HERCEPTIN 600 mg INJECTABLE SOLUTION IN VIAL

Introduction

Package Leaflet: Information for the User

Herceptin 600mg solution for injection in vial

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, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• 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. Storing 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 recognize specific proteins or antigens. Trastuzumab is designed to selectively bind to an antigen called the 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 slows down the growth of these cells, causing them to die.

Your doctor may prescribe Herceptin for the treatment of breast 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) with high levels of HER2. Herceptin may be prescribed in combination with chemotherapy medications paclitaxel or docetaxel as first-line 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 medications 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).

2. What you need to know before you use Herceptin

Do not use Herceptin:

• if you are allergic to trastuzumab (the active ingredient of Herceptin), to murine proteins (mouse), or to 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 reviews

Treatment with Herceptin alone or in combination with a taxane may affect the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two types of medications used to treat cancer). 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 (up to two to five years) treatment with Herceptin. If you develop any signs of heart failure (i.e., 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.

Tell your doctor, pharmacist, or nurse before you are given Herceptin if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmur), high blood pressure, have taken any medication for high blood pressure, or are currently taking any medication for high blood pressure.

• you have received or are currently receiving a medication called doxorubicin or epirubicin (medications for treating cancer). These medications (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 received any other cancer treatment in the past.

If you receive Herceptin with any other cancer medication, such as paclitaxel, docetaxel, an aromatase inhibitor, carboplatin, or cisplatin, you should also read the package leaflets for these medications.

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 eliminated from your body. Therefore, if you are going to take any new medication within 7 months after the end of treatment, you must inform your doctor, pharmacist, or nurse that you have been treated with Herceptin.

Pregnancy and breastfeeding

• If you are pregnant, think you may 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 Herceptin and for at least 7 months after the end of treatment.

• Your doctor will explain 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 given Herceptin. This can be harmful to the baby in the womb and has been associated with underdeveloped lungs, resulting in fetal death.

Breastfeeding

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

Consult your doctor, pharmacist, or nurse before taking any medication.

Driving and using machines

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

Sodium

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

3. How to use Herceptin

Before starting treatment with Herceptin, your doctor will determine the amount of HER2 in your tumor. Only patients with high levels of HER2 will be treated with Herceptin. Herceptin must be administered only by a doctor or nurse.

There are two different types (formulations) of Herceptin:

• one is administered as an intravenous infusion
• the other is administered as a subcutaneous injection.

It is essential to check the labeling of the medication to ensure that the correct formulation is being administered as prescribed. The subcutaneous Herceptin formulation is not for intravenous administration and should only be administered as a subcutaneous injection.

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

To avoid medication errors, it is crucial to check the labels of the vials to ensure that the medication being prepared and administered is Herceptin (trastuzumab) and not another product (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

The recommended dose is 600 mg. Herceptin is administered subcutaneously (under the skin) over 2 to 5 minutes every three weeks.

The injection site should be alternated between the left and right thigh. New injections should be administered at least 2.5 cm away from the previous site. The injection should not be given in areas where the skin is red, bruised, sensitive, or hard.

If other medications are being administered subcutaneously during treatment with Herceptin, a different injection site should be used.

Herceptin should not be mixed or diluted with other products.

If you interrupt treatment with Herceptin

Do not stop treatment with this medication without first talking to your doctor. All doses should be administered on time every three weeks. This helps your medication work properly.

It may take 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 about the use of this medication, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

During treatment with Herceptin, you may experience chills, fever, and other flu-like symptoms. These are very common (may affect more than 1 in 10 people). Other related symptoms include: 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 "Warnings and precautions").

Your doctor or nurse will check for side effects during administration and for at least 30 minutes after the first administration and for 15 minutes after subsequent administrations.

Serious side effects

Other side effects may occur at any time during treatment with Herceptin. 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 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 regularly during and after treatment, but you should inform your doctor immediately if you notice any of the symptoms described above.

• Tumor lysis syndrome (a set of metabolic complications that occur after cancer treatment, 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 faster or slower rhythm), seizures, vomiting, or diarrhea, and numbness or tingling in the mouth, hands, or feet.

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

There are two different types (formulations) of Herceptin:

• one is administered as an intravenous infusion over 30 to 90 minutes
• the other is administered as a subcutaneous injection over 2 to 5 minutes. In the clinical trial that compared these two formulations, infections and heart-related side effects that required hospital treatment were more frequent with the subcutaneous formulation. Local reactions at the injection site and increased blood pressure also occurred more frequently. Other side effects were similar.

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rash
• 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)
• taste changes
• low platelet count
• bruising
• numbness or tingling in the fingers or 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 or 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 insufficient clotting
• 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 levels of oxygen in the blood
• difficulty breathing while 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 can be due to your breast 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 side effects, consult your doctor, pharmacist, or nurse.

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through 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. Storing Herceptin

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.

Store in a refrigerator (2°C to 8°C).

Keep the vial in the outer packaging to protect it from light.

Do not freeze.

After opening the vial, the solution should be used immediately.

Do not use this medicine if you notice any solid particles or color changes 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 contents and additional information

Herceptin composition

• The active ingredient is trastuzumab. Each 5 ml vial contains 600 mg of trastuzumab.

• The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride monohydrate, α,α-trehalose dihydrate, L-methionine, polysorbate 20, water for injectable preparations.

Product appearance and container contents

Herceptin is an injectable solution presented in a glass vial with a butyl rubber stopper containing 5 ml (600 mg) of trastuzumab. The solution is transparent to opalescent, colorless to yellowish.

Each container contains 1 vial.

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 the last revision of this prospectus:

Other sources of information

Detailed information about 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.