B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Xtandi 40 mg soft capsules enzalutamide

Read all of this leaflet carefully before you start taking 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.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – 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 Xtandi is and what it is used for

• 2. What you need to know before you take Xtandi

• 3. How to take Xtandi

• 4. Possible side effects

• 5. How to store Xtandi

• 6. Contents of the pack and other information

1. What Xtandi is and what it is used for

Xtandi contains the active substance enzalutamide. Xtandi is used to treat adult men with prostate cancer that:

• – No longer responds to a hormone therapy or surgical treatment to lower testosterone

Or

• – Has spread to other parts of the body and responds to a hormone therapy or surgical treatment to lower testosterone.

How Xtandi works

Xtandi is a medicine that works by blocking the activity of hormones called androgens (such as testosterone). By blocking androgens, enzalutamide stops prostate cancer cells from growing and dividing.

2. What you need to know before you take Xtandi

Do not take Xtandi

• – If you are allergic to enzalutamide or any of the other ingredients of this medicine (listed in section 6).

• – If you are pregnant or may become pregnant (see ‘Pregnancy, breast-feeding and fertility’)

Warnings and precautions

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and fewer than one in every 1,000 people taking placebo (see ‘Other medicines and Xtandi’ below and section 4 ‘Possible side effects’).

If you are taking a medicine that can cause seizures or that can increase the susceptibility for having seizures (see ‘Other medicines and Xtandi’ below)

If you have a seizure during treatment:

See your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior reversible encephalopathy syndrome (PRES)

There have been rare reports of PRES, a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible. (See also section 4 ‘Possible side effects’).

Risk of new cancers (second primary malignancies)

There have been reports of new (second) cancers including cancer of the bladder and colon in patients treated with Xtandi.

See your doctor as soon as possible if you notice signs of gastrointestinal bleeding, blood in the urine, or frequently feel an urgent need to urinate when taking Xtandi.

Talk to your doctor before taking Xtandi

• – If you are taking any medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)

• – If you use chemotherapy like docetaxel

• – If you have problems with your liver

• – If you have problems with your kidneys

Please tell your doctor if you have any of the following:

Any heart or blood vessel conditions, including heart rhythm problems (arrhythmia), or are being treated with medicines for these conditions. The risk of heart rhythm problems may be increased when using Xtandi.

If you are allergic to enzalutamide, this may result in a rash or swelling of the face, tongue, lip or throat. If you are allergic to enzalutamide or any of the other ingredients of this medicine, do not take Xtandi.

Severe skin rash or skin peeling, blistering and/or mouth sores have been reported in association with Xtandi treatment. Seek medical attention immediately if you notice any of these symptoms.

If any of the above applies to you or you are not sure, talk to your doctor before taking this medicine.

Children and adolescents

This medicine is not for use in children and adolescents.

Other medicines and Xtandi

Tell your doctor if you are taking, have recently taken or might take any other medicines. You need to know the names of the medicines you take. Keep a list of them with you to show to your doctor when you are prescribed a new medicine. You should not start or stop taking any medicine before you talk with the doctor that prescribed Xtandi.

Tell your doctor if you are taking any of the following medicines. When taken at the same time as Xtandi, these medicines may increase the risk of a seizure:

• – Certain medicines used to treat asthma and other respiratory diseases (e.g. aminophylline, theophylline).

• – Medicines used to treat certain psychiatric disorders such as depression and schizophrenia (e.g. clozapine, olanzapine, risperidone, ziprasidone, bupropion, lithium, chlorpromazine, mesoridazine, thioridazine, amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).

• – Certain medicines for the treatment of pain (e.g. pethidine).

Tell your doctor if you are taking the following medicines. These medicines may influence the effect of Xtandi, or Xtandi may influence the effect of these medicines.

