ZERCEPAC 150 MG POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Zercepac 60 mg powder for concentrate for solution for infusion

Zercepac 150mg powder for concentrate for solution for infusion

Zercepac 420mg powder for concentrate for solution for infusion

trastuzumab

This medicine is subject to additional monitoring, which will help to quickly identify new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

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 get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Zercepac and what is it used for

Zercepac contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies recognize specific 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 quantities on the surface of some cancer cells and stimulates the growth of these cells. When Zercepac binds to HER2, it slows down the growth of these cells, causing them to die.

Your doctor may prescribe Zercepac 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. Zercepac may be prescribed in combination with chemotherapy medicines paclitaxel or docetaxel as first treatment for metastatic breast cancer or 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 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 used in combination with other cancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before you use Zercepac

Zercepac Do not use Zercepac:

• if you are allergic to trastuzumab, mouse proteins, or any of the other ingredients of this medicine (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 monitoring

Treatment with Zercepac alone or in combination with a taxane may affect the heart, especially if you have received an anthracycline (taxanes and anthracyclines are two types of medicines 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 3 months), and after (up to 2 to 5 years) treatment with Zercepac. If you develop any signs of heart failure, (inadequate pumping of blood by the heart), your heart function will be checked more frequently (every 6 to 8 weeks), you may receive treatment for heart failure, or you may need to stop treatment with Zercepac.

Talk to your doctor, pharmacist, or nurse before you are given Zercepac if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmur), or high blood pressure, have taken any medicine for high blood pressure, or are currently taking any medicine for high blood pressure.
• you have received doxorubicin or epirubicin (cancer medicines) in the past or are currently receiving them. These medicines (or any other anthracycline) can damage the heart muscle and increase the risk of heart problems when treated with Zercepac.
• you feel short of breath, especially if you are currently receiving a taxane. Zercepac 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 Zercepac.
• you have had any other cancer treatment in the past.

If you receive Zercepac with any other cancer medicine, 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

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

Other medicines and Zercepac

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

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

Pregnancy

• You must use an effective method of contraception during treatment with Zercepac and for at least 7 months after finishing treatment.
• Your doctor will explain the risks and benefits of taking Zercepac during pregnancy. In rare cases, a decrease in the fluid surrounding the developing baby in the womb (amniotic fluid) has been observed in pregnant women who received Zercepac. This can be harmful to the baby in the womb and has been associated with underdeveloped lungs, resulting in fetal death.

Breast-feeding

You must not breast-feed your baby during therapy with Zercepac and for 7 months after the last dose of Zercepac, as Zercepac may pass into your breast milk.

Talk to your doctor or pharmacist before taking any medicine.

Driving and using machines

Zercepac may affect your ability to drive or use machines. If you experience symptoms during treatment, such as dizziness, drowsiness, chills, or fever, do not drive or use machinery until these symptoms have disappeared.

Sodium

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

3. How to use Zercepac

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

The intravenous formulation of Zercepac is administered as an intravenous infusion ("drip") directly into a vein. The first dose of your treatment is administered over approximately 90 minutes and will be monitored 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 can receive will depend on your response to treatment. Your doctor will inform you about this.

To avoid medication errors, it is important to check the labels on the vials to ensure that the medicine being prepared and administered is Zercepac (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, Zercepac will be administered every 3 weeks. Zercepac can also be administered once a week for metastatic breast cancer.

If you stop treatment with Zercepac

Do not stop treatment with this medicine without talking to your doctor first. All doses should be taken at the right time every week or every 3 weeks (depending on your dosing schedule). This helps your medicine work properly.

It may take up to 7 months for Zercepac 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 on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Zercepac can cause side effects, although not everybody gets them. Some of these side effects can be serious and may require hospitalization.

Serious side effects

During administration of a Zercepac infusion, chills, fever, and other flu-like symptoms may occur. This is very common (affects more than 1 in 10 people). Other infusion-related symptoms 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 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 6 hours after the start of the first infusion and for 2 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.

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

• Heart problems can occur during treatment and occasionally after stopping treatment, and these can be serious. These include weakening of the heart muscle that can lead to heart failure, inflammation of the layer surrounding the heart (swelling, redness, heat, and pain), 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) of the legs or arms, palpitations (arrhythmias or irregular heartbeat) (see section 2. Cardiac monitoring)

Your doctor will regularly check your heart 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 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, 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 Zercepac has finished, you should talk to your doctor and inform them that you have been previously treated with Zercepac.

