Adcetris - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Adcetris 50 mg powder for concentrate for solution for infusion brentuximab vedotin

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

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 get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Adcetris is and what it is used for

• 2. What you need to know before you are given Adcetris

• 3. How Adcetris will be 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 anti-cancer agent, which is made up of a monoclonal antibody linked to a substance intended to kill cancer cells. This substance is delivered to cancer cells by the monoclonal antibody. A monoclonal antibody is a protein which recognises certain cancer cells.

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

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

Adcetris is used to treat patients with advanced classical Hodgkin lymphoma who have not had treatment before. Adcetris will be given to you together with doxorubicin, vinblastine and dacarbazine which are other chemotherapy medicines used to treat Hodgkin lymphoma.

Adcetris is used alone to lower the likelihood of classical Hodgkin lymphoma coming back after an autologous stem cell transplant in patients with certain risk factors.

Adcetris is also used alone to treat classical Hodgkin lymphoma that has:

• – come back after or not responded to an infusion of your own healthy stem cells into your body (autologous stem cell transplant), or

• – come back after or never responded to at least two previous therapies, and where you cannot receive additional combination anti-cancer treatments or have an autologous stem cell transplant.

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

Adcetris is used to treat patients with systemic anaplastic large cell lymphoma who have not had treatment before. Adcetris will be given to you together with cyclophosphamide, doxorubicin and prednisone which are other chemotherapy 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 anti-cancer treatments, or

• – come back after previous anti-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 where a specific type of protein is present on the cells’ surface.

Adcetris is used to treat cutaneous T-cell lymphoma in patients who have previously received at least one anti-cancer medicine that travels through the bloodstream.

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

• – are currently using bleomycin, an anti-cancer agent.

Warnings and precautions

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

• – have confusion, trouble thinking, memory loss, blurred or loss of vision, decreased strength, decreased control or sensation in one arm or leg, a change in the way of walking, or loss of balance, as these may be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalopathy (PML). If you have these symptoms prior to treatment with this medicine, tell your doctor immediately about any changes in these symptoms. You should also inform your partner or caregivers about your treatment, since they may notice symptoms that you are not aware of

• – have severe and persistent stomach pain, with or without nausea and vomiting, as these may be symptoms of a serious and potentially fatal condition known as pancreatitis (inflammation of the pancreas)

• – have new or worsening shortness of breath or cough as these may be symptoms of a serious and potentially fatal lung complication (pulmonary toxicity)

• – are taking, or have previously taken, medicines which may affect your immune system, such as chemotherapy or immunosuppres­sive agents

• – have, or think you have, an infection. Some infections may be serious and can be due to viruses, bacteria, or other causes that may be life-threatening

• – experience a whistling sound during breathing (wheezing)/dif­ficulty breathing, hives, itching, or swelling (signs of an infusion reaction). For more detailed information, see “Infusion reactions” in section 4

• – have any problems with a change in the sensitivity of the skin, especially in the hands or feet,

such as numbness, tingling, a burning sensation, pain, discomfort or weakness (neuropathy)

• – have headaches, feel tired, experience dizziness, look pale (anaemia), or have unusual bleeding or bruising under the skin, longer than usual bleeding after your blood has been drawn, or bleeding from your gums (thrombocytopenia)

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

• – experience dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances (this may be a potentially life-threatening complication known as tumour lysis syndrome)

• – experience flu-like symptoms followed by a painful red or purplish rash that spreads and blisters including extensive detachment of the skin that may be life-threatening (this may be a serious skin reaction known as Stevens-Johnson syndrome and toxic epidermal necrolysis)

• – experience widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome)

• – have new or worsening stomach pain, nausea, vomiting, constipation as these may be symptoms of a serious and potentially fatal stomach or intestinal complication (gastrointestinal complications)

• – have abnormal liver test results as this may be related to a serious and potentially fatal liver injury (hepatotoxicity). Liver disease and other medical conditions that may have been present before you start taking Adcetris and some medications that you are currently taking might increase the risk of liver injury

• – feel tired, have frequent urination, increased thirst, increased appetite with unintended weight loss, or irritability (hyperglycaemia)

• – get a burning sensation, feel pain or tenderness at or surrounding the infusion site during the infusion, this could indicate that Adcetris has leaked outside the blood vessel. Tell your doctor or nurse immediately. If Adcetris has leaked outside the blood vessel, skin redness, pain, discolouration, swelling, blistering, peeling, or infection of deeper layers of your skin (cellulitis) at or surrounding the infusion site can occur within days or weeks after the infusion.