This includes certain medicines used to:

• – Lower cholesterol (e.g. gemfibrozil, atorvastatin, simvastatin)

• – Treat pain (e.g. fentanyl, tramadol)

• – Treat cancer (e.g. cabazitaxel)

• – Treat epilepsy (e.g. carbamazepine, clonazepam, phenytoin, primidone, valproic acid)

• – Treat certain psychiatric disorders such as severe anxiety or schizophrenia (e.g. diazepam,

midazolam, haloperidol)

• – Treat sleep disorders (e.g. zolpidem)

• – Treat heart conditions or lower blood pressure (e.g. bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)

• – Treat serious disease related to inflammation (e.g. dexamethasone, prednisolone)

• – Treat HIV infection (e.g. indinavir, ritonavir)

• – Treat bacterial infections (e.g. clarithromycin, doxycycline)

• – Treat thyroid disorders (e.g. levothyroxine)

• – Treat gout (e.g. colchicine)

• – Treat stomach disorders (e.g. omeprazole)

• – Prevent heart conditions or strokes (e.g. dabigatran etexilate)

• – Prevent organ rejection (e.g. tacrolimus)

Xtandi might interfere with some medicines used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol) or might increase the risk of heart rhythm problems when used with some other medicines (e.g. methadone, used for pain relief and part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious mental illnesses).

Tell your doctor if you are taking any of the medicines listed above. The dose of Xtandi or any other medicines that you are taking may need to be changed.

Pregnancy, breast-feeding and fertility

• - Xtandi is not for use in women. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It must not be taken by women who are pregnant, may become pregnant, or who are breast-feeding.

• – This medicine could possibly have an effect on male fertility.

• – If you are having sex with a woman who can become pregnant, use a condom and another effective birth control method, during treatment and for 3 months after treatment with this medicine. If you are having sex with a pregnant woman, use a condom to protect the unborn child.

• – Female caregivers see section 3 ‘How to take Xtandi’ for handling and use.

Driving and using machines

Xtandi may have moderate influence on the ability to drive and use machines. Seizures have been reported in patients taking Xtandi. If you are at higher risk of seizures, talk to your doctor.

Xtandi contains sorbitol

This medicine contains 57.8 mg sorbitol (a type of sugar) per soft capsule. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Xtandi

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

The usual dose is 160 mg (four soft capsules), taken at the same time once a day.

Taking Xtandi

• – Swallow the soft capsules whole with water.

• – Do not chew, dissolve or open the soft capsules before swallowing.

• – Xtandi can be taken with or without food.

• – Xtandi should not be handled by persons other than the patient or his caregivers. Women who are or may become pregnant should not handle damaged or opened Xtandi capsules without wearing protection like gloves.

Your doctor may also prescribe other medicines while you are taking Xtandi.

If you take more Xtandi than you should

If you take more soft capsules than prescribed, stop taking Xtandi and contact your doctor. You may have an increased risk of seizure or other side effects.

If you forget to take Xtandi

• – If you forget to take Xtandi at the usual time, take your usual dose as soon as you remember.

• – If you forget to take Xtandi for the whole day, take your usual dose the following day.

• – If you forget to take Xtandi for more than one day, talk to your doctor immediately.

• - Do not take a double dose to make up for the dose you forgot.

If you stop taking Xtandi

Do not stop taking this medicine unless your doctor tells you to.

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

4. Possible side effects

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

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and in fewer than one in every 1,000 people taking placebo.

Seizures are more likely if you take more than the recommended dose of this medicine, if you take certain other medicines, or if you are at higher than usual risk of seizure.

If you have a seizure , see your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior Reversible Encephalopathy Syndrome (PRES)

There have been rare reports of PRES (may affect up to 1 in 1,000 people), a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible.

Other possible side effects include:

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

Tiredness, fall, broken bones, hot flushes, high blood pressure

Common (may affect up to 1 in 10 people)

Headache, feeling anxious, dry skin, itching, difficulty remembering, blockage of the arteries in the heart (ischemic heart disease), breast enlargement in men (gynaecomastia), symptom of restless legs syndrome (an uncontrollable urge to move a part of the body, usually the leg), reduced concentration, forgetfulness, change in sense of taste

Uncommon ( may affect up to 1 in 100 people)

Hallucinations, difficulty thinking clearly, low white blood cell count

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

Muscle pain, muscle spasms, muscular weakness, back pain, changes in ECG (QT prolongation), upset stomach including feeling sick (nausea), rash, being sick (vomiting), swelling of the face, lips, tongue and/or throat, reduction in blood platelets (which increases risk of bleeding or bruising), diarrhoea

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 Xtandi

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 cardboard wallet and outer carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not take any soft capsule that is leaking, damaged, or shows signs of tampering.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Xtandi contains

• – The active substance is enzalutamide. Each soft capsule contains 40 mg of enzalutamide.

