Midanex

Package leaflet: Information for the patient

Midanex 160 mg film-coated tablets

enzalutamide
Read this leaflet carefully before taking this medicine because 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet

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

1. What Midanex is and what it is used for

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

• Whose cancer no longer responds to hormonal therapy or surgical treatment to reduce testosterone, or
• Whose cancer 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 prostate removal or radiotherapy and have a rapidly rising PSA (prostate-specific antigen), but whose cancer has not yet spread to other parts of the body and still responds to hormonal therapy to reduce testosterone.

How Midanex works
Midanex 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 Midanex

Do not take Midanex

• 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 patients treated with enzalutamide and in fewer than 3 out of 1,000 patients treated with placebo (see "Other medicines and Midanex" 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 Midanex", below).
If you have a seizure during treatment:
Contact your doctor as soon as possible. Your doctor may decide that you should stop taking Midanex.
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 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 tumours (secondary primary tumours)
New (secondary) tumours, including bladder and colon cancer, have been reported in patients treated with enzalutamide.
Contact your doctor immediately if you notice signs of gastrointestinal bleeding, blood in the urine, or if you frequently feel a strong urge to urinate while taking Midanex.
Swallowing difficulties related to the product formulation
Cases of patients experiencing difficulty swallowing enzalutamide tablets, including choking incidents, have been reported. Swallow the tablets whole with an adequate amount of water.
Talk to your doctor before taking Midanex:

• If you have previously developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking enzalutamide 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 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 Midanex.
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 Midanex.
Severe skin rash or skin peeling, blisters and/or mouth ulcers, including Stevens-Johnson syndrome, have been reported in association with enzalutamide treatment. Stop using Midanex 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, talk to your doctor before taking
this medicine.
Children and adolescents
This medicine must not be used in children and adolescents.
Other medicines and Midanex
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 a new medicine is prescribed. Do not start or stop any treatment without first discussing it with the doctor who prescribed Midanex.
Tell your doctor if you are taking any of the following medicines. If taken together with Midanex, 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 Midanex, or Midanex may affect the action of these medicines.
This includes, for example, some 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, valproate)
• Treating certain psychiatric disorders such as severe anxiety or schizophrenia (e.g. diazepam, midazolam, haloperidol)
• Treating sleep disorders (e.g. zolpidem)
• Treating heart disease or lowering blood pressure (e.g. bisoprolol, digoxin, diltiazem, felodipine, nicardipine, nifedipine, propranolol, verapamil)
• Treating severe inflammatory conditions (e.g. dexamethasone, prednisolone)
• Treating HIV infections (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 disease or stroke (e.g. dabigatran etexilate)
• Preventing organ rejection (e.g. tacrolimus)

Midanex may interfere with certain 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 together with certain 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 Midanex or of any other medicine you are taking.
Pregnancy, breastfeeding and fertility

• Midanex 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, could become pregnant, or are breastfeeding with breast milk.

• This medicine may affect male fertility.

• If you have sexual intercourse with a woman who could become pregnant, use a condom and another effective method of contraception 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, during treatment and for 3 months after stopping treatment.

• If the person caring for the patient is a woman, see section 3 "How to take Midanex" for instructions on use and handling.

Driving and using machines
Midanex may have a moderate effect on the ability to drive and use machines. Seizures have been reported in patients taking Midanex. If you are at high risk of seizures, discuss this with your doctor.
Midanex contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. it is essentially "sodium-free".

3. How to take Midanex

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

The usual dose is 160 mg (one 160 mg film-coated tablet) taken once daily at the same time each day.

Taking Midanex

• Swallow the tablets whole with a sufficient amount of water.
• Do not cut, crush, or chew the tablets before swallowing.
• Midanex can be taken with or without food.
• Midanex 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 Midanex tablets without wearing protective gloves.

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

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

If you forget to take Midanex

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

If you stop taking Midanex
Do not stop taking this medicine unless instructed by your doctor.
If you have any doubts about how to use this medicine, consult 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 patients treated with enzalutamide and in fewer than 3 out of 1,000 patients treated with placebo.
The risk of seizures is higher if you take a dose of this medicine exceeding the recommended dose, if you take other medicines, or if you have an increased risk of seizures beyond normal.
If you have a seizure, contact your doctor as soon as possible. Your doctor may decide that you should stop treatment with Midanex.

Reversible posterior encephalopathy syndrome (PRES)
Rare cases of PRES have been reported in patients treated with enzalutamide (up to 1 in 1,000 people may be affected), a rare reversible condition affecting the brain. If you experience seizures, worsening headache, confusion, blindness, or other vision problems, contact your doctor immediately.

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, anxiety, dry skin, itching, memory impairment, blockage of heart arteries (ischaemic heart disease), enlargement of the breast in men (gynaecomastia), nipple pain, breast tenderness, symptoms of restless legs syndrome (an 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 levels of liver enzymes in blood tests (a sign of liver problems)

Frequency 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 ache including feeling unwell (nausea), 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 rings of lighter red (erythema multiforme), or another severe skin reaction presenting as flat reddish spots on the trunk, target-like or circular, 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), skin rash, malaise (vomiting), swelling of the face, lips, tongue and/or throat, reduced number of blood platelets (increased risk of bleeding or bruising), diarrhoea, reduced appetite.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Midanex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and 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 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 Midanex contains

• The active substance is enzalutamide.
• Each film-coated tablet contains 160 mg of enzalutamide.

The other components of the film-coated tablets are:

• Tablet core: Methacrylic acid-ethyl acrylate copolymer (1:1) Type A (contains sodium lauryl sulfate and polysorbate 80), colloidal anhydrous silica (E551), microcrystalline cellulose PH 102 (E460), sodium croscarmellose (E468), magnesium stearate (E470b).
• Tablet coating: Hypromellose 2910 (E464), macrogol 3350 (E1521), titanium dioxide (E171), yellow iron oxide (E172), talc (E553b).

Description of the appearance of Midanex and contents of the pack
Midanex 160 mg film-coated tablets are yellow, round, film-coated tablets, imprinted with "160" on one side, measuring 23 mm x 11 mm.
Each pack contains 28 film-coated tablets in aluminum-OPA/Alu/PVC blisters.

Marketing Authorization Holder
Farmitalia S.r.l.
Via Pinciana 25
00198 Rome
Italy

Manufacturers
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate,
Birzebbugia BBG3000
Malta

Pharos Pharmaceutical Oriented Services Ltd.
Lesvou Street End, Thesi Loggos Industrial Zone,
Metamorfossi, 14452
Greece

This medicinal product is authorized in the European Economic Area countries under the following names:
Netherlands: Midanex 160 mg filmomhulde tabletten
Italy: Midanex
Malta: Enzalutamide PharOS 160 mg film-coated tablets