Zercepac 150 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Zercepac 60 mg powder for concentrate for solution for infusion

Zercepac 150 mg powder for concentrate for solution for infusion

Zercepac 420 mg powder for concentrate for solution for infusion

trastuzumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read the entire leaflet carefully before you start using this medicine, as 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 Zercepac is and what it is used for
2. What you need to know before using Zercepac
3. How to use Zercepac
4. Possible side effects
5. How to store Zercepac
6. Contents of the pack and other information

1. What Zercepac is and what it is used for

Zercepac 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 Zercepac binds to HER2, it slows down the growth of these cells, leading to their death.

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 in which the original tumour has spread) with high levels of HER2. Zercepac 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 cancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before using Zercepac

Do not use Zercepac:

• if you are allergic to trastuzumab, mouse proteins (murine proteins), or any of the other ingredients of this medicine (listed in section 6).
• if you have severe breathing problems at rest due to your tumor or if you require oxygen therapy.

Warnings and precautions

Your doctor will closely monitor your treatment.

Heart assessments

Treatment with Zercepac 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 can range from moderate to severe and may be fatal. Therefore, your heart function must be evaluated before, during (every three months), and after treatment (up to two to five years) with Zercepac. 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 Zercepac.

Consult your doctor, pharmacist, or nurse before receiving Zercepac if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmur), or high blood pressure; or if you have taken any medicine for high blood pressure or are currently taking any such medicine.
• you have ever received or are currently receiving a medicine called
• doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracycline) can damage 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, particularly when first administered. This may be more serious if you already have shortness of breath. In very rare cases, patients with severe breathing difficulties before treatment have died after receiving Zercepac.
• you have ever received any other cancer treatment.

If you are receiving Zercepac together 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 patients under 18 years of age.

Other medicines and Zercepac

Use of Zercepac 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 Zercepac 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 Zercepac.

Pregnancy and breastfeeding

• If you are pregnant, think you might 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 Zercepac and for at least 7 months after the end of treatment.
• Your doctor will explain to you the risks and benefits of taking Zercepac 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 Zercepac. This may harm the unborn baby and has been associated with underdeveloped lungs, potentially resulting in fetal death.

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

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Zercepac 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 machines until these symptoms resolve.

Sodium

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

Polysorbate 20

Zercepac contains 0.24 mg of polysorbate 20 in each 60 mg vial, equivalent to 0.08 mg/ml
(after reconstitution with 3 ml of sterile water for injectable preparation).

Zercepac contains 0.6 mg of polysorbate 20 in each 150 mg vial, equivalent to 0.083 mg/ml
(after reconstitution with 7.2 ml of sterile water for injectable preparation).

Zercepac contains 1.7 mg of polysorbate 20 in each 420 mg vial, equivalent to 0.085 mg/ml
(after reconstitution with 20 ml of sterile water for injectable preparation).

Polysorbate 20 may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Zercepac

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

The intravenous formulation of Zercepac 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 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 may also be given once weekly for metastatic breast cancer.

If you interrupt treatment with Zercepac

Do not interrupt treatment with this medicine without first speaking to your doctor. All doses should be taken at the correct time, either weekly or every three weeks (depending on your dosing schedule). This helps ensure your medicine works 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 your treatment has ended.

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, Zercepac can cause adverse effects, although not everyone experiences them. Some of these adverse effects may be serious and require hospitalization.

Serious adverse effects

During administration of a Zercepac 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, 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 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 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.

Other serious adverse effects may occur at any time during treatment with Zercepac and are not limited to infusion-related reactions. Tell your doctor or nurse if you experience any of the following adverse effects:

• Heart problems may sometimes occur during treatment and occasionally after treatment has been stopped, and these can be serious. These include weakening of the heart muscle, which may possibly lead to heart failure, inflammation of the sac surrounding the heart (swelling, redness, warmth, and pain), and disturbances in heart rhythm. This may cause symptoms such as shortness of breath (even 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 during and after treatment, but you should contact 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, shorter breathing, fatigue, and confusion), heart problems (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 after your treatment with Zercepac has ended, you must consult your doctor and inform them that you were previously treated with Zercepac.