• – The other ingredients of the soft capsule are caprylocaproyl macrogol-8 glycerides,

butylhydroxyanisole (E320), and butylhydroxytoluene (E321).

• – The ingredients of the soft capsule shell are gelatin, sorbitol sorbitan solution (see section 2), glycerol, titanium dioxide (E171), and purified water.

• – The ingredients of the ink are iron oxide black (E172) and polyvinyl acetate phthalate.

What Xtandi looks like and contents of the pack

• – Xtandi soft capsules are white to off-white, oblong soft capsules (approximately 20 mm by

• 9 mm) with “ENZ” written on one side.

• – Each carton contains 112 soft capsules in 4 blister wallets of 28 soft capsules each.

Marketing Authorisation Holder and Manufacturer

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

The Netherlands

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

Belgie/Belgiqu­e/Belgien Astellas Pharma B.V. Branch Tél/Tel: + 32 (0)2 5580710	Lietuva Biocodex UAB Tel: + 370 37 408 681
Etnrapua Acme.iac OapMa EOOfl Ten.: + 359 2 862 53 72	Luxembourg/Lu­xemburg Astellas Pharma B.V.Branch Belgique/Belgien Tél/Tel: + 32 (0)2 5580710
Česká republika Astellas Pharma s.r.o. Tel: + 420 236 080300	Magyarország Astellas Pharma Kft. Tel.: + 36 1 577 8200
Danmark Astellas Pharma a/s Tlf: + 45 43 430355	Malta Astellas Pharmaceuticals AEBE Tel: + 30 210 8189900
Deutschland Astellas Pharma GmbH Tel: + 49 (0)89 454401	Nederland Astellas Pharma B.V. Tel: + 31 (0)71 5455745
Eesti Biocodex OÜ Tel: + 372 6 056 014	Norge Astellas Pharma Tlf: + 47 66 76 46 00
EZZáSa Astellas Pharmaceuticals AEBE Tql: + 30 210 8189900	Österreich Astellas Pharma Ges.m.b.H. Tel: + 43 (0)1 8772668
España Astellas Pharma S.A. Tel: + 34 91 4952700	Polska Astellas Pharma Sp.z.o.o. Tel.: + 48 225451 111
France Astellas Pharma S.A.S. Tél: + 33 (0)1 55917500	Portugal Astellas Farma, Lda. Tel: + 351 21 4401320
Hrvatska Astellas d.o.o. Tel: + 385 1 670 01 02	Romania S.C.Astellas Pharma SRL Tel: + 40 (0)21 361 04 95 /96 /92
Ireland Astellas Pharma Co. Ltd. Tel: + 353 (0)1 4671555	Slovenija Astellas Pharma d.o.o. Tel: + 386 14011 400
Ísland Vistor hf Sími: + 354 535 7000	Slovenská republika Astellas Pharma s.r.o., Tel: + 421 2 4444 2157
Italia Astellas Pharma S.p.A. Tel: + 39 02 921381	Suomi/Finland Astellas Pharma Puh/Tel: + 358 (0)9 85606000

Kvnpog

Astellas Pharmaceuticals AEBE

EXXaSa

Tql: + 30 210 8189900

Latvija

Biocodex SIA

Tel: + 371 67 619365

This leaflet was last revised in MM/YYYY.

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

Package leaflet: Information for the patient

Xtandi 40 mg film-coated tablets

Xtandi 80 mg film-coated tablets

enzalutamide

Read all of this leaflet carefully before you start taking 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.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – 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 Xtandi is and what it is used for

• 2. What you need to know before you take Xtandi

• 3. How to take Xtandi

• 4. Possible side effects

• 5. How to store Xtandi

• 6. Contents of the pack and other information

1. What Xtandi is and what it is used for

Xtandi contains the active substance enzalutamide. Xtandi is used to treat adult men with prostate cancer that:

• – No longer responds to a hormone therapy or surgical treatment to lower testosterone

Or

• – Has spread to other parts of the body and responds to a hormone therapy or surgical treatment to lower testosterone.

