Enhertu 100 mg powder for concentrate for solution for infusion

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Enhertu 100mg powder for concentrate for solution for infusion

trastuzumab deruxtecan

This medicinal product is subject to additional monitoring, which will enable rapid detection of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet includes information on how to report adverse reactions.

Read the entire leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Enhertu is and what it is used for

What Enhertu is

Enhertu is a cancer medicine containing the active substance trastuzumab deruxtecan. One part of the medicine is a monoclonal antibody that specifically binds to cells containing the HER2 protein on their surface (HER2-positive), as is the case with some cancer cells. The other active component of Enhertu is DXd, a substance capable of killing cancer cells. Once the medicine binds to HER2-positive cancer cells, DXd enters the cells and kills them.

What Enhertu is used for

Enhertu 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 surgically removed, and who have previously received one or more treatments specifically for HER2-positive breast cancer;
• Breast cancer with low HER2 expression or very low HER2 expression that has spread to other parts of the body (metastatic disease) or cannot be surgically removed, and who have received prior treatment. You will be tested to ensure that Enhertu is suitable for you;
• Non-small cell lung cancer with a HER2 mutation that has spread to other parts of the body or cannot be surgically removed, and who have received prior treatment. You will be tested to ensure that Enhertu is suitable for you;
• HER2-positive stomach cancer that has spread to other parts of the body or to areas near the stomach and cannot be surgically removed, and who have also received another treatment specifically for HER2-positive stomach cancer.

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

Do not take Enhertu

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

If you are unsure whether you are allergic, consult your doctor or nurse before receiving Enhertu.

Warnings and precautions

Talk to your doctor or nurse before or during treatment with Enhertu if you have:

• cough, shortness of breath, fever, or other new or worsening respiratory 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 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 cells called neutrophils;
• new or worsening shortness of breath, cough, fatigue, swelling of the ankles or legs, irregular heartbeat, sudden weight gain, dizziness, or loss of consciousness. These may be symptoms of a condition in which the heart cannot pump blood effectively enough (reduced left ventricular ejection fraction);
• 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 patients under 18 years of age. This is because there is no information available on its use in this age group.

Other medicines and Enhertu

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

Pregnancy, breastfeeding, contraception, and fertility

• Pregnancy

It is not recommended to use Enhertu during pregnancy because this medicine may harm the unborn baby.

If you are pregnant, think you might be pregnant, or plan to become pregnant before or during treatment, consult your doctor immediately.

• Breastfeeding

You must not breastfeed during treatment with Enhertu and for 7 months after your last dose. This is because it is not known whether Enhertu passes into breast milk. Discuss this with your doctor.

• Contraception

Use an effective method of contraception (birth control) to prevent pregnancy while receiving treatment with Enhertu.

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

Men taking Enhertu whose partner could become pregnant must 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 method of contraception is best for you. Also, consult your doctor before stopping contraception.

• Fertility

If you are a man being treated with Enhertu, you should not father a child during the 4 months after treatment, and you should seek advice about sperm preservation before starting treatment, as this 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 operate machinery. However, be cautious 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. Inform your doctor if you have any known allergies.

3. How Enhertu is administered

Enhertu will be administered 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;
  • HER2-mutant non-small cell lung cancer is 5.4 mg per kilogram of body weight every 3 weeks;
  • HER2-positive gastric cancer is 6.4 mg per kilogram of body weight every 3 weeks.
• Your doctor or nurse will administer Enhertu to you by intravenous infusion (drip) into a vein.
• Your first infusion will be given over a period of 90 minutes. If this is well tolerated, subsequent infusions will be given over a period of 30 minutes.
• Your doctor will decide how many treatments you will need.
• Before each Enhertu infusion, your doctor may give you medications to help prevent nausea and vomiting.
• If you experience 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 perform tests which may include:
  • blood tests to monitor blood cells, liver, and kidney function;
  • tests to monitor heart and lung function.
• Your doctor may reduce your dose, or temporarily or permanently stop your treatment depending on any side effects you experience.

If you miss an appointment for Enhertu

Contact your doctor immediately to reschedule your appointment.

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

If you interrupt treatment with Enhertu

Do not interrupt treatment with Enhertu without consulting your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If you experience any adverse effect, consult your doctor, even if they are adverse effects not listed in this leaflet.

Contact your doctor immediately if you notice any of the following symptoms. They may be signs of a serious, possibly life-threatening condition. Receiving immediate medical treatment may help prevent these problems from becoming more severe.

