ADCETRIS 50 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Adcetris 50 mg powder for concentrate for solution for infusion

brentuximab vedotin

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 further questions, ask your doctor.

• If you experience side effects, contact your doctor, even if you think they are not serious, or if they are listed in this leaflet. See section 4.

Contents of the pack

1. What Adcetris is and what it is used for
2. What you need to know before you use Adcetris

1. How to use Adcetris
2. Possible side effects
3. Storage of Adcetris

1. Contents of the pack and further information

1. What Adcetris is and what it is used for

Adcetris contains the active substance brentuximab vedotin, an anti-cancer medicine that consists of a monoclonal antibody attached to a substance designed to destroy cancer cells. The monoclonal antibody carries this substance to the cancer cells. A monoclonal antibody is a protein that recognizes certain cancer cells.

Hodgkin lymphoma, systemic anaplastic large cell lymphoma, and cutaneous T-cell lymphoma are different types of cancer of the white blood cells.

Classical Hodgkin lymphoma expresses specific proteins on the surface of the cells that are different from those of non-classical Hodgkin lymphoma.

Adcetris is used to treat patients with advanced classical Hodgkin lymphoma who have not received any previous treatment. You will be given Adcetris together with other chemotherapy medicines used to treat Hodgkin lymphoma. Adcetris may be given in combination with doxorubicin, vinblastine, and dacarbazine, or with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone.

Adcetris is used as monotherapy to reduce the likelihood of recurrence of classical Hodgkin lymphoma after an autologous stem cell transplant in patients with certain risk factors.

Adcetris is also used as monotherapy to treat classical Hodgkin lymphoma that:

• has come back or did not respond after a transplant of your own stem cells (autologous stem cell transplant), or
• has come back or never responded to at least two previous treatments, and when you cannot receive any other combination of cancer treatments or cannot undergo an autologous stem cell transplant.

Systemic anaplastic large cell lymphoma is a type of non-Hodgkin lymphoma located in the lymph nodes and/or other parts of the body.

Adcetris is used to treat patients with systemic anaplastic large cell lymphoma who have not received any previous treatment. You will be given Adcetris together with cyclophosphamide, doxorubicin, and prednisone, which are other chemotherapy medicines used to treat these diseases.

Adcetris is also used to treat systemic anaplastic large cell lymphoma that:

• did not respond to other types of cancer treatments or
• came back after previous cancer treatment.

Cutaneous T-cell lymphoma is a cancer of a certain type of white blood cell called a "T-cell" that mainly affects the skin. Adcetris is used to treat cutaneous T-cell lymphoma in cases where a specific type of protein is present on the surface of the cell.

Adcetris is used to treat cutaneous T-cell lymphoma in patients who have already received at least one cancer treatment that circulates in the bloodstream.

2. What you need to know before you use Adcetris

Do not use Adcetris

• if you are allergic to brentuximab vedotin or any of the other ingredients of this medicine (listed in section 6).
• if you are currently receiving bleomycin, a cancer medicine.

Warnings and precautions

When you receive this medicine for the first time and during the course of treatment, tell your doctor if:

• you experience confusion, difficulty thinking, memory loss, blurred vision or loss of vision, loss of strength, decreased control or sensation in an arm or leg, change in walking or loss of balance, as these may be symptoms of a serious and potentially life-threatening brain disease called progressive multifocal leukoencephalopathy (PML). If you experience these symptoms before treatment with this medicine, tell your doctor immediately about any change in these symptoms. You should also inform your partner or caregivers about your treatment, as they may notice symptoms that you are not aware of.

• you experience severe and persistent stomach pain, with or without nausea and vomiting, as these may be symptoms of a serious and potentially life-threatening disease known as pancreatitis (inflammation of the pancreas).

• you experience difficulty breathing or coughing, or if these worsen, as they may be symptoms of a serious and potentially life-threatening lung complication (pulmonary toxicity).

• you are taking or have previously taken medicines that may affect your immune system, such as chemotherapy or immunosuppressive drugs.
• you experience or think you may have an infection. Some infections can be serious and life-threatening due to viruses, bacteria, or other causes.
• you notice a whistling sound while breathing (wheezing) or difficulty breathing, hives, itching, or swelling (signs of an infusion reaction). For more detailed information, see "Infusion reactions" in section 4.

• you experience skin sensitivity changes, especially in your hands or feet, such as numbness, tingling, burning sensation, pain, discomfort, or weakness (neuropathy).

• you experience headaches, feel tired, dizzy, pale (anemia), or experience unusual bleeding or bruising under the skin, prolonged bleeding after blood sampling, or bleeding from the gums (thrombocytopenia).