How Xtandi works

Xtandi is a medicine that works by blocking the activity of hormones called androgens (such as testosterone). By blocking androgens, enzalutamide stops prostate cancer cells from growing and dividing.

2. What you need to know before you take Xtandi

Do not take Xtandi

• – If you are allergic to enzalutamide or any of the other ingredients of this medicine (listed in section 6).

• – If you are pregnant or may become pregnant (see ‘Pregnancy, breast-feeding and fertility’)

Warnings and precautions

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and fewer than one in every 1,000 people taking placebo (see ‘Other medicines and Xtandi’ below and section 4 ‘Possible side effects’).

If you are taking a medicine that can cause seizures or that can increase the susceptibility for having seizures (see ‘Other medicines and Xtandi’ below)

If you have a seizure during treatment:

See your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior reversible encephalopathy syndrome (PRES)

There have been rare reports of PRES, a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible. (See also section 4 ‘Possible side effects’).

Risk of new cancers (second primary malignancies)

There have been reports of new (second) cancers including cancer of the bladder and colon in patients treated with Xtandi.

See your doctor as soon as possible if you notice signs of gastrointestinal bleeding, blood in the urine, or frequently feel an urgent need to urinate when taking Xtandi.

Talk to your doctor before taking Xtandi

• – If you are taking any medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)

• – If you use chemotherapy like docetaxel

• – If you have problems with your liver

• – If you have problems with your kidneys

Please tell your doctor if you have any of the following:

Any heart or blood vessel conditions, including heart rhythm problems (arrhythmia), or are being treated with medicines for these conditions. The risk of heart rhythm problems may be increased when using Xtandi.

If you are allergic to enzalutamide, this may result in a rash or swelling of the face, tongue, lip or throat. If you are allergic to enzalutamide or any of the other ingredients of this medicine, do not take Xtandi.

Severe skin rash or skin peeling, blistering and/or mouth sores have been reported in association with Xtandi treatment. Seek medical attention immediately if you notice any of these symptoms.

If any of the above applies to you or you are not sure, talk to your doctor before taking this medicine.

Children and adolescents

This medicine is not for use in children and adolescents.

Other medicines and Xtandi

Tell your doctor if you are taking, have recently taken or might take any other medicines. You need to know the names of the medicines you take. Keep a list of them with you to show to your doctor when you are prescribed a new medicine. You should not start or stop taking any medicine before you talk with the doctor that prescribed Xtandi.

Tell your doctor if you are taking any of the following medicines. When taken at the same time as Xtandi, these medicines may increase the risk of a seizure:

• – Certain medicines used to treat asthma and other respiratory diseases (e.g. aminophylline, theophylline).

• – Medicines used to treat certain psychiatric disorders such as depression and schizophrenia (e.g. clozapine, olanzapine, risperidone, ziprasidone, bupropion, lithium, chlorpromazine, mesoridazine, thioridazine, amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).

• – Certain medicines for the treatment of pain (e.g. pethidine).

Tell your doctor if you are taking the following medicines. These medicines may influence the effect of Xtandi, or Xtandi may influence the effect of these medicines.

This includes certain medicines used to:

• – Lower cholesterol (e.g. gemfibrozil, atorvastatin, simvastatin)

• – Treat pain (e.g. fentanyl, tramadol)

• – Treat cancer (e.g. cabazitaxel)

• – Treat epilepsy (e.g. carbamazepine, clonazepam, phenytoin, primidone, valproic acid)

• – Treat certain psychiatric disorders such as severe anxiety or schizophrenia (e.g. diazepam,

midazolam, haloperidol)

• – Treat sleep disorders (e.g. zolpidem)

• – Treat heart conditions or lower blood pressure (e.g. bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)

