Dazublys

Package leaflet: Information for the user

Dazublys 150 mg powder for concentrate for solution for infusion

trastuzumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before 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, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Dazublys is and what it is used for

Dazublys contains the active substance trastuzumab, which is a monoclonal antibody.
Monoclonal antibodies bind to specific proteins or antigens. Trastuzumab is designed to selectively bind 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 trastuzumab binds to HER2, it blocks the growth of these cells and causes their death.
Your doctor may prescribe Dazublys 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. Trastuzumab may be prescribed in combination with the chemotherapeutic medicines 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 HER2 levels and metastatic breast cancer with hormone receptor-positive (cancer that is sensitive to female sex hormones);
• you have metastatic gastric cancer with high levels of HER2, in combination with other anticancer medicines, capecitabine or 5-fluorouracil and cisplatin.

2. What you need to know before you are given Dazublys

Do not use Dazublys if:

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

Warnings and precautions
Your doctor will closely monitor you during treatment.
Heart checks
Treatment with Dazublys, 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 can be fatal.
Heart function will therefore be monitored before, during (every three months), and after (up to two to
five years) treatment with Dazublys. 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 Dazublys.
Talk to your doctor, pharmacist, or nurse before being given Dazublys 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 Dazublys;
• you suffer from shortness of breath, especially if you are currently receiving a taxane. Dazublys can cause difficulty breathing, particularly the first time it is administered. This may be more severe if you already have breathing difficulties. Very rarely, patients with severe breathing difficulties before treatment have died after receiving Dazublys;
• you have received other cancer treatments.

If you are receiving Dazublys in combination with any other medicine used to treat cancer, 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
Dazublys is not recommended for patients under 18 years of age.
Other medicines and Dazublys
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 Dazublys to be eliminated from the body. Therefore, inform your doctor, pharmacist, or nurse that you have been administered Dazublys 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 a pregnancy, inform your doctor,
  pharmacist, or nurse before taking this medicine.

• You must use effective contraception during treatment with Dazublys and for at least 7 months after the end of treatment.

• Your doctor will discuss with you the risks and benefits of taking Dazublys during pregnancy. In rare cases, women treated with trastuzumab during pregnancy have experienced reduced 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 maturation, which has led to fetal death.

Breastfeeding
Do not breastfeed during treatment with Dazublys and for 7 months after the last dose of Dazublys, as Dazublys may pass into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Dazublys may affect your ability to drive or operate machinery. If you develop symptoms such as dizziness, drowsiness, chills, or fever during treatment, you should not drive or operate machinery until these symptoms have resolved.
Sodium
Dazublys contains less than 1 mmol of sodium (23 mg) per dose, i.e. it is practically sodium-free.
Polysorbate 20
This medicine contains 0.6 mg of polysorbate 20 per 150 mg/vial (21 mg/mL), equivalent to 0.6 mg/60 kg/7.4 mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Dazublys is administered

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 Dazublys. Dazublys must be administered only
by a doctor or a nurse. Your doctor will prescribe the dose and treatment schedule appropriate for you.
The dose of Dazublys depends on your body weight.
The first dose of treatment is administered over a period of 90 minutes, and you will be monitored by a
healthcare professional during administration in case you experience any adverse effects. If the first
dose is well tolerated, subsequent doses may be administered over a period of 30 minutes (see
section 2 “Warnings and precautions”). The number of infusions you will receive depends on your
response to treatment. Your doctor will discuss this with you.
Dazublys is administered as an intravenous infusion (intravenous infusion, drip); this intravenous
formulation is not for subcutaneous use and must be administered only as an intravenous infusion.
To prevent medication errors, it is important to check the vial labels to ensure that the medicine being
prepared and administered is Dazublys (trastuzumab) and not another trastuzumab-containing medicine
(e.g., trastuzumab emtansine or trastuzumab deruxtecan).
In patients with early breast cancer, metastatic breast cancer, and metastatic gastric cancer, Dazublys
is administered every 3 weeks. Dazublys may also be administered once weekly for the treatment of
metastatic breast cancer.
If you interrupt treatment with Dazublys
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 the treatment schedule). This allows
the medicine to work optimally.
It may take up to 7 months for Dazublys to be eliminated from the body. Therefore, your doctor may
decide to continue monitoring heart 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, trastuzumab can cause side effects, although not everyone experiences them. Some of these side effects can be serious and may require hospitalization.

During infusion of Dazublys, reactions such as 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 tremors, headache, dizziness, difficulty breathing, high or low blood pressure, heart rhythm disorders (palpitations, rapid or irregular heartbeat), facial or lip swelling, skin rashes, and feeling of fatigue. Some of these symptoms may be severe, and some patients have died (see section 2 “Warnings and precautions”).

These effects occur mainly with the first intravenous infusion (“drip” into the vein) and during the first hours after the start of infusion. They are generally temporary. You will be closely 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 experience 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 symptoms have improved.