Other side effects

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rash (hives)
• 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 of the hands and feet, 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:

• allergic reactions
• throat infections
• bladder and skin infections
• breast inflammation
• liver inflammation
• kidney disorders
• increased muscle tone (hypertonia)

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

• deafness
• skin rash with blisters
• wheezing (sibilant rhonchi)
• inflammation/scarring of the lungs

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

• jaundice
• anaphylactic reactions

Side effects of unknown frequency:cannot be estimated from the available data:

• abnormal blood clotting or coagulation disorders
• high levels of potassium
• 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 when lying down
• liver damage
• inflammation 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 have may be due to your cancer. If you are given Zercepac in combination with chemotherapy, some of the effects may also be due to the chemotherapy itself.

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

Reporting of 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 via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zercepac

Zercepac 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 which is stated on the carton and vial label after EXP. The expiry date is the last day of the month shown.
• Unopened vials should be stored in a refrigerator (2°C to 8°C).
• Do not freeze the reconstituted solution.
• Infusion solutions should be used immediately after dilution. If not used immediately, the in-use storage times and conditions are the responsibility of the user.
• Do not use Zercepac if you notice any particles or discoloration before administration.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Zercepac Composition

• The active ingredient is trastuzumab. Each vial contains either
• 60 mg of trastuzumab that dissolves in 3.0 ml of sterile water for injectable preparations, or
• 150 mg of trastuzumab that dissolves in 7.2 ml of water for injectable preparations, or
• 420 mg of trastuzumab that dissolves in 20.0 ml of sterile water for injectable preparations.

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

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

Product Appearance and Container Content

Zercepac is a powder for concentrate for solution for intravenous infusion, presented in a glass vial with a rubber stopper containing 60mg, 150 mg, or 420 mg of trastuzumab. It is a lyophilized powder in a white to pale yellow pellet. Each container contains 1 vial of powder.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona, Spain

Manufacturer

Accord Healthcare Polska Sp. z.o.o

ul Lutomierska 50, 95-200 Pabianice

Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

Date of Last Revision of this Leaflet: <{MM/AAAA}>

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

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

This information is intended for healthcare professionals only:

Zercepac IV is provided in sterile, preservative-free, non-pyrogenic, single-use vials.

To avoid medication errors, it is essential to check the labels of the vials to ensure that the medication being prepared and administered is Zercepac (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.

Since the medication does not contain antimicrobial preservatives or bacteriostatic agents, appropriate aseptic technique should be used for the reconstitution and dilution procedures. Care should be taken to ensure the sterility of the prepared solutions.

The vial of Zercepac reconstituted aseptically 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 polyethylene or polypropylene bags containing 9 mg/ml (0.9%) sodium chloride injection solution, the physical and chemical stability of Zercepac has been demonstrated for a period of up to 84 days at 2°C to 8°C, 7 days at 23°C to 27°C, and 24 hours at 30°C.

From a microbiological point of view, the reconstituted solution and the infusion solution of Zercepac should be used immediately. If not used immediately, the storage time until use and the storage conditions prior to use will be the responsibility of the user, unless the reconstitution and dilution take place under controlled and validated aseptic conditions.

Storage, handling, and aseptic preparation:

The preparation of the infusion should be:

• developed 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.

Instructions for Aseptic Reconstitution:

1. Using a sterile syringe, slowly inject the corresponding volume (as indicated below) of sterile water for injectable preparations (not supplied) into the vial containing the lyophilized Zercepac, directing the flow towards the lyophilized material. The use of other solvents for reconstitution should be avoided.
2. Gently swirl in circles to aid reconstitution. DO NOT SHAKE!

The formation of a slight foam after reconstitution is usual. Let the vial stand for approximately 5 minutes. The reconstituted Zercepac is a clear, colorless to pale yellow solution and should be essentially free of visible particles.

Zercepac 60 mg powder for concentrate for solution for infusion.

Reconstitution of the 60 mg vial with 3.0 ml of sterile water for injection produces a 3.1 ml solution for single dose that contains 21 mg/ml of trastuzumab, at a pH of approximately 6.0. An overfill of 8% allows the dose of 60 mg stated on the label to be withdrawn from each vial.

Zercepac 150 mg powder for concentrate for solution for infusion.

Reconstitution of the 150 mg vial with 7.2 ml of sterile water for injection produces a 7.5 ml solution for single dose that contains 21 mg/ml of trastuzumab, at a pH of approximately 6.0. An overfill of 5% allows the dose of 150 mg stated on the label to be withdrawn from each vial.

Zercepac 420 mg powder for concentrate for solution for infusion

Reconstitution of the 420 mg vial with 20.0 ml of sterile water for injection produces a 20.6 ml solution for single dose that contains approximately 21 mg/ml of trastuzumab, at a pH of approximately 6.0. An overfill of 3% allows the dose of 420 mg stated on the label to be withdrawn from each vial.

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

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) x 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) x 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 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 inspected visually for particles and discoloration before administration.