• – Treat serious disease related to inflammation (e.g. dexamethasone, prednisolone)

• – Treat HIV infection (e.g. indinavir, ritonavir)

• – Treat bacterial infections (e.g. clarithromycin, doxycycline)

• – Treat thyroid disorders (e.g. levothyroxine)

• – Treat gout (e.g. colchicine)

• – Treat stomach disorders (e.g. omeprazole)

• – Prevent heart conditions or strokes (e.g. dabigatran etexilate)

• – Prevent organ rejection (e.g. tacrolimus)

Xtandi might interfere with some medicines used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol) or might increase the risk of heart rhythm problems when used with some other medicines (e.g. methadone, used for pain relief and part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious mental illnesses).

Tell your doctor if you are taking any of the medicines listed above. The dose of Xtandi or any other medicines that you are taking may need to be changed.

Pregnancy, breast-feeding and fertility

• - Xtandi is not for use in women. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It must not be taken by women who are pregnant, may become pregnant, or who are breast-feeding.

• – This medicine could possibly have an effect on male fertility.

• – If you are having sex with a woman who can become pregnant, use a condom and another effective birth control method, during treatment and for 3 months after treatment with this medicine. If you are having sex with a pregnant woman, use a condom to protect the unborn child.

• – Female caregivers see section 3 ‘How to take Xtandi’ for handling and use.

Driving and using machines

Xtandi may have moderate influence on the ability to drive and use machines. Seizures have been reported in patients taking Xtandi. If you are at higher risk of seizures, talk to your doctor.

3. How to take Xtandi

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

The usual dose is 160 mg (four 40 mg film-coated tablets or two 80 mg film-coated tablets), taken at the same time once a day.

Taking Xtandi

• – Swallow the tablets whole with water.

• – Do not cut, crush or chew the tablets before swallowing.

• – Xtandi can be taken with or without food.

Xtandi should not be handled by persons other than the patient or his caregivers. Women who are or may become pregnant should not handle broken or damaged Xtandi tablets without wearing protection like gloves.

Your doctor may also prescribe other medicines while you are taking Xtandi.

If you take more Xtandi than you should

If you take more tablets than prescribed, stop taking Xtandi and contact your doctor. You may have an increased risk of seizure or other side effects.

If you forget to take Xtandi

• – If you forget to take Xtandi at the usual time, take your usual dose as soon as you remember.

• – If you forget to take Xtandi for the whole day, take your usual dose the following day.

• – If you forget to take Xtandi for more than one day, talk to your doctor immediately.

• - Do not take a double dose to make up for the dose you forgot.

If you stop taking Xtandi

Do not stop taking this medicine unless your doctor tells you to.

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

4. Possible side effects

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

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and in fewer than one in every 1,000 people taking placebo.

Seizures are more likely if you take more than the recommended dose of this medicine, if you take certain other medicines, or if you are at higher than usual risk of seizure.

If you have a seizure , see your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior Reversible Encephalopathy Syndrome (PRES)

There have been rare reports of PRES (may affect up to 1 in 1,000 people), a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible.

Other possible side effects include:

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

Tiredness, fall, broken bones, hot flushes, high blood pressure

Common (may affect up to 1 in 10 people)

Headache, feeling anxious, dry skin, itching, difficulty remembering, blockage of the arteries in the heart (ischemic heart disease), breast enlargement in men (gynaecomastia), symptom of restless legs syndrome (an uncontrollable urge to move a part of the body, usually the leg), reduced concentration, forgetfulness, change in sense of taste

Uncommon ( may affect up to 1 in 100 people)

Hallucinations, difficulty thinking clearly, low white blood cell count

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

Muscle pain, muscle spasms, muscular weakness, back pain, changes in ECG (QT prolongation), upset stomach including feeling sick (nausea), rash, being sick (vomiting), swelling of the face, lips, tongue and/or throat, reduction in blood platelets (which increases risk of bleeding or bruising), diarrhoea

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 Xtandi

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 cardboard wallet and outer carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Xtandi contains

The active substance is enzalutamide.

Each Xtandi 40 mg film-coated tablet contains 40 mg of enzalutamide.

