Adcetris 50 mg powder for concentrate for infusion solution

Package leaflet: Information for the user

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, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience side effects, talk to your doctor, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Adcetris is and what it is used for

Adcetris contains the active substance brentuximab vedotin, a cancer medicine composed of a monoclonal antibody linked to a substance designed to destroy cancer cells. The monoclonal antibody delivers this substance to cancer cells. A monoclonal antibody is a protein that recognizes specific cancer cells.

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

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

Adcetris is used to treat patients with advanced classical Hodgkin lymphoma who have not previously received any treatment. Adcetris will be given to you in combination with other chemotherapy medicines used to treat Hodgkin lymphoma. Adcetris may be administered 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 autologous stem cell transplant in patients with certain risk factors.

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

• has relapsed or did not respond after an infusion of your own stem cells (autologous stem cell transplant), or
• has relapsed or never responded to at least two previous treatments, and when no other combination of cancer treatments is suitable or when you cannot undergo 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 previously received any treatment. Adcetris will be given to you in combination 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:

• has not responded to other types of cancer treatments, or
• has relapsed after prior cancer treatment.

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

Adcetris is used to treat cutaneous T-cell lymphoma in patients who have already received at least one prior systemic cancer treatment.

2. What you need to know before using Adcetris

Do not use Adcetris

• if you are allergic to brentuximab vedotin or to 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 throughout your treatment, inform your doctor if:

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

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

• you develop new or worsening shortness of breath or cough, as these 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 have an infection or suspect you may have an infection. Some infections can be serious and caused by viruses, bacteria, or other factors that may be life-threatening.

• you notice a wheezing sound when breathing (wheezing), difficulty breathing, hives, itching, or swelling (signs of an infusion reaction). For more detailed information, see “Infusion reactions” in section 4.

• you have problems with skin sensation, 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 have unusual bleeding or bruising under the skin, prolonged bleeding after blood draw, or bleeding gums (thrombocytopenia).

• you have chills or shivering, or feel hot; you should take your temperature, as you may have a fever. Fever with low white blood cell count may be a sign of a serious infection.

• you feel dizzy, have reduced 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 purplish rash that spreads and forms blisters, leading to widespread skin peeling that may be potentially fatal (this could be a serious skin reaction called Stevens-Johnson syndrome or toxic epidermal necrolysis).

• you develop a widespread skin rash, high body temperature, and swollen lymph nodes (drug reaction with eosinophilia and systemic symptoms [DRESS] or drug hypersensitivity syndrome).

• you have new stomach pain or worsening of existing 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 results in a liver function test, as this may be related to serious and potentially life-threatening liver damage (hepatotoxicity). Liver disease, as well as other conditions present before starting Adcetris treatment, and certain medicines you are currently taking may increase the risk of liver injury.

• you feel tired, urinate frequently, feel increased thirst and appetite with unintended weight loss, or are irritable (hyperglycemia).

• you feel burning, pain, or tenderness at or around the infusion site during infusion, which may indicate extravasation of Adcetris from the blood vessel. Inform your doctor or nurse immediately. Extravasation of Adcetris from the blood vessel may lead to redness, pain, pigmentation, swelling, blistering, peeling, or infection of deeper skin layers (cellulitis) at or around the infusion site days or weeks after the infusion.

• you have kidney or liver problems.

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

Other medicines and Adcetris

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines. This includes herbal medicines and other medicines you may obtain without a prescription.

Pregnancy, breastfeeding, and fertility

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

Do 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 have sperm samples frozen and stored before treatment begins. Men are advised not to father a child during treatment with this medicine and for 6 months after the last dose.

Driving and using machines

This treatment may affect your ability to drive or operate machinery. If you feel unwell during treatment, do not drive or operate machinery.

Adcetris contains sodium

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

If you have any questions about how to use this medicine, ask the doctor or nurse who will administer the infusion.

Dosage and frequency

The dose of this medicine depends on your body weight.

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

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

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

Please refer to the package leaflets of these medicines used 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 neutropenia (low white blood cell count) or reduce its severity, which can increase the risk of infection. Inform your doctor if you have kidney or liver problems, as this may lead to a reduced starting dose or your doctor may not recommend using Adcetris.

• The usual dose of Adcetris when given as monotherapy is 1.8 mg/kg, administered once every 3 weeks for no more than one 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 intravenously (into a vein) as an infusion. The doctor or nurse will administer it over 30 minutes. You will also be monitored by the doctor or nurse during and after the infusion.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Infusion reactions

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

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

Infusion reactions with this medicine may affect more than 1 in 10 people.

These reactions usually occur from a few minutes to several hours after the infusion is completed. However, in rare cases, they may appear more than several hours after the infusion has ended. These infusion reactions can be severe or even fatal (known as anaphylactic reactions). The frequency with which infusion reactions with this medicine are severe or fatal is unknown.

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

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

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

If the infusion is resumed, your doctor may extend the time over which it is administered to improve your tolerance.

