trastuzumab deruxtecan: package leaflet

What Enhertu is

Enhertu is a cancer medicine that contains the active substance trastuzumab deruxtecan. One part of the medicine is a monoclonal antibody that attaches specifically to cells that have the protein HER2 on their surface (HER2-positive), as some cancer cells do. The other active part of Enhertu is DXd, a substance that can kill cancer cells. Once the medicine has attached to HER2-positive cancer cells, the DXd enters the cells and kills them.

What Enhertu is used for

Enhertu in combination with another drug called pertuzumab is used to treat adults who have:
- HER2-positive breast cancer that has spread to other parts of the body (metastatic) or cannot be taken out by surgery as first treatment. A test will be performed to make sure Enhertu in combination with pertuzumab is right for you.

Enhertu alone is used to treat adults who have:
- HER2-positive breast cancer that has spread to other parts of the body (metastatic disease) or cannot be removed by surgery, and have tried one or more other treatments specifically for HER2-positive breast cancer. A test will be performed to make sure Enhertu is right for you.
- HER2-low or HER2-ultralow breast cancer that has spread to other parts of the body (metastatic disease) or cannot be removed by surgery and have received prior therapy. A test will be performed to make sure Enhertu is right for you.
- HER2-mutant non-small cell lung cancer that has spread to other parts of the body or cannot be removed by surgery and have tried a prior treatment. A test will be performed to make sure Enhertu is right for you.
- HER2-positive stomach cancer that has spread to other parts of the body or to areas near the stomach that cannot be removed by surgery and have also tried another treatment specifically for HER2-positive stomach cancer.

• Other HER2-positive solid tumours that have spread to other parts of the body (metastatic disease) or cannot be taken out by surgery, and who have received prior treatment and have no other treatment options. A test will be performed to make sure Enhertu is right for you.

You must not be given Enhertu

• if you are allergic to trastuzumab deruxtecan or any of the other ingredients of this medicine (listed in section 6).

If you are not sure if you are allergic, talk to your doctor or nurse before you are given Enhertu.

Warnings and precautions

Talk to your doctor or nurse before you are given Enhertu, or during treatment, if you have:
- cough, shortness of breath, fever, or other new or worsening breathing problems. These may be symptoms of a serious and potentially fatal lung disease called interstitial lung disease. A history of lung disease or kidney problems may increase the risk of developing interstitial lung disease. Your doctor may have to monitor your lungs while you are taking this medicine.
- chills, fever, sores in your mouth, stomach pain or pain when urinating. These may be symptoms of an infection caused by a reduced number of white blood cells called neutrophils.
- new or worsening shortness of breath, cough, tiredness, swelling of ankles or legs, irregular heartbeat, sudden weight gain, dizziness, or loss of consciousness. These may be symptoms of a condition in which your heart cannot pump blood well enough (left ventricular dysfunction).
- liver problems. Your doctor may have to monitor your liver while you are taking this medicine.

Your doctor will carry out tests before and during treatment with Enhertu.

Children and adolescents

Enhertu is not recommended for anyone under the age of 18 years. This is because there is no information on how well it works in this age group.

Other medicines and Enhertu

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding, contraception and fertility

- Pregnancy
Enhertu is not recommended during pregnancy because this medicine may harm the unborn baby.
Speak with your doctor immediately if you are pregnant, think you may be pregnant or are planning to become pregnant before or during treatment.

- Breast-feeding
You should not breast-feed during treatment with Enhertu and for at least 7 months after your last dose. This is because it is not known whether Enhertu passes into breast milk. Talk to your doctor about this.

- Contraception
Use effective contraception (birth control) to avoid becoming pregnant while being treated with Enhertu.

Women taking Enhertu should continue contraception for at least 7 months after the last dose of Enhertu.

Men taking Enhertu whose partner may become pregnant should use effective contraception:
- during treatment and
- for at least 4 months after the last dose of Enhertu.

Talk to your doctor about the best contraception for you. Also talk to your doctor before you stop your contraception.

- Fertility
If you are a man being treated with Enhertu, you should not father a child for 4 months after treatment and take advice on conserving sperm before treatment because the medicine may reduce your fertility. Therefore, discuss this with your doctor before starting treatment.

Driving and using machines

Enhertu is not likely to reduce your ability to drive or use machines. Be careful if you feel tired, dizzy, or have a headache.