Each Xtandi 80 mg film-coated tablet contains 80 mg of enzalutamide.

The other ingredients of the film-coated tablets are:

• Tablet core: Hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate.
• Tablet coating: Hypromellose, talc, macrogol 8000, titanium dioxide (E171), yellow iron oxide (E172).

What Xtandi looks like and contents of the pack

• – Xtandi soft capsules are white to off-white, oblong soft capsules (approximately 20 mm by

• 9 mm) with “ENZ” written on one side.

• – Each carton contains 112 soft capsules in 4 blister wallets of 28 soft capsules each.

Marketing Authorisation Holder and Manufacturer

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

The Netherlands

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

Belgie/Belgiqu­e/Belgien Astellas Pharma B.V. Branch Tél/Tel: + 32 (0)2 5580710	Lietuva Biocodex UAB Tel: + 370 37 408 681
Etnrapua Acme.iac OapMa EOOfl Ten.: + 359 2 862 53 72	Luxembourg/Lu­xemburg Astellas Pharma B.V.Branch Belgique/Belgien Tél/Tel: + 32 (0)2 5580710
Česká republika Astellas Pharma s.r.o. Tel: + 420 236 080300	Magyarország Astellas Pharma Kft. Tel.: + 36 1 577 8200
Danmark Astellas Pharma a/s Tlf: + 45 43 430355	Malta Astellas Pharmaceuticals AEBE Tel: + 30 210 8189900
Deutschland Astellas Pharma GmbH Tel: + 49 (0)89 454401	Nederland Astellas Pharma B.V. Tel: + 31 (0)71 5455745
Eesti Biocodex OÜ Tel: + 372 6 056 014	Norge Astellas Pharma Tlf: + 47 66 76 46 00
EZZáSa Astellas Pharmaceuticals AEBE Tql: + 30 210 8189900	Österreich Astellas Pharma Ges.m.b.H. Tel: + 43 (0)1 8772668
España Astellas Pharma S.A. Tel: + 34 91 4952700	Polska Astellas Pharma Sp.z.o.o. Tel.: + 48 225451 111
France Astellas Pharma S.A.S. Tél: + 33 (0)1 55917500	Portugal Astellas Farma, Lda. Tel: + 351 21 4401320
Hrvatska Astellas d.o.o. Tel: + 385 1 670 01 02	Romania S.C.Astellas Pharma SRL Tel: + 40 (0)21 361 04 95 /96 /92
Ireland Astellas Pharma Co. Ltd. Tel: + 353 (0)1 4671555	Slovenija Astellas Pharma d.o.o. Tel: + 386 14011 400
Ísland Vistor hf Sími: + 354 535 7000	Slovenská republika Astellas Pharma s.r.o., Tel: + 421 2 4444 2157
Italia Astellas Pharma S.p.A. Tel: + 39 02 921381	Suomi/Finland Astellas Pharma Puh/Tel: + 358 (0)9 85606000

Kvnpog

Astellas Pharmaceuticals AEBE

EXXaSa

Tql: + 30 210 8189900

Latvija

Biocodex SIA

Tel: + 371 67 619365

This leaflet was last revised in MM/YYYY.

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

Package leaflet: Information for the patient

Xtandi 40 mg film-coated tablets

Xtandi 80 mg film-coated tablets

enzalutamide

Read all of this leaflet carefully before you start taking 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.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – 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 Xtandi is and what it is used for

• 2. What you need to know before you take Xtandi

• 3. How to take Xtandi

• 4. Possible side effects

• 5. How to store Xtandi

• 6. Contents of the pack and other information

1. What Xtandi is and what it is used for

Xtandi contains the active substance enzalutamide. Xtandi is used to treat adult men with prostate cancer that:

• – No longer responds to a hormone therapy or surgical treatment to lower testosterone

Or

• – Has spread to other parts of the body and responds to a hormone therapy or surgical treatment to lower testosterone.

How Xtandi works

Xtandi is a medicine that works by blocking the activity of hormones called androgens (such as testosterone). By blocking androgens, enzalutamide stops prostate cancer cells from growing and dividing.

