Ontruzant

Package leaflet: Information for the user

Ontruzant 150 mg powder for concentrate for solution for infusion, 420 mg powder for concentrate for solution for infusion

trastuzumab
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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 present in large amounts on the surface of certain tumour cells and stimulates their growth. When Ontruzant binds to HER2, it blocks the growth of these cells and causes their death.

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

• you have early-stage breast cancer with high levels of a protein called HER2
• you have metastatic breast cancer (breast cancer that has spread away from the primary tumour) with high levels of HER2. Ontruzant may be prescribed in combination with the chemotherapeutic agents paclitaxel or docetaxel as first treatment for metastatic breast cancer, or it may be prescribed alone when other treatments have proven ineffective. It is also used in combination with medicines called aromatase inhibitors for the treatment of patients with high levels of HER2 and metastatic breast cancer with hormone receptor-positive tumours (cancer sensitive to female sex hormones)
• you have metastatic gastric cancer with high levels of HER2, in combination with the other anticancer medicines 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 tumour or require oxygen therapy.

Warnings and precautions
Your doctor will monitor you closely during treatment.
Heart checks
Treatment with Ontruzant, either alone or in combination with a taxane, may affect the heart,
particularly if you have previously received an anthracycline (taxanes and anthracyclines are two other types of
medicines used to treat tumours).
These effects may range from moderate to severe and may be fatal. Heart function will therefore be monitored
before, during (every three months), and after (up to two to five years) treatment with Ontruzant. If you develop
signs of heart failure (i.e. the heart's inability to pump blood adequately), you may require more frequent heart
function monitoring (every six to eight weeks), may need treatment for heart failure, or may have to discontinue
treatment with Ontruzant.
Talk to your doctor, pharmacist, or nurse before receiving Ontruzant if:

• you have had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, or if you have taken or are currently taking any medicine to treat high blood pressure
• you have taken or are currently taking a medicine called doxorubicin or epirubicin (medicines used to treat tumours). These medicines (or any other anthracycline) can damage heart muscle and increase the risk of heart problems when taking Ontruzant
• you suffer from shortness of breath, especially if you are currently receiving a taxane. Ontruzant can cause difficulty breathing, particularly the first time it is administered. This may be more serious if you already have breathing difficulties. Very rarely, patients with severe respiratory problems before treatment have died after receiving Ontruzant
• you have received other cancer treatments.

If you are receiving Ontruzant in combination with any other cancer medicine, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin, you should also read the package leaflet for these medicines.
Children and adolescents
Ontruzant is not recommended for use in individuals under 18 years of age.
Other medicines and Ontruzant
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
It may take up to 7 months for Ontruzant to be eliminated from the body. Therefore, you must inform your doctor,
pharmacist, or nurse that you have been treated with Ontruzant if you start taking any new medicine within 7 months
after stopping treatment.
Pregnancy

• If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor, pharmacist, or nurse before taking this medicine.
• You must use effective contraception during treatment with Ontruzant and for at least 7 months after the end of treatment.
• Your doctor will discuss with you the risks and benefits of taking Ontruzant during pregnancy. In rare cases, women treated with Ontruzant during pregnancy have experienced a reduction in the fluid (amniotic fluid) surrounding the developing baby in the womb. This condition may be harmful to the unborn baby and has been associated with incomplete lung development, which has led to fetal death.

Breast-feeding
Do not breast-feed during treatment with Ontruzant and for 7 months after receiving the last dose, as Ontruzant may pass into breast milk.
Consult your doctor or pharmacist before taking any medicine.
Driving and using machines
Ontruzant may affect your ability to drive or operate machinery. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, do not drive or use machinery until these symptoms have resolved.
Sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.

