Prospect: 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 this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section4.

1.What Ontruzant is and for what it is used

2.What you need to know beforestarting to useOntruzant

3.Howto useOntruzant

4.Possible adverse effects

5.Storage of Ontruzant

6.Contents of the package and additional information

Ontruzant contains the active ingredient trastuzumab, which is a monoclonal antibody. Monoclonal antibodies bind to 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, stimulating their growth. When Ontruzant binds to HER2, it slows the growth of these cells and causes them to die.2

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

•youhave early-stage breast cancerwith high levels of the HER2 protein;

•youhave metastatic breast cancer(breast cancer that has spread beyond the original tumor) with high levels of HER2. Ontruzant may be prescribed in combination with the chemotherapy medications paclitaxel or docetaxel as first-line treatment for metastatic breast cancer or it may be prescribed alone if other treatments have not been effective. 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);

•youhave metastatic gastric cancerwith high levels of HER2, when combined with other cancer medications such as capecitabina or 5-fluorouracilo and cisplatino.

No use Ontruzant

•If you are allergic to trastuzumab, mouse proteins, or any of the other components of this medication (listed in section6);

•If you have severe respiratory problems at rest due to your cancer or if you need oxygen treatment.

Advertencias y precauciones

Your doctor will closely monitor your treatment.

Revisiones del corazón

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

The effects can be moderate to severe and may cause death. Therefore, your cardiac function will be reviewed before, during (every threemonths), and after (two to fiveyears) treatment with Ontruzant. If you experience any signs of heart failure (inadequate blood pumping by your heart), your cardiac function may be reviewed more frequently (every six to eightweeks), you may receive treatment for heart failure, or you may need to discontinue treatment with Ontruzant.

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, are currently taking or have taken high blood pressure medication;

•You are currently taking or have taken a medication called doxorubicin or epirubicin (medications used to treat cancer). These medications (or any other anthracycline) may damage the heart muscle and increase the risk of heart problems with Ontruzant;

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

•You have ever taken another cancer treatment.

If you receive Ontruzant in combination with another medication to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5‑fluorouracil, or cisplatin, you should also read the prospectuses for these medications.

Niños y adolescentes

Ontruzant is not recommended for individuals under 18years.

Otros medicamentos y Ontruzant

Use of Ontruzant with other medications:Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication.

It may take up to 7months for Ontruzant to be eliminated from the body. Therefore, if you are to take a new medication within 7months of completing treatment, inform your doctor, pharmacist, or nurse that you have received treatment with Ontruzant.

Embarazoy lactancia

•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 effective birth control during treatment with Ontruzant and for at least 7months 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) surrounding the developing fetus in the uterus has been observed in pregnant women treated with Ontruzant. This condition may be harmful to the fetus in the uterus and has been associated with a complete lung development problem leading to fetal death.

Lactancia

Do not breastfeed your child during treatment with Ontruzant or within 7months after the last dose, as Ontruzant may pass to your child through breast milk.

Consult your doctor or pharmacist before using this medication.

Conducción y uso de máquinas

Ontruzant may affectyourabilitytodriveavehicleoroperatemachinery. Ifyou experience symptoms during treatment such as dizziness, drowsiness,chills, or fever, do not driveor use machineryuntil these symptoms disappear.

Sodio

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

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

Ontruzant is administered as an intravenous infusion (IV drip). This intravenous formulation cannot be administered subcutaneously and should only be administered as an IV infusion.

The first dose of your treatment is administered over 90 minutes, and a healthcare professional will monitor you while you receive the treatment in case you experience any adverse effects (see section 2 “Warnings and Precautions”). If you tolerate the first dose well, subsequent doses can be administered over 30 minutes. The number of infusions you will receive will depend on your response to treatment. Your doctor will inform you about this.

To avoid medication errors, it is essential to check the labeling of the vial to ensure that the medication being prepared and administered is Ontruzant (trastuzumab) and not another product containing trastuzumab (e.g. trastuzumab emtansina).

Ontruzant is administered every 3 weeks for early-stage breast cancer, metastatic breast cancer, and metastatic gastric cancer. Ontruzant can also be administered once a week for metastatic breast cancer or trastuzumab deruxtecan).

If You Interrupt Treatment with Ontruzant

Do not stop using this medication without consulting your doctor first. All doses should be administered at the correct time, either weekly or every 3 weeks (depending on your dosing schedule). This ensures the medication 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 cardiac function even after treatment has been completed.

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

Like all medicines, Ontruzant can cause side effects, although not everyone will experience them. Some of these side effects can be severe and may require hospitalization.

During the administration of an Ontruzant infusion, you may experience chills, fever, and other symptoms similar to the flu. These effects are very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: nausea, vomiting, pain, muscle tension, agitation, headache, dizziness, shortness of breath, high or low blood pressure, irregular heart rhythm, facial and lip swelling, skin rash, and fatigue. Some of these symptoms can be severe and some patients have died (see section 2 “Warnings and precautions”).

These effects mainly occur with the first intravenous infusion (“drip” in a vein) and during the first 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 two hours after the start of subsequent infusions. If you experience a reaction, the infusion will be administered more slowly or stopped, and you may be given a treatment to counteract the side effects. The infusion can be resumed once your symptoms have improved.

In some cases, symptoms appear after six hours after the start of the infusion. If this happens, contact your doctor immediately. Sometimes, symptoms may improve and then worsen.

Severe side effects

Other side effects can occur at any time during treatment with Ontruzant, and not just related to the infusion.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 severe. These include heart muscle weakness that may cause heart failure, inflammation of the heart's outer layer, and irregular heart rhythm. This may 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 must inform them immediately if you observe any of the above symptoms.

