Enzalutamide Zentiva

Patient Information Leaflet

Enzalutamide Zentiva 40 mg film-coated tablets, 80 mg film-coated tablets

Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What Enzalutamide Zentiva is and what it is used for

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

• That no longer responds 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
• For patients who have previously undergone prostate removal or radiotherapy and have a rapidly rising PSA, but whose cancer has not spread to other parts of the body and still responds to hormonal therapy to reduce testosterone.

How Enzalutamide Zentiva works
Enzalutamide Zentiva is a medicine that works by blocking the activity of hormones called androgens (such as testosterone). By blocking androgens, enzalutamide stops the growth and division of prostate cancer cells.

2. What you need to know before taking Enzalutamide Zentiva

Do not take Enzalutamide Zentiva

• 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 may become pregnant (see "Pregnancy, breast-feeding and fertility")

Warnings and precautions
Seizures
Seizure events have been reported in 6 out of 1,000 patients treated with enzalutamide and in fewer than 3 out of 1,000 patients treated with placebo (see "Other medicines and Enzalutamide Zentiva" below and section 4, "Possible side effects").
If you are taking a medicine that may cause seizures or increase the risk of seizures (see "Other medicines and Enzalutamide Zentiva" below).
If you experience a seizure during treatment:
Contact your doctor as soon as possible. Your doctor may decide that you should stop taking Enzalutamide Zentiva.

Reversible posterior encephalopathy syndrome (PRES)
Rare cases of PRES, a rare reversible condition affecting the brain, have been reported in patients treated with enzalutamide. If you experience seizures, worsening headache, confusion, blindness, or other vision problems, contact your doctor immediately (see also section 4, "Possible side effects").

Risk of new tumours (secondary primary tumours)
New (secondary) tumours, including bladder and colon cancer, have been reported in patients treated with enzalutamide.
Contact your doctor as soon as possible if you notice signs of gastrointestinal bleeding, blood in your urine, or if you frequently feel a strong urge to urinate while taking Enzalutamide Zentiva.

Swallowing difficulties related to the product formulation
Cases of patients experiencing difficulty swallowing other enzalutamide-containing products, including choking incidents, have been reported. Swallowing difficulties and choking incidents were more commonly observed in patients taking capsules and may be related to the larger size of the product. Swallow the tablets whole with sufficient water.

Talk to your doctor before taking Enzalutamide Zentiva:

• If you have previously developed a severe skin rash or skin peeling, blisters, and/or mouth ulcers after taking Enzalutamide Zentiva or other medicines
• If you are taking medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)
• If you are using a chemotherapy drug such as docetaxel
• If you have liver problems
• If you have kidney problems

Tell your doctor if you have any of the following conditions:
Any heart or blood vessel disorder, including heart rhythm problems (arrhythmias), or if you are being treated with medicines for these conditions. The risk of heart rhythm problems may increase with the use of Enzalutamide Zentiva.
If you are allergic to enzalutamide, you may develop skin rashes or swelling of the face, tongue, lips, or throat. If you are allergic to enzalutamide or to any of the other ingredients of this medicine, do not take Enzalutamide Zentiva.
Severe skin rash, skin peeling, blisters, and/or mouth ulcers, including Stevens-Johnson syndrome, have been reported in association with Enzalutamide Zentiva treatment. Stop using Enzalutamide Zentiva and contact your doctor immediately if you notice any of the symptoms associated with these serious skin reactions described in section 4.
If you are in any of the conditions listed above or if you are unsure, consult your doctor before taking this medicine.

Children and adolescents
This medicine must not be used in children and adolescents.

Other medicines and Enzalutamide Zentiva
Tell your doctor if you are taking, have recently taken, or might take any other medicines. You should know the names of the medicines you are taking. Keep a list of them to show your doctor when you are prescribed a new medicine. Do not start or stop any treatment without first discussing it with the doctor who prescribed Enzalutamide Zentiva.

Tell your doctor if you are taking any of the following medicines. When taken together with Enzalutamide Zentiva, these medicines may increase the risk of seizures:

• Some 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)
• Some medicines used to treat pain (e.g. meperidine)

Tell your doctor if you are taking any of the following medicines. These medicines may affect the action of Enzalutamide Zentiva, or Enzalutamide Zentiva may affect their action. Examples include 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, valproate)
• 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 severe inflammatory conditions (e.g. dexamethasone, prednisolone)
• Treat HIV infections (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 disease or stroke (e.g. dabigatran etexilate)
• Prevent organ rejection (e.g. tacrolimus)

Enzalutamide Zentiva 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 together with certain other medicines [e.g. methadone (used to relieve pain and in drug detoxification programs), moxifloxacin (an antibiotic), antipsychotics (used for severe mental illnesses)].
Inform your doctor if you are taking any of the medicines listed above. It may be necessary to adjust the dose of Enzalutamide Zentiva or of any other medicine you are taking.

Pregnancy, breast-feeding and fertility

• Enzalutamide Zentiva is not indicated for use in women. This medicine may cause harm to the unborn child or potential pregnancy loss if taken by pregnant women. It must not be taken by women who are pregnant, who may become pregnant, or who are breast-feeding.
• This medicine may affect male fertility.
• If you have sexual intercourse with a woman who may become pregnant, use a condom and another effective contraceptive method during treatment and for 3 months after stopping treatment. If you have sexual intercourse with a pregnant woman, use a condom to protect the unborn child.
• If the patient is being cared for by a woman, see section 3 “How to take Enzalutamide Zentiva” for instructions on use and handling.

Driving and using machines
Enzalutamide Zentiva may have a moderate effect on the ability to drive and use machines. Seizures have been reported in patients taking Enzalutamide Zentiva. If you are at high risk of seizures, discuss this with your doctor.