Enhertu contains polysorbate 80

This medicine contains 1.5 mg of polysorbate 80 in each 100 mg vial.
Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Enhertu will be given to you in a hospital or clinic:
- The recommended dose of Enhertu for the treatment of:
- HER2-positive or HER2-low or HER2-ultralow breast cancer, HER2-mutant non-small cell lung cancer, or other HER2-positive solid tumours is 5.4 mg for every kilogram of your body weight, every 3 weeks.
- HER2-positive stomach cancer is 6.4 mg for every kilogram of your body weight, every 3 weeks.
- The recommended dose of Enhertu in combination with pertuzumab for the treatment of:
- HER2-positive breast cancer is 5.4 mg for every kilogram of your weight followed by pertuzumab, with approximately 30 minutes between infusions, every 3 weeks.
- Your doctor or nurse will give you Enhertu by infusion (drip) into your vein.
- Your first infusion will be given over 90 minutes. If this goes well, the infusion on your next visits may be given over 30 minutes.
- Your doctor will decide how many treatments you need.
- Before each Enhertu infusion, your doctor may give you medicines to help prevent nausea and vomiting.
- If you get infusion-related symptoms, your doctor or nurse may slow down your infusion or interrupt or stop your treatment.
- Before and during treatment with Enhertu, your doctor will carry out tests that may include:
- blood tests to check your blood cells, liver and kidneys.
- testing to check your heart and lungs.
- Your doctor may lower your dose, or temporarily or permanently stop your treatment depending on your side effects.

If you miss an appointment to get Enhertu

Contact your doctor right away to reschedule your appointment.

It is very important that you do not miss a dose of this medicine.

If you stop receiving Enhertu

Do not stop treatment with Enhertu without checking with your doctor.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor if you get any side effects, including those not listed in this leaflet.

Speak with your doctor immediately if you notice any of the following symptoms. They may be signs of a serious, possibly fatal, condition. Getting medical treatment right away may help keep these problems from becoming more serious.

Very common (may affect more than 1 in 10 people)
- A lung disease called interstitial lung disease with symptoms that can include cough, shortness of breath, fever, or other new or worsening breathing problems
- An infection caused by reduced number of neutrophils (a type of white blood cell) with symptoms that can include chills, fever, sores in your mouth, stomach pain or pain when urinating
- A heart problem called left ventricular dysfunction with symptoms that can include new or worsening shortness of breath, cough, tiredness, swelling of ankles or legs, irregular heartbeat, sudden weight gain, dizziness or unconsciousness

Other side effects
The frequency and severity of side effects may vary with the dose you received. Tell your doctor or nurse if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people)
- nausea (feeling sick), vomiting
- feeling tired (fatigue)
- blood tests showing decreased red or white blood cells, or platelets
- constipation
- hair loss (alopecia)
- decreased appetite
- diarrhoea
- blood tests showing increased levels of the liver enzymes such as transaminases
- abdominal (belly) pain
- infections of the nose and throat, including flu-like symptoms
- pain in muscles and bones
- fever
- cough
- blood tests showing low blood potassium levels
- blisters in or around your mouth (stomatitis)
- headache
- lung problems (interstitial lung disease)
- weight loss
- decreased number of lymphocytes

Common (may affect up to 1 in 10 people)
- rash
- blood tests showing increased levels of bilirubin, alkaline phosphatase or creatinine
- breathing difficulties (dyspnoea)
- indigestion (dyspepsia)

• nosebleed (epistaxis)
• swelling of ankles and feet (peripheral oedema)
• coughing with phlegm, fever, chills (pneumonia)
• dizziness
• altered/bad taste in mouth (dysgeusia)
• itching (pruritus)
• skin discolouration
• dry eye
• blurry vision
• excessive gas in the stomach or intestine, bloating (abdominal distention)
• feeling thirsty, dry mouth (dehydration)
• fever along with a decreased number of white blood cells called neutrophils
• inflammation of the stomach
• reactions related to the infusion of the medicine which may include fever, chills, flushing, itching or rash

Reporting of side effects

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

Enhertu will be stored by healthcare professionals at the hospital or clinic where you receive treatment. The storage details are as follows:
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the outer carton and vial after EXP. The expiry date refers to the last day of that month.
- Store in a refrigerator (2 °C - 8 °C). Store in the original carton in order to protect from light.
Do not freeze.
- The prepared solution for infusion is stable for up to 24 hours at 2 °C - 8 °C protected from light and must be discarded thereafter.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

What Enhertu contains

- The active substance is trastuzumab deruxtecan.
One vial of powder for concentrate for solution for infusion contains 100 mg of trastuzumab deruxtecan. After reconstitution, one vial of 5 mL solution contains 20 mg/mL of trastuzumab deruxtecan.
- The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 (E433).