3. How to use Ontruzant

Before starting treatment, your doctor will determine the amount of HER2 in the tumour. 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 the dose and treatment schedule appropriate for you. The dose of Ontruzant depends on your body weight.
Ontruzant is given as an intravenous infusion (intravenous “drip”). This intravenous formulation is not intended for subcutaneous use and must be administered solely by intravenous infusion.
The first dose of treatment is administered over a period of 90 minutes, during which you will be monitored by a healthcare professional in case you experience any adverse effects (see section 2 “Warnings and precautions”). If the first dose is well tolerated, subsequent doses may be administered over a period of 30 minutes. The number of infusions you will receive depends on your response to treatment. Your doctor will discuss this with you.
To avoid medication errors, it is important to check the vial labels to ensure that the medicine being prepared and administered is Ontruzant (trastuzumab) and not another trastuzumab-based medicine (e.g. trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Ontruzant is administered every 3 weeks. Ontruzant may also be administered once weekly for the treatment of metastatic breast cancer.
If you interrupt treatment with Ontruzant
Do not stop taking this medicine without first discussing it with your doctor. All doses must be taken at the correct time, either weekly or every three weeks (depending on your dosing schedule). This helps the medicine work 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 cardiac function even after treatment has ended.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Ontruzant can cause side effects, although not everybody gets them. Some of these side effects can be serious and may require hospitalisation.

During infusion of Ontruzant, you may experience chills, fever, and other flu-like symptoms. These side effects are very common (may affect more than 1 in 10 people). Other infusion-related symptoms include: nausea, vomiting, pain, increased muscle tension and tremors, headache, dizziness, breathing difficulties, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), swelling of the face and lips, skin rash, and feeling of fatigue. Some of these symptoms can be severe, and some patients have died (see section 2 “Warnings and precautions”).

These effects occur mainly with the first intravenous infusion (“IV drip”) and during the first hours after the start of infusion. They are generally temporary. You will be monitored by a healthcare professional 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, the infusion will be slowed down or stopped, and you may be given treatment to counteract the side effects. The infusion may be resumed once your symptoms have improved.

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

Serious side effects

Other serious side effects may occur at any time during treatment with Ontruzant, not only in relation to an infusion. Tell your doctor or nurse immediately if you notice any of the following side effects:

• Heart problems, which may sometimes be serious, can occur during treatment and occasionally after treatment has been stopped. These include weakening of the heart muscle, which may lead to heart failure, inflammation of the lining around the heart, and heart rhythm disorders. These may cause symptoms such as shortness of breath (including at night), cough, fluid retention (swelling) in the legs or arms, and palpitations (rapid or irregular heartbeat) (see section 2, “Cardiac monitoring”).

Your doctor will monitor your heart regularly during and after treatment, but you must inform your doctor immediately if you notice any of the symptoms listed above.

• Tumour lysis syndrome (a group of metabolic complications occurring after anti-tumour treatment, characterised 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 (rapid or slow heartbeat), seizures, vomiting or diarrhoea, and tingling around the mouth, hands, or feet.

If you experience any of the above symptoms after completing treatment with Ontruzant, you must see a doctor and inform them about your previous treatment with Ontruzant.

The following side effects may occur at any time during treatment with Ontruzant, not only in relation to an infusion.

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

• infections
• diarrhoea
• constipation
• dyspepsia (heartburn)
• fatigue
• rash
• chest pain
• abdominal pain
• joint pain
• low numbers of red blood cells and white blood cells (which help fight infections), sometimes associated with fever
• muscle pain
• conjunctivitis
• watery eyes
• nosebleeds
• runny nose
• hair loss
• tremor
• hot flush
• dizziness
• nail disorders
• weight loss
• loss of appetite
• insomnia (inability to sleep)
• altered taste
• low platelet count
• bruising
• numbness or tingling in the 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 numbness in the hands and/or feet
• shortness of breath
• headache
• cough
• vomiting
• nausea

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

• allergic reactions
• dry mouth and dry skin
• throat infections
• dry eyes
• bladder and skin infections
• sweating
• breast inflammation
• feeling weak and unwell
• liver inflammation
• kidney disorders
• hypertension (increased muscle tone or tension)
• asthma
• arm and/or leg pain
• lung infection
• itchy rash
• drowsiness
• haemorrhoids
• itching
• leg cramps
• back pain
• neck pain
• bone pain
• acne
• depression
• anxiety

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

• deafness
• skin rash with hives
• wheezing
• inflammation or scarring in the lungs (fibrosis)

Rare side effects of Ontruzant (may affect up to 1 in 1,000 people):

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

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

• impaired or abnormal blood clotting
• high levels of potassium
• swelling or bleeding at the back of the eyes
• shock
• abnormal heart rhythm
• respiratory distress
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low levels of oxygen in the blood
• difficulty breathing when lying down
• liver damage
• swelling of face, lips, and throat
• kidney failure

During pregnancy:

• abnormally low levels of fluid around the baby in the uterus
• inadequate development of the baby’s lungs in the uterus
• abnormal development of the baby’s kidneys in the uterus

Some of the side effects that occur may be due to the underlying carcinoma. If you are receiving Ontruzant in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.

