Prospect: Information for the User

Trazimera150mg powder for concentrate forsolutionforinfusion

Trazimera 420mg powder for concentrate for solution for infusion

trastuzumab

Read this prospect thoroughly before starting to use this medicine, because

it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

Trazimera contains trastuzumab as its active substance, which is a monoclonal antibody. Monoclonal antibodies specifically recognize proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called the human epidermal growth factor receptor 2 (HER2). The HER2 is found in large quantities on the surface of some cancer cells and stimulates the growth of these cells. When Trazimera binds to HER2, it slows down the growth of these cells, causing them to die.

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

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

• you have metastatic breast cancer (breast cancer in which the original tumor has spread) with high levels of HER2. Trazimera may be prescribed in combination with the chemotherapy medications paclitaxel or docetaxel as first-line 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 medications called aromatase inhibitors in 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, and it is combined with other cancer medications such as capecitabina or 5-fluorouracilo and cisplatino.

No useTrazimerasi

•is allergic to trastuzumab, mouse proteins (from rat) or to any of the other components of this medication (listed in section 6);

•has severe respiratory problems at rest due to your tumor or if you need oxygen treatment.

Advertencias y precauciones

Your doctor will closely monitor your treatment.

Cardiac reviews

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

Consult your doctor, pharmacist or nurse before Trazimera is administered to you if:

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

•you have ever received or are currently receiving a medication called doxorubicin or epirubicin (medications used to treat cancer). These medications (or any other anthracycline) may damage the 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 may cause difficulty breathing, especially when administered for the first time. This could be more severe if you already have shortness of breath. In very rare cases, patients with severe respiratory problems before treatment have died when Trazimera was administered;

•you have ever had any other cancer treatment.

If you receive Trazimera in combination with any other medication to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil or cisplatin, you should also read the prospectuses of these medications.

Children and adolescents

Trazimera is not recommended for individuals under 18 years.

Other medications and Trazimera

Inform your doctor, pharmacist or nurse if you are using, have used recently or may need to use any other medication.

It may take up to 7 months for Trazimera to be completely eliminated from the body. Therefore, if you are to take any new medication within 7 months of completing treatment, you should inform your doctor, pharmacist or nurse that you have been treated with Trazimera.

Pregnancy

•If you are pregnant, think you may be pregnant or intend to become pregnant, consult your doctor, pharmacist or nurse before using this medication.

•You should use an effective contraceptive method during treatment with Trazimera and for at least 7 months after completing treatment.

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

Breastfeeding

You should not breastfeed your baby during Trazimera therapy and for up to 7 months after the last dose of Trazimera, as Trazimera may reach your baby through your milk.

Consult your doctor or pharmacist before taking a medication.

Driving and operating machinery

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

Before starting treatment withTrazimera, your doctor will determine the amount of HER2 in your tumor. Only patients with a large amount of HER2 will be treated withTrazimera. Trazimeramust be administered only by a doctor or nurse. Your doctor will prescribe an appropriate dose and treatment regimen foryou. The dose ofTrazimerawill depend on your body weight.

The intravenous formulation ofTrazimerais not for subcutaneous administration and must only be administered intravenously.

The intravenous formulation ofTrazimerais administered as an intravenous infusion (“drip”) directly into a vein. The first dose of your treatment is administered in about 90minutes and will be monitored by a healthcare professional while it is being administered, in case any adverse reactions occur. If the initial dose has been well tolerated, subsequent doses may be administered in 30minutes (see section2 “Warnings and precautions”). The number of infusions you can receive will depend on your response to treatment. Your doctor will inform you about this.

To avoid medication errors, it is essential to check the labels on the vials to ensure that the medication being prepared and administered isTrazimera(trastuzumab) and notanother product that contains trastuzumab (e.g.trastuzumab emtansinaor trastuzumab deruxtecan).

For early breast cancer, metastatic breast cancer, and metastatic gastric cancer,Trazimerawill be administered every 3weeks.Trazimeracan also be administered once a week for metastatic breast cancer.

If you interrupt treatment withTrazimera

Do not stop treatment with this medication without first talking to your doctor. All doses must be taken at the right time, either weekly or every three weeks (depending on your dosing schedule). This helps your medication work properly.

It may take up to7months for Trazimera to be eliminated from your body. Therefore, yourdoctormay decide to continue monitoring yourheartfunction, evenafteryou have completed your treatment.

If you have any other questions about the use of this medication, ask yourdoctor, pharmacistor nurse.

Like all medicines, Trazimera can cause side effects, although not everyone will experience them. Some of these side effects can be severe and require hospitalization.Hospitalization.