• – have kidney or liver problems

Your doctor will perform regular blood tests to make sure that it is safe for you to receive this medicine.

Other medicines and Adcetris

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

Pregnancy, breast-feeding and fertility

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

You should 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 unborn baby.

It is important to tell your doctor before and during treatment if you are pregnant, think you may be pregnant, or are planning to get pregnant.

If you are breast-feeding, you should discuss with your doctor whether you should receive this medicine.

Men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men are advised not to father a child during treatment with this medicine and for up to 6 months following the last dose of this medicine.

Driving and using machines

Your treatment may influence your ability to drive or operate machines. If you feel unwell during treatment then do not drive or operate machines.

Adcetris contains sodium

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

• 3. How Adcetris will be given

If you have any questions on the use of this medicine, ask the doctor or nurse who is giving you 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 cyclophosphamide, doxorubicin and prednisone is 1.8 mg/kg given every 3 weeks for approximately 4–6 months.

See the package leaflets for 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 that will help prevent development or reduce the severity of neutropenia (decrease of white blood cell count) which can increase the risk of infection. Tell your doctor if you have kidney or liver problems as your doctor may lower your starting dose or may not recommend Adcetris.

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

Adcetris is to be given to adults only. It is not for use in children.

How Adcetris is given

This medicine is given to you into a vein (intravenously) as an infusion. It is given by your doctor or nurse over 30 minutes. Your doctor or nurse will also monitor you during and after the infusion.

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

4. Possible side effects

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

Infusion reactions

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

• – a rash

• – shortness of breath

• – difficulty breathing

• – cough

• – a tight chest

• – fever

• – back pain

• – chills

• – headache

• – feeling sick (nausea) or being sick (vomiting).

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

In general, these types of reactions occur within minutes to several hours following completion of the infusion. However, they may develop more than several hours after completion of the infusion but this is uncommon. These infusion reactions can be serious or even fatal (known as an anaphylactic reaction). It is not known how frequently infusion-related reactions to this medicine are serious or fatal.

You may be given other medicines such as

• – anti-histamines, corticosteroids or paracetamol

to help reduce any of the reactions above if you have already experienced these when receiving this type of medicine.

If you think you have previously had a similar reaction, tell your doctor BEFORE you are given this medicine.

If you develop infusion reactions (as stated previously), your doctor may stop giving this medicine and start support treatment.

If your infusion is restarted, your doctor may increase the time over which your infusion is given so that you may be able to tolerate it better.

Tell your doctor straight away if you notice any of the following symptoms because some of them may be signs of a serious or possibly fatal condition:

• – progressive multifocal leukoencephalopathy (PML) symptoms such as confusion, trouble thinking, memory loss, blurred or loss of vision, decreased strength, decreased control or sensation in one arm or leg, a change in the way of walking, or loss of balance (for more detailed information, see section 2) (affects less 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 blisters including

extensive detachment of the skin (may affect up to 1 in 100 people)

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

• – a 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 shivering (may affect up to 1 in 10 people)

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

• – unusual bleeding or bruising under the skin, longer than usual bleeding after your blood has been drawn, or bleeding from your gums (these may be signs of thrombocyopenia which may affect up to 1 in 10 people)

• – headaches, experience dizziness, look pale (these may be signs of anaemia, which may affect more than 1 in 10 people)

• – widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome) (frequency cannot be estimated from the 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 level of white blood cells

• – upper respiratory tract infection

• – decrease in weight

• – 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

• – sore, creamy-yellow, raised patches in the mouth (thrush)

• – decreased level of blood platelets

• – dizziness

• – blisters which may crust or scab

• – increased level of blood sugar

• – increased liver enzyme levels

• – unusual hair loss or thinning

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

• – Tumour lysis syndrome – a potentially life-threatening condition in which you may experience

dizziness, decreased urination, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm disturbances.

• – new or recurring cytomegalovirus (CMV) infection

• – an infection in the blood (sepsis) and/or septic shock (a life-threatening form of sepsis)

• – Stevens-Johnson syndrome and toxic epidermal necrolysis – a rare, serious disorder in which

you may experience flu-like symptoms followed by a painful red or purplish rash that spreads and blisters including extensive detachment of the skin

• – decreased level of white blood cells with a fever

• – damage to the nerves and nerve coverings (demyelinating polyneuropathy)

Not known side effects (frequency cannot be estimated from the available data)

• – Leaking of drug out of the vein into surrounding tissues (also called extravasation). Extravasation may result in skin redness, pain, discolouration,swe­lling, blistering, peeling, or infection of the deeper layers of the skin (cellulitis) at or surrounding the infusion site.

