Xtandi 40 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Xtandi 40 mg film-coated tablets

Xtandi 80 mg film-coated tablets

enzalutamide

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Xtandi is and what it is used for
2. What you need to know before taking 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 has stopped responding to hormonal therapy or surgical treatment to reduce testosterone

Or

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

Or

• Who have previously undergone prostatectomy or radiation and have a rapid rise in PSA, but whose cancer has not spread to other parts of the body and still responds to hormonal therapy to reduce testosterone

How Xtandi works

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

2. What you need to know before taking Xtandi

Do not take Xtandi

• If you are allergic to enzalutamide or to any of the other ingredients of this medicine (listed in section 6)
• If you are pregnant or could become pregnant (see “Pregnancy, breastfeeding and fertility”)

Warnings and precautions

Seizures

Seizures have been reported in 6 out of 1,000 people taking Xtandi, and in fewer 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 increase the risk of having seizures (see “Other medicines and Xtandi” below).

If you experience a seizure during treatment:

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

Reversible posterior encephalopathy syndrome (RPES)

Rare cases of RPES, a rare, reversible brain disorder, have been reported in patients treated with Xtandi. If you have a seizure, worsening headache, confusion, blindness, or other vision problems, contact your doctor immediately. (See also section 4 “Possible side effects”).

Risk of new cancers (secondary primary malignancies)

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

Contact your doctor immediately if you notice any signs of gastrointestinal bleeding, blood in the urine, or frequently feel a strong urge to urinate while taking Xtandi.

Swallowing difficulty related to product formulation

Cases of patients experiencing difficulty swallowing this medicine, including choking incidents, have been reported. Swallowing difficulties and choking episodes were observed more frequently in patients receiving capsules, which may be related to the larger size of the product. Swallow the tablets whole with sufficient water.

Talk to your doctor before starting Xtandi

• If you have ever developed severe skin rashes, skin peeling, blistering, and/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

Tell your doctor if you have:

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

If you are allergic to enzalutamide, taking it could cause a rash or swelling of the face, tongue, lips, or throat. Do not take Xtandi if you are allergic to enzalutamide or to any of the other ingredients of this medicine.

Severe skin rashes, skin peeling, blistering, and/or mouth ulcers, including Stevens-Johnson syndrome, have been reported with Xtandi treatment. Stop using Xtandi and seek immediate medical attention if you notice any symptoms related to these serious skin reactions described in section 4.

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 must not be given to children or adolescents.

Other medicines and Xtandi

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines. You should know the names of all medicines you are taking. Keep a list with you to show your doctor when prescribed a new medicine. Do not start or stop taking any medicine without first 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 together 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 pain medicines (e.g. meperidine)

Tell your doctor if you are taking any of the following medicines. These medicines may affect the action of Xtandi, or Xtandi may affect the action 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 serious inflammatory conditions (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 certain medicines used to treat heart rhythm problems (e.g. quinidine, procainamide, amiodarone, 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 serious mental illnesses]).

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

Pregnancy, breastfeeding and fertility

• Xtandi is not intended for use in women. This medicine may harm the fetus or cause miscarriage if taken by a pregnant woman. It must not be given to pregnant women, women who could become pregnant, or women who are breastfeeding.
• This medicine may affect male fertility.
• If you have sexual intercourse 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 sexual intercourse with a pregnant woman, you must use a condom to protect the fetus.
• For female caregivers, see section 3 “How to take Xtandi” for handling and use recommendations.

Driving and using machines

The effect of Xtandi on the ability to drive and use machines may be moderate. Seizures have been reported in patients taking Xtandi. If you are at increased risk of seizures, you should consult your doctor.

Xtandi contains sodium

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

3. How to take Xtandi

Follow exactly the instructions for using this medicine given by your doctor. If in 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 daily.

How to take Xtandi

• Swallow the tablets whole with sufficient 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).

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 an increased risk of experiencing a seizure or other adverse effects.

If you forget to take Xtandi

• If you forget to take Xtandi at your usual time, take the usual dose as soon as you remember.
• If you forget to take Xtandi for the entire 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 dose to make up for forgotten doses.

If you stop taking Xtandi

Do not stop taking this medicine unless instructed by your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences 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 placebo.

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

If you have a seizure, contact 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 (may affect up to 1 in 1,000 people) have been reported, a rare, reversible condition affecting the brain, in patients treated with Xtandi. If you experience a seizure, worsening headache, confusion, blindness, or other vision problems, contact your doctor immediately.

Other possible adverse effects are:

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

Headache, fatigue, falls, bone fractures, hot flushes, high blood pressure

Common (may affect up to 1 in 10 people)

Feeling anxious, dry skin, itching, difficulty remembering, blockage of the heart arteries (ischaemic heart disease), enlargement of the breast in men (gynaecomastia), breast tenderness, pain when touching the breast, symptoms of restless legs syndrome (uncontrollable need to move part of the body, usually the legs), difficulty concentrating, forgetfulness, change in taste sensation, difficulty thinking clearly

Uncommon (may affect up to 1 in 100 people)

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

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

Muscle pain, muscle spasms, muscle weakness, back pain, changes in electrocardiogram (prolongation of QT interval), difficulty swallowing this medicine including choking, stomach discomfort including feeling dizzy (nausea), a skin reaction causing red spots or patches on the skin which may look like a target or "bull's eye" with a dark red center surrounded by paler red rings (erythema multiforme), or another serious skin reaction presenting as flat, reddish, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital, and eye ulcers which may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), rash, vomiting, swelling of the face, lips, tongue and/or throat, decreased number of platelets in the blood (which increases the risk of bleeding or bruising), diarrhoea, decreased appetite

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 stated on the cardboard pocket pack and on the outer container, following “EXP”. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Xtandi

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 components of the film-coated tablets are:

• Tablet core: hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, sodium croscarmellose, magnesium stearate.
• Tablet coating: hypromellose, talc, macrogol 8000, titanium dioxide (E 171), yellow iron oxide (E 172).

Appearance of the product and contents of the pack

Xtandi 40 mg film-coated tablets are film-coated, round, yellow tablets, marked with “E 40”. Each pack contains 112 tablets in 4 blisters, presented in pocket packs containing 28 tablets each.

Xtandi 80 mg film-coated tablets are film-coated, oval, yellow tablets, marked with “E 80”. Each pack contains 56 tablets in 4 blisters, presented in pocket packs containing 14 tablets each.

Marketing Authorisation Holder

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

The Netherlands

Manufacturer

Delpharm Meppel B.V.

Hogemaat 2

7942 JG Meppel

The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: MM/YYYY.

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