2. What you need to know before you take Xtandi

Do not take Xtandi

• – If you are allergic to enzalutamide or any of the other ingredients of this medicine (listed in section 6).

• – If you are pregnant or may become pregnant (see ‘Pregnancy, breast-feeding and fertility’)

Warnings and precautions

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and fewer than one in every 1,000 people taking placebo (see ‘Other medicines and Xtandi’ below and section 4 ‘Possible side effects’).

If you are taking a medicine that can cause seizures or that can increase the susceptibility for having seizures (see ‘Other medicines and Xtandi’ below)

If you have a seizure during treatment:

See your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior reversible encephalopathy syndrome (PRES)

There have been rare reports of PRES, a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible. (See also section 4 ‘Possible side effects’).

Risk of new cancers (second primary malignancies)

There have been reports of new (second) cancers including cancer of the bladder and colon in patients treated with Xtandi.

See your doctor as soon as possible if you notice signs of gastrointestinal bleeding, blood in the urine, or frequently feel an urgent need to urinate when taking Xtandi.

Talk to your doctor before taking Xtandi

• – If you are taking any medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)

• – If you use chemotherapy like docetaxel

• – If you have problems with your liver

• – If you have problems with your kidneys

Please tell your doctor if you have any of the following:

Any heart or blood vessel conditions, including heart rhythm problems (arrhythmia), or are being treated with medicines for these conditions. The risk of heart rhythm problems may be increased when using Xtandi.

If you are allergic to enzalutamide, this may result in a rash or swelling of the face, tongue, lip or throat. If you are allergic to enzalutamide or any of the other ingredients of this medicine, do not take Xtandi.

Severe skin rash or skin peeling, blistering and/or mouth sores have been reported in association with Xtandi treatment. Seek medical attention immediately if you notice any of these symptoms.

If any of the above applies to you or you are not sure, talk to your doctor before taking this medicine.

Children and adolescents

This medicine is not for use in children and adolescents.

Other medicines and Xtandi

Tell your doctor if you are taking, have recently taken or might take any other medicines. You need to know the names of the medicines you take. Keep a list of them with you to show to your doctor when you are prescribed a new medicine. You should not start or stop taking any medicine before you talk with the doctor that prescribed Xtandi.

Tell your doctor if you are taking any of the following medicines. When taken at the same time as Xtandi, these medicines may increase the risk of a seizure:

• – Certain medicines used to treat asthma and other respiratory diseases (e.g. aminophylline, theophylline).

• – Medicines used to treat certain psychiatric disorders such as depression and schizophrenia (e.g. clozapine, olanzapine, risperidone, ziprasidone, bupropion, lithium, chlorpromazine, mesoridazine, thioridazine, amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).

• – Certain medicines for the treatment of pain (e.g. pethidine).

Tell your doctor if you are taking the following medicines. These medicines may influence the effect of Xtandi, or Xtandi may influence the effect of these medicines.

This includes certain medicines used to:

• – Lower cholesterol (e.g. gemfibrozil, atorvastatin, simvastatin)

• – Treat pain (e.g. fentanyl, tramadol)

• – Treat cancer (e.g. cabazitaxel)

• – Treat epilepsy (e.g. carbamazepine, clonazepam, phenytoin, primidone, valproic acid)

• – Treat certain psychiatric disorders such as severe anxiety or schizophrenia (e.g. diazepam,

midazolam, haloperidol)

• – Treat sleep disorders (e.g. zolpidem)

• – Treat heart conditions or lower blood pressure (e.g. bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)

• – Treat serious disease related to inflammation (e.g. dexamethasone, prednisolone)

• – Treat HIV infection (e.g. indinavir, ritonavir)

• – Treat bacterial infections (e.g. clarithromycin, doxycycline)

• – Treat thyroid disorders (e.g. levothyroxine)

• – Treat gout (e.g. colchicine)

• – Treat stomach disorders (e.g. omeprazole)

• – Prevent heart conditions or strokes (e.g. dabigatran etexilate)

• – Prevent organ rejection (e.g. tacrolimus)

Xtandi might interfere with some medicines used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone and sotalol) or might increase the risk of heart rhythm problems when used with some other medicines (e.g. methadone, used for pain relief and part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious mental illnesses).

