Kanjinti 420 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

KANJINTI 150 mg powder for concentrate for solution for infusion

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

1. What KANJINTI is and what it is used for

KANJINTI 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 trastuzumab binds to HER2, the growth of these cells is slowed down, leading to their death.

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 medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer, or it may be prescribed only if other treatments have not been successful. It is also used in combination with other medicines 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 used in combination with other anticancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before using KANJINTI

Do not use KANJINTI:

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

• if you have severe breathing problems at rest due to your tumour or if you require oxygen treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Heart checks

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 medicines used to treat cancer). The effects may range from moderate to severe and may result in death. Therefore, your heart function must be 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 monitored 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), high blood pressure, have taken any medicine for high blood pressure, or are currently taking any medicine for high blood pressure.
• you have ever received or are currently receiving a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage the heart muscle and increase the risk of heart problems during treatment with KANJINTI.
• you feel short of breath, especially if you are currently receiving a taxane. KANJINTI can cause difficulty breathing, particularly when first administered. 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 when given trastuzumab.
• you have previously received any other cancer treatment.

If you are receiving KANJINTI 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

KANJINTI is not recommended for use in patients under 18 years of age.

Other medicines and KANJINTI

Use of KANJINTI with other medicines: 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 KANJINTI 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 KANJINTI.

Pregnancy and breastfeeding

• If you are pregnant, think you may 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 KANJINTI and for at least 7 months after the end of treatment.
• Your doctor will explain the risks and benefits of taking KANJINTI during pregnancy. In rare cases, a reduction in the fluid surrounding the developing baby in the womb (amniotic fluid) has been observed in pregnant women who received trastuzumab. This may harm the unborn baby and has been associated with underdeveloped lungs, resulting in fetal death.

Breastfeeding

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

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

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

Sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; that 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 must be administered only by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen appropriate for you. The dose of KANJINTI depends on your body weight.

It is important to review the medicine labeling to ensure that the correct formulation prescribed is being administered. The intravenous formulation of KANJINTI is not for subcutaneous administration and must be administered only intravenously.

The intravenous formulation of KANJINTI 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 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 weekly for metastatic breast cancer.

If you interrupt treatment with KANJINTI

Do not stop treatment with this medicine without first speaking 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 ensure your medicine works properly.

KANJINTI may take up to 7 months 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 how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, KANJINTI can produce adverse effects, although not everyone experiences them. Some of these adverse effects may be serious and 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 may be serious, and some patients have died (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 subsequent infusions. If you have a reaction, the infusion may be slowed down 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, 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 trastuzumab, not only related to the infusion. Tell your doctor or nurse if you experience any of the following adverse effects:

• Heart problems may sometimes occur during treatment and occasionally after stopping treatment, 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 arms or legs, palpitations (arrhythmias or irregular heartbeat) (see section 2. Cardiac monitoring).

Your doctor will periodically monitor your heart function during and after treatment, but you must notify 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 blood calcium levels). Symptoms may include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (heart palpitations or faster or slower heartbeat), seizures, 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 must consult your doctor and inform them that you have previously been treated with KANJINTI.

Other adverse effects

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

• infections
• diarrhea
• constipation
• stomach burning (dyspepsia)
• fatigue
• skin rash (cutaneous rash)
• chest pain
• abdominal pain
• joint pain
• low red and white blood cell counts (white blood cells help fight infection), sometimes with fever
• muscle pain
• conjunctivitis
• tearing
• nosebleeds
• nasal discharge
• hair loss
• tremor
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• taste disturbance
• low platelet count
• bruising
• numbness or tingling in fingers and toes, which may 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 adverse effects (may affect up to 1 in 10 people):

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

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

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

• jaundice
• anaphylactic reactions

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

• abnormal blood clotting or failure to clot
• high levels of potassium
• inflammation or bleeding at the back of the eyes
• shock
• irregular 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 adverse effects you may experience could be due to your cancer. If you are given KANJINTI in combination with chemotherapy, some of the effects may also be due to the chemotherapy itself.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of KANJINTI

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

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 - 8°C). Do not freeze the reconstituted solution. Keep in the original packaging to protect from light.

Infusion solutions should be used immediately after dilution. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user and, in general, should not exceed 24 hours at 2°C - 8°C. Do not use this medicine if you notice any foreign particles or discoloration before administration.

Medicines must 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. Contents of the pack and other information

Composition of KANJINTI

The active substance is trastuzumab. Each vial contains:

• 150 mg of trastuzumab dissolved in 7.2 ml of water for injections, or

• 420 mg of trastuzumab dissolved in 20 ml of water for injections.

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

• The other components are histidine, histidine monohydrochloride, trehalose dihydrate, polysorbate 20.

Appearance of the product and contents of the container

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

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:
Amgen Europe B.V.
Minervum 7061,
NL-4817 ZK Breda,
The Netherlands

Marketing Authorization Holder

Amgen Europe B.V.
Minervum 7061,
NL-4817 ZK Breda,
The Netherlands

Manufacturer

Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet

Other sources of information

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

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

This information is intended for healthcare professionals only

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

Always keep this medicinal product in its original closed packaging at a temperature of 2°C - 8°C in a refrigerator.

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

The vial of KANJINTI reconstituted aseptically with sterile 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.

After aseptic dilution into 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 up to 30 days at 2°C - 8°C and subsequently for 24 hours at temperatures not exceeding 30°C.

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

Storage, handling and aseptic preparation:

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

• be carried out under aseptic conditions by qualified personnel in accordance with good practices, especially regarding the aseptic preparation of parenteral products;
• be prepared in a laminar airflow cabinet or biological safety cabinet using standard precautions for the safe handling of intravenous agents;
• be followed by appropriate storage of the prepared intravenous infusion solution 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 injections (not supplied). The use of other solvents for reconstitution should be avoided. This results in a 7.4 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 4% overfill volume allows the 150 mg dose indicated on the label 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 injections (not supplied). The use of other solvents for reconstitution should be avoided. This results in a 21 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 5% overfill volume allows the 420 mg dose indicated on the label to be withdrawn from each vial.

Aseptic reconstitution instructions

Handle KANJINTI carefully during reconstitution. Excessive foaming during reconstitution or agitation of the reconstituted solution may cause problems in accurately withdrawing the intended amount of KANJINTI from the vial.

1. Using a sterile syringe, slowly inject the appropriate volume (as described above) of sterile water for injection into the vial containing the lyophilized KANJINTI, directing the stream onto the lyophilized powder.

2. Gently swirl to aid reconstitution. DO NOT SHAKE.

Slight foaming after reconstitution is normal. Allow the vial to stand undisturbed for approximately 5 minutes. The reconstituted KANJINTI is a clear, colorless to pale yellow solution and should be essentially free of visible particles.

Aseptic dilution instructions for the reconstituted solution

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) × Dose (4 mg/kg initial dose or 2 mg/kg 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) × Dose (8 mg/kg initial dose or 6 mg/kg 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 sodium chloride 9 mg/ml (0.9%) for injection. Do not use with glucose-containing solutions. The bag should be inverted several times to mix the solution and avoid foaming. Parenteral solutions should be visually inspected for particulate matter and discoloration prior to administration.