If you experience any side effect, talk to your doctor, pharmacist, or nurse.

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ontruzant

Ontruzant must be stored by healthcare professionals at 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 outer carton and on the label of the vial after “Exp.”. The expiry date refers to the last day of that month.
• Store the vial in a refrigerator (2°C - 8°C) prior to reconstitution.
• Do not freeze the reconstituted solution.
• Infusion solutions should be used immediately after dilution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C.
• Do not use Ontruzant if you notice any particles or change in colour before administration.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Ontruzant contains

• The active substance is trastuzumab. Each vial contains either:
  • 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 components are L-histidine hydrochloride monohydrate, L-histidine, α,α-trehalose dihydrate, polysorbate 20.

Description of the appearance of Ontruzant and contents of the pack
Ontruzant is a powder for concentrate for solution for intravenous infusion, supplied in a
glass vial sealed with a rubber stopper containing either 150 mg or 420 mg of trastuzumab. The
powder is a white to pale yellow pellet. Each pack contains 1 vial of powder.
Marketing Authorisation 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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Organon Belgium Organon Pharma B.V. Lithuania atstovybė
Tel/Tél: 0080066550123 (+32 2 2418100) Tel.: + 370 52041693
[email protected] [email protected]
България Luxembourg/Luxemburg
Органон (И.А.) Б.В. - клон България Organon Belgium
Тел.: +359 2 806 3030 Tel/Tél: 0080066550123 (+32 2 2418100)
[email protected] [email protected]
Česká republika Magyarország
Organon Czech Republic s.r.o. Organon Hungary Kft.
Tel.: +420 233 010 300 Tel.: +36 1 766 1963
[email protected] [email protected]
Danmark Malta
Organon Denmark ApS Organon Pharma B.V., Cyprus branch
Tlf: + 45 44 84 68 00 Tel.: +356 22778116
[email protected] [email protected]
Deutschland Nederland
Organon Healthcare GmbH N.V. Organon
Tel: 0800 3384 726 (+49 (0) 89 2040022 10) Tel.: 00800 66550123 (+32 2 2418100)
[email protected] [email protected]
Eesti Norge
Organon Pharma B.V. Estonian RO Organon Norway AS
Tel: +372 66 61 300 Tlf: +47 24 14 56 60
[email protected] [email protected]
Ελλάδα Österreich
BIANEΞ Α.Ε Organon Austria GmbH
Τηλ: +30 210 80091 11 Tel: +43 (0) 1 263 28 65
[email protected] [email protected]
España Polska
Organon Salud, S.L. Organon Polska Sp. z o.o.
Tel: +34 91 591 12 79 Tel: +48 22 105 50 01
[email protected]
France Portugal
Organon France Organon Portugal, Sociedade Unipessoal Lda.
Tél: + 33 (0) 1 57 77 32 00 Tel: +351 218705500
[email protected]
Hrvatska România
Organon Pharma d.o.o. Organon Biosciences S.R.L.
Tel: + 385 1 638 4530 Tel: + 40 21 527 29 90
[email protected] [email protected]
Ireland Slovenija
Organon Pharma (Ireland) Limited Organon Pharma B.V., Oss, podružnica Ljubljana
Tel: +353 15828260 Tel: + 386 1 300 10 80
[email protected] [email protected]
Ísland Slovenská republika
Vistor hf. Organon Slovakia s. r. o.
Sími: + 354 535 7000 Tel: +421 2 44 88 98 88
[email protected]
Italia Suomi/Finland
Organon Italia S.r.l. Organon Finland Oy
Tel: +39 06 90259059 Puh/Tel: +358 (0) 29 170 3520
[email protected] [email protected]
Κύπρος Sverige
Organon Pharma B.V., Cyprus branch Organon Sweden AB
Τηλ.: +357 22866730 Tel: +46 8 502 597 00
[email protected] [email protected]
Latvija United Kingdom (Northern Ireland)
Ārvalsts komersanta “Organon Pharma B.V.” Organon Pharma (UK) Limited
pārstāvniecība Tel: +44 (0) 208 159 3593
Tel: + 371 66968876 [email protected]
[email protected]
More detailed information on this medicinal product 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.

