PATIENT INFORMATION: PACKAGE INSERT

KANJINTI 150 mg powder for concentrate for solution for infusion

KANJINTI 420 mg powder for concentrate for solution for infusion

trastuzumab

Read this entire package insert carefully before starting to use this medicine, because it contains important information for you.

- Keep this package insert, as you may need to read it again.

- If you have any questions, consult your doctor or pharmacist.

- If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is KANJINTI and how is it used

2. What you need to know before starting to use KANJINTI

3. How to use KANJINTI

4. Possible adverse effects

5. Storage of KANJINTI

6. Contents of the package and additional information

KANJINTI 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 trastuzumab binds to HER2, it slows down the growth of these cells, causing them to die.

Your doctor may prescribe KANJINTI 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. KANJINTI 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 use KANJINTI:

• If you are allergic to trastuzumab, mouse proteins, or any of the other components of this medication (listed in section 6).

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

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac reviews

Treatment with KANJINTI 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 will need to review your cardiac function before, during (every three months), and after (up to two to five years) treatment with KANJINTI. If you develop any signs of heart failure, (inadequate blood pumping by the heart), your doctor will review how your heart is functioning more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to discontinue treatment with KANJINTI.

Consult your doctor, pharmacist, or nurse before receiving KANJINTI 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 (cancer medications). These medications (or any other anthracyclines) may damage the heart muscle and increase the risk of heart problems when treated with KANJINTI.

•You feel short of breath, especially if you are currently receiving a taxane. KANJINTI may cause breathing difficulties, 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 difficulties before treatment have died when given trastuzumab.

• You have ever had any other cancer treatment.

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

Children and adolescents

KANJINTI is not recommended for individuals under 18 years old.

Other medications and KANJINTI

Use of KANJINTI with other medications: Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication.

KANJINTI may take up to 7 months 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 KANJINTI.

Pregnancy and breastfeeding

• 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 KANJINTI and for at least 7 months after completing treatment.

• Your doctor will explain the risks and benefits of taking KANJINTI 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 trastuzumab. 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 KANJINTI therapy and for up to 7 months after the last dose, as KANJINTI may reach your baby through breast milk.

Consult your doctor or pharmacist before taking any medication.

Driving and operating machinery

KANJINTI 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 have resolved.

Sodium

This medication contains less than 23 mg of sodium (1 mmol) per dose; it is essentially "sodium-free".

Before starting treatment with KANJINTI, your doctor will determine the amount of HER2 in your tumor. Only patients with a large amount of HER2 will be treated with KANJINTI. KANJINTI must be administered only by a doctor or nurse. Your doctor will prescribe an appropriate dose and treatment regimen for you. The dose of KANJINTI depends on your body weight.

It is essential to review the medication labeling to ensure that the correct formulation is being administered as prescribed. The intravenous formulation of KANJINTI is not for subcutaneous administration and should only be administered intravenously.

The intravenous formulation of KANJINTI is administered as an intravenous infusion ("drip") directly into a vein. The first dose of your treatment is administered over 90 minutes, and you will be monitored by a healthcare professional while receiving it, in case any adverse reactions occur. If the initial dose has been well tolerated, subsequent doses may be administered in 30 minutes (see section 2 "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 is KANJINTI (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

For early-stage breast cancer, metastatic breast cancer, and metastatic gastric cancer, KANJINTI will be administered every 3 weeks. KANJINTI can also be administered once a week for metastatic breast cancer.

If You Interrupt Treatment with KANJINTI

Do not stop treatment with this medication without first speaking with your doctor. All doses should be taken at the correct time, either weekly or every 3 weeks (depending on your dosing schedule). This helps your medication work effectively.

It may take up to 7 months for KANJINTI to be eliminated from your body. Therefore, your doctor may decide to continue monitoring your heart function even after completing treatment.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

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

During the administration of a KANJINTI infusion, you may experience chills, fever, and other symptoms similar to the flu. This is very common (may 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, changes in heart rhythm (palpitations, arrhythmias, or irregular heartbeat), swelling of the face and lips, 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 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 during two hours after the start of the rest of the infusions. If you have any reaction, they may be able to administer the infusion more slowly or interrupt the infusion and give you a treatment to counteract the side effects. The infusion can continue once your symptoms have improved.

Occasionally, symptoms begin after 6 hours after the start of 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 trastuzumab and are not related to the infusion.Inform your doctor or nurse if you experience any of the following side effects:

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

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

• Tumor lysis syndrome (a collection 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, shorter breathing, fatigue, and confusion), heart problems (palpitations or an irregular heartbeat). Convulsions, vomiting, or diarrhea and tingling in the mouth, hands, or feet.