Tell your doctor if you are taking any of the medicines listed above. The dose of Xtandi or any other medicines that you are taking may need to be changed.

Pregnancy, breast-feeding and fertility

• - Xtandi is not for use in women. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It must not be taken by women who are pregnant, may become pregnant, or who are breast-feeding.

• – This medicine could possibly have an effect on male fertility.

• – If you are having sex with a woman who can become pregnant, use a condom and another effective birth control method, during treatment and for 3 months after treatment with this medicine. If you are having sex with a pregnant woman, use a condom to protect the unborn child.

• – Female caregivers see section 3 ‘How to take Xtandi’ for handling and use.

Driving and using machines

Xtandi may have moderate influence on the ability to drive and use machines. Seizures have been reported in patients taking Xtandi. If you are at higher risk of seizures, talk to your doctor.

3. How to take Xtandi

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

The usual dose is 160 mg (four 40 mg film-coated tablets or two 80 mg film-coated tablets), taken at the same time once a day.

Taking Xtandi

• – Swallow the tablets whole with water.

• – Do not cut, crush or chew the tablets before swallowing.

• – Xtandi can be taken with or without food.

Xtandi should not be handled by persons other than the patient or his caregivers. Women who are or may become pregnant should not handle broken or damaged Xtandi tablets without wearing protection like gloves.

Your doctor may also prescribe other medicines while you are taking Xtandi.

If you take more Xtandi than you should

If you take more tablets than prescribed, stop taking Xtandi and contact your doctor. You may have an increased risk of seizure or other side effects.

If you forget to take Xtandi

• – If you forget to take Xtandi at the usual time, take your usual dose as soon as you remember.

• – If you forget to take Xtandi for the whole day, take your usual dose the following day.

• – If you forget to take Xtandi for more than one day, talk to your doctor immediately.

• - Do not take a double dose to make up for the dose you forgot.

If you stop taking Xtandi

Do not stop taking this medicine unless your doctor tells you to.

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

4. Possible side effects

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

Seizures

Seizures were reported in 5 in every 1,000 people taking Xtandi, and in fewer than one in every 1,000 people taking placebo.

Seizures are more likely if you take more than the recommended dose of this medicine, if you take certain other medicines, or if you are at higher than usual risk of seizure.

If you have a seizure , see your doctor as soon as possible. Your doctor may decide that you should stop taking Xtandi.

Posterior Reversible Encephalopathy Syndrome (PRES)

There have been rare reports of PRES (may affect up to 1 in 1,000 people), a rare, reversible condition involving the brain, in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness or other vision problems, please contact your doctor as soon as possible.

Other possible side effects include:

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

Tiredness, fall, broken bones, hot flushes, high blood pressure

Common (may affect up to 1 in 10 people)

Headache, feeling anxious, dry skin, itching, difficulty remembering, blockage of the arteries in the heart (ischemic heart disease), breast enlargement in men (gynaecomastia), symptom of restless legs syndrome (an uncontrollable urge to move a part of the body, usually the leg), reduced concentration, forgetfulness, change in sense of taste

Uncommon ( may affect up to 1 in 100 people)

Hallucinations, difficulty thinking clearly, low white blood cell count

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

Muscle pain, muscle spasms, muscular weakness, back pain, changes in ECG (QT prolongation), upset stomach including feeling sick (nausea), rash, being sick (vomiting), swelling of the face, lips, tongue and/or throat, reduction in blood platelets (which increases risk of bleeding or bruising), diarrhoea

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 Xtandi

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 cardboard wallet and outer carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Xtandi contains

The active substance is enzalutamide.

Each Xtandi 40 mg film-coated tablet contains 40 mg of enzalutamide.

Each Xtandi 80 mg film-coated tablet contains 80 mg of enzalutamide.

The other ingredients of the film-coated tablets are:

• Tablet core: Hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate.
• Tablet coating: Hypromellose, talc, macrogol 8000, titanium dioxide (E171), yellow iron oxide (E172).