Package Insert: Information for the User

Herceptin 600 mg Injectable Solution in Vial

trastuzumab

Read this package insert carefully before starting to use this medication, because

it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

Herceptin contains trastuzumab as its active substance, 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 Herceptin binds to the 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-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. Herceptin may be prescribed in combination with chemotherapy medications paclitaxel or docetaxel as the 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).

No use Herceptin:

• if you are allergic to trastuzumab (the active ingredient in Herceptin), 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 assessments

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 cancer medications). The effects can be moderate to severe and may be fatal. Therefore, you should have your cardiac 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 blood pumping by the heart), your doctor will check how your heart is functioning more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to discontinue treatment with Herceptin.

Consult your doctor, pharmacist, or nurse before Herceptin is administered 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 ever received or are currently receiving a medication called doxorubicin or epirubicin (cancer medications). These medications (or any other anthracyclines) may 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 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 Herceptin was administered.

• you have ever received any other cancer treatment.

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

Children and adolescents

Herceptin is not recommended for individuals under 18 years old.

Other medications and Herceptin

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

Herceptin may take up to 7 months to be 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 Herceptin.

Pregnancy and breastfeeding

• 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 Herceptin and for at least 7 months after completing 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 fetus in the womb (amniotic fluid) has been observed in pregnant women who received Herceptin. 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 Herceptin therapy and for 7 months after the last dose of Herceptin, as Herceptin may reach your baby through breast milk.

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

Driving and operating machinery

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 disappear.

Sodium

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

Before starting treatment with Herceptin, your doctor will determine the amount of HER2 in your tumor. Only patients with a large amount 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:

It is essential to review the medication labeling to ensure that the correct formulation is being administered as prescribed. The subcutaneous formulation of Herceptin at fixed doses 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 (or vice versa) if deemed appropriate for you.

To avoid medication errors, it is crucial to check the labels on 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 as a subcutaneous injection (under the skin) for 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, has bruises, is sensitive, or is hardened.

If other subcutaneous medications are being used during Herceptin treatment, 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 speaking with your doctor. All doses should be administered at the correct time every three weeks. This helps your medication work effectively.

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 completing treatment.

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

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

During treatment with Herceptin, you may experience chills, fever, and other symptoms similar to the flu.These are very common (can affect more than 1 in 10 people). Other related symptoms are: feeling unwell (nausea), vomiting, pain, muscle tension, agitation, headache, dizziness, difficulty breathing, changes in blood pressure, heart rhythm disturbances (palpitations, arrhythmias, or irregular heartbeat), swelling of the face and lips, rash, and feeling tired. Some of these symptoms can be serious and some patients have died (see "Warnings and precautions").

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

Severe side effects

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

• Sometimes, heart problems can occur during treatment and occasionally after stopping treatment, and these can be serious. These include weakening of the heart muscle that may cause heart failure, inflammation of the heart's outer layer, 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).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 in the blood). Symptoms can include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (palpitations or irregular heartbeat). Convulsions, vomiting, diarrhea, and numbness in the mouth, hands, or feet.

If you experience any of these symptoms after your treatment with Herceptin has ended, you should consult your doctor and inform them that you were previously 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 that compared these two formulations, infections and side effects affecting the heart and requiring hospital treatment were more common with the subcutaneous formulation. Also, more local reactions at the injection site and more increases in blood pressure occurred. Other side effects were similar.

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

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

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

Very rare side effects of Herceptin:can affect up to 1 in 1,000 people:

• Jaundice
• Anaphylactic reactions

Other side effects reported with the use of Herceptin:could not be estimated from the available data:

Abnormal blood clotting or bleeding

High potassium levels

Inflammation or bleeding in the back of the eyes

Shock

Abnormal heart rhythm

Difficulty breathing

Respiratory failure

Acute fluid accumulation in the lungs

Acute narrowing of the airways

Abnormally low oxygen levels in the blood

Difficulty breathing while lying down

Liver damage

Inflammation of the face, lips, and throat

Renal failure

Abnormally low levels of fluid surrounding the fetus in the womb

Failure of the lungs to develop in the fetus

Abnormal development of the kidneys in the fetus

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 EXP. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C).

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

Do not freeze.

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

Do not use this medication if you observe any solid particles or color changes before administration.

Medications should not be disposed of through drains or trash.Ask your pharmacist how to dispose ofthe containers and medications that you no longerneed.This will help protect the environment.

Composition of Herceptin

• The active ingredient is trastuzumab. Each vial of 5 ml 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, polisorbate 20, water for injection preparations.

Aspect of the product and content of the package

Herceptin is an injectable solution that is 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 package contains 1 vial.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible for manufacturing

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:

Last review date of this leaflet:

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:9Hhttp://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.