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

Other side effects

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

• Infections

• Diarrhea

• Constipation

• Heartburn (dyspepsia)

• Fatigue

• Skin rash

• Chest pain

• Abdominal pain

• Joint pain

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

• Muscle pain

• Conjunctivitis

• Lacrimation

• Nasal discharge

• Hair loss

• Tremor

• Hot flashes

• Dizziness

• Nail changes

• Weight loss

• Loss of appetite

• Difficulty sleeping (insomnia)

• Taste alteration

• Low platelet count

• Cardenales

• Numbness or tingling in the fingers of the hands and feet, which occasionally may 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 side effects(may affect up to 1 in 10 people):

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

• Deafness

• Rash with blisters

• Wheezing (popping sounds)

• Inflammation/cicatrisation of the lungs

Very rare side effects(may affect up to 1 in 1,000 people)

• Jaundice

• Anaphylactic reactions

Other side effects reported(frequency cannot be estimated from available data):

• Abnormal blood coagulation or coagulopathy

• 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 fluid levels surrounding the fetus in the uterus

• Failure of the lungs of the fetus to develop in the uterus

• Abnormal development of the kidneys of the fetus in the uterus

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

If you experience side effects, inform your doctor, pharmacist, or nurse.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it's possible side effects that do not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

KANJINTI will be stored by healthcare professionals in the hospital or clinic.

Keep this medication out of 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 CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C - 8°C). Do not freeze the reconstituted solution. Store in the original packaging to protect it from light.

Solutions for infusion must be used immediately after dilution.If not used immediately, the storage time until use and the conditions of such storage before use will be the responsibility of the user and, in general, should not exceed 24 hours between 2°C and 8°C.Do not use this medication if you observe any foreign particles or discoloration before administration.

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

Composition of KANJINTI

The active ingredient is trastuzumab. Each vial contains:

• 150 mg of trastuzumab that dissolves in 7.2 ml of water for injectable preparations or
• 420 mg of trastuzumab that dissolves in 20 ml of water for injectable preparations.

• The resulting solution contains approximately 21 mg/ml of trastuzumab.
• The other components are histidine, monohydrochloride of histidine, trehalose dihydrate, polisorbate 20.

Appearance of the product and contents of the package

KANJINTI is a lyophilized powder for concentrate for solution for intravenous infusion, which is presented in a glass vial with a rubber stopper that contains 150 mg or 420 mg of trastuzumab. It is a white to pale yellow pellet lyophilized powder. Each package contains 1 vial of powder.

Holder of the marketing authorization and responsible for manufacturing

Amgen Europe B.V.

Minervum 7061,

NL-4817 ZK Breda,

Netherlands

Holder of the marketing authorization

Amgen Europe B.V.

Minervum 7061,

NL-4817 ZK Breda,

Netherlands

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization:

Last review date of this leaflet

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu/

On the website of the European Medicines Agency, this leaflet can be found in all languages of the European Union/European Economic Area.

This information is intended only for healthcare professionals

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

Always keep this medication in its original closed container at a temperature of 2°C - 8°C in the refrigerator.

Aseptic technique must be ensured when preparing the infusion. The preparation must be:

• developed under aseptic conditions by qualified personnel in accordance with good practices, especially regarding the aseptic preparation of parenteral products.
• prepared in a laminar flow cabinet or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared infusion solution for intravenous administration to ensure maintenance of aseptic conditions.

KANJINTI 150 mg powder for concentrate for solution for infusion

Each vial of KANJINTI 150 mg is reconstituted with 7.2 ml of water for injectable preparations (not supplied). The use of other solvents for reconstitution should be avoided. This produces a 7.4 ml single-dose solution containing approximately 21 mg/ml of trastuzumab. A 4% overfill allows the 150 mg dose reflected on the label to be extracted from each vial.

KANJINTI 420 mg powder for concentrate for solution for infusion

Each vial of KANJINTI 420 mg is reconstituted with 20 ml of water for injectable preparations (not supplied). The use of other solvents for reconstitution should be avoided. This produces a 21 ml single-dose solution containing approximately 21 mg/ml of trastuzumab. A 5% overfill allows the 420 mg dose reflected on the label to be extracted from each vial.

Instructions for aseptic reconstitution

Handle KANJINTI carefully during reconstitution. If excessive foam is produced during reconstitution or the reconstituted solution is agitated, it may cause problems with the amount of KANJINTI that can be extracted from the vial.

1) Using a sterile syringe, slowly inject the corresponding volume (as described above) of sterile water for injectable preparations into the vial containing the KANJINTI lyophilized powder, directing the flow towards the lyophilized powder.

2) Gently move the vial in a circular motion to help reconstitution. DO NOT SHAKE.

A slight foam may form after reconstitution. Leave the vial at rest for approximately 5 minutes. The reconstituted KANJINTI is a transparent, colorless to pale yellow solution that should be essentially free of visible particles.

Instructions for aseptic dilution of the reconstituted solution

The required volume of solution will be determined:

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

Volumen(ml) =Peso corporal(kg)×dosis(4mg/kg initial dose or2mg/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 of trastuzumab/kg of body weight or every 3-week doses of 6 mg of trastuzumab/kg of body weight

Volumen(ml) =Peso corporal(kg)×dosis(8mg/kg initial dose or 6 mg/kg for subsequent doses)

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

The appropriate amount of solution will be extracted from the vial using a sterile syringe and needle and added to a 250 ml bag of infusion solution containing 9 mg/ml (0.9%) sodium chloride injection solution. Do not use with solutions containing glucose. The bag should be inverted several times to mix the solution and prevent foam formation. Parenteral solutions must be visually inspected for particles and discoloration before administration.