Tell your doctor immediately if you notice any of the following symptoms, as some of them may indicate a serious or potentially fatal condition:

• 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 the way you walk or loss of balance (for more detailed information, see section 2) (affects fewer than 1 in 100 people)

• symptoms of inflammation of the pancreas (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 painful red or purplish rash that spreads and forms blisters, leading to widespread shedding of the skin (may affect up to 1 in 100 people)

• changes 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 weak (may affect more than 1 in 10 people)

• constipation (may affect more than 1 in 10 people)

• diarrhoea, vomiting (may affect more than 1 in 10 people)

• chills or shivering (may affect up to 1 in 10 people)

• feeling tired, frequent urination, increased thirst and appetite with unintended weight loss and irritability (may be signs of hyperglycaemia, which may affect up to 1 in 10 people)

• unusual bleeding or bruising under the skin, prolonged bleeding after blood draw, 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 anaemia, which may affect more than 1 in 10 people)

• you develop a widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome) (frequency cannot be estimated from available data)

You may experience 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)

• decrease in white blood cell count

• 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

• mouth ulcers, formation of raised, painful yellowish patches in the mouth (aphthae)

• decrease in the number of platelets in the blood

• dizziness

• blisters that may dry or crust over

• increased blood sugar levels

• increased levels of liver enzymes

• hair loss or unusual hair thinning

Uncommon adverse effects (may affect up to 1 in 100 people)

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

• new or recurrent infection with cytomegalovirus (CMV)

• blood infection (sepsis) and/or septic shock (a potentially fatal form of sepsis)

• Stevens-Johnson syndrome and toxic epidermal necrolysis – a rare, serious disorder in which you may have flu-like symptoms followed by a painful red or purplish rash that spreads and forms blisters, leading to widespread shedding of the skin

• decrease in white blood cells, with fever

• nerve damage and damage to the nerve coverings (demyelinating peripheral neuropathy)

Adverse effects of unknown frequency (cannot be estimated from available data)

• Leakage of the medicine from the vein into surrounding tissues (also known as extravasation). Extravasation may result in redness, pain, discolouration, swelling, blistering, peeling, or infection of the deeper layers of the skin (cellulitis) at or around the infusion site.

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

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

• decrease in white blood cell count

• decrease in white blood cell count with fever

• upper respiratory tract infection

• weight loss

• infection

• nausea

• abdominal pain

• hair loss or unusual hair thinning

• muscle pain

• joint pain or swollen and painful joints

• dizziness

• loss of appetite

• difficulty sleeping

• bone pain

• blisters that may crust over

Common adverse effects (may affect up to 1 in 10 people)

• blood infection (sepsis) and/or septic shock (a potentially fatal form of sepsis); pneumonia

• mouth ulcers or inflammation in the mouth

• ulcers, formation of raised, painful yellowish patches in the mouth (aphthae)

• itching

• decrease in the number of platelets in the blood

• increased blood sugar levels

• increased levels of liver enzymes

Uncommon adverse effects (may affect up to 1 in 100 people)

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

• Stevens-Johnson syndrome and toxic epidermal necrolysis – a rare, serious disorder in which you may have flu-like symptoms followed by a painful red or purplish rash that spreads and forms blisters, leading to widespread shedding of the skin

• new or recurrent infection with cytomegalovirus (CMV)

Other uncommon adverse effects (may affect up to 1 in 100 people)

Tachycardia (fast heartbeat) 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 of age), you may experience adverse effects more frequently.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can 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 Adcetris

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

Do not use this medicine after the expiry date stated on the label of the vial and the carton after EXP. The expiry date refers to 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 notice particles or discoloration before administration.

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

6. Contents of the pack and other 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 components are monohydrate citric acid (E330), disodium citrate dihydrate (E331), α,α-trehalose dihydrate, and polysorbate 80 (E433). See further information on sodium and polysorbate 80 in section 2.

Appearance of the product and contents of the pack

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

Each Adcetris pack consists of one 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

For further information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary: 01/2025.

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

This information is intended for healthcare professionals only:

Traceability

To improve the traceability of biological medicines, the name and batch number of the administered medicine should be clearly recorded.

Disposal

Adcetris is for single use only.

Any unused medicine and materials that have come into contact with it should be disposed of in accordance with local regulations.

Reconstitution instructions

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

1. Direct the stream towards the vial wall, not directly onto 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, colourless solution or slightly opalescent, with a final pH of 6.6.
4. The reconstituted solution should be inspected visually for foreign particles and/or discoloration. If foreign particles and/or discoloration are observed, the medicine must be discarded.

Preparation of 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 injections to achieve a final concentration of 0.4–1.2 mg/ml of Adcetris. The recommended diluent volume is 150 ml. After reconstitution, Adcetris may also be diluted in 5% dextrose solution for injections or in lactated Ringer's solution for injections.

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

Any remaining medicine in the vial after the volume to be diluted has been withdrawn must be discarded in accordance with local regulations.

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

After dilution, administer the Adcetris solution immediately at the recommended infusion rate.

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