KANJINTI 420 MG POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

Introduction

PATIENT INFORMATION LEAFLET

KANJINTI 150 mg powder for concentrate for solution for infusion

KANJINTI 420 mg powder for concentrate for solution for infusion

trastuzumab

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 further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is KANJINTI and what is it used for

KANJINTI contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies recognize specific proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called human epidermal growth factor receptor 2 (HER2). 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 breast cancer with high levels of a protein called HER2.
• you have metastatic breast cancer (breast cancer that has spread from the original tumor) with high levels of HER2. KANJINTI may be prescribed in combination with chemotherapy medications such as paclitaxel or docetaxel as a 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 medications called aromatase inhibitors in patients with high levels of HER2 and positive hormone receptor for metastatic breast cancer (cancer that is sensitive to female sex hormones).
• you have metastatic gastric cancer with high levels of HER2, and it is combined with other cancer medications such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before you use KANJINTI

Do not 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 with a taxane may affect the heart, especially if you have received an anthracycline (taxanes and anthracyclines are two types of medications used to treat cancer) in the past. The effects can be moderate to severe and can be fatal. Therefore, you will need to have your heart function checked 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 pumping of blood by the heart), your heart function will be checked more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to stop treatment with KANJINTI.

Talk to your doctor, pharmacist, or nurse before you are given 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 received or are currently receiving a medication called doxorubicin or epirubicin (medications for treating cancer). These medications (or any other anthracyclines) can 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 can 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 breathing difficulties before treatment have died when given trastuzumab.
• you have had any other cancer treatment in the past.

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

Children and adolescents

KANJINTI is not recommended for children under 18 years of age.

Other medications and KANJINTI

Using KANJINTI with other medications: Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medication.

It may take up to 7 months for KANJINTI to be completely eliminated from your body. Therefore, if you are going to take any new medication within 7 months after finishing treatment, you should tell your doctor, pharmacist, or nurse that you have been treated with KANJINTI.

Pregnancy and breastfeeding

• You must use an effective contraceptive method during treatment with KANJINTI and for at least 7 months after finishing 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 baby in the uterus (amniotic fluid) has been observed in pregnant women who received trastuzumab. This can be harmful to the baby in the uterus and has been associated with underdeveloped lungs, resulting in fetal death.

Breastfeeding

You should not breastfeed your baby during therapy with KANJINTI and up to 7 months after the last dose, as KANJINTI may pass into your milk.

Talk to your doctor or pharmacist before taking any medication.

Driving and using machines

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 disappear.

Sodium

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

3. How to use KANJINTI

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

It is essential to check the labeling of the medication 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 approximately 90 minutes, and you will be observed by a healthcare professional while it is being administered, in case any adverse reaction occurs. If the initial dose has been well tolerated, subsequent doses may be administered over 30 minutes (see section 2 "Warnings and precautions"). The number of infusions you may receive will depend on your response to treatment. Your doctor will inform you about this.

To avoid medication errors, it is crucial 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 breast cancer, metastatic breast cancer, and metastatic gastric cancer, KANJINTI will be administered every 3 weeks. KANJINTI may also be administered once a week for metastatic breast cancer.

If you interrupt treatment with KANJINTI

Do not stop treatment with this medication 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 medication work properly.

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 you finish treatment.

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

4. Possible side effects

Like all medications, KANJINTI can cause side effects, although not everyone gets them. Some of these side effects can be serious and may require hospitalization.

During administration of a KANJINTI 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, 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 effects usually occur during the first intravenous infusion ("drip" into a vein) and during the first few hours after the start of the infusion. They are usually temporary. 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 subsequent infusions. If you have any reaction, the infusion may be administered more slowly or stopped, and you may be given treatment to counteract the side effects. The infusion can continue once your symptoms have improved.

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

Severe side effects

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

• Heart problems can occur during treatment and occasionally after stopping treatment, and these can be severe. These include weakening of the heart muscle that can lead to heart failure, inflammation of the layer surrounding the heart, and changes in heart rhythm. This can cause symptoms such as shortness of breath (even if it is 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 regularly during and after treatment, but you should tell your doctor immediately if you notice any of the symptoms mentioned above.

• Tumor lysis syndrome (a set of metabolic complications that occur after cancer treatment, 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, shortness of breath, fatigue, and confusion), heart problems (heart palpitations or a faster or slower heartbeat), seizures, vomiting, or diarrhea, and tingling in the mouth, hands, or feet.