During the administration of a Trazimera infusion, chills, fever, and other symptoms similar to the flu may occur. This is very common (can affect more than 1 in 10 people). Other symptoms related to the infusion are: feeling unwell (nausea), vomiting, pain, increased muscle tension, and agitation, headache, dizziness, difficulty breathing, decreased or increased blood pressure, heart rhythm disturbances (palpitations, arrhythmias, or irregular heartbeat), facial and lip swelling, rash, and feeling tired. Some of these symptoms can be severe and some patients have died (see section 2 “Warnings and precautions”).

These side effects mainly occur during the first intravenous infusion (“drip” in vein) and during the first hours after starting the infusion. They are usually transient. A healthcare professional will monitor you during the infusion and, for at least six hours, after starting the first infusion and for two hours after starting the rest of the infusions. If you have any reaction, they may administer the infusion more slowly or interrupt the infusion and give you treatment to counteract the side effects. The infusion can continue once your symptoms have improved.

Occasionally, symptoms start after 6 hours after starting the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms can improve and worsen later.

Severe side effects

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

•Cardiac problems can occur during treatment and occasionally after stopping treatment, and these can be severe. These include heart muscle weakness that may cause heart failure, inflammation of the heart layer, and heart rhythm disturbances. This can cause symptoms such as shortness of breath (even at night), cough, fluid retention (swelling) in the legs or arms, palpitations (arrhythmias or irregular heartbeat) (see 2. Cardiac reviews).

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

•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 can include kidney problems (weakness, shorter breathing, fatigue, and confusion), heart problems (palpitations or irregular heartbeat), seizures, vomiting, or diarrhea, and tingling in the mouth, hands, or feet.

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

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

•Infections

•Diarrea

•Constipation

•Stomach burning (dyspepsia)

•Fatigue

•Rash (cutaneous rash)

•Chest pain

•Abdominal pain

•Joint pain

•Low red and white blood cell count (which helps fight infection)sometimes with fever

•Muscle pain

•Conjunctivitis

•Excessive tearing

•Nasal bleeding

•Nasal secretion

•Hair loss

•Tremor

•Seizures

•Dizziness

•Alteration of nails

•Weight loss

•Loss of appetite

•Difficulty sleeping (insomnia)

•Alteration of taste

•Low platelet count

•Cardinal signs

•Numbness or tingling in the fingers of the hands and feet, which occasionally can extend to the rest of the extremity

•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 (can affect up to 1 in 10 people):

(hypertonia)•Pulmonary alteration

Rare (can affect up to 1 in 100 people):

•Deafness

•Rash with blisters

•Wheezing (pitos)

•Lung inflammation/cicatrisation

Very rare (can affect up to 1 in 1,000 people):

•Jaundice

•Anaphylactic reactions

Unknown frequency (cannot be estimated from available data):

•Abnormal blood coagulation or coagulation insufficiency

•High potassium levels

•Inflammation or hemorrhages in the back of the eyes

•Shock

•Abnormal heart rhythm

•Difficulty breathing

•Respiratory insufficiency

•Acute accumulation of fluid in the lungs

•Acute narrowing of the airways

•Abnormally low oxygen levels in the blood

•Difficulty breathing while lying down

•Liver damage

•Inflammation of the face, lips, and throat

•Renal failure

•Abnormally low levels of fluid surrounding the fetus in the uterus

•Failure of the baby's lungs to develop in the uterus

•Abnormal development of the baby's kidneys in the uterus

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

Inform your doctor, pharmacist, or nurse if you experience any side effects.

Reporting side effects

Inform your doctor, pharmacist, or nurse if you experience any side effects, even if they are not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the vial label after EXP. The expiration date is the last day of the month indicated.

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

Store in the original packaging to protect it from light.

Unopened Trazimera vials can be stored at a temperature of up to 30°C for a single period of up to 3 months.Once removed from refrigerated storage, Trazimera should not be returned to the refrigerator.Dispose of at the end of this 3-month period or before the expiration date indicated on the vial, whichever occurs first. Record the date of “dispose before” in the date space provided on the box.

Solutions for infusion must be used immediately after dilution.Do not use this medication if you observe any foreign particles or discoloration before administration.

Medicines should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

CompositionofTrazimera

• The active ingredient is trastuzumab.A vial contains:

• 150mg of trastuzumab that dissolves in 7.2ml of sterile water for injection, or
• 420mg of trastuzumab that dissolves in 20ml of sterile water for injection.

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

• The other components are L-histidine hydrochloride monohydrate, L-histidine, sucrose, polisorbate 20 (E432).

Aspect of the product and content of the package

Trazimerais a lyophilized powder for concentrate forsolutionforintravenous infusion, which is presented in a glass vial with a rubber stopper that contains 150mg or 420mg of trastuzumab. The powder is a white cake.Each package contains 1vial of powder.