Occasionally, symptoms begin more than six hours after the start of infusion. If this occurs, contact your doctor immediately. Sometimes symptoms may improve initially but worsen later.

Serious side effects

Other serious side effects may occur at any time during treatment with Dazublys, 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 can sometimes be serious, may 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 of 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 described above.

• Tumor lysis syndrome (a group of metabolic complications occurring after anti-tumor treatment, characterized by high levels of potassium and phosphate in the blood and low calcium levels). Symptoms may include kidney problems (weakness, shortness of breath, fatigue, and confusion), heart problems (rapid or slow heartbeat), seizures, vomiting or diarrhea, and tingling around the mouth, hands, or feet.

If you experience any of the symptoms described above after completing treatment with Dazublys, contact your doctor and inform them about your previous treatment with Dazublys.

Very common side effects of Trastuzumab: may affect more than 1 in 10 people

• infections
• diarrhea
• constipation
• chest burning (dyspepsia)
• fatigue
• skin rashes
• chest pain
• abdominal pain
• joint pain
• low red and white blood cell counts (which help fight infections), sometimes associated with fever
• muscle pain
• conjunctivitis
• excessive tearing
• nosebleeds
• runny nose
• hair loss
• tremor
• hot flashes
• dizziness
• nail problems
• weight loss
• loss of appetite
• inability to sleep (insomnia)
• 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 blisters 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 Trastuzumab: 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 the arms and/or legs
• itchy skin rash
• drowsiness
• hemorrhoids
• itching
• dry mouth and dry skin
• dry eyes
• sweating
• fatigue and malaise
• anxiety
• depression
• asthma
• lung infection
• lung disorders
• back pain
• neck pain
• bone pain
• acne
• leg cramps

Uncommon side effects of Trastuzumab: may affect up to 1 in 100 people

• deafness
• skin rash with hives
• wheezing
• lung inflammation or scarring (fibrosis)

Rare side effects of Trastuzumab: may affect up to 1 in 1000 people

• jaundice
• anaphylactic reactions

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

• blood clotting abnormalities or changes
• high potassium levels
• swelling or bleeding deep in the eye
• shock
• abnormal heart rhythm
• respiratory distress
• respiratory failure
• acute accumulation of fluid in the lungs
• acute narrowing of the airways
• abnormally low oxygen levels in the blood
• difficulty breathing when lying down
• liver damage
• swelling of the face, lips, and throat
• kidney failure
• abnormally low levels of amniotic fluid around the unborn baby
• inadequate development of the baby’s lungs in the womb
• abnormal development of the baby’s kidneys in the womb

Some of the side effects experienced may be due to cancer itself. If you are receiving Dazublys in combination with chemotherapy, some of these side effects may also be due to the chemotherapy.

If you experience any side effects, inform your doctor, pharmacist, or nurse.

Reporting of side effects

If you experience any side effect, 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 Dazublys

Dazublys 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 carton and on the label of the vial after "Exp./EXP". The expiry date refers to the last day of that month.
• Store the vial in a refrigerator (2 °C - 8 °C) prior to first use.
• Do not freeze the reconstituted solution.
• Infusion solutions should be used immediately after dilution. If not used immediately, storage times and conditions prior to use are the responsibility of the user and should normally not exceed 48 hours at 2 °C - 8 °C.
• Do not use Dazublys if you notice any particles or change in colour before administration.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Dazublys contains

• The active substance is trastuzumab. Each vial contains: 150 mg of trastuzumab to be dissolved in 7.2 mL of sterile water for injections, or. 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 (E 432).
• This medicine contains 0.6 mg of polysorbate 20 per 150 mg/vial (21 mg/mL), equivalent to 0.6 mg/60 kg/7.4 mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