What Enhertu looks like and contents of the pack

Enhertu is a white to yellowish-white lyophilised powder supplied in a clear amber vial with a rubber stopper, aluminium seal and plastic flip-off cap.
Each carton contains 1 vial.

Marketing Authorisation Holder
Daiichi Sankyo Europe GmbH
Zielstattstrasse 48
81379 Munich
Germany

Manufacturer
Daiichi Sankyo Europe GmbH
Luitpoldstrasse 1
85276 Pfaffenhofen
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Daiichi Sankyo Belgium N.V.-S.A
Tél/Tel: +32-(0) 2 227 18 80
Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
Daiichi Sankyo Belgium N.V.-S.A
Tél/Tel: +32-(0) 2 227 18 80

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
Daiichi Sankyo Nordics ApS
Tlf.: +45 80 83 12 11

Malta
Daiichi Sankyo Europe GmbH
Tel: +49-(0) 89 7808 0

Deutschland
Daiichi Sankyo Deutschland GmbH
Tel: +49-(0) 89 7808 0

Nederland
Daiichi Sankyo Nederland B.V.
Tel: +31-(0) 20 4 07 20 72

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
Daiichi Sankyo Nordics ApS
Tlf: +45 80 83 12 11

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
Daiichi Sankyo Austria GmbH
Tel: +43 (0) 1 485 86 42 0

España
Daiichi Sankyo España, S.A.
Tel: +34 91 539 99 11

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel: +48 22 245 73 00

France
Daiichi Sankyo France S.A.S.
Tél: +33 (0) 1 55 62 14 60

Portugal
Daiichi Sankyo Portugal, Unip. LDA
Tel: +351 21 4232010

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
Daiichi Sankyo Ireland Ltd
Tel: +353-(0) 1 489 3000

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Icepharma hf
Sími: +354 540 8000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Daiichi Sankyo Italia S.p.A.
Tel: +39-06 85 2551

Suomi/Finland
Daiichi Sankyo Nordics ApS
Puh/Tel: +45 80 83 12 11

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
Daiichi Sankyo Nordics ApS
Tel: +45 80 83 12 11

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

This leaflet was last revised in {MM/YYYY}

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.
The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

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

------------------------------------------------------------------------------------------------------------------- The following information is intended for healthcare professionals only:

In order to prevent medicinal product errors, check the vial labels to ensure that the medicinal product being prepared and administered is Enhertu (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine.

Appropriate procedures for the preparation of chemotherapeutic medicinal products should be used.
Appropriate aseptic technique should be used for the following reconstitution and dilution procedures.

Reconstitution
- Reconstitute immediately before dilution.
- More than one vial may be needed for a full dose. Calculate the dose (mg), the total volume of reconstituted Enhertu solution required, and the number of vial(s) of Enhertu needed.
- Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 mL of water for injection into each vial to obtain a final concentration of 20 mg/mL.
- Swirl the vial gently until completely dissolved. Do not shake.
- From a microbiological point of view, the product should be used immediately. If not used immediately, chemical and physical in-use stability has been demonstrated for up to 48 hours at 2 ºC to 8 ºC. Store the reconstituted Enhertu vials in a refrigerator at 2 °C to 8 °C, protected from light. Do not freeze.
- The reconstituted product contains no preservative and is intended for single use only.

Dilution
- Withdraw the calculated amount from the vial(s) using a sterile syringe. Inspect the reconstituted solution for particulates and discolouration. The solution should be clear and colourless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discoloured.
- Dilute the calculated volume of reconstituted Enhertu in an infusion bag containing 100 mL of 5% glucose solution for infusion. Do not use sodium chloride solution. An infusion bag made of polyvinylchloride or polyolefin (copolymer of ethylene and polypropylene) is recommended.
- Gently invert the infusion bag to thoroughly mix the solution. Do not shake.
- Cover the infusion bag to protect from light.
- If not used immediately, store at room temperature (≤ 30 ºC) for up to 4 hours including preparation and infusion or in a refrigerator at 2 °C to 8 °C for up to 24 hours, protected from light. Do not freeze.
- Discard any unused portion left in the vial.

Administration
- If the prepared infusion solution was stored refrigerated (2 ºC to 8 ºC), it is recommended that the solution be allowed to equilibrate to room temperature prior to administration, protected from light.
- Administer Enhertu as an intravenous infusion only with a 0.20 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter.
- The initial dose should be administered as a 90-minute intravenous infusion. If the prior infusion was well tolerated, subsequent doses of Enhertu may be administered as 30-minute infusions. Do not administer as an intravenous push or bolus.
- Cover the infusion bag to protect from light.
- Do not mix Enhertu with other medicinal products or administer other medicinal products through the same intravenous line.

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.