• you experience chills or shaking, or a feeling of heat; you should take your temperature, as you may have a fever. Fever with a low white blood cell count can be a sign of a serious infection.

• you experience dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath, or other changes in heart rhythm (this may be a potentially life-threatening complication called tumor lysis syndrome).

• you experience flu-like symptoms followed by a painful red or purple rash that spreads and forms blisters, leading to widespread skin peeling, which can be life-threatening (this may be a serious skin reaction called Stevens-Johnson syndrome or toxic epidermal necrolysis).
• you experience a widespread rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
• you experience new or worsening stomach pain, nausea, vomiting, constipation, as these may be symptoms of a serious and potentially life-threatening intestinal or stomach complication (gastrointestinal complications).

• you have abnormal liver test results, as this may be related to serious and potentially life-threatening liver damage (hepatotoxicity). Liver disease, as well as other conditions that may have been present before starting treatment with Adcetris, and some medicines you are currently taking may increase the risk of liver injury.

• you feel tired, urinate frequently, notice increased thirst and appetite with unintended weight loss, or are irritable (hyperglycemia).
• you experience burning, pain, or pain when touched in the infusion area or around it during infusion, which could indicate extravasation of Adcetris from the blood vessel. Inform your doctor or nurse immediately. Extravasation of Adcetris from the blood vessel may result in redness, pain, pigmentation, swelling, blistering, peeling, or infection of the deeper layers of the skin (cellulitis) in the infusion area or around it, days or weeks after infusion.
• you have kidney or liver problems.

Your doctor will perform regular blood tests to ensure that you can receive this medicine safely.

Other medicines and Adcetris

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and other medicines that you can obtain without a prescription.

Pregnancy, breastfeeding, and fertility

You and your partner must use two effective methods of contraception during your treatment with this medicine. Women must continue to use contraceptive methods for 6 months after the last dose of Adcetris.

You must not use this medicine if you are pregnant, unless you and your doctor decide that the benefit to you outweighs the potential risk to the fetus.

It is important that you inform your doctor before and during treatment if you are pregnant, think you may be pregnant, or plan to become pregnant.

If you are breastfeeding, you should discuss with your doctor whether you should receive this medicine.

Men treated with this medicine are advised to ask that their semen be frozen and stored before treatment. Men are advised not to father a child during treatment with this medicine and for 6 months after the last dose of the medicine.

Driving and using machines

Treatment may affect your ability to drive or use machines. If you feel unwell during treatment, do not drive or use machines.

Adcetris contains sodium

This medicine contains 13.2 mg of sodium (a major component of cooking/table salt) per vial. This is equivalent to 0.7% of the maximum recommended daily intake of sodium for an adult.

Adcetris contains polysorbate 80

This medicine contains 2.0 mg of polysorbate 80 per vial of Adcetris, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Adcetris

In case of doubt about the use of this medicine, ask your doctor or nurse who administers the infusion.

Dose and frequency

The dose of this medicine depends on your body weight.

• The usual dose of Adcetris given in combination with doxorubicin, vinblastine, and dacarbazine is 1.2 mg/kg, given every 2 weeks, for 6 months.

• The usual dose of Adcetris given in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone is 1.8 mg/kg, given every 3 weeks, for up to 6 months.

• The usual dose of Adcetris given in combination with cyclophosphamide, doxorubicin, and prednisone is 1.8 mg/kg, given every 3 weeks, for approximately 4 to 6 months.

Consult the package leaflets of these medicines given in combination with Adcetris for additional information on their use and effects. After the first dose of Adcetris in combination with chemotherapy, your doctor may also give you a medicine to help prevent the development of neutropenia (a decrease in the number of white blood cells) or to reduce the severity of this condition, which can increase the risk of infection. Inform your doctor if you have kidney or liver problems, as this may reduce your starting dose or not recommend the use of Adcetris.

• The usual dose of Adcetris given as monotherapy is 1.8 mg/kg, given every 3 weeks, for no more than 1 year. Your doctor may reduce your starting dose to 1.2 mg/kg if you have liver or kidney problems.

Adcetris should only be administered to adults. It is not intended for use in children.

How Adcetris is administered

This medicine will be given to you in a vein (intravenously) through an infusion. The doctor or nurse will administer it over 30 minutes. The doctor or nurse will also monitor you during and after the infusion.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Infusion Reactions

Medicines of this type (monoclonal antibodies) can cause infusion reactions such as:

• a rash
• shortness of breath
• difficulty breathing
• cough
• chest tightness
• fever
• back pain
• chills
• headache
• feeling of discomfort (nausea) or being sick (vomiting)

Infusion reactions to this medicine can affect more than 1 in 10 people.

