Herceptin 150 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Herceptin 150 mg 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 as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, including any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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 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 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 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 hormone receptor-positive 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 using Herceptin

Do not use Herceptin:

• if you are allergic to trastuzumab, mouse (murine) proteins, or any of the other
  components of this medicine (listed in section 6).

• if you have severe breathing problems at rest due to your tumour, 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 previously received an anthracycline (taxanes and anthracyclines are two types of medicines used to treat cancer). The effects may range from moderate to severe and may be fatal. Therefore, your heart function will 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 (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.

Consult 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) may 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 may cause difficulty breathing, particularly when first administered. 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 are receiving Herceptin together with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflets for these medicines.

Children and adolescents

Herceptin is not recommended in patients under 18 years of age.

Other medicines and Herceptin

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

It may take up to 7 months for Herceptin to be completely eliminated from the body. Therefore, if you plan to take any new medicine within 7 months after stopping Herceptin 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 completing treatment.

• Your doctor will explain the risks and benefits of using Herceptin during pregnancy. In rare cases, a reduced amount of fluid surrounding the developing baby in the womb (amniotic fluid) has been observed in pregnant women who received Herceptin. This may harm 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 your breast milk and reach your baby.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Herceptin may affect your ability to drive 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 have resolved.

Herceptin contains polysorbate

Herceptin contains 0.6 mg of polysorbate 20 in each 150 mg vial, equivalent to 0.083 mg/ml (after reconstitution with 7.2 ml of sterile water for injection). 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 tumour. Only patients with high levels of HER2 will be treated with Herceptin. Herceptin must be administered only by a doctor or nurse. Your doctor will prescribe a dose and treatment regimen appropriate for you. The dose of Herceptin depends on your body weight.

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 labelling 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 given intravenously.

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

The intravenous formulation of Herceptin is given as an intravenous infusion ("drip") directly into a vein. The first dose of your treatment is administered over approximately 90 minutes, and you will be monitored by a healthcare professional during administration for any adverse reactions. If the initial dose is well tolerated, subsequent doses may be given over 30 minutes (see section 2 “Warnings and precautions”). The number of infusions you receive will depend on your response to treatment. Your doctor will inform you about this.

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 containing trastuzumab (e.g. trastuzumab emtansine or trastuzumab deruxtecan).

For early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Herceptin is given every 3 weeks. Herceptin may also be given once a week for metastatic breast cancer.

If you interrupt treatment with Herceptin

Do not stop treatment with this medicine without first talking to your doctor. All doses should be taken at the correct time, either weekly or every three weeks (depending on your dosing schedule). This helps ensure 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 you have completed your treatment.

If you have any further questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, Herceptin can cause adverse effects, although not everyone experiences them. Some of these adverse effects may be serious and require hospitalization.

During the administration of a Herceptin infusion, chills, fever, and other flu-like symptoms may occur. This is very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: feeling unwell (nausea), vomiting, pain, increased muscle tension 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 may be severe, and in some patients they have been fatal (see section 2 “Warnings and precautions”).

These effects occur mainly during the first intravenous infusion (“drip” into a vein) and within 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 for two hours after the start of subsequent infusions. If you have a reaction, your infusion may be slowed down or stopped, and you may be given treatment to counteract the adverse effects. The infusion may be resumed once your symptoms have improved.

Occasionally, symptoms begin more than 6 hours after the start of the infusion. If this happens to you, contact your doctor immediately. Sometimes, symptoms may improve and then worsen again later.

Serious adverse effects

Other adverse effects may occur at any time during treatment with Herceptin, not only related to the infusion. Inform your doctor or nurse if you experience any of the following adverse effects:

• Heart problems may sometimes occur during treatment and occasionally after treatment has been stopped, and these may be serious. These include weakening of the heart muscle, which could possibly lead to heart failure, inflammation of the sac surrounding the heart, and disturbances in heart rhythm. This may cause symptoms such as shortness of breath (even shortness of breath at night), cough, fluid retention (swelling) in the legs or arms, palpitations (arrhythmias or irregular heartbeat) (see section 2. Heart checks).

Your doctor will periodically monitor your heart function during and after treatment, but you must contact your doctor immediately if you notice any of the symptoms described above.

• Tumor lysis syndrome (a group of metabolic complications occurring after cancer treatment, characterized by high levels of potassium and phosphate in the blood and low levels of calcium). 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 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 have previously been treated with Herceptin.

