Adcetris 50 mg polvo para concentrado para solucion para perfusion

Patient Information Leaflet: Information for the Patient

Adcetris 50 mg Powder for Concentrate for Solution for Infusion

brentuximab vedotina

Read 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, consult your doctor.

• If you experience any side effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

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

1. Contents of the pack and additional information

Adcetris contains the active ingredientbrentuximab vedotina, a cancer medication formed by a monoclonal antibody linked to a substance intended to destroy cancer cells. The monoclonal antibody transports this substance to cancer cells. A monoclonal antibody is a protein that recognizes certain cancer cells.

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

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

Adcetris is used to treat patients with advanced classic Hodgkin lymphoma who have not received any previous treatment. Adcetris will be given along with doxorubicin, vinblastine, and dacarbazine, which are other chemotherapy medications used to treat Hodgkin lymphoma.

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

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

• has recurred or not responded after a perfusion in the body of their own stem cells (autologous stem cell transplant), or
• has recurred or never responded to at least two previous treatments, and when it cannot receive any other combination of cancer treatments or cannot undergo autologous stem cell transplant.

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

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

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

• has not responded to other types of cancer treatments or has recurred after a previous cancer treatment.

Cutaneous T-cell lymphoma is a cancer of a specific type of white blood cell called “T cell” that mainly affects the skin. Adcetris is used to treat cutaneous T-cell lymphoma when 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 through the bloodstream.

No use Adcetris

• If you are allergic to brentuximab vedotina or any of the other components of this medication (listed in section 6).
• If you are currently receiving bleomycin, a cancer medication.

Warnings and Precautions

When you first receive this medication and during the course of treatment, inform 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 gait or loss of balance, as these may be symptoms of a severe and potentially fatal brain disease called multifocal progressive leukoencephalopathy (MPL). If you experience these symptoms before treatment with this medication, inform your doctor immediately of any change in these symptoms. You should also inform your partner or caregivers about your treatment, as they may observe symptoms of which you are not aware.

• You experience severe and persistent stomach pain, with or without nausea and vomiting, as these may be symptoms of a severe and potentially fatal 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 severe and potentially fatal lung complication (pulmonary toxicity).

• You are taking or have taken previously medications that may affect your immune system, such as chemotherapy or immunosuppressive drugs.
• You experience or suspect an infection. Some infections may be severe and caused by viruses, bacteria, or other causes that may be life-threatening.
• You notice a hissing sound during breathing (sibilance) or difficulty breathing, hoarseness, itching, or swelling (signs of a perfusion reaction). For more detailed information, see "Perfusion Reactions" in section 4.

• You experience numbness, tingling, burning sensation, pain, discomfort, or weakness, especially in the hands or feet, as these may be symptoms of neuropathy.

• You experience headaches, feel tired, experience dizziness, are pale (anemia), or experience unusual bleeding or bruising under the skin, prolonged bleeding after blood draws, or bleeding in the gums (thrombocytopenia).

• You experience chills or shivering, or a sensation of heat; you should take your temperature, as you may have a fever. Fever with a low white blood cell count may be a sign of a severe infection.

• You experience dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath, or other arrhythmias (this may be a potentially life-threatening complication known as tumor lysis syndrome).

• You experience flu-like symptoms followed by a red or purplish painful rash that spreads and forms blisters, leading to widespread skin peeling that may be potentially fatal (this may be a severe skin reaction known as Stevens-Johnson syndrome or toxic epidermal necrolysis).

• You experience a generalized skin rash, elevated body temperature, and lymphadenopathy (DRESS or drug hypersensitivity syndrome).
• You experience new stomach pain or worsening of existing stomach pain, nausea, vomiting, constipation, as these may be symptoms of severe and potentially fatal gastrointestinal complications (gastrointestinal complications).

• You experience abnormal liver function test results, as this may be related to severe and potentially fatal liver damage (hepatotoxicity). Liver disease, as well as other conditions that may have been present before starting treatment with Adcetris and some medications you are currently taking, may increase the risk of liver injury.

• You feel tired, urinate frequently, experience increased thirst and appetite, and unwanted weight loss, or are irritable (hyperglycemia).

• You experience burning, pain, or pain on palpation in the perfusion area or around it during perfusion, 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 erythema, pain, pigmentation, swelling, blistering, exfoliation, or infection of the deeper layers of the skin (cellulitis) in the perfusion area or around it days or weeks after perfusion.
• You have kidney or liver problems.

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

Other Medications and Adcetris

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

Pregnancy, Breastfeeding, and Fertility

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

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

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

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

Men treated with this medication 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 medication or in the 6 months following the last dose of the medication.

Driving and Operating Machinery

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 medication contains 13.2 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 0.7% of the recommended daily maximum sodium intake for an adult.

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

Dose and frequency

The dose of this medication depends on your body weight.

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

• The usual dose of Adcetris administered in combination with cyclophosphamide, doxorubicin

and prednisone is 1.8 mg/kg, administered every 3 weeks, for approximately 4 to 6 months.

Consult the prospectuses of these medications administered 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 medication to help prevent the development of neutropenia (decrease in white blood cell count) or to reduce the severity of this disease, which may increase the risk of infection. Inform your doctor if you have kidney or liver problems, as this may decrease your starting treatment dose or not recommend the use of Adcetris.

• The usual dose of Adcetris administered as monotherapy is 1.8 mg/kg, administered once every 3 weeks for no more than 1 year. Your doctor may decrease your starting treatment 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 medication will be administered to you 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 other doubts about the use of this medication, ask your doctor.

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

Infusion Reactions

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

• hives

• shortness of breath
• difficulty breathing

• cough

• chest tightness
• fever

• back pain
• chills

• headache
• nausea or vomiting

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

These reactions usually occur between a few minutes and several hours after the infusion is completed. However, in rare cases, they can occur more than several hours after the infusion is completed. These infusion reactions can be severe or even life-threatening (known as anaphylactic reactions). The frequency of severe or life-threatening infusion reactions of this medicine is unknown.

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

Inform your doctor before they administer this medicine if you think you have previously experienced a similar reaction.

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

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

Inform your doctor immediately 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 multifocal progressive leukoencephalopathy (MPL) such as confusion, difficulty thinking, memory loss, blurred vision or loss of vision, weakness, loss of 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 purplish painful rash that spreads and forms blisters, leading to widespread skin peeling (may affect up to 1 in 100 people)

• 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)

• 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 tired, frequent urination, increased thirst and appetite with unwanted 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 extraction, or bleeding of 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)

• experiencing a generalized skin rash, elevated body temperature, and lymphadenopathy (DRESS or drug hypersensitivity syndrome) (frequency cannot be estimated from available data)

You may experience the following side effects:

The following side effects have been reported with Adcetris monotherapy:

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

• reduction 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 side effects(may affect up to 1 in 10 people)

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

• decreased platelet count in the blood
• dizziness

• blistering that may dry or form a scab
• increased blood sugar
• increased liver enzymes

• hair loss or weakening

Rare side effects(may affect up to 1 in 100 people)

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

• 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 purplish painful rash that spreads and forms blisters, leading to widespread skin peeling

• leukopenia with fever

• nerve damage and demyelination (polyneuropathy)

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

• Medication extravasation - the medication leaking out of the vein into the surrounding tissues. Extravasation may lead to erythema, pain, discoloration, swelling, blistering, desquamation, or infection of the deeper layers of the skin (cellulitis) in the infusion area or around it.

The following side effects have been reported with Adcetris combination therapy with chemotherapy medications:

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

• reduction in white blood cell count
• reduction in white blood cell count with fever

• upper respiratory tract infection
• weight loss

• infection
• nausea

• abdominal pain
• hair loss or weakening
• muscle pain

• joint pain or swollen and painful joints

• dizziness
• loss of appetite

• insomnia
• bone pain

• blistering that may form a scab

Common side 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
• mouth ulcers, formation of yellowish painful plaques in the mouth (aphthae)
• itching
• decreased platelet count in the blood

• increased blood sugar
• increased liver enzymes

Rare side effects(may affect up to 1 in 100 people)

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

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

• new or recurrent cytomegalovirus (CMV) infection

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

Reporting of side effects

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

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

Do not use this medication after the expiration date that appears on the vial label and on the box after EXP. The expiration date is the last day of the month indicated.

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

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

Reconstituted/diluted solution:Use immediately or store in the refrigerator (between 2 °C and 8 °C) and use within 24 hours.

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

Medications should not be disposed of through drains or trash. The doctor or nurse will dispose of this medication. This will help protect the environment.