In general, these reactions occur between a few minutes and several hours after the infusion is completed. However, in rare cases, they may appear more than several hours after the infusion is completed. These infusion reactions can be severe or even life-threatening (known as anaphylactic reactions). It is unknown how often infusion reactions to this medicine are severe or life-threatening.

You may be given other medicines such as antihistamines, corticosteroids, or paracetamol to help reduce any of the above reactions if you have already suffered from them when receiving this type of medicine.

If you think you have previously suffered from a similar reaction, inform your doctor BEFORE this medicine is administered to you.

If you develop infusion reactions (such as those indicated above), your doctor may stop administering this medicine and initiate supportive treatment.

If the infusion is resumed, your doctor may extend the time during which it is administered so that you can tolerate it better.

Report immediately to your doctor if you observe any of the following symptoms, as some of them may be indicative of a serious or potentially life-threatening process:

• symptoms of progressive multifocal leukoencephalopathy (PML) such as confusion, difficulty thinking, memory loss, blurred vision or loss of vision, loss of strength, decreased control or sensation in an arm or leg, change in gait or loss of balance (for more detailed information, see section 2) (affects less than 1 in 100 people)

• symptoms of pancreatitis such as severe and persistent stomach pain, with or without nausea and vomiting (may affect up to 1 in 100 people).
• shortness of breath or cough (may affect more than 1 in 10 people)
• flu-like symptoms followed by a red or purple painful rash that spreads and forms blisters, leading to widespread skin peeling (may affect up to 1 in 100 people)

• a change in sensation or sensitivity, especially in the skin, numbness, tingling, discomfort, burning sensation, weakness, or pain in hands or feet (neuropathy; may affect more than 1 in 10 people).

• feeling of weakness (may affect more than 1 in 10 people).

• constipation (may affect more than 1 in 10 people).
• diarrhea, vomiting (may affect more than 1 in 10 people).

• chills or shivering (may affect up to 1 in 10 people).
• feeling of tiredness, frequent urination, increased thirst and appetite with unintended weight loss and irritability (may be signs of hyperglycemia, which may affect up to 1 in 10 people).

• unusual bleeding or bruising under the skin, prolonged bleeding after blood sampling, or bleeding from the gums (may be signs of thrombocytopenia, which may affect up to 1 in 10 people).

• headaches, dizziness, paleness (may be signs of anemia, which may affect more than 1 in 10 people).
• suffers from a generalized skin rash, elevated body temperature, and lymphadenopathy (DRESS or drug hypersensitivity syndrome) (frequency cannot be estimated from the available data).

You may suffer from the following adverse effects:

The following adverse effects have been reported with Adcetris monotherapy:

Very Common Adverse Effects(may affect more than 1 in 10 people)

• reduction in the number of white blood cells
• upper respiratory tract infection
• weight loss

• infection
• nausea

• abdominal pain
• itching
• muscle pain

• joint pain or swollen and painful joints

Common Adverse Effects(may affect up to 1 in 10 people)

• pneumonia
• ulcers, formation of elevated painful yellowish plaques in the mouth (aphthae)

• decrease in the number of platelets in the blood
• dizziness

• blisters that can dry out or form crusts
• increased blood sugar
• increased liver enzyme levels

• unusual hair loss or weakening

Uncommon Adverse Effects(may affect up to 1 in 100 people)

• tumor lysis syndrome - a life-threatening process in which you may experience dizziness, reduced urination, confusion, vomiting, nausea, swelling, shortness of breath, or other heart rhythm disturbances

• new or recurrent cytomegalovirus (CMV) infection

• blood infection (sepsis) and/or septic shock (a potentially life-threatening form of sepsis)
• Stevens-Johnson syndrome and toxic epidermal necrolysis - a rare severe disorder in which you may experience flu-like symptoms followed by a red or purple painful rash that spreads and forms blisters, leading to widespread skin peeling

• decrease in the number of white blood cells, with fever

• nerve and nerve sheath damage (demyelinating polyneuropathy)

Adverse Effects of Unknown Frequency(cannot be estimated from the available data)

• Medicine spillage outside the vein into the surrounding tissues (also called extravasation). Extravasation can lead to redness, pain, discoloration, swelling, blistering, peeling, or infection of the deeper skin layers (cellulitis) in the infusion area or around it.

