ENHERTU 100 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

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

You must not be given Enhertu

• if you are allergic to trastuzumab deruxtecán 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 respiratory problems. These may be symptoms of a serious and potentially life-threatening 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 need to monitor your lungs while you are taking this medicine;
• chills, fever, mouth sores, stomach pain or pain when urinating. These may be symptoms of an infection caused by a decrease in a type of white blood cell called neutrophils;
• new or worsening shortness of breath, cough, tiredness, swelling of ankles or legs, irregular heartbeats, sudden weight gain, dizziness or fainting. These may be symptoms of a condition in which the heart cannot pump blood properly (left ventricular dysfunction);
• liver problems. Your doctor may need to monitor your liver while you are taking this medicine.

Your doctor will perform tests before and during treatment with Enhertu.

Children and adolescents

Enhertu is not recommended for children under 18 years. This is because there is no information on how 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, breastfeeding and fertility

• Pregnancy

Enhertu is not recommendedduring pregnancy because this medicine may harm the fetus.

If you are pregnant, think you may be pregnant or are planning to have a baby before or during treatment, talk to your doctor immediately.

• Breastfeeding

You must not breastfeedduring treatment with Enhertu and for 7 months after your last dose. This is because it is not known if Enhertu passes into breast milk. Talk to your doctor about this.

• Contraception

Use an effective method of contraception (birth control) to prevent pregnancy while you are being treated with Enhertu.

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

Men who are taking Enhertu and whose partner may become pregnant should use an effective method of contraception:

• during treatment and
• for at least 4 months after the last dose of Enhertu.

Talk to your doctor about which contraceptive method is best for you. Also, talk to your doctor before stopping contraception.

• Fertility

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

Driving and using machines

Enhertu is unlikely to affect 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.

3. How Enhertu is given

Enhertu will be given to you in a hospital or clinic:

• The recommended dose of Enhertu for the treatment of:
• • HER2-positive breast cancer, with low HER2 expression or very low HER2 expression is 5.4 mg per kilogram of body weight every 3 weeks;
  • non-squamous lung cancer with a HER2 mutation is 5.4 mg per kilogram of body weight every 3 weeks;
  • HER2-positive stomach cancer is 6.4 mg per kilogram of body weight every 3 weeks.
• Your doctor or nurse will give you Enhertu through a drip (infusion) into a vein.
• Your first infusion will be given over a period of 90 minutes. If this goes well, the infusion at your next visits will be given over a period of 30 minutes.
• Your doctor will decide how many treatments you need.
• Before each infusion with Enhertu, your doctor may give you medicines to help prevent nausea and vomiting.
• If you have symptoms related to the infusion, your doctor or nurse may slow down your infusion, or stop or pause your treatment.
• Before and during treatment with Enhertu, your doctor will perform tests that may include:
• • blood tests to check your blood cells, liver and kidneys;
  • tests to check your heart and lungs.
• Your doctor may reduce your dose, or stop your treatment temporarily or permanently depending on your side effects.

If you miss an appointment to receive Enhertu

Contact your doctor immediately to reschedule your appointment.

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

If you stop treatment with Enhertu

Do not stop treatment with Enhertu without talking to your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet.

Talk to your doctor immediatelyif you notice any of the following symptoms. They can be signs of a serious, potentially life-threatening condition. Getting medical treatment right away can help prevent 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 may include cough, shortness of breath, fever or other new or worsening respiratory problems.
• An infection caused by a decrease in neutrophils (a type of white blood cell) with symptoms that may include chills, fever, mouth sores, stomach pain or pain when urinating.
• A heart problem called left ventricular dysfunction with symptoms that may include new or worsening shortness of breath, cough, tiredness, swelling of ankles or legs, irregular heartbeats, sudden weight gain, dizziness or fainting.

