Package Insert: Information for the Patient

Xtandi 40mg Film-Coated Tablets

Xtandi 80mg Film-Coated Tablets

enzalutamida

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor.
• This medication has been prescribed to you alone, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this package insert. See section4.

Xtandi contains the active ingredient enzalutamida. Xtandi is used to treat adult men with prostate cancer :

• That has stopped responding to hormone therapy or surgical treatment to reduce testosterone

Or

• That has spread to other parts of the body and responds to hormone therapy or surgical treatment to reduce testosterone

Or

• That have undergone prior prostate removal or radiation and have a rapid increase in PSA, but the cancer has not spread to other parts of the body and responds to hormone therapy to reduce testosterone

How Xtandi works

Xtandi is a medication that acts by blocking the activity of certain hormones called androgens (such as testosterone). By blocking androgens, enzalutamida causes prostate cancer cells to stop growing and dividing.

Do not take Xtandi

• If you are allergic to enzalutamide or any of the other ingredients of this medicine (including those listed in section6)
• If you are pregnant or may become pregnant (see “Pregnancy, breastfeeding and fertility”)

Warnings and precautions

Seizures

Seizures have been reported in 6 of every 1000people taking Xtandi, and in fewer than 3 of every 1000people taking placebo (see “Other medicines and Xtandi” later and “Possible side effects” in section4).

If you are taking a medicine that can cause seizures or that can increase the risk of seizures (see “Other medicines and Xtandi” later).

If you have a seizure during treatment:

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

Posterior reversible encephalopathy syndrome (PRES)

Rare cases of PRES, a rare, reversible brain disease, have been reported in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness, or other vision problems, contact your doctor as soon as possible. (See also section4 “Possible side effects”).

Risk of new cancers (primary secondary malignancies)

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

Consult your doctor as soon as possible if you notice any signs of gastrointestinal bleeding, blood in the urine, or feel a frequent urgent need to urinate while taking Xtandi.

Difficulty swallowing related to the product formulation

Cases of patients who have experienced difficulty swallowing this medicine, including cases of choking, have been reported. Difficulty swallowing and choking episodes were observed more frequently in patients receiving capsules, which may be related to a larger product size. Swallow the tablets whole with a sufficient amount of water.

Consult your doctor before starting to take Xtandi

• If you have ever developed severe skin eruptions or skin peeling, blistering, or mouth ulcers after taking Xtandi or other medicines
• If you are taking medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)
• If you are receiving chemotherapy, such as docetaxel
• If you have liver problems
• If you have kidney problems

Inform your doctor if you have:

Any cardiac or vascular alteration, including arrhythmias, or if you are being treated with medicines to correct these alterations. The risk of arrhythmias may be increased with the use of Xtandi.

If you are allergic to enzalutamide, its administration may cause a rash or facial, tongue, lip, or throat inflammation. If you are allergic to enzalutamide or any of the other ingredients of this medicine, do not take Xtandi.

Severe skin eruptions or skin peeling, blistering, or mouth ulcers, including Stevens-Johnson syndrome, have been associated with Xtandi treatment. Stop using Xtandi and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section4.

If any of the above applies to you or if you are unsure, consult your doctor before taking this medicine.

Children and adolescents

This medicine should not be administered to children or adolescents.

Other medicines and Xtandi

Inform your doctor if you are taking, have taken recently, or may need to take any other medicine. You need to know the names of the medicines you are taking. Bring a list of these with you to show your doctor when they prescribe a new medicine. Do not start or stop taking any medicine before consulting the doctor who prescribed Xtandi.

Inform your doctor if you are taking any of the following medicines. These medicines may increase the risk of seizures when taken with Xtandi:

• Determined 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)
• Determined medicines for pain treatment (e.g. pethidine)

Inform 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 determined medicines used to:

• Reduce 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 cardiac problems or reduce blood pressure (e.g. bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)
• Treat severe inflammatory diseases (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 cardiac problems or stroke (e.g. dabigatran etexilate)
• Prevent organ rejection (e.g. tacrolimus)

Xtandi may interfere with some medicines used to treat cardiac rhythm problems (e.g. quinidine, procainamide, amiodarone, and sotalol) or may increase the risk of cardiac rhythm problems when used with certain medicines (e.g. methadone [used for pain relief and as part of drug detoxification], moxifloxacin [an antibiotic], antipsychotics [used for severe mental illnesses]).

Inform your doctor if you are taking any of the medicines mentioned above. It may be necessary to modify the dose of Xtandi or any other medicine you are taking.

