and throat
• kidney failure
• abnormally low levels of fluid surrounding the fetus in the womb
• failure of the baby's lungs to develop in the womb
• abnormal development of the baby's kidneys in the womb

Some of the side effects you may experience could be due to your cancer. If you are given Trazimera in combination with chemotherapy, some of the side effects may also be due to the chemotherapy itself.

Reporting of side effects

If you experience any side effects, inform your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 following EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Keep in the original packaging to protect from light.

Unopened Trazimera vials may be stored at a temperature up to 30°C for a single period of up to 3 months. Once removed from refrigerated storage, Trazimera must not be returned to the refrigerator. Discard at the end of this 3-month period or before the expiry date indicated on the vial, whichever occurs first. Record the “discard by” date in the date space provided on the carton.

The diluted infusion solution should be used immediately after dilution. Do not use this medicine if you notice any foreign particles or discoloration prior to administration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Pack contents and other information

Composition of Trazimera

• The active substance is trastuzumab. One vial contains:

• 150 mg of trastuzumab dissolved in 7.2 ml of sterile water for injectable preparations, or

• 420 mg of trastuzumab dissolved in 20 ml of sterile water for injectable preparations.

The resulting solution contains approximately 21 mg/ml of trastuzumab.

• The other components are L-histidine monohydrochloride monohydrate, L-histidine, sucrose, polysorbate 20 (E 432).

Appearance of the product and contents of the container

Trazimera is a powder for concentrate for solution for infusion, supplied in a glass vial with a rubber stopper containing 150 mg or 420 mg of trastuzumab. The powder is a white cake. Each pack contains 1 vial of powder.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870 Puurs-Sint-Amands

Belgium

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

Date of last revision of this leaflet: MM/YYYY.

Other sources of information

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

This leaflet is available on the European Medicines Agency website in all languages of the European Union/European Economic Area.

This information is intended for healthcare professionals only:

Trazimera intravenous is supplied in sterile, single-use vials that are preservative-free and non-pyrogenic.

To avoid 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 product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicine in its original closed packaging, stored at 2°C – 8°C in a refrigerator.

Unopened Trazimera vials may be stored at temperatures up to 30°C for a single period of up to 3 months. Once removed from refrigerated storage, Trazimera must not be returned to the refrigerator. Discard at the end of this 3-month period or before the expiry date indicated on the vial, whichever occurs first. Record the “discard by” date in the date space provided on the carton.

After aseptic dilution in 9 mg/ml (0.9%) sodium chloride injection solution, Trazimera infusion solutions are physically and chemically stable for up to 30 days between 2°C – 8°C and for 24 hours at temperatures not exceeding 30°C.

From a microbiological standpoint, the reconstituted solution and the Trazimera infusion solution should be used immediately. If not used immediately, the duration of storage prior to use and the storage conditions are the responsibility of the user and, in general, should not exceed 24 hours between 2°C – 8°C, unless reconstitution and dilution have been carried out under controlled and validated aseptic conditions.

Appropriate aseptic techniques must be used for reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. Since the medicine contains no antimicrobial preservatives or bacteriostatic agents, an aseptic technique must be used.

Storage, handling, and aseptic preparation:

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

• be performed under aseptic conditions by trained personnel in accordance with good practices, especially for the aseptic preparation of parenteral products;
• be followed by appropriate storage of the prepared intravenous infusion solution to ensure maintenance of aseptic conditions.

If the prepared solution is intended to be stored for more than 24 hours before use, reconstitution and dilution must be performed in a laminar airflow cabinet or biological safety cabinet, using standard precautions for the safe handling of intravenous agents.

A Trazimera vial aseptically reconstituted with water for injections (not supplied) is 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

Appropriate aseptic techniques must be used. Each 150 mg vial of Trazimera is reconstituted with 7.2 ml of sterile water for injections (not supplied). The use of other solvents for reconstitution must be avoided. This results in a 7.4 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 4% overfill ensures that the labeled dose of 150 mg can be withdrawn from each vial.

Trazimera 420 mg powder for concentrate for solution for infusion

Appropriate aseptic techniques must be used. Each 420 mg vial of Trazimera is reconstituted with 20 ml of sterile water for injections (not supplied). The use of other solvents for reconstitution must be avoided. This results in a 20.6 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 5% overfill ensures that the labeled dose of 420 mg can be withdrawn from each vial.

Trazimera must be handled carefully during reconstitution. Excessive foaming during reconstitution or agitation of the reconstituted Trazimera may cause problems with the amount of Trazimera that can be withdrawn from the vial.

Instructions for aseptic reconstitution:

1. Using a sterile syringe, slowly inject the appropriate volume (as indicated above) of sterile water for injections into the vial containing the lyophilized Trazimera.
2. Gently swirl to aid reconstitution. DO NOT SHAKE!

The formation of slight foam after reconstitution is normal. Allow the vial to stand for approximately 5 minutes. Reconstituted Trazimera is a clear, colorless to pale yellow-brown solution and should be essentially free from visible particles.

The required volume of solution will be determined:

• Based on the initial dose of 4 mg trastuzumab/kg body weight or subsequent weekly doses of 2 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) x dose (4 mg/kg initial dose or 2 mg/kg for subsequent doses)

21 (mg/ml, concentration of the reconstituted solution)

• The required volume of solution will be determined based on the initial dose of 8 mg trastuzumab/kg body weight or subsequent doses every three weeks of 6 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) x dose (8 mg/kg initial dose or 6 mg/kg for subsequent doses)

21 (mg/ml, concentration of the reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to an intravenous infusion bag made of polyvinyl chloride, polyethylene, polypropylene, or ethylene-vinyl acetate, or to a glass infusion bottle, containing 250 ml of 9 mg/ml (0.9%) sodium chloride injection solution. It must not be used with glucose-containing solutions. The bag or bottle should be inverted several times to mix the solution and avoid foam formation. Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration.