Herzuma 420 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Herzuma 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 adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Herzuma is and what it is used for

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

Your doctor may prescribe Herzuma 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 tumour has spread) with high levels of HER2. Herzuma 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 the presence of female sex hormones).
• you have metastatic gastric cancer with high levels of HER2, and it is used in combination with other cancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before using Herzuma

Do not use Herzuma 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 treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac evaluations

Treatment with Herzuma alone or in combination with a taxane may affect the heart, especially if you have previously received an anthracycline (taxanes and anthraciclines are two types of medicines used to treat cancer). The effects may range from moderate to severe and may be fatal. Therefore, your cardiac function must be evaluated before, during (every three months), and after (up to two to five years) treatment with Herzuma. If you develop any signs of heart failure (inadequate blood pumping 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 Herzuma.

Consult your doctor, pharmacist, or nurse before receiving Herzuma 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 the heart muscle and increase the risk of heart problems when treated with trastuzumab.

• you feel short of breath, especially if you are currently receiving a taxane. Trastuzumab can cause difficulty breathing, particularly when first administered. This may 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 previously received any other cancer treatment.

If you receive Herzuma 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

Herzuma is not recommended for patients under 18 years of age.

Other medicines and Herzuma

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

Pregnancy

• 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 Herzuma and for at least 7 months after the end of treatment.
• Your doctor will explain the risks and benefits of taking Herzuma 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 Herzuma. 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 Herzuma and for 7 months after the last dose of Herzuma, as Herzuma may pass into your breast milk and reach your baby.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Herzuma 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 machinery until these symptoms resolve.

Sodium

Herzuma contains less than 1 mmol of sodium (23 mg) per dose; this is considered “essentially sodium-free”.

Polysorbate 20

This medicine contains 1.7 mg of polysorbate 20 in each 420 mg dose unit. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Herzuma

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

Herzuma 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 effects. 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 Herzuma (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, Herzuma is administered every 3 weeks. Herzuma may also be given once a week for metastatic breast cancer.

If you interrupt treatment with Herzuma

Do not stop treatment with this medicine without first talking 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 that your medicine works properly.

It may take up to 7 months for Herzuma 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, this medicine can cause adverse effects, although not everyone will experience them. Some of these adverse effects may be serious and require hospitalization.

During infusion of Herzuma, 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 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 starting 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 administered more slowly or stopped, and you may be given treatment to counteract the adverse effects. The infusion may be resumed 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 serious adverse effects may occur at any time during treatment with Herzuma, not only during infusion. Inform your doctor or nurse if you experience any of the following:

• 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 may lead to heart failure, inflammation of the membrane 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, Cardiac monitoring).

Your doctor will periodically monitor your heart function 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 occurring 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 (palpitations or faster or slower heart rate), seizures, vomiting or diarrhea, and tingling in the mouth, hands, or feet.

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

Other 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 (which 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 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

Other common adverse effects (may affect up to 1 in 10 people):

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

• deafness
• skin rash with blisters
• wheezing (whistling breathing)
• inflammation/scarring of the lungs

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

• jaundice
• anaphylactic reactions

Other side effects with unknown frequency (frequency 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 Herzuma 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 type of side effect, talk to your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Herzuma

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

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

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

Infusion solutions should be used immediately after dilution. Do not use Herzuma 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. Package contents and other information

Composition of Herzuma

The active substance is trastuzumab. Each vial contains 420 mg of trastuzumab, which is dissolved in 20 ml of water for injections. The resulting solution contains approximately 21 mg/ml of trastuzumab.

• The other components are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Appearance of the product and contents of the container

• Herzuma is a powder for concentrate for solution. It is supplied in a glass vial with a rubber stopper containing 420 mg of trastuzumab. It is a white to pale yellow pellet-shaped lyophilisate. Each Herzuma pack contains 1 or 2 vials. Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Celltrion Healthcare Hungary Kft.
Váci út 1-3. WestEnd Office Building B tower
1062 Budapest
Hungary

Manufacturer

Nuvisan GmbH
Wegenerstraße 13,
89231 Neu Ulm,
Germany

Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France

Kymos S.L.
Ronda Can Fatjó 7B
(Parc Tecnològic del Vallès)
Cerdanyola del Vallès,
08290 Barcelona,
Spain

Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany

For further information on this medicine, please contact the local representative of the Marketing Authorisation Holder:

Date of last review of this summary: <{MM/YYYY}>.

Other sources of information

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

This summary 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 medicine being prepared and administered is Herzuma (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

Always keep this medicine in its original closed packaging in a refrigerator at a temperature between 2°C and 8°C.

Appropriate aseptic methods 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.

The Herzuma vial reconstituted aseptically with sterile water for injections (not supplied) is chemically and physically stable for 7 days 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 Herzuma has been demonstrated for up to 30 days at 2°C – 8°C and for 24 hours at temperatures not exceeding 30°C.

From a microbiological standpoint, the reconstituted solution and the Herzuma infusion solution should be used immediately. If not used immediately, the storage time prior to use and the storage conditions shall be the responsibility of the user and, in general, should not exceed 24 hours between 2°C – 8°C, unless the reconstitution and dilution were carried out 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 trained 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.

Each Herzuma vial 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 21 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 4% overfill allows the labeled dose of 420 mg to be withdrawn from each vial.

Herzuma must be handled carefully during reconstitution. Excessive foaming during reconstitution or agitation of the reconstituted Herzuma may cause difficulties in withdrawing the full amount of Herzuma from the vial.

Instructions for aseptic reconstitution:

1. Using a sterile syringe, slowly inject 20 ml of sterile water for injections into the vial containing the lyophilized Herzuma, directing the stream onto the lyophilized powder.
2. Gently swirl to assist reconstitution. DO NOT SHAKE!

Slight foaming after reconstitution is normal. Allow the vial to stand for approximately 5 minutes. The reconstituted Herzuma is a clear, colorless to pale yellow solution and should be essentially free from 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 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 for subsequent doses)

21 (mg/ml, concentration of 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 for subsequent doses)

21 (mg/ml, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to an infusion bag made of polyvinyl chloride, polyethylene, or polypropylene containing 250 ml of 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 avoid foam formation. Parenteral solutions should be inspected visually for particles and discoloration prior to administration.