Ontruzant 150 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ontruzant 150 mg powder for concentrate for solution for infusion

Ontruzant 420 mg powder for concentrate for solution for infusion

trastuzumab

Read the entire 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, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Ontruzant is and what it is used for

Ontruzant contains the active substance trastuzumab, which is a monoclonal antibody. Monoclonal antibodies bind to 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 amounts on the surface of certain cancer cells, stimulating their growth. When Ontruzant binds to HER2, it slows the growth of these cells and causes them to die.

Your doctor may prescribe Ontruzant for the treatment of breast or gastric cancer if:

• you have early-stage breast cancer with high levels of the HER2 protein;
• you have metastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Ontruzant 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 effective. It may also be used in combination with other medicines called aromatase inhibitors in patients with high HER2 levels 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, when used in combination with other anticancer medicines such as capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before using Ontruzant

Do not use Ontruzant

• if you are allergic to trastuzumab, mouse proteins (murine proteins), or any of the other ingredients of this medicine (listed in section 6);
• if you have severe breathing problems at rest due to your cancer or if you require oxygen therapy.

Warnings and precautions

Your doctor will closely monitor your treatment.

Heart assessments

Treatment with Ontruzant (alone or in combination with a taxane) may affect the heart, especially if you have previously received an anthracycline (taxanes and anthracyclines are two other classes of medicines used to treat cancer).

The effects can range from moderate to severe and may be fatal. Therefore, your cardiac function will be evaluated before, during (every three months), and after (two to five years) treatment with Ontruzant. If you develop any signs of heart failure (inadequate pumping of blood by your heart), your cardiac function may be assessed more frequently (every six to eight weeks), you may receive treatment for heart failure, or you may need to discontinue Ontruzant treatment.

Consult your doctor, pharmacist, or nurse before receiving Ontruzant if:

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

• you are currently taking or have previously taken a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems with Ontruzant;

• you feel short of breath, especially if you are currently receiving a taxane. Ontruzant may cause difficulty breathing, particularly when first administered. Breathing difficulties may be more severe if you already have trouble breathing. In very rare cases, patients who already had breathing difficulties before treatment died after receiving Ontruzant;

• you have previously received any other cancer treatment.

If you are receiving Ontruzant together with another cancer medicine 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

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

Other medicines and Ontruzant

Using Ontruzant 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 Ontruzant to be eliminated from the body. Therefore, if you are to take a new medicine within 7 months after stopping treatment, inform your doctor, pharmacist, or nurse that you have received Ontruzant.

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 effective contraception during treatment with Ontruzant and for at least 7 months after completing treatment.
• Your doctor will explain the risks and benefits of using Ontruzant during pregnancy. In rare cases, a decrease in the fluid (amniotic fluid) surrounding the developing fetus in the uterus has been observed in pregnant women treated with Ontruzant. This may harm the unborn baby and has been associated with underdeveloped lungs, potentially resulting in fetal death.

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

Consult your doctor or pharmacist before using this medicine.

Driving and using machines

Ontruzant 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 resolve.

Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; hence, it is essentially "sodium-free."

Ontruzant contains polysorbate

Ontruzant 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). Ontruzant contains 1.7 mg of polysorbate 20 in each 420 mg vial, equivalent to 0.085 mg/ml (after reconstitution with 20 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 Ontruzant

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

Ontruzant is given as an infusion into a vein (intravenous infusion, “drip”). This intravenous formulation cannot be administered subcutaneously and must only be given as an intravenous infusion.

The first dose of your treatment is administered over 90 minutes, and a healthcare professional will monitor you during treatment for any adverse reactions (see section 2 “Warnings and precautions”). If you tolerate the first dose well, subsequent doses may be given over 30 minutes. The number of infusions you will receive depends on your response to treatment. Your doctor will inform you about this.

To prevent medication errors, it is important to check the vial label to ensure that the medicine being prepared and administered is Ontruzant (trastuzumab) and not another product containing trastuzumab (e.g. trastuzumab emtansine).

Ontruzant is administered every 3 weeks for early breast cancer, metastatic breast cancer, and metastatic gastric cancer. Ontruzant may also be administered once weekly for metastatic breast cancer (but not for trastuzumab deruxtecan).

If you interrupt treatment with Ontruzant

Do not stop using this medicine without first consulting your doctor. All doses should be administered at the correct time, either weekly or every three weeks (depending on your dosing schedule). This ensures the medicine works as effectively as possible.

It may take up to 7 months for Ontruzant to be eliminated from the body. Therefore, your doctor may decide to continue monitoring your heart function even after 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, Ontruzant can cause adverse effects, although not everyone experiences them. Some of these adverse effects may be serious and may lead to hospitalization.

During administration of an Ontruzant infusion, chills, fever, and other flu-like symptoms may occur. These effects are very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and agitation, headache, dizziness, difficulty breathing, high or low blood pressure, disturbances in heart rhythm (palpitations, arrhythmias, or irregular heartbeat), swelling of the face and lips, skin rash, and feeling tired. Some of these symptoms may be serious, and some patients have died (see section 2, "Warnings and precautions").

These effects occur mainly during the first intravenous infusion ("drip" into a vein) 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 at least 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 restarted once your symptoms have improved.

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

Serious adverse effects

Other adverse effects may occur at any time during treatment with Ontruzant, not only during the infusion. Tell 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 (including shortness of breath at night), cough, fluid retention (swelling) in the legs or arms, and palpitations (arrhythmias or irregular heartbeat) (see section 2, "Heart checks").

