Prospect: 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 expedite 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.

Zercepac contains the active ingredient trastuzumab, 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 Zercepac binds to the 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-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. Zercepac may be prescribed in combination with the chemotherapy medications paclitaxel or docetaxel as a 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 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 Zercepac:

• if you are allergic to trastuzumab, mouse proteins or any of the other components of this medication (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 reviews

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 medications used to treat cancer). The effects can be moderate to severe and may cause death. Therefore, you should review your cardiac function before, during (every three months) and after (up to two to five years) treatment with Zercepac. If you develop any signs of heart failure, (inadequate blood pumping by the heart), your doctor will check how your heart functions more frequently (every six to eight weeks), you may receive treatment for heart failure or you may have to interrupt treatment with Zercepac.

Consult your doctor, pharmacist or nurse before Zercepac is administered to you 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 having heart problems when treated with Zercepac.
• you feel short of breath, especially if you are currently receiving a taxane. Zercepac may cause breathing difficulties, 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 Zercepac was administered.
• you have ever had any other cancer treatment.

If you receive Zercepac in combination 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

Zercepac is not recommended for individuals under 18 years.

Other medications and Zercepac

Use of Zercepac with other medications: Inform your doctor, pharmacist or nurse if you are using, have used recently or may have to use any other medication.

Zercepac may take up to 7 months to be completely eliminated from the body. Therefore, if you are to take any new medication within 7 months of completing treatment, you should inform your doctor, pharmacist or nurse that you have been treated with Zercepac.

Pregnancy

• 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 should use an effective contraceptive method during treatment with Zercepac and for at least 7 months after completing 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 fetus in the womb (amniotic fluid) has been observed in pregnant women who received Zercepac. This may be harmful to the fetus and has been associated with underdeveloped lungs resulting in fetal death.

Breastfeeding

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

Consult your doctor or pharmacist before taking a medication.

Driving and operating machinery

Zercepac may affect your ability to drive a vehicle 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 disappear.

Sodium

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

Before starting treatment with Zercepac, your doctor will determine the amount of HER2 in your tumor. Only patients with a large amount of HER2 will be treated with Zercepac. Zercepac must be administered only by a doctor or nurse. Your doctor will prescribe an appropriate dose and treatment regimen 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 90 minutes and will be monitored by a healthcare professional while it is being administered, in case any adverse reactions occur. If the initial dose has been well tolerated, subsequent doses may be administered in 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 essential to check the labels on the vials to ensure that the medication being prepared and administered is Zercepac (trastuzumab) and not another product that contains trastuzumab (e.g. trastuzumab emtansina 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 Interrupt Treatment with Zercepac

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 3 weeks (depending on your dosing schedule). This helps your medication 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 completing your treatment.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

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

Severe side effects

During the administration of a Zercepac 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 symptoms related to the infusion are: feeling unwell (nausea), vomiting, pain, muscle tension, agitation, headache, dizziness, difficulty breathing, decreased or increased blood pressure, heart rhythm disturbances (palpitations, arrhythmias, or irregular heartbeat), facial and lip swelling, rash, and feeling tired. Some of these symptoms can be severe, 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 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 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 interrupt 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 the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms can improve and worsen later.

Other severe side effects can occur at any time during treatment with Zercepac and are not related to the infusion only.Inform your doctor or nurse if you experienceany of the following side effects:

• Sometimes, heart problems can occur during treatment and occasionally after stopping treatment, and these can be severe. These include heart muscle weakness that may cause heart failure, inflammation of the heart's outer layer (swelling, redness, heat, and pain) and heart rhythm disturbances. This can cause symptoms such as shortness of breath (even at night), cough, 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 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 levels of calcium). Symptoms can include kidney problems (weakness, shorter breathing, fatigue, and confusion), heart problems (palpitations or a faster or slower heart rate). Convulsions, 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 should consult your doctor and inform them that you were previously treated with Zercepac.

Other side effects

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

• Infections
• Diarhea
• Constipation
• Stomach burning (dyspepsia)
• Fatigue
• Rash on the skin (urticaria)
• 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
• Runny eyes
• Nasal bleeding
• Nasal discharge
• Hair loss
• Tremors
• Headaches
• Dizziness
• Changes in nails
• Weight loss
• Loss of appetite
• Difficulty sleeping (insomnia)
• Changes in taste
• Low platelet count
• Cardinal

Numbness or tingling in the fingers of the hands and feet, which occasionally can extend to the rest of the extremity.

