Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - yescarta

Document Subject

Generated Narrative: MedicinalProductDefinition mp5b44b92baabcf0684d3d21b26b5583ec

identifier: http://ema.europa.eu/identifier/EU/1/18/1299/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Yescarta 0.4 – 2 × 108 cells dispersion for infusion

type: Full name

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part: nan

type: Invented name part

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part: nan

type: Scientific name part

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type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-5b44b92baabcf0684d3d21b26b5583ec

identifier: http://ema.europa.eu/identifier/EU/1/18/1299/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - yescarta

Attesters

What is in this leaflet

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

Yescarta is a gene therapy medicine used for treating adults with aggressive diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma (FL) affecting your lymph tissue (part of the immune system) that affects a type of white blood cell called B lymphocytes and other organs in your body. Too many of these abnormal white blood cells accumulate in your tissue and this is the cause of the symptoms you may have.

The medicine is made specially for you as a single administration of your own modified white blood cells.

You must not be given Yescarta:

• if you are allergic to axicabtagene ciloleucel or any of the other ingredients of this medicine (listed in section 6).
• If you cannot receive treatment, called lymphodepleting chemotherapy, which reduces the number of white blood cells in your blood (see also section 3, How Yescarta is given).

Warnings and precautions
Yescarta is made from your own white blood cells and must only be given to you (autologous use).

Before you are given Yescarta you must tell your doctor if you:

• have problems with your nervous system (such as fits, stroke, or memory loss).
• have kidney problems.
• have low blood cell levels (blood counts).
• have had a stem cell transplant in the last 4 months.
• have any lung, heart or blood pressure (low or raised) problems.
• have signs or symptoms of graft-versus-host disease. This happens when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhoea and bloody stools.
• notice the symptoms of your cancer are getting worse. If you have lymphoma this might include fever, feeling weak, night sweats, sudden weight loss.
• have an infection. The infection will be treated before the Yescarta infusion.
• have had hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.

If any of the above apply to you (or you are not sure), talk to your doctor before being given Yescarta.

Tests and checks Before you are given Yescarta your doctor will:

• Check your lungs, heart and blood pressure.
• Look for signs of infection; any infection will be treated before you are given Yescarta.
• Check if your cancer is getting worse.
• Look for signs of graft-versus-host disease that can happen after a transplant.
• Check your blood for uric acid and for how many cancer cells there are in your blood. This will show if you are likely to develop a condition called tumour lysis syndrome. You may be given medicines to help prevent the condition.
• Check for hepatitis B, hepatitis C or HIV infection.
• Check if you had a vaccination in the previous 6 weeks or are planning to have one in the next few months.

After you have been given Yescarta Tell your doctor or nurse immediately if you have any of the following:

• Chills, extreme tiredness, weakness, dizziness, headache, cough, shortness of breath, or rapid heartbeat, which may be symptoms of a condition known as cytokine release syndrome. Take your temperature twice a day for 3-4 weeks after treatment with Yescarta. If your temperature is high, see your doctor immediately.
• Fits, shaking, or difficulty speaking or slurred speech, loss of consciousness or decreased level of consciousness, confusion and disorientation, loss of balance or coordination.
• Fever, which may be a symptom of an infection.
• Extreme tiredness, weakness and shortness of breath, which may be symptoms of a lack of red blood cells.
• Bleeding or bruising more easily, which may be symptoms of low levels of cells in the blood known as platelets.
• Blurred vision, loss of vision or double vision, difficulty speaking, weakness or clumsiness of an arm or a leg, a change in the way you walk or problems with your balance, personality changes, changes in thinking, memory and orientation leading to confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalopathy (PML). These symptoms may start several months after treatment has ended and they usually develop slowly and gradually over weeks or months. It is important that your relatives or caregivers are also aware of these symptoms, since they may notice symptoms that you are not aware of.

Your doctor will regularly check your blood counts as the number of blood cells and other blood components may decrease.

Do not donate blood, organs, tissues or cells for transplants.

If any of the above apply to you (or you are not sure), talk to your doctor or nurse before you are given Yescarta. Your doctor may need to take special care of you during your treatment with Yescarta.

In some cases, it might not be possible to go ahead with the planned treatment with Yescarta. For example:

• If Yescarta infusion is delayed for more than 2 weeks after you have received preparatory chemotherapy you may have to receive more preparative chemotherapy.

Children and adolescents Yescarta must not be used in children and adolescents below 18 years of age because Yescarta has not been studied in this age group.

Other medicines and Yescarta Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

Before you are given Yescarta tell your doctor or nurse if you are taking any medicines that weaken your immune system such as corticosteroids, since these medicines may interfere with the effect of Yescarta.

In particular, you must not be given certain vaccines called live vaccines:

• In the 6 weeks before you are given the short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body for the Yescarta cells.
• During Yescarta treatment.
• After treatment while the immune system is recovering.

Talk to your doctor if you need to have any vaccinations.

Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine. This is because the effects of Yescarta in pregnant or breast-feeding women are not known, and it may harm your unborn baby or your breast-fed child.