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
• tearing
• nosebleeds
• nasal discharge
• hair loss
• tremor
• hot flashes
• dizziness
• nail changes
• weight loss
• loss of appetite
• difficulty sleeping (insomnia)
• altered taste
• low platelet count
• bruising
• numbness or tingling in fingers and toes, which occasionally may extend 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 of weakness and discomfort
• anxiety
• depression
• asthma
• lung infection
• pulmonary disorders
• 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/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 potassium levels
• 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 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 any adverse effects, inform 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 included in Appendix V. By reporting adverse 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 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.

• Keep unopened vials refrigerated (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 duration prior to use and the storage conditions shall be 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 foreign particles or discoloration before administration.

• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Herceptin

• The active substance is trastuzumab. Each vial contains 150 mg of trastuzumab, which is dissolved in 7.2 ml of water for injections. The resulting solution contains approximately 21 mg/ml of trastuzumab.

• The other components are histidine hydrochloride monohydrate, histidine, α,α-trehalose dihydrate, and polysorbate 20 (E432) (see section 2 “Herceptin contains polysorbate”).

Appearance of the product and contents of the pack

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

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorisation Holder.

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

Detailed information on this medicine is available on the European Medicines Agency website: 7Hhttps://www.ema.europa.eu/

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

This information is intended for healthcare professionals only:

Herceptin IV is supplied in sterile, preservative-free, non-pyrogenic, single-use vials.

To avoid medication errors, it is important to check vial labels 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).

Always keep this medicine in its original closed packaging at a temperature of 2 °C–8 °C in a refrigerator.

Appropriate aseptic technique must be used for reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. Since the medicine contains no antimicrobial preservatives or bacteriostatic agents, an aseptic technique must be used.

The vial of Herceptin reconstituted aseptically with sterile water for injections (not supplied) is chemically and physically stable for 48 hours at 2 °C–8 °C after reconstitution and must not be frozen.

After aseptic dilution into 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 up to 30 days at 2 °C–8 °C and for 24 hours at temperatures not exceeding 30 °C.

From a microbiological standpoint, the reconstituted solution and the Herceptin infusion solution should be used immediately. If not used immediately, the storage time prior to use and the storage conditions shall be the responsibility of the user and, in general, should not exceed 24 hours between 2 °C and 8 °C, unless reconstitution and dilution take place under controlled and validated aseptic conditions.

Storage, handling, and aseptic preparation:

Aseptic handling must be ensured when preparing the infusion. The preparation must be:

• carried out under aseptic conditions by trained personnel in accordance with good practices, particularly regarding the aseptic preparation of parenteral products;
• prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents;
• followed by appropriate storage of the prepared infusion solution to ensure maintenance of aseptic conditions.

Each vial of Herceptin is reconstituted with 7.2 ml of water for injections (not supplied). The use of other solvents for reconstitution must be avoided. This yields a 7.4 ml solution for single dose containing approximately 21 mg/ml of trastuzumab. A 4% overfill allows the labeled dose of 150 mg to be withdrawn from each vial.

Herceptin must be handled carefully during reconstitution. Excessive foaming during reconstitution or agitation of the reconstituted Herceptin may cause difficulties in withdrawing the full dose from the vial.

Instructions for aseptic reconstitution:

1. Using a sterile syringe, slowly inject 7.2 ml of water for injections into the vial containing the lyophilized Herceptin, directing the stream onto the lyophilized powder.
2. Gently swirl to aid reconstitution. DO NOT SHAKE!

The formation of slight foam after reconstitution is normal. Allow the vial to stand undisturbed 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 volume of solution required will be determined:

• based on the initial dose of 4 mg trastuzumab/kg body weight or subsequent weekly doses of 2 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) × Dose (4 mg/kg initial dose or 2 mg/kg subsequent doses)
21 (mg/ml, concentration of reconstituted solution)

• or based on the initial dose of 8 mg trastuzumab/kg body weight or every-three-week doses of 6 mg trastuzumab/kg body weight:

Volume (ml) = Body weight (kg) × Dose (8 mg/kg initial dose or 6 mg/kg subsequent doses)
21 (mg/ml, concentration of reconstituted solution)

The appropriate amount of solution should be withdrawn from the vial using a sterile needle and syringe and added to an infusion bag made of polyvinyl chloride, polyethylene, or polypropylene containing 250 ml of 0.9% sodium chloride solution. Do not use with solutions containing glucose. The bag should be inverted several times to mix the solution and avoid foam formation. Parenteral solutions should be inspected visually for particles and discoloration prior to administration.