Holder of themarketing authorizationofcommercialization

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Responsible for themanufacturing

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870Puurs-Sint-Amands

Belgium

You can requestmore informationregarding this medication by addressing the local representative of theholder of themarketing authorization.

Last review date of this leaflet:12/2024

Other sources of information

The detailed information of this medicationis available on the website of the European Medicines Agency:https://www.ema.europa.eu

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

This information is intended solely for healthcare professionals:

Trazimeraintravenous is provided in sterile, single-use vials,free ofpreservativesandnon-pyrogenic.

To avoid medication errors, it is essential to check the labels on the vials to ensure that the medication being prepared and administered is Trazimera (trastuzumab) and not another product that contains trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicationin its original, closedcontainerat a temperatureof 2°C–8°C in a refrigerator.

Unopened vials of Trazimeracan be stored at a temperature of up to 30°C for a single period of up to 3months.Once removed from refrigerated storage,Trazimerashould not be returned to the refrigerator.Dispose of at the end of this 3month period or before the expiration date indicated on the vial, whichever occurs first. Record the "discard by" date in the space provided on the box.

After aseptic dilutionin0.9% sodium chloride injection, Trazimerasolutions for intravenous infusion are physically and chemically stable for up to30daysbetween2°C – 8°Candfor24hours at temperatures not exceeding30°C.

From a microbiological point of view, the reconstituted solution and the Trazimerasolution for infusion should be used immediately. If not used immediately, the storage time until use and the conditions of such storage will be the responsibility of the user and, in general, should not exceed 24hours between 2°C – 8°C, unless reconstitution and dilution take place under controlled and validated aseptic conditions.

Aseptic methods should be employed for the reconstitution and dilution procedures. Care should be taken to ensure the sterility of the prepared solutions. Since the product does not contain antimicrobial preservatives or bacteriostatic agents, aseptic technique should be used.

Storage, handling, and aseptic preparation:

Aseptic handling should be ensured when preparing the infusion. The preparation should be:

• performed under aseptic conditions by trained personnel in accordance with good practices, especiallyfor the aseptic preparation of parenteral products.
• followed by adequate storage of the prepared intravenous infusion solution that ensures the maintenance of aseptic conditions.

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

A vial of reconstituted Trazimeraprepared aseptically with sterile water for injection (not supplied) ischemically and physicallystable for 48hours at 2°C–8°C after reconstitution and should not be frozen.

Trazimera150mg lyophilized powder for concentrate forsolutionforintravenous infusion

Aseptic methods should be employed. Each vial of 150mg of Trazimerashould be reconstituted with 7.2ml of sterile water for injection (not supplied). Other solvents for reconstitution should be avoided. This produces asolutionof 7.4ml for single-dose that contains approximately 21mg/ml of trastuzumab. A 4% overfill allows the 150mg dose reflected on the label to beextractedfrom each vial.

Trazimera420mg lyophilized powder for concentrate forsolutionforintravenous infusion

Aseptic methods should be employed. Each vial of 420mg of Trazimerashould be reconstituted with20ml of sterile water for injection (not supplied). Other solvents for reconstitution should be avoided. This produces asolutionof20.6ml for single-dose that contains approximately 21mg/ml of trastuzumab.A 5% overfill allows the 420mg dose reflected on the label to beextractedfrom each vial.

Trazimerashould be handled carefully during reconstitution. If excessive foam is produced during reconstitution or the reconstituted Trazimerais agitated, it may cause problems with the amount of Trazimerathat can be extracted from the vial.

Instructions for aseptic reconstitution:

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

A slight foam formation after reconstitution is usual. Leave the vial at rest for approximately 5minutes.Trazimerareconstituted is a transparent, colorless to pale yellow-brown solution and should be essentially free of visible particles.

The required solution volume will be determined:

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

Volumen(ml)=Weightcorporal(kg) xdosis(4mg/kg initial dose or2mg/kg for subsequent doses)

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

• based on the initial dose of 8mg of trastuzumab/kg of body weight or doses every 3 weeks of 6mg of trastuzumab/kg of body weight

Volumen(ml)=Weight corporal(kg)xdosis(8mg/kg initial dose or6mg/kg for subsequent doses)

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

The appropriate amount of solution should be extracted from the vialusing a sterile syringe and needleand added to a polyvinyl chloride, polyethylene, polypropylene, or ethylene-vinyl acetate bag, or a glass vial for intravenous infusion, that contains 250ml of 0.9% sodium chloride injection. Do not use with solutions that contain glucose. The bag or vial should be inverted several times to mix the solution and prevent foam formation. Parenteral solutions should be visually inspected for particles and discoloration before administration.