If you experience any of these symptoms when your treatment with KANJINTI has finished, you should talk to 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 count of red and white blood cells (which help fight infection) sometimes with fever
• muscle pain
• conjunctivitis
• tearing
• nasal bleeding
• nasal discharge
• hair loss
• tremors
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling in the fingers and toes, which can occasionally extend 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 side effects(may affect up to 1 in 10 people):

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

• hearing loss
• skin rash with blisters
• wheezing (whistling)
• inflammation/scarring of the lungs

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

• jaundice
• anaphylactic reactions

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

• abnormal blood clotting or coagulation failure
• high levels of potassium
• inflammation or bleeding in the back of the eyes
• shock
• abnormal heart rhythm
• difficulty breathing
• respiratory failure
• acute fluid accumulation 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
• kidney 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 given KANJINTI in combination with chemotherapy, some of the side effects may also be due to the chemotherapy itself.

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

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects 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 medication.

5. Storage of KANJINTI

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

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

Do not use this medication after the expiration date stated on the carton and on the label of the vial after EXP. The expiration date is the last day of the month shown.

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

Infusion solutions should be used immediately after dilution. If not used immediately, the storage time before use and storage conditions are the responsibility of the user and should not exceed 24 hours between 2°C and 8°C. Do not use this medication if you notice any foreign particles or discoloration before administration.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Container Contents and Additional Information

KANJINTI Composition

The active ingredient is trastuzumab. Each vial contains:

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

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

Product Appearance and Container Contents

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

Marketing Authorization Holder and Manufacturer

Amgen Europe B.V.

Minervum 7061,

NL-4817 ZK Breda,

Netherlands

Authorization Holder

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 marketing authorization holder:

Date of Last Revision of this Prospectus

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/

The prospectus can be found on the European Medicines Agency website 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.

A suitable aseptic technique should be used 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, an aseptic technique should be used.

The aseptically reconstituted vial of KANJINTI with sterile water for injectable preparations (not supplied) is chemically and physically stable for 48 hours at 2°C - 8°C after reconstitution and should not be frozen.

After aseptic dilution in polyvinyl chloride, polyethylene, or polypropylene bags containing 9 mg/ml (0.9%) sodium chloride injection solution, the physical and chemical stability of KANJINTI has been demonstrated for a period of up to 30 days at 2°C - 8°C and subsequently for 24 hours at a temperature not exceeding 30°C.

From a microbiological point of view, the reconstituted solution and the infusion solution of KANJINTI should be used immediately. If not used immediately, the storage time before use and the storage conditions will be the responsibility of the user and, in general, should not exceed 24 hours at 2°C to 8°C, unless the reconstitution and dilution are performed under controlled and validated aseptic conditions.

Storage, handling, and aseptic preparation:

Aseptic handling should be ensured when preparing the infusion. The preparation should 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 usual precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared infusion solution for intravenous administration to ensure the 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 single-dose solution of 7.4 ml containing approximately 21 mg/ml of trastuzumab. A 4% overfill allows the labeled dose of 150 mg to be withdrawn 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 single-dose solution of 21 ml containing approximately 21 mg/ml of trastuzumab. A 5% overfill allows the labeled dose of 420 mg to be withdrawn from each vial.

Instructions for Aseptic Reconstitution

KANJINTI should be handled carefully during reconstitution. If excessive foam is produced during reconstitution or the reconstituted solution is shaken, it may cause problems with the amount of KANJINTI that can be withdrawn 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.

1. Gently swirl in a circular motion to aid reconstitution. DO NOT SHAKE.

The formation of a slight foam after reconstitution is normal. Allow the vial to stand for approximately 5 minutes. The reconstituted KANJINTI is a clear, colorless to pale yellow solution and 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:

Volume(ml) = Body Weight(kg) × Dose(4mg/kg initial dose or 2mg/kg for subsequent doses)

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

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

Volume(ml) = Body Weight(kg) × Dose(8mg/kg initial dose or 6mg/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 a polyvinyl chloride, polyethylene, or polypropylene infusion bag containing 250 ml of 9 mg/ml (0.9%) sodium chloride injection solution. It should not be used with solutions containing glucose. The bag should be inverted several times to mix the solution and avoid foam formation. Parenteral solutions should be visually inspected for particles and discoloration before administration.