• If you are pregnant or think you may be pregnant after treatment with Yescarta, talk to your doctor immediately.
• You will be given a pregnancy test before treatment starts. Yescarta can only be given if the results show you are not pregnant.

Discuss pregnancy with your doctor if you have received Yescarta.

Driving and using machines Some people may feel tired, dizzy or have some shaking after being given Yescarta. If this happens to you, do not drive or use heavy machines until at least 8 weeks after infusion or until your doctor tells you that you have completely recovered.

Yescarta contains sodium, dimethyl sulphoxide (DMSO), and residual gentamicin This medicine contains 300 mg sodium (main component of cooking/table salt) in each infusion bag. This is the equivalent to 15% of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains DMSO and residual gentamicin which may cause severe allergic reactions.

Yescarta will always be given to you by a healthcare professional. It is given by a drip (infusion) into a vein (intravenously).

• Since Yescarta is made from your own white blood cells, your cells will be collected from you to prepare your medicine. Your doctor will take some of your blood using a catheter placed in your vein (a procedure call leukapheresis). Some of your white blood cells are separated from your blood and the rest of your blood is returned to your vein. This can take 3 to 6 hours and may need to be repeated.
• Your white blood cells are sent away to make Yescarta. It usually takes about 3 to 4 weeks to receive your Yescarta therapy but the time may vary.

Other medicines given before Yescarta treatment During the 30 to 60 minutes before you are given Yescarta you may be given other medicines. This is to help prevent infusion reactions and fever. These other medicines may include:

• Paracetamol.
• An antihistamine such as diphenhydramine.

Prior to receiving Yescarta, you will be given other medicines such as preparative chemotherapy, which will allow your modified white blood cells in Yescarta to multiply in your body when the medicine is given to you.

Your doctor or nurse will check carefully that this medicine is yours.

How Yescarta is given Yescarta will always be given to you by a doctor in a qualified treatment centre.

• Yescarta is given in a single dose.
• Your doctor or nurse will give you a single infusion of Yescarta through a catheter placed into your vein (intravenous infusion) over about 30 minutes.

You must receive Yescarta infusion in a qualified clinical facility and be discharged only when your doctor thinks it is safe for you to go home. Your doctor may do blood tests to check for side effects.

After Yescarta is given

• Plan to stay within proximity from the hospital where you were treated for at least 4 weeks after you have been given Yescarta. Your doctor will recommend that you return to the hospital daily for at least 10 days and will consider whether you need to stay at the hospital as an in-patient for the first 10 days after infusion. This is so your doctor can check if your treatment is working and help you if you have any side effects.

If you miss an appointment Call your doctor or the qualified treatment centre as soon as possible to make another appointment.

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

Serious side effects
Yescarta can cause side effects to your immune system or your nervous system. Yescarta can also increase your risk of getting an infection. These side effects may be serious or life-threatening, and can lead to death.

Tell your doctor immediately if you get any of the following side effects after being given Yescarta, as you may need urgent medical treatment:

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

• Fever, chills, low blood pressure which may cause symptoms such as dizziness or lightheadedness, fast heartbeat, irregular heartbeat (arrythmia), low oxygen in blood which can lead to shortness of breath or difficulty breathing. These may be signs of a serious condition called cytokine release syndrome.
• Loss of consciousness or decreased level of consciousness, confusion or disorganised thinking, memory loss, difficulty speaking or slurred speech, difficulty understanding speech due to disturbances of brain function (encephalopathy). Other signs include involuntary shaking (tremor), sudden confusion with agitation, disorientation, hallucination or irritability (delirium), lack of energy or strength, muscular weakness, difficulty moving (motor dysfunction).
• Feeling warm, fever, chills or shivering which may be signs of infection (including bacterial or viral). Infections can be due to abnormally low number of white blood cells or low level of antibodies called immunoglobulins in the blood which help fight infections.

Other serious side effects which require immediate medical care are:

Common (may affect up to 1 in 10 people)

• Fits (seizures, including seizures that may be prolonged and life-threatening).
• Sudden, unexpected stopping of the heart (cardiac arrest) or heart failure.
• Blood clots: symptoms can include pain in the chest or upper back, difficulty breathing, coughing up blood or cramping pain, swelling in a single leg, warm and darkened skin around the painful area.
• Inability to breathe on one one s own (respiratory failure).
• Failure of the kidneys causing your body to hold onto fluid.
• Build-up of fluids in lungs (pulmonary oedema) which can lead to difficulty in breathing.

Uncommon (may affect up to 1 in 100 people)

• Condition of severe systemic inflammation which symptoms may include fever, rash, enlarged liver, spleen and lymph nodes.
• Improper functioning of at least 2 organs (eg, liver, lungs and kidneys) that requires medical treatment and/or procedures to restore normal organ function.

Other possible side effects The following other side effects have been reported with Yescarta.