The following information is intended exclusively for healthcare professionals:

Ontruzant is supplied in sterile, single-use vials that are preservative-free and pyrogen-free.
To avoid medication errors and to ensure that the drug being prepared and administered is Ontruzant (trastuzumab) and not another trastuzumab-containing product (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is important to check the vial label.
Always store the medicinal product in its original closed packaging at a temperature of 2°C–8°C in a refrigerator.
Follow appropriate aseptic techniques during reconstitution and dilution procedures. Care must be taken to ensure sterility of the prepared solutions. The medicinal product does not contain antimicrobial preservatives or bacteriostatic agents; therefore, aseptic techniques must be used.
A vial of Ontruzant reconstituted aseptically with sterile water for injections (not supplied) remains chemically and physically stable for 7 days 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 chemical and physical stability of Ontruzant has been demonstrated for up to 30 days at 2°C–8°C and for up to 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 the product is not used immediately, the storage period and conditions prior to and during use are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Aseptic preparation, handling, and storage
Aseptic handling of the medicinal product must be ensured during infusion preparation.
Preparation must:

• Be performed under aseptic conditions by trained personnel in accordance with good manufacturing practices, particularly observing aseptic techniques for the preparation of parenteral medicinal products.
• Be carried out under laminar flow hoods or within biologically safe environments, applying standard precautions for the safe handling of intravenous agents.
• Be followed by appropriate storage of the infusion solution, ensuring maintenance of aseptic conditions.

Ontruzant 150 mg powder for concentrate for solution for infusion
Each 150 mg Ontruzant vial is reconstituted with 7.2 mL of sterile water for injections (not supplied). Avoid using other solvents for reconstitution. This results in 7.4 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. An overfill of 4% ensures withdrawal from the vial of the intended dose of 150 mg.

Ontruzant 420 mg powder for concentrate for solution for infusion
Each 420 mg Ontruzant vial is reconstituted with 20 mL of sterile water for injections (not supplied). Avoid using other solvents for reconstitution. This results in 21 mL of solution for single dose, containing approximately 21 mg/mL of trastuzumab. An overfill of 5% ensures withdrawal from the vial of the intended dose of 420 mg.

Aseptic reconstitution instructions
Ontruzant must be handled carefully during the reconstitution process.
Excessive foaming occurring during reconstitution or agitation of reconstituted Ontruzant
may result in difficulties in terms of the amount of Ontruzant that can be withdrawn from
the vial.

• Using a sterile syringe, slowly inject the appropriate volume (as stated above) of water for injections into the vial containing the Ontruzant lyophilisate, directing the stream onto the lyophilized material.
• Gently rotate the vial to facilitate reconstitution. DO NOT SHAKE!

Slight foaming during reconstitution is not unusual. Allow the vial to stand undisturbed in an upright position for approximately 5 minutes. Once reconstituted, Ontruzant appears as a clear, colourless to slightly yellow solution, free from visible particles.

Aseptic dilution instructions for the reconstituted solution
Determine the volume of solution required:

• based on a loading dose of 4 mg of trastuzumab/kg body weight, or a subsequent weekly maintenance dose of 2 mg of trastuzumab/kg body weight: Body weight (kg) x dose ( 4 mg/kg for loading dose or 2 mg/kg for maintenance dose) Volume (mL) = 21 (mg/mL, concentration of reconstituted solution)

• based on a loading dose of 8 mg of trastuzumab/kg body weight, or a subsequent dose of 6 mg of trastuzumab/kg body weight every 3 weeks: Body weight (kg) x dose ( 8 mg/kg for loading dose or 6 mg/kg for maintenance dose) Volume (mL) = 21 (mg/mL, concentration of reconstituted solution)

Withdraw the required amount of solution from the vial using a sterile needle and syringe and transfer it into a polyvinylchloride, polyethylene or polypropylene infusion bag containing 250 mL of 0.9% sodium chloride solution. Do not use glucose-containing solutions. The bag should be gently inverted to mix the solution, avoiding foaming. Parenteral solutions should be visually inspected for particulate matter and discoloration prior to administration.