Description of the appearance of trastuzumab and contents of the pack
Trastuzumab is a powder for concentrate for solution for intravenous infusion supplied in a
glass vial sealed with a rubber stopper containing 150 mg of trastuzumab. The powder is a
white to pale yellow pellet. Each pack contains 1 vial of powder.
Marketing Authorisation Holder
CuraTeQ Biologics s.r.o
Trtinova 260/1, Cakovice,
19600 Prague
Czech Republic
Manufacturer
APL Swift Services Malta Ltd.
HF26, Hal Far Industrial Estate,
Qasam Industrijali Hal Far,
Birzebbugia, BBG 3000
Malta
For further information on this medicine, contact the local representative of the marketing authorisation holder:
België/Belgique/Belgien Lietuva
Aurobindo NV/SA UAB Orion Pharma
Tél/Tel: +32 24753540 Tel: +370 5 276 9499
България Luxembourg/Luxemburg
Curateq Biologics s.r.o. Aurobindo NV/SA
Phone: +420220990139 Tel/Tél: +32 24753540
[email protected]
Česká republika Magyarország
Curateq Biologics s.r.o. Orion Pharma Kft.
Phone: +420220990139 Tel.: +36 1 239 9095
[email protected]
Danmark Malta
Orion Pharma A/S Curateq Biologics s.r.o.
Tlf.: +45 8614 0000 Tel: +420220990139
[email protected]
Deutschland Nederland
PUREN Pharma GmbH Co. KG Aurobindo Pharma B.V.
Tel: +49 895589090 Tel: +31 35 542 99 33
Eesti Norge
Orion Pharma Eesti OÜ Orion Pharma AS
Tel: +372 66 44 550 Tlf: +47 4000 42 10
Ελλάδα Österreich
Curateq Biologics s.r.o. Orion Pharma GmbH
Τηλ: +420220990139 Tel: +49 40 899 6890
[email protected]
España Polska
Aurovitas Spain, S.A.U Aurovitas Pharma Polska
Tel: +34 91 630 86 45 Sp. z o.o.
Tel.: +48 22 311 20 00
France Portugal
ARROW GENERIQUES Generis Farmacutica S. A
Tél: +33 4 72 72 60 72 Tel: +351 21 4967120
Hrvatska România
Curateq Biologics s.r.o. Curateq Biologics s.r.o.
Tel: +420220990139 Tel: +420220990139
[email protected] [email protected]
Ireland Slovenija
Curateq Biologics s.r.o. Orion Pharma d.o.o.
Tel: +420220990139 Tel: +386 (0) 1 600 8015
[email protected]
Ísland Slovenská republika
Vistor hf. Curateq Biologics s.r.o.
Sími: +354 535 7000 Tel: +420220990139
[email protected]
Italia Suomi/Finland
Aurobindo Pharma (Italia) S.r.l. Orion Corporation
Tel: +39 02 9639 2601 Puh/Tel: +358 10 4261
Κύπρος Sverige
Curateq Biologics s.r.o. Orion Pharma AB
Τηλ:: +420220990139 Tel: +46 8 623 6440
[email protected]
Latvija
Orion Corporation
Orion Pharma pārstāvniecība
Tel: +371 20028332
More detailed information on this medicine is available on the website of the European Medicines Agency: https://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 physicians or healthcare professionals

Dazublys for intravenous use is supplied in sterile, preservative-free, non-pyrogenic, single-use vials.
To avoid medication errors and ensure that the drug being prepared and administered is Dazublys and not another product containing trastuzumab (e.g., trastuzumab emtansine or trastuzumab deruxtecan), it is essential to verify the vial label.
The medicinal product must always be stored in its original closed packaging at a temperature of 2 °C – 8 °C in a refrigerator.
For reconstitution and dilution procedures, an appropriate aseptic technique must be used. Care must be taken to ensure sterility of the prepared solutions. Since the product contains no antimicrobial preservatives or bacteriostatic agents, aseptic technique must be strictly observed.
A vial of Dazublys reconstituted aseptically with sterile water for injections (not supplied) remains 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 sodium chloride 9 mg/mL (0.9%) injection solution, the chemical and physical stability of Dazublys has been demonstrated for up to 48 hours at 5 °C ± 3 °C and 30 °C ± 2 °C.
From a microbiological standpoint, the reconstituted solution and the trastuzumab infusion solution should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature between 2 °C and 8 °C, unless the reconstitution and dilution were performed under controlled and validated aseptic conditions.

Preparation, handling, and aseptic storage:
During infusion preparation, aseptic handling must be ensured. Preparation must:

• be carried out under aseptic conditions by trained personnel in accordance with good practice guidelines, particularly regarding aseptic preparation of parenteral products;
• be performed within laminar airflow hoods or in biologically safe environments, adopting standard precautions for the safe handling of intravenous agents;
• be followed by appropriate storage of the infusion solution, ensuring maintenance of aseptic conditions.

Each vial of Dazublys is reconstituted with 7.2 mL of sterile water for injection (not supplied). The use of other reconstitution solvents should be avoided. This results in a 7.4 mL solution for single-dose use, containing approximately 21 mg/mL of trastuzumab. A 4% overfill volume ensures that the labeled dose of 150 mg can be withdrawn from each vial.
Dazublys must be handled carefully during reconstitution. Excessive foaming during reconstitution or agitation of the reconstituted solution may affect the amount of trastuzumab that can be withdrawn from the vial.

Instructions for reconstitution:

1. Using a sterile syringe, slowly inject 7.2 mL of sterile water for injection into the vial containing the Dazublys lyophilized powder, directing the stream onto the lyophilized cake;
2. 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, Dazublys appears as a clear, colorless to pale yellow solution, free from visible particles.

Determine the required volume of solution:

• based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly maintenance dose of 2 mg trastuzumab/kg body weight;
• based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent dose of 6 mg trastuzumab/kg body weight every 3 weeks.

The appropriate volume of solution should be withdrawn from the vial using a sterile needle and syringe and added to a polyvinyl chloride, polyethylene, or polypropylene bag containing 250 mL of 0.9% sodium chloride solution. Do not use with 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. Once the infusion is prepared, it should be administered immediately. If aseptically diluted, it may be stored for up to 48 hours at 5 °C ± 3 °C and 30 °C ± 2 °C.