Herceptin 600 mg solution for injection in vial

Patient Information Leaflet

Introduction

Patient Information Leaflet

Herceptin 600mg Injectable Solution 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 as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Herceptin is and what it is used for

Herceptin 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 Herceptin binds to HER2, the growth of these cells is slowed down, leading to their death.

Your doctor may prescribe Herceptin for the treatment of breast 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 tumour has spread) with high levels of HER2. Herceptin 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).

2. What you need to know before using Herceptin

Do not use Herceptin:

• if you are allergic to trastuzumab (the active substance in Herceptin), mouse proteins (mouse), or to 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 treatment.

Warnings and precautions

Your doctor will closely monitor your treatment.

Heart checks

Treatment with Herceptin 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 result in death. Therefore, your heart function must be 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 monitored 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 receiving Herceptin if:

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

• you have previously or are currently receiving a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage 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, particularly when administered for the first time. This could 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 Herceptin.

• you have previously received any other cancer treatment.

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

Children and adolescents

Herceptin is not recommended for use in individuals under 18 years of age.

Other medicines and Herceptin

Using Herceptin 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 Herceptin to be 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 Herceptin.

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 Herceptin and for at least 7 months after stopping treatment.

• Your doctor will explain the risks and benefits of taking Herceptin 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 Herceptin. This may be harmful to the unborn baby and has been associated with underdeveloped lungs, resulting in fetal death.

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

Talk to your doctor, pharmacist, or nurse before taking any medicine.

Driving and using machines

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

Herceptin contains sodium

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

Herceptin contains polysorbate

Herceptin contains 2.0 mg of polysorbate 20 in each 600 mg/5 ml vial, equivalent to 0.4 mg/ml. Polysorbate 20 may cause allergic reactions. Inform your doctor if you have any known allergies.

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

It is important to check the medicine label to ensure that the correct formulation prescribed is being administered. The fixed-dose subcutaneous formulation of Herceptin is

not for intravenous administration and must be administered only 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 important to check the vial labels to ensure that the medicine 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 by subcutaneous injection (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, tender, or hard.

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

Herceptin must not be mixed or diluted with other products.

If you interrupt treatment with Herceptin

Do not stop treatment with this medicine without first talking to your doctor. All doses should be administered at the correct time every three weeks. This helps ensure that your medicine works 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 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, this medicine can cause adverse effects, although not everyone gets them. Some of these adverse effects may be serious and require hospitalization.

During treatment with Herceptin, chills, fever, and other flu-like symptoms may occur. These are very common (may affect more than 1 in 10 people). Other related symptoms include: feeling unwell (nausea), vomiting, pain, increased muscle tension, restlessness, 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 may be serious, and some patients have died (see section “Warnings and precautions”).

Your doctor or nurse will monitor you for adverse effects during administration and for at least 30 minutes after the first dose, and for 15 minutes after subsequent doses.

Serious adverse effects

Other adverse effects may occur at any time during treatment with Herceptin. Tell your doctor or nurse if you experience any of the following adverse effects:

• Heart problems may sometimes occur during treatment and occasionally after stopping treatment, and these may be serious. These include weakening of the heart muscle, which could possibly lead to heart failure, inflammation of the lining surrounding the heart, and disturbances in heart rhythm. This may cause symptoms such as: shortness of breath (including 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 function 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, 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 around the mouth, hands, or feet.

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

There are two 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 comparing these two formulations, infections and adverse effects affecting the heart that required hospital treatment were more frequent with the subcutaneous formulation. There were also more local reactions at the injection site and more increases in blood pressure. Other adverse effects were similar.

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

• infections
• diarrhea
• constipation
• heartburn (dyspepsia)
• fatigue
• skin rash (cutaneous rash)
• chest pain
• abdominal pain
• joint pain
• low red and white blood cell counts (which help fight infection), sometimes with fever
• muscle pain
• conjunctivitis
• excessive tearing
• nosebleeds
• nasal discharge
• hair loss
• tremor
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• taste disturbances
• low platelet count
• bruising
• numbness or tingling in fingers and toes, which may 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 adverse effects of Herceptin: 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 arms and/or legs
• itchy skin rash
• drowsiness (somnolence)
• hemorrhoids
• itching, dry mouth, and dry skin
• dry eyes
• sweating
• feeling weak and unwell
• anxiety
• depression
• asthma
• lung infection
• pulmonary disorder
• back pain
• neck pain
• bone pain
• acne
• leg cramps

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

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

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

• jaundice
• anaphylactic reactions

Other adverse effects reported with the use of Herceptin: 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 womb
• abnormal development of the baby's kidneys in the womb

Some of the adverse effects you may experience could be due to your breast cancer. If you are receiving Herceptin in combination with chemotherapy, some of the effects may also be due to the chemotherapy itself.

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Herceptin

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.

Store in a refrigerator (between 2 ºC and 8 ºC).

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 changes in colour before administration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Herceptin

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

• The other components are recombinant human hyaluronidase (rHuPH20), histidine hydrochloride monohydrate, histidine, α,α-trehalose dihydrate, methionine, polysorbate 20 (E432), water for injections (see section 2 “Herceptin contains polysorbate”).

Nature and contents of the container

Herceptin is an injectable solution supplied in a glass vial with a butyl rubber stopper containing 5 ml (600 mg) of trastuzumab. The solution is from transparent to opalescent, colourless to slightly yellow.

Each pack contains 1 vial.

Marketing Authorization Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer responsible for manufacturing

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: <{MM/AAAA}><{month YYYY}>.

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: 9Hhttps://www.ema.europa.eu.

This leaflet is available on the European Medicines Agency website in all languages of the European Union/European Economic Area.