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

• Decrease in the number of red blood cells (cells that carry oxygen): symptoms can include extreme tiredness with a loss of energy.
• Low number of cells that help clot the blood (thrombocytopenia): symptoms can include excessive or prolonged bleeding or bruising.
• Low levels of sodium or phosphate seen in blood tests.
• High levels of uric acid or sugar (glucose) seen in blood tests.
• Decreased appetite.
• Difficulty sleeping.
• Headache.
• Dizziness.
• Fast heartbeat.
• Irregular heartbeat (arrhythmia).
• Low blood pressure.
• High blood pressure.
• Cough.
• Nausea, constipation, diarrhoea, abdominal pain, vomiting.
• Increase in liver enzymes seen in blood tests.
• Skin rash or skin problems.
• Muscle and joint pain, back pain.
• Build up of fluids in tissue (oedema) which can lead to swelling, weight gain, and decreased output of urine.
• Extreme tiredness.

Common (may affect up to 1 in 10 people)

• Fungal infection.
• Alteration of the blood ability to form clots (coagulopathy): symptoms can include excessive or prolonged bleeding or bruising.
• Hypersensitivity: symptoms such as rash, hives, itching, swelling and anaphylaxis.
• Low levels of albumin, potassium or calcium seen in blood tests.
• Dehydration.
• Weight loss.
• Anxiety.
• Mood disorders.
• Loss of control of body movements.
• Weakness or inability to move on one side of the body, making it hard to perform everyday activities like eating or dressing.
• Loss of movement in muscles of the face.
• Pain in the hands or feet.
• Muscle spasm.
• Changes in vision which makes it difficult to see things (visual impairment).
• Low oxygen in blood.
• Fluid around the lungs (pleural effusion).
• Shortness of breath, difficulty breathing.
• Nasal inflammation.
• Dry mouth, difficulty swallowing.
• High levels of bilirubin seen in blood tests.
• Infusion related reactions: symptoms such as dizziness or fainting, flushing, rash, itching, fever, shortness of breath or vomiting, abdominal pain and diarrhoea.
• Pain.

Uncommon (may affect up to 1 in 100 people)

• Paralysis of all four limbs.
• Swelling of spinal cord which may cause partial or total paralysis of limbs and torso.
• Difficulty understanding numbers.
• Weakness in the legs or arms.
• Breakdown of muscle tissue that leads to the release of muscle fibre into the blood.

Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines on your own.

Reporting of side effects If you get any side effects, talk to your doctor or nurse. 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 Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

The following information is intented for doctors only.

Do not use this medicine after the expiry date which is stated on the container label and infusion bag.

Store frozen in vapour phase of liquid nitrogen -150 C until thawed for use. Do not refreeze.

What Yescarta contains

• The active substance is axicabtagene ciloleucel. Each patient-specific single infusion bag contains a dispersion of anti-CD19 CAR T cells in approximately 68 mL for a target dose of 2 106 anti-CD19 CAR-positive viable T cells/kg.

• The other ingredients (excipients) are: Cryostor CS10 (contains DMSO), sodium chloride, human albumin. See section 2 Yescarta contains sodium, dimethyl sulphoxide (DMSO), and residual gentamicin .

This medicine contains genetically modified human blood cells.

What Yescarta looks like and contents of the pack Yescarta is a clear to opaque, white to red dispersion for infusion, supplied in an infusion bag individually packed in a metal cassette. A single infusion bag contains approximately 68 mL of cell dispersion.

Marketing Authorisation Holder and Manufacturer Kite Pharma EU B.V. Tufsteen 1 2132 NT Hoofddorp The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien Gilead Sciences Belgium SRL-BV T l/Tel: + 32 (0) 24 01 35 Lietuva Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1
Gilead Sciences Ireland UC .: + 353 (0) 1 686 1Luxembourg/Luxemburg Gilead Sciences Belgium SRL-BV T l/Tel: + 32 (0) 24 01 35 esk republika Gilead Sciences s.r.o. Tel: + 420 910 871 Magyarorsz g Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1Danmark Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1Malta Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1Deutschland Gilead Sciences GmbH Tel: + 49 (0) 89 899890-0

Nederland Gilead Sciences Netherlands B.V. Tel: + 31 (0) 20 718 36 Eesti Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1Norge Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1
Gilead Sciences . . : + 30 210 8930 sterreich Gilead Sciences GesmbH Tel: + 43 1 260 Espa a Gilead Sciences, S.L. Tel: + 34 91 378 98 Polska Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8France Gilead Sciences T l: + 33 (0) 1 46 09 41 Portugal Gilead Sciences, Lda. Tel: + 351 21 7928Hrvatska Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1Rom nia Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1Ireland Gilead Sciences Ireland UC Tel: + 353 (0) 214 825 Slovenija Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1 sland Gilead Sciences Sweden AB S mi: + 46 (0) 8 5057 1Slovensk republika Gilead Sciences Slovakia s.r.o. Tel: + 421 232 121 Italia Gilead Sciences S.r.l. Tel: + 39 02 439Suomi/Finland Gilead Sciences Sweden AB Puh/Tel: + 46 (0) 8 5057 1
Gilead Sciences . . : + 30 210 8930 Sverige Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1Latvija Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1United Kingdom (Northern Ireland) Gilead Sciences Ireland UC Tel: + 44 (0) 8000 113This leaflet was last revised in

Other sources of information

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