• 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:can affect up to 1 in 10 people:

• Allergic reactions
• Throat infections
• Urinary and skin infections
• Breast inflammation
• Liver inflammation
• Renal disorders
• Increased muscle tone or tension

(hypertonia)

• Pain in the arms and/or legs
• Rash on the skin with itching
• Sleepiness (somnolence)
• Hemorrhoids
• Itching
• Mouth and skin dryness
• Eye dryness
• Sweating
• Feeling weak and unwell
• Anxiety
• Depression
• Asthma
• Pulmonary infections
• Pulmonary changes
• Back pain
• Neck pain
• Bone pain
• Acne
• Leg cramps

Rare side effects:can affect up to 1 in 100 people:

• Deafness
• Rash on the skin with blisters
• Wheezing (popping sounds)
• Pulmonary inflammation/cicatrisation

Very rare side effects:can 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 coagulation or coagulation deficiency
• High potassium levels
• Inflammation or hemorrhages in the back of the eyes
• Shock
• Abnormal heart rhythm
• Difficulty breathing
• Respiratory insufficiency
• 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
• Face, lip, and throat inflammation
• Renal 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 Zercepac in combination with chemotherapy, some of the side effects may also be due to the chemotherapy itself.

If you experience any side effects, inform 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 thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

• 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.
• Sealed vials must be stored in a refrigerator (between 2°C and 8°C).
• Do not freeze the reconstituted solution.
• Solutions for infusion must be used immediately after dilution. If not used immediately, the storage time until use and the conditions of such storage before use will be the responsibility of the user.
• Do not use Zercepac if you observe any foreign particles or discoloration before administration.
• Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Zercepac

• The active principle is trastuzumab. Each vial contains either
• 60 mg of trastuzumab dissolved in 3.0 ml of sterile water for injectable preparations, or
• 150 mg of trastuzumab dissolved in 7.2 ml of water for injectable preparations, or
• 420 mg of trastuzumab dissolved 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, polisorbate 20.

Appearance of the product and contents of the package

Zercepac is a lyophilized powder for concentrate for solution for intravenous infusion, presented 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 lyophilized powder in pellet form. Each package contains 1 vial of powder.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona, s/n,

Edifici Est 6th floor,

08039 Barcelona, Spain

Responsible for manufacturing

Accord Healthcare Polska Sp. z.o.o

ul Lutomierska 50, 95-200 Pabianice

Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

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

The detailed information on this medicine 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:

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

To avoid medication errors, it is essential to check the labels on 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 store this medicine in its original packaging, closed, at a temperature of 2°C-8°C in a refrigerator.

Since the medicine does not contain antimicrobial preservatives or bacteriostatic agents, an appropriate aseptic procedure should be used for the reconstitution and dilution procedures. It is essential to ensure the sterility of the prepared solutions.

The vial of reconstituted Zercepac 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 injectable solution of 9 mg/ml (0.9%) of sodium chloride, the physical and chemical stability of Zercepac has been demonstrated for a period of 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 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 conditions of such storage before use will be the responsibility of the user, unless 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 with regard to the aseptic preparation of parenteral products.
• prepared in a laminar flow cabinet or biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared infusion solution for intravenous administration to ensure 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 powder. Avoid using other solvents for reconstitution.
2. Mix gently 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 Zercepac is a transparent, colorless to pale yellow solution essentially free of visible particles.

Zercepac 60 mg powder for concentrate for solution for infusion.

The reconstitution of the 60 mg vial with 3.0 ml of sterile water for injection produces 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 reflected on the label to be extracted from each vial.

Zercepac 150 mg powder for concentrate for solution for infusion.

The reconstitution of the 150 mg vial with 7.2 ml of sterile water for injection produces 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 reflected on the label to be extracted from each vial.

Zercepac 420 mg powder for concentrate for solution for infusion

The reconstitution of the 420 mg vial with 20.0 ml of sterile water for injection produces 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 reflected on the label to be extracted from each vial.

Zercepac should be handled carefully during reconstitution. Excessive foam formation during reconstitution or agitation of the reconstituted Zercepac may cause problems with the amount of Zercepac that can be extracted from the vial.

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) =Body weight(kg) xdose(4mg/kg initial dose or2mg/kg for subsequent doses)

21(mg/ml, concentration of the reconstituted solution)

• Determine the required solution volume 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:

Volumen(ml) =Body weight(kg) xdose(8mg/kg initial dose or 6 mg/kg for subsequent doses)

21(mg/ml, concentration of the reconstituted solution)

The appropriate amount of solution should be extracted from the vial using a sterile syringe and needle and added to a polyethylene or polypropylene infusion bag containing 250 ml of 9 mg/ml (0.9%) sodium chloride solution. Do not use 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.