The following adverse effects have been reported with Adcetris combination therapy with chemotherapy medicines:

Very Common Adverse Effects(may affect more than 1 in 10 people)

• reduction in the number of white blood cells
• reduction in the number of white blood cells with fever

• upper respiratory tract infection
• weight loss

• infection
• nausea

• abdominal pain
• unusual hair loss or weakening
• muscle pain

• joint pain or swollen and painful joints

• dizziness
• loss of appetite

• sleeplessness
• bone pain

• blisters that can form crusts

Common Adverse Effects(may affect up to 1 in 10 people)

• blood infection (sepsis) and/or septic shock (a potentially life-threatening form of sepsis); pneumonia
• mouth ulcers or inflammation
• ulcers, formation of elevated painful yellowish plaques in the mouth (aphthae)
• itching
• decrease in the number of platelets in the blood

• increased blood sugar
• increased liver enzyme levels

Uncommon Adverse Effects(may affect up to 1 in 100 people)

• tumor lysis syndrome - a life-threatening process in which you may experience dizziness, reduced urination, confusion, vomiting, nausea, swelling, shortness of breath, or other heart rhythm disturbances

• Stevens-Johnson syndrome and toxic epidermal necrolysis - a rare severe disorder in which you may experience flu-like symptoms followed by a red or purple painful rash that spreads and forms blisters, leading to widespread skin peeling

• new or recurrent cytomegalovirus (CMV) infection

Other Uncommon Adverse Effects(may affect up to 1 in 100 people)

Tachycardia (rapid heart rate) has been reported with Adcetris in combination with other chemotherapy medicines (etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone).

If you are an elderly patient (≥ 65 years), you may experience adverse effects more frequently.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Adcetris

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date that appears on the label of the vial and on the carton after EXP. The expiry date is the last day of the month indicated.

Unopened Vial:Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep the vial in the original packaging to protect it from light.

Reconstituted/Diluted Solution:Use immediately or store in a refrigerator (between 2 °C and 8 °C) and use within 24 hours.

Do not use this medicine if you observe particles or discoloration before administration.

Medicines should not be disposed of via wastewater or household waste. Your doctor or nurse will dispose of this medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Adcetris

• The active substance is brentuximab vedotin. Each vial contains 50 mg of brentuximab vedotin. After reconstitution, each ml of solution contains 5 mg of Adcetris.

• The other ingredients are citric acid monohydrate (E330), sodium citrate dihydrate (E331), α,α-trehalose dihydrate, and polysorbate 80 (E433). See more information about sodium and polysorbate 80 in section 2.

Appearance and Package Contents

Adcetris is a white or off-white paste or powder for concentrate for solution for infusion supplied in a glass vial.

Each package of Adcetris consists of a vial.

Marketing Authorization Holder

Takeda Pharma A/S

Delta Park 45

2665 Vallensbaek Strand

Denmark

Manufacturer

Takeda Austria GmbH

St. Peter-Straße 25

A-4020 Linz

Austria

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet: 01/2025.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Traceability

In order to improve the traceability of biological medicines, the name and batch number of the medicine administered must be clearly recorded.

Disposal

Adcetris is for single use.

Disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

Reconstitution Instructions

Each single-use vial must be reconstituted with 10.5 ml of water for injection to achieve a final concentration of 5 mg/ml. Each vial contains a 10% overfill, i.e., there are 55 mg of Adcetris per vial and a total reconstituted volume of 11 ml.

1. Direct the stream towards the vial wall, not directly at the paste or powder.
2. Gently rotate the vial to facilitate dissolution. DO NOT SHAKE.
3. The reconstituted solution in the vial is a clear or slightly opalescent colorless solution with a final pH of 6.6.
4. The reconstituted solution must be visually inspected for particulate matter and/or color changes. If particulate matter and/or color changes are observed, the medicine must be discarded.

Preparation of the Infusion Solution

The appropriate amount of reconstituted Adcetris should be withdrawn from the vial(s) and added to an infusion bag containing sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a final concentration of 0.4-1.2 mg/ml of Adcetris. The recommended diluent volume is 150 ml. Once reconstituted, Adcetris can also be diluted in 5% dextrose solution for injection or lactated Ringer's solution for injection.

Gently invert the bag to mix the solution containing Adcetris. DO NOT SHAKE.

Any remaining medicine in the vial after withdrawing the volume to be diluted should be discarded in accordance with local regulations.

Do not add other medicines to the prepared Adcetris infusion solution or to the infusion equipment. The infusion line should be flushed after administration with sodium chloride 9 mg/ml (0.9%) solution for injection, 5% dextrose solution for injection, or lactated Ringer's solution for injection.

After dilution, the Adcetris solution should be infused immediately at the recommended infusion rate.

The total storage time of the solution, from reconstitution to infusion, should not exceed 24 hours.