Pregnancy, breastfeeding and fertility

• Xtandi is not indicated in women. This medicine may be harmful to the fetus or maycause a miscarriage if taken by a pregnant woman. It should not be administered to women who are pregnant, may become pregnant, or are breastfeeding.
• This medicine may affect male fertility.
• If you have sex with a fertile woman, you should use a condom and another effective contraceptive method during treatment and for 3months after treatment with this medicine. If you have sex with a pregnant woman, you should use a condom to protect the fetus.
• For women caregivers, see section3 “How to take Xtandi” for handling and use recommendations.

Driving and operating machines

The influence of Xtandi on the ability to drive and operate machines may be moderate. Seizures have been reported in patients taking Xtandi. If you have a higher risk of seizures, consult your doctor.

Xtandi contains sodium

This medicine contains less than 1mmol of sodium (23mg) per coated tablet; this is, essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

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

How to Take Xtandi

• Swallow the tablets whole with a sufficient amount of water.
• Do not break, crush, or chew the tablets before swallowing.
• Xtandi can be taken with or without food.
• Xtandi should not be handled by anyone other than the patient or their caregivers. Pregnant women or women who may become pregnantshould not handle Xtandi without protection (e.g., gloves) broken or damaged tablets.

Your doctor may also prescribe other medications 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 a higher risk of experiencing a seizure or other adverse effects.

If You Forget to Take Xtandi

• If you forget to take Xtandi at the usual time, take the usual dose as soon as you remember.
• If you forget to take Xtandi all day, take the usual dose the next day.
• If you forget to take Xtandi for more than a day, consult your doctor immediately.
• Do Not Take a Double Doseto make up for missed doses.

If You Stop Taking Xtandi

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

If you have any other questions about the use of this medication, ask your doctor.

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

Seizures

Seizures have been reported in 6 out of every 1,000 people taking Xtandi, and in fewer than 3 out of every 1,000 people taking a placebo.

Seizures are more likely if you take a higher dose of this medicine than recommended, if you take certain medicines, or if you have a higher risk than usual of having a seizure.

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

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

RPLS, a rare, reversible brain disease, has been reported in rare cases (may affect up to 1 in 1,000 people), in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness, or other vision problems, contact your doctor as soon as possible.

Other possible side effects are:

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

Fatigue, falls, bone fractures, hot flashes, high blood pressure

Common(may affect up to 1 in 10 people)

Headache, feeling anxious, dry skin, itching, difficulty remembering, blockage of the heart's arteries (ischemic heart disease), enlargement of the breast in men (gynecomastia), nipple pain, breast tenderness, symptom of restless legs syndrome (involuntary need to move a part of the body, usually the legs), loss of concentration, forgetfulness, change in sense of taste, difficulty thinking clearly

Uncommon(may affect up to 1 in 100 people)

Hallucinations, low white blood cell count, elevated liver enzyme levels in blood tests (a sign of liver problems)

Frequency not known(the frequency cannot be estimated from the available data)

Muscle pain, muscle spasms, muscle weakness, back pain, changes in the electrocardiogram (prolongation of the QT interval),difficulty swallowing this medicine including choking,stomach discomfort including feeling queasy (nausea),a skin reaction that causes red spots or patches on the skin, which may appear as a target or a "bull's eye" with a dark red center surrounded by lighter red rings (erythema multiforme) or another severe skin reaction that presents flat, red patches, often with central blisters, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes that may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome),eruption, vomiting, facial swelling, lips, tongue, and/or throat swelling, decrease in the number of platelets in the blood (which increases the risk of bleeding or hematoma), diarrhea, decreased appetite

Reporting of side effects

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

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

Do not use this medication after the expiration date that appears on the carton pocket pouch and on the outer packaging after “CAD”. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Xtandi Composition

The active ingredient is enzalutamide.

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

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

The other components of the film-coated tablets are:

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

Appearance of the product and contents of the pack

Xtandi 40 mg film-coated tablets are yellow, round, film-coated tablets with the engraving “E 40”. Each pack contains 112 tablets in 4 blisters in pocket-sized boxes of 28 tablets each.

Xtandi 80 mg film-coated tablets are yellow, oval, film-coated tablets with the engraving “E 80”. Each pack contains 56 tablets in 4 blisters in pocket-sized boxes of 14 tablets each.

Marketing Authorization Holder

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Responsible Person

Delpharm Meppel B.V.

Hogemaat 2

7942 JG Meppel

Netherlands

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

Last update of the summary of product characteristics:MM/YYYY.

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