Other side effects

The frequency and severity of side effects may vary depending on the dose 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
• fatigue
• decreased appetite
• blood tests showing a decrease in red or white blood cells, or platelets
• hair loss
• diarrhea
• constipation
• blood tests showing an increase in liver enzymes such as transaminases
• muscle and bone pain
• stomach (abdominal) pain
• fever
• weight loss
• lung infection
• infections of the nose and throat, including symptoms similar to flu
• headache
• mouth sores
• cough
• blood tests showing low levels of potassium in the blood
• swelling of ankles and feet
• indigestion
• difficulty breathing
• altered sense of taste/bad taste in the mouth

Common(may affect up to 1 in 10 people)

• nosebleeds
• dizziness
• rash
• blood tests showing an increase in bilirubin, alkaline phosphatase or creatinine
• blood tests showing a decrease in red blood cells, white blood cells and platelets (pancytopenia)
• itching
• dry eye
• skin discoloration
• blurred vision
• thirst, dry mouth
• swelling
• fever with a decrease in the number of white blood cells called neutrophils
• stomach inflammation
• excess gas in the stomach or intestine
• reactions related to the infusion of the medicine that may include fever, chills, flushing, itching or skin rash

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Enhertu

Enhertu will be stored by healthcare professionals in the hospital or clinic where you receive treatment. The storage information is 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 carton and vial after EXP. The expiry date refers to the last day of the month stated.
• Store in a refrigerator (2°C - 8°C). Do not freeze.
• The prepared infusion solution is stable for 24 hours at a temperature between 2°C and 8°C, protected from light, and must be discarded after this time.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container contents and additional information

Composition of Enhertu

• The active substance is trastuzumab deruxtecan.

A vial of powder for concentrate for solution for infusion contains 100 mg of trastuzumab deruxtecan. After reconstitution, a 5 ml vial of solution contains 20 mg/ml of trastuzumab deruxtecan.

• The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, and polysorbate 80.

Appearance of the product and container contents

Enhertu is a white to yellowish-white lyophilized powder presented in a transparent amber-colored vial with a rubber stopper, an aluminum cap, and a plastic snap-off cap.

Each carton contains one vial.

Marketing authorization holder

Daiichi Sankyo Europe GmbH

Zielstattstrasse 48

81379 Munich

Germany

Manufacturer

Daiichi Sankyo Europe GmbH

Luitpoldstrasse 1

85276 Pfaffenhofen

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of last revision of this prospectus:03/2025.

This medicinal product has been authorized with a "conditional approval". This approval mechanism means that more information on this medicinal product is expected.

The European Medicines Agency will review the new information on this medicinal product at least once a year, and this prospectus will be updated as necessary.

Other sources of information

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

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This information is intended solely for healthcare professionals:

To avoid medication errors, check the labels of the vials to ensure that the medicinal product being prepared and administered is Enhertu (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine.

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

Reconstitution

• Reconstitute immediately before dilution.
• More than one vial may be needed to obtain the full dose. Calculate the dose (mg), the total volume of reconstituted Enhertu solution needed, and the number of Enhertu vials 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.
• Gently swirl the vial until completely dissolved. Do not shake.
• From a microbiological point of view, the product should be used immediately. If not used immediately, its chemical and physical stability has been demonstrated for a maximum of 48 hours at a temperature between 2°C and 8°C. Store the reconstituted Enhertu vials in a refrigerator at a temperature between 2°C and 8°C, protected from light. Do not freeze.
• The reconstituted product does not contain any preservative and is intended for single use.

Dilution

• Withdraw the calculated volume from the vial(s) using a sterile syringe. Inspect the reconstituted solution for particulate matter or color change. The solution should be clear and colorless to pale yellow. Do not use the solution if visible particles are observed or if the solution is cloudy or has changed color.
• 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. A polyvinyl chloride or polyolefin (copolymer of ethylene and polypropylene) infusion bag is recommended.
• Gently invert the infusion bag to mix the solution well. Do not shake.
• Cover the infusion bag to protect it from light.
• If not used immediately, store at room temperature (≤30°C) for up to 4 hours, including preparation and infusion time, or in a refrigerator at a temperature between 2°C and 8°C for up to 24 hours, protected from light. Do not freeze.
• Discard any unused remaining product in the vial.

Administration

• If the prepared infusion solution is stored refrigerated (2°C to 8°C), it is recommended to allow the solution to reach room temperature before administration, protected from light.

• Administer Enhertu as an intravenous infusion only with an in-line polyethersulfone (PES) or polysulfone (PS) filter of 0.20 or 0.22 microns.
• The initial dose should be administered as a 90-minute intravenous infusion. If the previous infusion was well tolerated, subsequent doses of Enhertu may be administered as 30-minute infusions. Do not administer as a rapid intravenous injection or bolus intravenous injection.
• Cover the infusion bag to protect it from light.
• Do not mix Enhertu with other medicinal products or administer other medicinal products through the same intravenous line.

Disposal

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.