XTANDI 40 mg FILM-COATED TABLETS

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 have been reported in 6 out of 1,000 people taking Xtandi, and in less than 3 out of 1,000 people taking placebo (see “Other medicines and Xtandi” below and “Possible side effects” in section 4).

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

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 disease that affects the brain, 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 section 4 “Possible side effects”).

Risk of new cancers (second primary malignancies)

Reports of new (second) cancers have been received 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 frequently feel an 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 more frequently observed 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 Xtandi

• If you have ever developed severe skin rash or skin peeling, blistering, and/or ulcers in the mouth 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

Tell your doctor if you have:

Any heart or blood vessel disorder, including heart rhythm problems (arrhythmias), or if you are being treated with medicines to correct these disorders. The risk of heart rhythm problems may be increased with the use of Xtandi.

If you are allergic to enzalutamide, its administration could cause a rash or swelling of the face, tongue, lips, 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 ulcers in the mouth, including Stevens-Johnson syndrome, have been reported in association 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 section 4.

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

Children and adolescents

This medicine must not be administered to children or 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 are taking. Carry a list of these with you to show your doctor when you are prescribed a new medicine. Do not start or stop taking any medicine before consulting the doctor who prescribed Xtandi.

Tell your doctor if you are taking any of the following medicines. These medicines may increase the risk of having a seizure when taken with Xtandi:

• 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 pain treatment (e.g., pethidine).

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

This includes certain medicines used for:

• Lowering cholesterol (e.g., gemfibrozil, atorvastatin, simvastatin)
• Treating pain (e.g., fentanyl, tramadol)
• Treating cancer (e.g., cabazitaxel)
• Treating epilepsy (e.g., carbamazepine, clonazepam, phenytoin, primidone, valproic acid)
• Treating certain psychiatric disorders such as severe anxiety or schizophrenia (e.g., diazepam, midazolam, haloperidol)
• Treating sleep disorders (e.g., zolpidem)
• Treating heart problems or lowering blood pressure (e.g., bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)
• Treating severe inflammatory diseases (e.g., dexamethasone, prednisolone)
• Treating HIV infection (e.g., indinavir, ritonavir)
• Treating bacterial infections (e.g., clarithromycin, doxycycline)
• Treating thyroid disorders (e.g., levothyroxine)
• Treating gout (e.g., colchicine)
• Treating stomach disorders (e.g., omeprazole)
• Preventing heart problems or stroke (e.g., dabigatran etexilate)
• Preventing organ rejection (e.g., tacrolimus)

Xtandi may interfere with some medicines used to treat heart rhythm problems (e.g., quinidine, procainamide, amiodarone, and sotalol) or may increase the risk of heart 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]).

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

Pregnancy, breast-feeding and fertility

• Xtandi is not indicated in women. This medicine may be harmful to the fetus or may cause abortion if taken by a pregnant woman. It must not be administered to pregnant women, women who may become pregnant, or women who are breast-feeding.
• This medicine may affect male fertility.
• If you have sex with a woman of childbearing age, you must use a condom and another effective contraceptive method during treatment and for 3 months after treatment with this medicine. If you have sex with a pregnant woman, you must use a condom to protect the fetus.
• In the case of female caregivers, see section 3 “How to take Xtandi” for handling and use recommendations.

Driving and using machines

The influence of Xtandi on the ability to drive and use machines may be moderate. Seizures have been reported in patients who have taken Xtandi. If you are at a higher risk of having seizures, you should consult your doctor.

Xtandi contains sodium

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

3. How to take Xtandi

Follow exactly the instructions of administration of this medicine given by your doctor. In case of doubt, consult your doctor again.

The recommended 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.

How to take Xtandi

• Swallow the tablets whole with a sufficient amount of water.
• Do not split, 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 pregnant should not handle broken or damaged Xtandi tablets without protection (e.g., gloves).

It is also possible that your doctor will 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 a higher risk of having a seizure or other side 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 for the whole day, take the usual dose the next day.
• If you forget to take Xtandi for more than one day, consult your doctor immediately.
• Do not take a double doseto make up for forgotten doses.

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 have been reported in 6 out of 1,000 people taking Xtandi, and in less than 3 out of 1,000 people taking placebo.

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

Posterior Reversible Encephalopathy Syndrome (PRES)

Rare cases of PRES (affecting up to 1 in 1,000 people), a rare, reversible disease that affects the brain, 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.

Other possible side effects are:

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

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

Common(may affect up to 1 in 10 people)

Headache, feeling anxious, dry skin, itching, difficulty remembering, blockage of heart arteries (ischemic heart disease), increase in breast size in men (gynecomastia), nipple pain, breast tenderness, restless legs syndrome (an uncontrollable urge to move a part of the body, usually the legs), lack of concentration, memory loss, change in taste, difficulty thinking clearly

Uncommon(may affect up to 1 in 100 people)

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

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

Muscle pain, muscle spasms, muscle weakness, back pain, changes in the electrocardiogram (QT interval prolongation), difficulty swallowing this medicine, including choking, stomach upset, including feeling sick (nausea), a skin reaction that causes red spots or patches on the skin, which may look like a target or a “bull’s eye” with a red center surrounded by pale red rings (erythema multiforme), or other severe skin reaction with red patches, not raised, target-like or circular patches on the trunk, often with central blisters, skin peeling, mouth ulcers, throat ulcers, genital ulcers, and eye ulcers that may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), rash, vomiting, swelling of the face, lips, tongue, and/or throat, decrease in platelet count in the blood (which increases the risk of bleeding or bruising), diarrhea, decreased appetite

Reporting of side effects

If you experience any side effects, talk to your doctor, even if it is possible that they are 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.

5. Storage of 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 carton and on the blister pack after “EXP”. The expiry date refers to the last day of the month shown.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Xtandi Composition

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

Product Appearance and Packaging Contents

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

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

Marketing Authorization Holder

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Manufacturer

Delpharm Meppel B.V.

Hogemaat 2

7942 JG Meppel

Netherlands

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:MM/AAAA.

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