Other adverse effects

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rash (rash)
• chest pain
• abdominal pain
• joint pain
• low red and white blood cell counts (which help fight infection), sometimes with fever
• muscle pain
• conjunctivitis
• watery eyes
• nosebleeds
• nasal discharge
• hair loss
• tremor
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising

numbness or tingling in fingers and toes, which occasionally may 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:

• allergic reactions
• throat infections
• bladder and skin infections
• breast inflammation
• liver inflammation
• kidney disorders
• increased muscle tone or tension (hypertonia)
• pain in the arms and/or legs
• itchy skin rash
• drowsiness (somnolence)
• hemorrhoids
• itching
• dry mouth and dry skin
• dry eyes
• sweating
• feeling of weakness and discomfort
• anxiety
• depression
• asthma
• lung infection
• pulmonary disorder
• back pain
• neck pain
• bone pain
• acne
• leg cramps

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

• deafness
• blistering skin rash
• wheezing
• lung inflammation/scarring

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

• jaundice
• anaphylactic reactions

Adverse effects of unknown frequency: 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
• 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 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 adverse effects you may experience could be due to your cancer. If Zercepac is administered in combination with chemotherapy, some of the effects may also be due to the chemotherapy itself.

If you experience any adverse effects, inform your doctor, pharmacist, or nurse.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may 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 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 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.
• Keep unopened vials refrigerated (between 2°C and 8°C).
• Do not freeze the reconstituted solution.
• 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.
• Do not use Zercepac 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. Pack contents and other information

Composition of Zercepac

• The active substance is trastuzumab. Each vial contains either:
• 60 mg of trastuzumab, which is dissolved in 3.0 ml of sterile water for injection, or
• 150 mg of trastuzumab, which is dissolved in 7.2 ml of sterile water for injection, or
• 420 mg of trastuzumab, which is dissolved in 20.0 ml of sterile water for injection.

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

• The other components are histidine hydrochloride monohydrate, histidine, ?,?-trehalose dihydrate, polysorbate 20 (E432) (see section 2 “Zercepac contains polysorbate”).

Description of the product and contents of the pack

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

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona, s/n,

Edifici Est 6th floor,

08039 Barcelona, Spain

Manufacturer

Accord Healthcare Polska Sp. z.o.o

ul Lutomierska 50, 95-200 Pabianice

Poland

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

AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PT / PL / RO / SE / SI / SK / ES

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica A.E.

Tel: +30 210 7488 821

Date of latest revision of this leaflet: <{MM/YYYY}>.

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

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

This information is intended for healthcare professionals only:

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

To avoid medication errors, it is important to check vial labels 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).

Always store this medicine in its original closed packaging at a temperature of 2 °C–8 °C in a refrigerator.

Since the medicine does not contain antimicrobial preservatives or bacteriostatic agents, appropriate aseptic techniques must be used during reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions.

The vial of Zercepac reconstituted aseptically with sterile water for injection (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 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 up to 84 days at 2 °C–8 °C, 7 days at 23 °C–27 °C, and 24 hours at 30 °C.

From a microbiological standpoint, the reconstituted solution and the infusion solution of Zercepac should be used immediately. If not used immediately, the storage time and conditions prior to use are the responsibility of the user, unless reconstitution and dilution have taken place under controlled and validated aseptic conditions.

Storage, handling and aseptic preparation:

The preparation of the infusion must:

• be carried out by qualified personnel in accordance with good practices, particularly 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 infusion solution to ensure maintenance of aseptic conditions.

Instructions for aseptic reconstitution:

1. Using a sterile syringe, slowly inject the appropriate volume (as indicated below) of sterile water for injection (not supplied) into the vial containing the lyophilised Zercepac, directing the stream onto the lyophilised powder. The use of other solvents for reconstitution must be avoided.
2. Gently swirl to aid reconstitution. DO NOT SHAKE!

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

Zercepac 60 mg powder for concentrate for solution for intravenous infusion.

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

Zercepac 150 mg powder for concentrate for solution for intravenous infusion.

Reconstitution of the 150 mg vial with 7.2 ml of sterile water for injection yields a 7.5 ml single-dose solution containing 21 mg/ml of trastuzumab, at a pH of approximately 6.0. A 5 % overfill allows the 150 mg dose indicated on the label to be withdrawn from each vial.

Zercepac 420 mg powder for concentrate for solution for intravenous infusion.

Reconstitution of the 420 mg vial with 20.0 ml of sterile water for injection yields a 20.6 ml single-dose solution containing approximately 21 mg/ml of trastuzumab, at a pH of approximately 6.0. A 3 % overfill allows the 420 mg dose indicated on the label to be withdrawn from each vial.

Zercepac must be handled carefully during reconstitution. Excessive foaming during reconstitution or shaking of the reconstituted Zercepac may cause problems in accurately withdrawing the intended amount 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 trastuzumab/kg body weight or subsequent weekly doses of 2 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) x Dose (4 mg/kg initial dose or 2 mg/kg 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) x Dose (8 mg/kg initial dose or 6 mg/kg 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 a polyethylene or polypropylene infusion bag containing 250 ml of 9 mg/ml (0.9 %) sodium chloride 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 particulate matter and discolouration prior to administration.