Enzalutamide Zentiva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to take Enzalutamide Zentiva

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.

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

Administration of Enzalutamide Zentiva

• Swallow the tablets whole with a sufficient amount of water.
• Do not cut, crush, or chew the tablets before swallowing.
• Enzalutamide Zentiva may be taken with or without food.
• Enzalutamide Zentiva must not be handled by anyone other than the patient or their caregiver. Women who are pregnant or who could become pregnant must not handle broken or damaged Enzalutamide Zentiva tablets without wearing protective gloves.

Your doctor may prescribe other medicines to be taken during treatment with Enzalutamide Zentiva.

If you take more Enzalutamide Zentiva than you should
If you take more tablets than prescribed, stop taking Enzalutamide Zentiva and contact your doctor immediately. You may be at an increased risk of seizures or other adverse effects.

If you forget to take Enzalutamide Zentiva

• If you forget to take Enzalutamide Zentiva at your usual time, take your usual dose as soon as you remember.
• If you forget to take Enzalutamide Zentiva for an entire day, take your usual dose the next day.
• If you forget to take Enzalutamide Zentiva for more than one day, speak to your doctor immediately.
• Do not take a double dose to make up for a missed dose.

If you stop taking Enzalutamide Zentiva
Do not stop taking this medicine unless instructed by your doctor.
If you have any questions about how to use this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Seizures
Seizures have been reported in 6 out of 1,000 people treated with Enzalutamide Zentiva and in fewer than 3 out of 1,000 people treated with placebo.
The risk of seizures is higher if you take a dose of this medicine higher than recommended, if you take other medicines, or if you have a higher-than-normal risk of seizures.
If you experience a seizure, contact your doctor as soon as possible. Your doctor may decide that you should stop treatment with Enzalutamide Zentiva.
Reversible posterior encephalopathy syndrome (PRES)
Rare cases of PRES (may affect up to 1 in 1,000 patients) have been reported in patients treated with Enzalutamide Zentiva. PRES is a rare, reversible condition affecting the brain. If you have seizures, worsening headache, confusion, blindness, or other vision problems, contact your doctor immediately.
Other possible side effects include:
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
• Anxiety
• Dry skin
• Itching
• Memory disturbances
• Blockage of the heart's arteries (ischaemic heart disease)
• Enlargement of the breasts in men (gynaecomastia)
• Nipple pain
• Breast tenderness
• Symptoms of restless legs syndrome (uncontrollable urge to move part of the body, usually the legs)
• Reduced concentration
• Forgetfulness
• Altered sense of 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)

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

• Muscle pain
• Muscle cramps
• Muscle weakness
• Back pain
• Changes in electrocardiogram (ECG) (QT prolongation)
• Difficulty swallowing this medicine, including choking
• Stomach discomfort, including feeling unwell (nausea)
• Skin reaction causing red spots or patches on the skin that may look like a target or "bull's eye", with a dark red centre surrounded by rings of lighter red (erythema multiforme), or another serious skin reaction presenting as flat reddish spots on the trunk, resembling targets or circular lesions, often with central blisters, skin peeling, mouth, throat, nose, genital, or eye ulcers, which may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome)
• Rash
• Feeling unwell (vomiting)
• Swelling of the face, lips, tongue, and/or throat
• Reduced number of platelets in the blood (increased risk of bleeding or bruising)
• Diarrhoea
• Reduced appetite

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Enzalutamide Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard outer and
on the carton after Exp. The expiry date refers to the last day of that month.
Enzalutamide Zentiva 40 mg film-coated tablets
PVC/PCTFE/PVC//Al, PVC/PE/PVDC//Al
This medicine does not require any special storage conditions.
Enzalutamide Zentiva 80 mg film-coated tablets
PVC/PCTFE/PVC//Al
This medicine does not require any special storage conditions.
PVC/PE/PVDC//Al
Do not store above 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information What Enzalutamide Zentiva contains

• The active substance is enzalutamide. Each Enzalutamide Zentiva 40 mg film-coated tablet contains 40 mg of enzalutamide. Each Enzalutamide Zentiva 80 mg film-coated tablet contains 80 mg of enzalutamide.
• The other components are:

Tablet core:
Microcrystalline cellulose
Sodium croscarmellose
Hypromellose phthalate
Sodium lauryl sulfate
Low-substituted hydroxypropyl cellulose
Colloidal silicon dioxide
Magnesium stearate
Tablet coating:
Hypromellose (E 464)
Titanium dioxide (E 171)
Macrogol
Yellow iron oxide (E 172)

Description of the appearance of Enzalutamide Zentiva and package contents
Enzalutamide Zentiva 40 mg are round, film-coated tablets, yellow to light yellow in colour, with "3415" engraved on one side and "TV" on the other.
Enzalutamide Zentiva 40 mg is available in PVC/PCTFE/PVC//Alu or PVC/PE/PVDC//Alu blisters or calendar packs containing 112 film-coated tablets.
Enzalutamide Zentiva 80 mg are oval, film-coated tablets, yellow to light yellow in colour, with "3416" engraved on one side and "TV" on the other.
Enzalutamide Zentiva 80 mg is available in PVC/PCTFE/PVC//Alu or PVC/PE/PVDC//Alu blisters or calendar packs containing 56 film-coated tablets, or in unit-dose divisible blisters in PVC/PCTFE/PVC//Alu or PVC/PE/PVDC//Alu, or unit-dose divisible calendar packs containing 56x1 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano, Italy

Manufacturer
Actavis International Ltd; 4, Sqaq tal-Gidi off Valletta Road, Luqa LQA 6000, Malta
Balkanpharma-Dupnitsa AD, 3 Samokovsko Shosse Str., Dupnitsa, 2600, Bulgaria

This medicinal product is authorised in the Member States of the European Economic Area under the following names: