Adcetris

Package leaflet: Information for the patient

Adcetris 50 mg powder for concentrate for solution for infusion

brentuximab vedotin
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

1. What Adcetris is and what it is used for
2. What you need to know before being given Adcetris
3. How Adcetris is given
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, an anticancer medicine composed of
a monoclonal antibody linked to a substance designed to destroy tumor cells. The substance is released
against tumor cells by the monoclonal antibody. A monoclonal antibody is a protein that recognizes specific tumor cells.
Hodgkin lymphoma, systemic anaplastic large cell lymphoma, and cutaneous T-cell lymphoma are
types of cancer affecting white blood cells.
Classical Hodgkin lymphoma expresses specific proteins on the surface of cells, which differ from those found in non-classical Hodgkin lymphoma.
Adcetris is used to treat patients with previously untreated advanced classical Hodgkin lymphoma. Adcetris will be given to you in combination with other chemotherapeutic medicines used to treat Hodgkin lymphoma. Adcetris may be administered in combination with doxorubicin, vinblastine, and dacarbazine, or it may be given with etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone.
Adcetris is used alone 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 alone to treat classical Hodgkin lymphoma that:

• has relapsed or did not respond to an infusion of healthy stem cells from your own body (autologous stem cell transplant), or
• has relapsed or never responded to at least two previous therapies, and when additional combination anticancer treatments cannot be administered or an autologous stem cell transplant cannot be performed.

Systemic anaplastic large cell lymphoma is a type of non-Hodgkin lymphoma found in lymph nodes and/or other parts of the body.
Adcetris is used to treat patients with previously untreated systemic anaplastic large cell lymphoma. Adcetris will be given to you in combination with cyclophosphamide, doxorubicin, and prednisone, which are other chemotherapeutic medicines used to treat these conditions.
Adcetris is also used to treat systemic anaplastic large cell lymphoma that:

• has not responded to other types of anticancer therapies, or
• has relapsed after prior anticancer treatment.

Cutaneous T-cell lymphoma is a cancer affecting a specific type of white blood cells called "T-cells" and primarily involves the skin. Adcetris is used to treat cutaneous T-cell lymphoma when a particular type of protein is present on the surface of these cells.
Adcetris is used to treat cutaneous T-cell lymphoma in patients who have already been treated with at least one blood-borne chemotherapeutic medicine.

2. What you should know before being given 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 taking bleomycin, an anticancer medicine.

Warnings and precautions
When you receive this medicine for the first time and during the treatment cycle, inform your doctor
if:

• you experience confusion, find it difficult to concentrate, have memory loss, blurred vision or loss of vision, feel weak, have reduced control or sensation in an arm or leg, notice changes in your gait, or loss of balance, as these may be symptoms of a serious and potentially fatal brain disorder called progressive multifocal leukoencephalopathy (PML). If you have these symptoms before treatment with this medicine, inform your doctor immediately of any changes in such symptoms. Inform your partner or caregiver 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 condition that can be fatal, 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 lung complication that can be fatal (pulmonary toxicity).
• you are taking, or have previously taken, medicines that affect the immune system, such as chemotherapy or immunosuppressive medicines.
• you have, or think you may have, an infection. Some infections can be serious and caused by viruses, bacteria, or other agents that may lead to death.
• you experience wheezing (shortness of breath), difficulty breathing, hives, itching, or swelling (signs of an infusion-related reaction). For more detailed information, see “Infusion-related reactions”, section 4.
• you have changes in skin sensation, particularly in hands or feet, such as numbness, tingling, burning sensation, pain, discomfort, or weakness (neuropathy).
• you have headache, feel tired, dizzy, pale (anemia), or have unusual bleeding or bruising under the skin, prolonged bleeding after blood draws, or bleeding gums (thrombocytopenia).
• you experience chills or shivering, or a feeling of warmth; check your temperature, as you may have a fever. Fever accompanied by low white blood cell count may indicate a serious infection.
• you feel dizzy, urinate less, are confused, vomit, feel nauseous, have swelling, shortness of breath, or heart rhythm disturbances (this could be a complication that may be fatal, called tumor lysis syndrome).
• you have flu-like symptoms followed by a painful red or purplish rash that spreads and forms blisters, including extensive skin peeling that may be fatal (this could be a serious skin reaction called Stevens-Johnson syndrome or toxic epidermal necrolysis).
• you develop widespread rash, fever, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• you have stomach pain, nausea, vomiting, new or worsening constipation, as these may be symptoms of a serious stomach or intestinal complication that can be fatal (gastrointestinal complications).
• you have abnormal liver function tests, as this may indicate serious liver damage that can be fatal (hepatotoxicity). If you had liver disease before starting Adcetris, or have other medical conditions, or are currently taking other medicines, your risk of liver damage may be increased.
• you feel tired, urinate frequently, are unusually thirsty, have increased appetite but lose weight unintentionally, or feel irritable (hyperglycemia).
• during the infusion you feel a burning sensation, pain, or tenderness at or around the infusion site; this may indicate leakage of Adcetris from the blood vessel. Inform your doctor or nurse immediately. If Adcetris leaks from the blood vessel, redness, pain, skin discoloration, swelling, blistering rash, peeling, or deep skin infection (cellulitis) may occur at or around the infusion site within days or weeks after the infusion.
• you have kidney or liver problems.

Your doctor will perform periodic blood tests to ensure that receiving this medicine is safe for you.
Other medicines and Adcetris
Inform your doctor if you are taking, have recently taken, or start taking any other medicines. This includes herbal preparations and other medicines available without a doctor’s prescription.
Pregnancy, breastfeeding and fertility
You and your partner must use two effective methods of contraception during 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 to inform your doctor before and during treatment if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
If you are breastfeeding, discuss with your doctor whether it is appropriate for you to take this medicine.
Men undergoing treatment with this medicine are advised to request freezing and storage of sperm samples before treatment. 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 salt) per vial. This is equivalent to 0.7% of the recommended maximum daily dietary 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 known allergies.

3. How Adcetris is administered

If you have any doubts about the use of this medicine, consult the doctor or nurse who administers the infusion to you.

Dose and frequency
The dose of this medicine depends on body weight.

• The usual dose of Adcetris given in combination with doxorubicin, vinblastine, and dacarbazine is 1.2 mg/kg 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 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 every 3 weeks for approximately 4–6 months.

Please refer to the package leaflets of these medicines used in combination with Adcetris for additional information on their use and side effects. After the first dose of Adcetris in combination with chemotherapy, your doctor may also administer a medicine to help prevent or reduce the severity of neutropenia (reduction in white blood cell count), which can increase the risk of infection. Inform your doctor if you have kidney or liver problems, as your initial dose may be reduced or Adcetris may not be recommended.

• The usual dose of Adcetris when given alone is 1.8 mg/kg, administered every 3 weeks for no more than one year. Your doctor may reduce the initial dose to 1.2 mg/kg if you have kidney or liver problems.

Adcetris must only be administered to adult patients. It should not be used in children.

How Adcetris is administered
This medicine is administered intravenously (by intravenous infusion). It is given by a doctor or nurse over a period of 30 minutes. Your doctor or nurse will monitor you during and after the infusion.

If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Infusion-related reactions
This type of medicine (monoclonal antibodies) can cause infusion-related reactions such as:

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

Infusion-related reactions with this medicine may affect more than 1 in 10 people.
In general, these types of reactions occur within a period ranging from a few minutes to several hours after the end of the infusion. However, they may also occur several hours after the infusion has ended, although this is not common. Such infusion-related reactions (known as anaphylactic reactions) can be serious or even fatal. It is not known how frequently such infusion-related reactions with this medicine are serious or fatal.
You may be given other medicines, such as antihistamines, corticosteroids or paracetamol, to help relieve any of the above reactions, especially if you have previously experienced similar reactions when given a medicine of this type.
If you think you have had such a reaction in the past, inform your doctor BEFORE this medicine is administered to you.
If you develop infusion-related reactions (as listed above), your doctor may stop the infusion and start supportive treatment.
If the infusion is resumed, your doctor may extend the infusion time so that you can better tolerate it.

Tell your doctor immediately if you notice any of the following symptoms, which in some cases may indicate a serious or possibly fatal condition:

• symptoms of progressive multifocal leukoencephalopathy, such as confusion, difficulty concentrating, memory loss, blurred vision or loss of vision, fatigue, reduced control or sensation in an arm or leg, changes in walking, or loss of balance (affects fewer than 1 in 100 people) (for more detailed information, see section 2)
• 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)
• breathlessness or cough (may affect more than 1 in 10 people)
• flu-like symptoms followed by a painful red or purple rash spreading with the appearance of blisters, including extensive skin peeling (may affect up to 1 in 100 people)
• changes in sensation or sensitivity, particularly of the skin, numbness, tingling, malaise, burning sensation, weakness or pain in the 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)
• diarrhoea, vomiting (may affect more than 1 in 10 people)
• chills or tremors (may affect up to 1 in 10 people)
• feeling tired, frequent urination, increased thirst, increased appetite with unintentional weight loss, and irritability (may be signs of hyperglycaemia and may affect up to 1 in 10 people)
• unusual bleeding or bruising under the skin, prolonged bleeding after blood draws, or bleeding gums (may be signs of thrombocytopenia and may affect up to 1 in 10 people)
• headache, dizziness, paleness (may be signs of anaemia and may affect more than 1 in 10 people)
• widespread rash, increased body temperature, and swollen lymph nodes (DRESS syndrome 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 alone:

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

• decreased levels of white blood cells
• upper respiratory tract infection
• weight loss
• infection
• nausea
• abdominal pain
• itching
• muscle pain
• joint pain or painful, swollen joints

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

• pneumonia
• development of painful, raised, cream-yellow patches inside the mouth (candidiasis)
• reduced platelet count
• dizziness
• blistering, which may become crusted or form eschars
• increased blood sugar levels
• increased liver enzyme levels
• hair loss or unusual thinning of hair

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

• tumour lysis syndrome – a potentially fatal condition that may cause dizziness, reduced urine output, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances
• new or recurrent cytomegalovirus (CMV) infection
• blood infection (sepsis) and/or septic shock (a life-threatening form of sepsis)
• Stevens-Johnson syndrome and toxic epidermal necrolysis – a rare, serious condition that may cause flu-like symptoms followed by a painful red or purple rash spreading with blistering, including extensive skin peeling
• reduced white blood cell count with fever
• nerve damage and damage to the nerve sheath (demyelinating polyneuropathy)

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

• leakage of the medicine from the vein into surrounding tissue (also known as extravasation). Extravasation may cause redness, pain, skin discoloration, swelling, blistering rash, sloughing or infection of deep skin layers (cellulitis) at or around the infusion site.

The following side effects have been reported with Adcetris in combination with chemotherapeutic medicines:

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

• decreased white blood cell count
• decreased white blood cell count with fever
• upper respiratory tract infection
• weight loss
• infection
• nausea
• abdominal pain
• hair loss or unusual thinning of hair
• muscle pain
• joint pain or painful, swollen joints
• dizziness
• reduced appetite
• inability to sleep
• bone pain
• blistering, which may become crusted or form eschars

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

• blood infection (sepsis) and/or septic shock (a life-threatening form of sepsis); pneumonia
• irritation or inflammation in the mouth
• development of painful, raised, cream-yellow patches inside the mouth (candidiasis)
• reduced platelet count in the blood
• itching
• increased blood sugar levels
• increased liver enzyme levels

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

• tumour lysis syndrome – a potentially fatal condition that may cause dizziness, reduced urine output, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances
• Stevens-Johnson syndrome – a rare, serious condition that may cause flu-like symptoms followed by a painful red or purple rash spreading with blistering, including extensive skin peeling
• new or recurrent cytomegalovirus (CMV) infection

Other uncommon side effects (may affect up to 1 in 100 people)
Cases of rapid heartbeat (tachycardia) have been reported with Adcetris in combination with other chemotherapeutic medicines (etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone).
If you are an elderly patient (≥ 65 years of age), you may experience serious adverse events more frequently.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Adcetris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and packaging following "Exp". The expiry date refers to the last day of that month.
Unopened vial: Store in the refrigerator (2 °C–8 °C). Do not freeze.
Keep the vial in its original packaging to protect from light.
Reconstituted/diluted solution: use immediately or store refrigerated (2 °C–8 °C) and use within 24 hours.
Do not use this medicine if you notice the presence of particles or any change in colour before administration.
Do not dispose of any medicine via wastewater or household waste. Your doctor or nurse will dispose of this medicine appropriately. This will help protect the environment.

6. Package contents and other information

What Adcetris contains

• 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). For further information on sodium and polysorbate 80, see section 2.

Description of the appearance of Adcetris and contents of the pack
Adcetris is a powder or compacted powder for concentrate for solution for infusion, white to off-white in colour, supplied in a glass vial.
Each Adcetris pack consists of a single vial.

Marketing Authorisation 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 medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Takeda Belgium NV Takeda, UAB
Tél/Tel: +32 2 464 06 11 Tel: +370 521 09 070
[email protected] [email protected]

България Luxembourg/Luxemburg
Такеда България ЕООД Takeda Belgium NV
Тел.: +359 2 958 27 36 Tél/Tel: +32 2 464 06 11
[email protected] [email protected]

Česká republika Magyarország
Takeda Pharmaceuticals Czech Republic s.r.o. Takeda Pharma Kft.
Tel: +420 234 722 722 Tel.: +36 1 270 7030
[email protected] [email protected]

Danmark Malta
Takeda Pharma A/S Drugsales Ltd
Tlf.: +45 46 77 10 10 Tel: +356 21419070
[email protected] [email protected]

Deutschland Nederland
Takeda GmbH Takeda Nederland B.V.
Tel: +49 (0)800 825 3325 Tel: +31 20 203 5492
[email protected] [email protected]

Eesti Norge
Takeda Pharma OÜ Takeda AS
Tel: +372 6177 669 Tlf: +47 800 800 30
[email protected] [email protected]

Ελλάδα Österreich
Takeda ΕΛΛΑΣ Α.Ε. Takeda Pharma Ges.m.b.H.
Tηλ: +30 210 6387800 Tel: +43 (0) 800-20 80 50
[email protected] [email protected]

España Polska
Takeda Farmacéutica España, S.A. Takeda Pharma Sp. z o.o.
Tel: +34 917 90 42 22 Tel.: +48223062447
[email protected] [email protected]

France Portugal
Takeda France SAS Takeda Farmacêuticos Portugal, Lda.
Tél: +33 1 40 67 33 00 Tel: +351 21 120 1457
[email protected] [email protected]

Hrvatska România
Takeda Pharmaceuticals Croatia d.o.o. Takeda Pharmaceuticals SRL
Tel: +385 1 377 88 96 Tel: +40 21 335 03 91
[email protected] [email protected]

Ireland Slovenija
Takeda Products Ireland Ltd Takeda Pharmaceuticals farmacevtska družba
Tel: 1800 937 970 d.o.o.
[email protected] Tel: +386 (0) 59 082 480
[email protected]

Ísland Slovenská republika
Vistor ehf. Takeda Pharmaceuticals Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 (2) 20 602 600
[email protected] [email protected]

Italia Suomi/Finland
Takeda Italia S.p.A. Takeda Oy
Tel: +39 06 502601 Puh/Tel: 0800 774 051
[email protected] [email protected]

Κύπρος Sverige
A.POTAMITIS MEDICARE LTD Takeda Pharma AB
Tηλ: +357 22583333 Tel: 020 795 079
[email protected] [email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

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

The following information is intended exclusively for healthcare professionals:

Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly recorded.
Disposal
Adcetris is for single use only.
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local applicable regulations.
Instructions for reconstitution
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% overage, resulting in 55 mg of Adcetris per vial and a total reconstituted volume of 11 mL.

1. Direct the stream towards the vial wall and not directly onto the powder.
2. Gently swirl the vial in a circular motion to facilitate dissolution. DO NOT SHAKE.
3. The reconstituted solution in the vial is a clear to slightly opalescent, colourless solution, with a final pH of 6.6.
4. The reconstituted solution should be inspected visually for the presence of foreign particles and/or discoloration. If either is observed, the medicinal product must be discarded.

Preparation of infusion solution
Withdraw the exact volume of reconstituted Adcetris from the vial (or vials) and add it to an infusion bag containing 9 mg/mL (0.9%) Sodium Chloride Solution for Injections to achieve a final concentration of 0.4–1.2 mg/mL of Adcetris.
The recommended dilution volume is 150 mL. After reconstitution, Adcetris may also be diluted in 5% Dextrose Solution for Injections or Lactated Ringer's Solution for Injections.
Gently invert the infusion bag to mix the Adcetris solution. DO NOT SHAKE.
Any medicinal product remaining in the vial after withdrawal of the required volume for dilution must be discarded in accordance with local applicable regulations.
Do not add other medicinal products to the prepared Adcetris infusion solution or to the intravenous infusion set. The infusion line must be flushed after administration with either 9 mg/mL (0.9%) Sodium Chloride 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, from reconstitution to completion of infusion, must not exceed 24 hours.