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

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

• – decreased level of white blood cells

• – decreased level of white blood cells with a fever

• – upper respiratory tract infection

• – decrease in weight

• – infection

• – nausea

• – abdominal pain

• – unusual hair loss or thinning

• – muscle pain

• – joint pain or painful, swollen joints

• – dizziness

• – decreased appetite

• – not being able to sleep

• – bone pain

• – blisters which may crust or scab

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

• – an infection in the blood (sepsis) and/or septic shock (a life-threatening form of sepsis); pneumonia

• – sore or inflammation in the mouth

• – sore, creamy-yellow, raised patches in the mouth (thrush)

• – decreased level of blood platelets

• – itching

• – increased level of blood sugar

• – increased liver enzyme levels

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

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

• – Stevens-Johnson syndrome – a rare, serious disorder in which you may experience flu-like

symptoms followed by a painful red or purplish rash that spreads and blisters including extensive detachment of the skin

• – new or recurring cytomegalovirus (CMV) infection

If you are an older patient (> 65 years of age) you may experience serious adverse events more frequently.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in 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 which is stated on the vial label and the carton after EXP. The expiry date refers to the last day of that month.

Unopened vial: Store in a refrigerator (2 °C-8 °C). Do not freeze.

Keep the vial in the original carton in order to protect from light.

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

Do not use this medicine if you notice any particulate matter or discolouration prior to administration.

Do not throw away any medicines via wastewater or household waste. The doctor or nurse will dispose of this medicine. These measures will help protect the environment.

6. Contents of the pack 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 ingredients are citric acid monohydrate, sodium citrate dihydrate, a,a-trehalose dihydrate, and polysorbate 80 See section 2 for further information about sodium.

What Adcetris looks like and contents of the pack

Adcetris is a white to off-white cake or powder for concentrate for solution for infusion provided in a glass vial.

EXXáSa TAKEDA EAAAZ A.E Tql: +30 210 6387800	Österreich Takeda Pharma Ges.m.b.H. Tel: +43 (0) 800 20 80 50
España Takeda Farmacéutica España S.A Tel: +34 917 90 42 22	Polska Takeda Pharma sp. z o.o. Tel.: + 48 22 608 13 00
France Takeda France SAS Tél: + 33 1 40 67 33 00	Portugal Takeda Farmacéuticos Portugal, Lda. Tel: + 351 21 120 1457
Hrvatska Takeda Pharmaceuticals Croatia d.o.o. Tel: +385 1 377 88 96	Romania Takeda Pharmaceuticals SRL Tel: +40 21 335 03 91
Ireland Takeda Products Ireland Limited Tel: 1800 937 970	Slovenija Takeda Pharmaceuticals farmacevtska družba d.o.o. Tel: + 386 (0) 59 082 480
Ísland Vistor hf. Sími: +354 535 7000	Slovenská republika Takeda Pharmaceuticals Slovakia s.r.o. Tel: +421 (2) 20 602 600
Italia Takeda Italia S.p.A. Tel: +39 06 502601	Suomi/Finland Takeda Oy Puh/Tel: +358 20 746 5000
Kúnpog A. Potamitis Medicare Ltd Tql: +357 22583333	Sverige Takeda Pharma AB Tel: +46 8 731 28 00
Latvija Takeda Latvia SIA Tel: +371 67840082	United Kingdom (Northern Ireland) Takeda UK Ltd Tel: +44 (0) 2830 640 902

This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Detailed information on this medicine is available on the European Medicines Agency website:

The following information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Disposal

Adcetris is for single use only.

Any unused product or waste material should be disposed of in accordance with local requirements.

Instructions for reconstitution

Each single use vial must be reconstituted with 10.5 mL of water for injections to a final concentration of 5 mg/mL. Each vial contains a 10% overfill giving 55 mg of Adcetris per vial and a total reconstituted volume of 11 mL.

• 1. Direct the stream toward the wall of the vial and not directly at the cake or powder.

• 2. Gently swirl the vial to aid 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 any foreign particulate matter and/or discolouration. In the event of either being observed, discard the medicinal product.