HERCEPTIN 150 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Herceptin 150mg powder for concentrate for solution for infusion

trastuzumab

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.

• Keep this leaflet, as 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 Herceptin and what is it used for
2. What you need to know before you use Herceptin
3. How to use Herceptin
4. Possible side effects
5. Storage of Herceptin
6. Contents of the pack and other information

1. What is Herceptin and what is it used for

Herceptin contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies recognise 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 Herceptin binds to HER2, it stops the growth of these cells, leading to their death.

Your doctor may prescribe Herceptin 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 tumour) with high levels of HER2. Herceptin may be prescribed in combination with chemotherapy medicines 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 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 Herceptin

Do not use Herceptin:

• 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 tumour or if you need oxygen treatment.

• if you have severe respiratory problems at rest due to your tumour or if you need oxygen treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Cardiac monitoring

Treatment with Herceptin 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 three months) and after (for up to two to five years) treatment with Herceptin. If you develop any signs of heart failure (inadequate pumping of blood by the heart), your heart function will be checked more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to stop treatment with Herceptin.

Talk to your doctor, pharmacist or nurse before Herceptin 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 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 anthracyclines) can damage the heart muscle and increase the risk of heart problems when treated with Herceptin.

• you feel short of breath, especially if you are currently receiving a taxane. Herceptin 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 Herceptin.

• you have had any other cancer treatment in the past.

If you receive Herceptin with any other cancer medicine, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil or cisplatin, you should also read the package leaflets of these medicines.

Children and adolescents

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

Other medicines and Herceptin

Using Herceptin 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 up to 7 months for Herceptin 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 Herceptin.

Pregnancy and breast-feeding

• You must use an effective method of contraception during treatment with Herceptin and for at least 7 months after finishing treatment.

• Your doctor will discuss the risks and benefits of taking Herceptin 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 Herceptin. 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 Herceptin and for 7 months after the last dose of Herceptin, as Herceptin may pass into your breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Herceptin 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 resolved.

3. How to use Herceptin

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

There are two different types (formulations) of Herceptin:

• one is administered as an infusion into a vein (intravenous infusion)
• the other is administered as an injection under the skin (subcutaneous injection).

It is essential to check the labelling of the medicine to ensure that the correct formulation is being administered as prescribed. The intravenous formulation of Herceptin is not for subcutaneous administration and must only be administered intravenously.

Your doctor may consider switching your treatment from intravenous Herceptin to subcutaneous Herceptin (and vice versa) if they consider it appropriate for you.

The intravenous formulation of Herceptin is administered as an intravenous infusion directly into a vein. The first dose of your treatment is administered over approximately 90 minutes, and you will be observed by a healthcare professional while it is being administered, in case you experience any adverse reactions. 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 essential to check the labels of the vials to ensure that the medicine being prepared and administered is Herceptin (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, Herceptin will be administered every 3 weeks. Herceptin can also be administered once a week for metastatic breast cancer.

If you stop treatment with Herceptin

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 three weeks (depending on your dosing schedule). This helps your medicine work properly.

It may take up to 7 months for Herceptin 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, Herceptin can cause side effects, although not everybody gets them. Some of these side effects can be serious and may require hospitalisation.

During administration of a Herceptin 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 tone 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 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 six hours after the start of the first infusion and for two hours after the start of subsequent infusions. If you experience any reaction, the infusion may be administered more slowly or the infusion may be 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.

Serious side effects

Other side effects may occur at any time during treatment with Herceptin and not only related to the infusion. Tell your doctor or nurse if you experience 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 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 monitor your heart regularly during and after treatment, but you should tell your doctor immediately if you notice any of the symptoms mentioned above.

• Tumour lysis syndrome (a set of metabolic complications that occur after cancer treatment and are characterised 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 diarrhoea and tingling in the mouth, hands or feet.

If you experience any of these symptoms after your treatment with Herceptin has finished, you should contact your doctor and inform them that you have been previously treated with Herceptin.

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

• infections
• diarrhoea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin 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
• nasal bleeding
• nasal discharge
• hair loss
• tremors
• hot flushes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling in the fingers and toes, which can 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

Common side effects of Herceptin:may affect up to 1 in 10 people:

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

• hearing loss
• skin rash with blisters
• wheezing (whistling)
• inflammation/scarring of the lungs

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

• jaundice
• anaphylactic reactions

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

• abnormal blood clotting or coagulation failure
• high levels of potassium
• inflammation or bleeding in the back of the eyes
• shock
• abnormal heart rhythm
• difficulty breathing
• respiratory failure
• sudden accumulation of fluid in the lungs
• sudden 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 experience may be due to your cancer. If you are given Herceptin in combination with chemotherapy, some of the side 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. This includes any possible side effects 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 Herceptin

Herceptin 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 on the label of the vial after EXP. The expiry date is the last day of the month shown.

• The unopened vials should be stored in a refrigerator (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 time before use and storage conditions are the responsibility of the user and, in general, should not exceed 24 hours between 2°C and 8°C.

• Do not use this medicine if you notice any particles or discolouration 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

Herceptin Composition

• The active ingredient is trastuzumab. Each vial contains 150 mg of trastuzumab, which is dissolved 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 monohydrate, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Product Appearance and Container Content

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

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

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

Date of Last Revision of this Prospectus:

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

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

This information is intended for healthcare professionals only:

Herceptin IV is provided in sterile, preservative-free, and 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 Herceptin (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.

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

The vial of Herceptin 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 polyvinyl chloride, polyethylene, or polypropylene bags containing 9 mg/ml (0.9%) sodium chloride injection solution, the physical and chemical stability of Herceptin has been demonstrated for a period of up to 30 days at 2°C-8°C and 24 hours at a temperature not exceeding 30°C.

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

Storage, handling, and aseptic preparation:

Aseptic handling should be ensured when preparing the infusion. The preparation should 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 biological safety cabinet using standard precautions for the safe handling of intravenous agents.
• followed by adequate storage of the prepared infusion solution to ensure the maintenance of aseptic conditions.

Each vial of Herceptin is reconstituted with 7.2 ml of water for injectable preparations (not supplied). The use of other solvents for reconstitution should be avoided. This produces a single-dose solution of 7.4 ml, which contains approximately 21 mg/ml of trastuzumab. A 4% overfill allows the labeled dose of 150 mg to be withdrawn from each vial.

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

Instructions for aseptic reconstitution:

1. Using a sterile syringe, slowly inject 7.2 ml of water for injectable preparations into the vial containing the Herceptin lyophilized powder, directing the flow towards the lyophilized powder.
2. Gently swirl in a circular motion to aid reconstitution. DO NOT SHAKE!

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

• The required volume of solution will be determined 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 polyvinyl chloride, polyethylene, or polypropylene infusion bag containing 250 ml of 0.9% sodium chloride injection solution. Solutions containing glucose should not be used. The bag should be inverted several times to mix the solution and avoid foam formation. Parenteral solutions should be visually inspected for particles and discoloration before administration.