Composition of Adcetris

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

• The other components are citric acid monohydrate, sodium citrate dihydrate, α,α-trehalose dihydrate, and polisorbate 80. See more information on sodium in section 2.

Appearance of the product and contents of the pack

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

Each pack of Adcetris consists of a vial.

Marketing Authorization Holder

Takeda Pharma A/S

Delta Park 45

2665 Vallensbaek Strand

Denmark

Responsible Person

Takeda Austria GmbH

St. Peter-Straße 25

A-4020 Linz

Austria

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

België/Belgique/BelgienLietuva

Takeda BelgiumTakeda, UAB

Tel: +32 2 464 06 11Tel: +370 521 09 070

[email protected]

????????Luxembourg/Luxemburg

?????? ????????Takeda Belgium

???.: + 359 2 958 27 36Tél/Tel: +32 2 464 06 11

[email protected]

Ceská republikaMagyarország

Takeda PharmaceuticalsTakeda Pharma Kft.

Czech Republic s.r.o.Tel.: +361 2707030

Tel: + 420 234 722 722

DanmarkMalta

Takeda Pharma A/STakeda Italia S.p.A.

Tlf: +45 46 77 11 11Tel: +39 06 502601

DeutschlandNederland

Takeda GmbHTakeda Nederland bv

Tel: +49 (0) 800 825 3325Tel: +31 23 56 68 777

[email protected][email protected]

EestiNorge

Takeda Pharma ASTakeda Nycomed AS

Tel: +372 6177 669Tlf: +47 6676 3030

[email protected]

Ελλ?δαÖsterreich

TAKEDA ΕΛΛΑΣ Α.ΕTakeda Pharma Ges.m.b.H.

Tηλ: +30 210 6387800Tel: +43 (0) 800 20 80 50

[email protected]

EspañaPolska

Takeda Farmacéutica España S.A.Takeda Pharma sp. z o.o

Tel: +34 917 90 4222Tel.: + 48 22 608 13 00

[email protected]

FrancePortugal

Takeda France SASTakeda Farmacêuticos Portugal, Lda.

Tél: + 33 1 40 67 33 00Tel: + 351 21 120 1457

[email protected]

HrvatskaRomânia

Takeda Pharmaceuticals Croatia d.o.o.Takeda Pharmaceuticals SRL

Tel: +385 1 377 88 96Tel: +40 21 335 03 91

IrelandSlovenija

Takeda Products Ireland LimitedTakeda GmbH, Podružnica Slovenija

Tel: +44 (0)1628 537 900Tel: + 386 (0) 59 082 480

ÍslandSlovenská republika

Vistor hf.Takeda Pharmaceuticals Slovakia s.r.o.

Sími: +354 535 7000Tel: +421 (2) 20 602 600

vistor@vistor.is

ItaliaSuomi/Finland

Takeda Italia S.p.A.Takeda Oy

Tel: +39 06 502601Puh/Tel: +358 20 746 5000

[email protected]

Κ?προςSverige

A. POTAMITIS MEDICARE LTDTakeda Pharma AB

Tηλ: +357 22583333Tel: +46 8 731 28 00

[email protected][email protected]

LatvijaUnited Kingdom

Takeda Latvia SIATakeda UK Ltd

Tel: +371 67840082Tel: +44 (0)1628 537 900

Date of the last revision of this leaflet: 11/2022.

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

----------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Traceability

To improve the traceability of biological medicinal products, the name and batch number of the medicinal product administered must be clearly recorded.

Disposal

Adcetris is for single use only.

The unused medicinal product and all materials that have been in contact with it must be disposed of in accordance with local regulations.

Instructions for reconstitution

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 wall of the vial, 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 colourless, transparent or slightly opalescent solution with a final pH of 6.6.
4. The reconstituted solution must be visually inspected for foreign particles and/or colour changes. If foreign particles and/or colour changes are observed, the medicinal product must be discarded.

Preparation of the infusion solution

The appropriate amount of reconstituted Adcetris must 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 dextrose 5% solution for injection or in lactated Ringer's solution for injection.

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

Any remaining medicinal product in the vial, after withdrawing the volume to be diluted, must be disposed of in accordance with local regulations.

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

The Adcetris infusion solution must be infused immediately at the recommended infusion rate.

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