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 new or worsening respiratory problems.
• An infection due to 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, fatigue, swelling of the ankles or legs, irregular heartbeat, sudden weight gain, dizziness, or loss of consciousness.

Other adverse effects

The frequency and severity of adverse effects may vary depending on the dose received. Inform your doctor or nurse if you notice any of the following adverse effects:

Very common (may affect more than 1 in 10 people)

• nausea (feeling sick), vomiting
• fatigue
• blood tests showing decreased red blood cells, white blood cells, or platelets
• decreased appetite
• hair loss
• diarrhea
• constipation
• blood tests showing increased blood levels of liver enzymes such as transaminases
• muscle and bone pain
• abdominal (stomach) pain
• weight loss
• fever
• nose and throat infections, including flu-like symptoms
• headache
• blood tests showing low levels of potassium in the blood
• blisters in or around the mouth
• cough
• indigestion
• swelling of the ankles and feet

Common (may affect up to 1 in 10 people)

• difficulty breathing
• lung infection
• blood tests showing increased levels of bilirubin, alkaline phosphatase, or creatinine
• nosebleeds
• dizziness
• rash
• blood tests showing decreased red blood cells, white blood cells, and platelets (pancytopenia)
• altered taste sensation / bad taste in the mouth
• dry eye
• itching
• swelling
• blurred vision
• skin discoloration
• thirst, dry mouth
• fever together with a decrease in the number of white blood cells called neutrophils
• excess gas in the stomach or intestines
• inflammation of the stomach
• reactions related to the drug infusion, which may include fever, chills, flushing, itching, or skin rash

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Enhertu

Enhertu will be stored by healthcare professionals at 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 stated on the carton and vial after CAD/EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.
• The prepared infusion solution is stable for up to 24 hours at a temperature between 2 °C and 8 °C, protected from light, and must be discarded after this period.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Enhertu

• The active substance is trastuzumab deruxtecan.

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

• The other components are L-histidine, L-histidine hydrochloride monohydrate, sucrose and polysorbate 80 (E 433).

Nature of the product and contents of the container

Enhertu is a lyophilized powder, white to slightly yellowish-white in colour, supplied in a clear amber glass vial with a rubber stopper, an aluminium cap and a removable plastic flip-off seal.

Each carton contains one vial.

Marketing Authorisation Holder

Daiichi Sankyo Europe GmbH

Zielstattstrasse 48

81379 Munich

Germany

Manufacturer

Daiichi Sankyo Europe GmbH

Luitpoldstrasse 1

85276 Pfaffenhofen

Germany

More information about this medicinal product is available upon request to the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: {MM/YYYY}.

This medicinal product has been authorised under a "conditional approval". This type of approval means that further information on this medicinal product is expected.

The European Medicines Agency will review new information on this medicinal product at least once a year, and this leaflet 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.

This information is intended for healthcare professionals only:

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

Appropriate procedures for the handling of cytotoxic medicinal products must be followed. Aseptic technique should be used for the following reconstitution and dilution procedures.

Reconstitution

• Reconstitute immediately before dilution.
• More than one vial may be required to obtain the complete dose. Calculate the required dose (mg), the total volume of reconstituted Enhertu solution needed, and the number of Enhertu vials required.
• Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 ml of water for injections into each vial to achieve a final concentration of 20 mg/ml.
• Gently rotate the vial until the powder is completely dissolved. Do not shake.
• From a microbiological standpoint, 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 a temperature between 2 °C and 8 °C. Store 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 particulate matter or discoloration. The solution should be clear and colourless to pale yellow. Do not use the solution if visible particles are present or if the solution is cloudy or discoloured.
• Dilute the calculated volume of reconstituted Enhertu into an infusion bag containing 100 ml of 5% glucose solution for infusion. Do not use sodium chloride solution. A polyvinyl chloride or polyolefin (ethylene and polypropylene copolymer) infusion bag is recommended.
• Gently invert the infusion bag to ensure thorough mixing. 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 2 °C to 8 °C for up to 24 hours, protected from light. Do not freeze.
• Discard any unused portion remaining in the vial.

Administration

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

• Administer Enhertu as an intravenous infusion using only an in-line filter of polyethersulfone (PES) or polysulfone (PS) with a pore size of 0.20 or 0.22 microns.

• The first 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 intravenous bolus.

• 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

Any unused medicinal product and all materials that have come into contact with it should be disposed of in accordance with local requirements.