Prospect: information for the user

Herzuma 150mg powder for concentrate for solution for infusion

trastuzumab

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully 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 do not appear in this prospect. See section 4.

1.What is Herzuma and what it is used for

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

3.How to use Herzuma

4.Possible adverse effects

5.Storage of Herzuma

6.Contents of the package and additional information

Herzuma contains trastuzumab as its active ingredient, 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 Herzuma binds to HER2, it slows down the growth of these cells, causing them to die.

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 tumor has spread) with high levels of HER2. Herzuma 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.

Do not use Herzuma:

?if you are allergic to trastuzumab, mouse proteins, or any of the other components of this medication (including those 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

Consult your doctor or nurse before starting to use Herzuma

Your doctor will closely monitor your treatment.

Cardiac reviews

Treatment with Herzuma 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 Herzuma. 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 Herzuma.

Consult your doctor, pharmacist, or nurse before Herzuma is administered 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 anthracycline) may 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 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 difficulties before treatment have died when trastuzumab was administered.

?you have ever had any other cancer treatment.

If you receive Herzuma 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 for these medications.

Children and adolescents

Herzuma is not recommended for individuals under 18 years.

Other medications and Herzuma

Use of Herzuma with other medications: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 Herzuma to be completely eliminated from the body. Therefore, if you are to take any new medication within 7 months after completing treatment, you should inform your doctor, pharmacist, or nurse that you have been treated with Herzuma.

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 must use an effective contraceptive method during treatment with Herzuma and for at least 7 months after completing treatment.

?Your doctor will explain the risks and benefits of taking Herzuma 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 Herzuma. This can be harmful to the fetus and has been associated with underdeveloped lungs resulting in fetal death.

Breastfeeding

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

Consult your doctor or pharmacist before taking a medication.

Driving and operating machinery

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

Sodium

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

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

Herzuma is administered as an intravenous infusion (“drip”) directly into a vein. The first dose of your treatment is administered over approximately 90minutes and you will be monitored by a healthcare professional while receiving it, in case any adverse effects occur. If the initial dose has been well tolerated, subsequent doses may be administered in 30minutes (seesection2“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 Herzuma (trastuzumab) and not trastuzumab emtansine.

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

If You Interrupt Treatment with Herzuma

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

It may take up to 7months 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 other questions about using this medication, ask your doctor, pharmacist, or nurse.

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

During the administration of a Herzuma infusion, you may experience chills, fever, and other symptoms similar to the flu. This is very common (can affect more than 1 in 10 people). Other infusion-related symptoms include: feeling unwell (nausea), vomiting, pain, muscle tension, agitation, headache, dizziness, difficulty breathing, wheezing (whistling), decreased or increased blood pressure, heart rhythm changes (palpitations, arrhythmias, or irregular heartbeat), facial and lip swelling, rash, and feeling tired. Some of these symptoms can be serious 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 temporary. 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 stop 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, contact your doctor immediately. Sometimes, symptoms can improve and worsen later.

Severe side effects

Other side effects can occur at any time during treatment with Herzuma 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 serious. These effects include weakened heart muscle that may cause heart failure, inflammation of the heart's outer layer, and heart rhythm changes. This can cause symptoms such as shortness of breath (even at night), coughing, 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.

• The 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, shortness of breath, fatigue, and confusion), heart problems (palpitations or irregular heartbeat), seizures, vomiting, diarrhea, and tingling in the mouth, hands, or feet.

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

Very common side effects(can 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 helps fight infection) sometimes with fever

?muscle pain

?conjunctivitis

?tearfulness

?nasal bleeding

?nasal discharge

?hair loss

?shaking

?seizures

?headache

?dizziness

?change in nails

?weight loss

?loss of appetite

?difficulty sleeping (insomnia)

?change in taste

?low platelet count

?cardinal signs

?numbness or tingling in the fingers of the hands and feet

?redness, swelling, or ulcers in the mouth and/or throat

?pain, swelling, redness, or tingling in the hands and/or feet

?difficulty breathing

?headache

?coughing

?vomiting

?nausea

Common side effects(can affect up to 1 in 10 people):

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

?jaundice

?anaphylactic reactions

Other side effects reported with the use of Herzuma(the frequency cannot be estimated from the available data):

?abnormal blood clotting or bleeding

?high potassium levels

?inflammation or bleeding in 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 oxygen levels in the blood

?difficulty breathing while lying down

?liver damage

?inflammation of the face, lips, and throat

?kidney failure

?abnormally low fluid levels 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 may 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.

If you experience side effects, consult 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 is a possible side effect that does not appear in this leaflet. You can also report them directly through theAppendix Vincluded in thenational notification system. 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 CAD. The expiration date is the last day of the month indicated.

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

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 disposed of 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.

Composition of Herzuma

?The active ingredient is trastuzumab. Each vial contains 150 mg of trastuzumab that dissolves in 7.2 ml of water for injectable preparations. The resulting solution contains approximately 21 mg/ml of trastuzumab.

?The other components are L-histidine hydrochloride, L-histidine, α,α-trehalose dihydrate, and polisorbate 20.

Appearance of the product and contents of the package

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

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B tower

Hungary

Manufacturer

Millmount Healthcare Ltd.

Block 7

City North Business Campus

Stamullen, Co. Meath K32 YD60

Ireland

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

Last review date of this leaflet:<{MM/AAAA}>.

Other sources of information

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

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

This information is intended solely for healthcare professionals

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

Use appropriate aseptic methods for the preparation of the infusion solution. Ensure the sterility of the prepared solutions. As the medication does not contain antimicrobial preservatives or bacteriostatic agents, use aseptic technique.

The Herzuma vial reconstituted aseptically with sterile water for injectable preparations (not supplied) is chemically and physically stable for 7 days at 2°C to 8°C after reconstitution and should not be frozen.

After aseptic dilution in polyvinyl chloride, polyethylene, or polypropylene bags containing 0.9% sodium chloride solution, the physical and chemical stability of Herzuma has been demonstrated for a period of up to 30 days at 2°C to 8°C and 24 hours at a temperature not exceeding 30°C.

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

Storage, handling, and aseptic preparation

Ensure aseptic handling 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 biosafety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared infusion solution to ensure maintenance of aseptic conditions.

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

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

Instructions for aseptic reconstitution:

1) Using a sterile syringe, slowly inject 7.2 ml of sterile water for injectable preparations into the vial containing the Herzuma lyophilisate, directing the flow towards the lyophilisate.

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

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

Instructions for aseptic dilution of the reconstituted solution

Determine the required solution volume:

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

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

21(mg/ml, reconstituted solution concentration)

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

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

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

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

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

21(mg/ml, reconstituted solution concentration)

Determine the required solution volume:

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

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

21(mg/ml, reconstituted solution concentration)

The appropriate amount of solution should be extracted from the vial and added to a polyvinyl chloride, polyethylene, or polypropylene bag containing 250 ml of 0.9% sodium chloride 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 should be visually inspected for particles and discoloration before administration.