• The 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 irregular heartbeat). Convulsions, vomiting, diarrhea, and tingling in the mouth, hands, or feet.

If you experience any of the above symptoms after completing treatment with Ontruzant, you must see your doctor and tell them that you received treatment with Ontruzant.

The following side effects can occur at any time during treatment with Ontruzant, and not just related to the infusion.

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

• Infections

• Diarrhea

• Constipation

• Dyspepsia (stomach burning)

• Fatigue

• Skin rash

• Chest pain

• Abdominal pain

• Joint pain

• Low red and white blood cell counts (which help fight infections), sometimes with fever

• Muscle pain

• Conjunctivitis

• Lacrimation

• Nasal bleeding

• Mucositis

• Hair loss

• Tremors

• Seizures

• Vomiting

• Nausea

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

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

• Jaundice (yellowing of the skin or eyes)

• Anaphylactic reactions

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

• Abnormal or altered blood coagulation

• High potassium levels

• Inflammation/hemorrhages in the back of the eyes

• Shock

• Abnormal heart rhythm

• Difficulty breathing

• Respiratory insufficiency

• 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

• Swelling of the face, lips, and throat

• Renal failure

During pregnancy:

• Abnormally low levels of fluid surrounding the fetus in the womb

• Inability 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 experience may be due to your cancer. If you are given Ontruzant in combination with chemotherapy, some of the side effects may also be due to the chemotherapy.

If you experience any type of side effect, consult your doctor, pharmacist, or nurse.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Ontruzant will be stored by healthcare professionals in the hospital or clinic.

•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 CAD. The expiration date is the last day of the month indicated.

•Sealed vials must be stored in a refrigerator (between 2°C and 8°C).

•Do not freeze the reconstituted solution.

•Infusion solutions must be used immediately after dilution. If not used immediately, the storage time until use and the conditions of such storage before use will be the responsibility of the user, and in general, should not exceed 24 hours between 2°C and 8°C.

•Do not use this medication if you observe particles or discoloration before administration.

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

Composition of Ontruzant

• The active ingredient is trastuzumab. Each vial contains:

• 150 mg of trastuzumab that must be dissolved in 7.2 ml of water for injectable preparations, or
• 420 mg of trastuzumab that must be dissolved in 20 ml of water for injectable preparations.

• The resulting solution contains approximately 21 mg/ml of trastuzumab.
• The other components are L-histidine hydrochloride monohydrate, L-histidine, α,α-trehalose dihydrate, polisorbate 20.

Appearance of the product and contents of the package

Ontruzant is a lyophilized powder for concentrate for solution for intravenous infusion, which is supplied in a glass vial with a rubber stopper that contains 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
Netherlands

Responsible for manufacturing

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://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.

This information is intended solely for healthcare professionals:

Ontruzant is supplied in sterile, non-pyrogenic, non-preserved, and single-use vials.

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

Always store this medicine in the original closed container at a temperature between 2°C and 8°C in a refrigerator.

Use aseptic technique when preparing the infusion. The preparation must be:

•developed under aseptic conditions by qualified personnel in accordance with good practices, especially regarding the aseptic preparation of parenteral products.

•prepared in a laminar flow cabinet or a biological safety cabinet using standard precautions for the safe handling of intravenous agents.

•followed by proper storage of the prepared infusion solution to ensure maintenance of aseptic conditions.

Ontruzant150 mg lyophilized powder for concentrate for solution for infusion

Each vial of Ontruzant150 mgmust be reconstituted with 7.2ml of water for injectable preparations (not supplied). Avoid using other solvents for reconstitution. This produces a 7.4ml single-dose solution containing approximately 21mg/ml of trastuzumab. A 4% overfill allows the 150mg dose reflected on the label to be extracted from each vial.

Ontruzant420 mg lyophilized powder for concentrate for solution for infusion

Each vial of Ontruzant420 mgmust be reconstituted with 20ml of water for injectable preparations (not supplied). Avoid using other solvents for reconstitution. This produces a 21ml single-dose solution containing approximately 21mg/ml of trastuzumab. A 5% overfill allows the 420mg dose reflected on the label to be extracted from each vial.

Instructions for aseptic reconstitution

Handle Ontruzant carefully during reconstitution. If excessive foam forms during reconstitution or Ontruzant reconstituted is agitated, there may be problems with the amount of Ontruzant that can be extracted from the vial.

• Using a sterile syringe, slowly inject the corresponding volume (as described above)of water for injectable preparations into the vial containing Ontruzant lyophilized powder, directing the flow towards the lyophilized powder.
• Maintain the vial in a gentle, rotating motion to facilitate reconstitution. DO NOT AGITATE.

A slight foam formation after reconstitution is normal. Leave the vial undisturbed for approximately 5minutes. Ontruzant reconstituted is a transparent, colorless to pale yellow solution and should be essentially free of visible particles.

Instructions for aseptic dilution of the reconstituted solution

Determine the volume of solution required:

•according to a loading dose of 4mg of trastuzumab/kg of body weight or a weekly maintenance dose of 2mg of trastuzumab/kg of body weight:

•according to a loading dose of 8mg of trastuzumab/kg of body weight or a maintenance dose every 3weeks of 6mg of trastuzumab/kg of body weight:

The appropriate amount of solution should be extracted from the vial using a sterile syringe and needle and added to a 250ml infusion bag of 0.9% sodium chloride solution. Do not use glucose solutions. The bag should be inverted carefully to mix the solution and avoid foam formation. Parenteral solutions should be visually inspected for particles and discoloration before administration.