Your doctor will monitor your heart periodically during and after treatment, but you must inform them immediately if you notice any of the symptoms listed 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 may include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (palpitations or a faster or slower heartbeat), seizures, vomiting or diarrhea, and tingling in the mouth, hands, or feet.

If you experience any of the symptoms listed above after completing treatment with Ontruzant, you must see a doctor and inform them that you have received treatment with Ontruzant.

The following adverse effects may occur at any time during treatment with Ontruzant, not only during the infusion.

Very common adverse effects of Ontruzant (may affect more than 1 in 10 people):

• infections
• diarrhea
• constipation
• dyspepsia (indigestion, heartburn)
• fatigue
• skin rash
• chest pain
• abdominal pain
• joint pain
• low levels of red blood cells and white blood cells (which help fight infections), sometimes with fever
• muscle pain
• conjunctivitis
• watery eyes
• nosebleeds
• mucus production
• hair loss
• tremor
• hot flashes
• dizziness
• nail disorders
• weight loss
• loss of appetite
• insomnia (inability to sleep)
• altered taste
• low platelet levels
• bruising
• numbness or tingling in the fingers and toes, which may occasionally spread to the rest of the limb
• redness, swelling, or sores in the mouth and/or throat
• pain, swelling, redness, or tingling in the hands and/or feet
• shortness of breath
• headache
• cough
• vomiting
• nausea

Common adverse effects of Ontruzant (may affect up to 1 in 10 people):

Uncommon adverse effects of Ontruzant (may affect up to 1 in 100 people):

• deafness
• skin rash with bumps
• wheezing (whistling sounds)
• lung inflammation/scarring

Rare adverse effects of Ontruzant (may affect up to 1 in 1000 people):

• jaundice (yellowing of the skin or eyes)
• anaphylactic reactions

Other adverse effects reported with the use of Ontruzant (frequency cannot be estimated from available data):

• abnormal or altered blood clotting
• high potassium levels
• inflammation/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

During pregnancy:

• abnormally low levels of amniotic fluid surrounding the fetus in the uterus
• inability of the baby's lungs to develop in the uterus
• abnormal development of the baby's kidneys in the uterus

Some of the adverse effects you experience may be due to your cancer. If you are given Ontruzant together with chemotherapy, some of the effects may also be due to the chemotherapy.

If you experience any type of adverse effect, 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 included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ontruzant

Ontruzant 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.
• 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 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 particles or discoloration before administration.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ontruzant

• The active substance is trastuzumab. Each vial contains:

  • 150 mg of trastuzumab to be dissolved in 7.2 ml of water for injections, or
  • 420 mg of trastuzumab to be dissolved in 20 ml of water for injections.

• The resulting solution contains approximately 21 mg/ml of trastuzumab.

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

Nature and contents of the container

Ontruzant is a powder for concentrate for solution for intravenous infusion, supplied in a glass vial with a rubber stopper containing 150 mg or 420 mg of trastuzumab. The powder is a white to pale yellow pellet. Each carton contains 1 vial of powder.

Marketing Authorization Holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Manufacturer

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

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

Date of latest review of this leaflet:

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

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

This information is intended for healthcare professionals only:

Ontruzant 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 Ontruzant (trastuzumab) and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan).

This medicine must always be stored in its original closed packaging at a temperature between 2°C and 8°C in a refrigerator.

An 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 employed.

The Ontruzant vial reconstituted aseptically with sterile water for injections (not supplied) is chemically and physically stable for 7 days at 2°C to 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 Ontruzant has been demonstrated for up to 30 days at 2°C to 8°C and for 24 hours at temperatures not exceeding 30°C.

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

Storage, handling, and aseptic preparation

Aseptic handling must be ensured when preparing the infusion. Preparation must:

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

Ontruzant 150 mg powder for concentrate for solution for infusion

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

Ontruzant 420 mg powder for concentrate for solution for infusion

Each Ontruzant 420 mg vial is reconstituted with 20 ml of water for injections (not supplied). The use of other solvents for reconstitution should be avoided. This results in a 21 ml single-dose solution containing approximately 21 mg/ml of trastuzumab. A 5% overfill allows the labeled 420 mg dose to be withdrawn from each vial.

Aseptic reconstitution instructions

Ontruzant must be handled carefully during reconstitution. Excessive foaming during reconstitution or shaking of reconstituted Ontruzant may result in difficulties with the amount of Ontruzant that can be withdrawn from the vial.

• Using a sterile syringe, slowly inject the appropriate volume (as described above) of Water for Injections into the vial containing the lyophilized Ontruzant, directing the stream onto the lyophilized powder.
• Gently swirl the vial to assist reconstitution. DO NOT SHAKE.

The formation of slight foam after reconstitution is normal. Allow the vial to stand undisturbed for approximately 5 minutes. Reconstituted Ontruzant is a clear, colorless to pale yellow solution and should be essentially free of visible particles.

Aseptic dilution instructions for the reconstituted solution

The required volume of solution will be determined:

• based on a loading dose of 4 mg of trastuzumab/kg body weight or a subsequent weekly dose of 2 mg of trastuzumab/kg body weight:

• based on a loading dose of 8 mg of trastuzumab/kg body weight or a subsequent dose every 3 weeks of 6 mg of trastuzumab/kg body weight:

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. Glucose solutions must not be used. The bag should be gently inverted to mix the solution and avoid foam formation. Parenteral solutions should be inspected visually for particles and discoloration prior to administration.