Midamid

Patient Information Leaflet

Midamid 40 mg film-coated tablets, 80 mg film-coated tablets

enzalutamide
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 effect, including any not listed in this leaflet, talk to your doctor. See section 4.

Contents of this leaflet

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

1. What Midamid is and what it is used for

Midamid contains the active substance enzalutamide. Midamid 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 responds to hormonal therapy or surgical treatment to reduce testosterone, or
• Who have previously undergone prostatectomy or radiotherapy and have a rapidly rising PSA (prostate-specific antigen), but whose cancer has not spread to other parts of the body and responds to hormonal therapy to reduce testosterone.

How Midamid works
Midamid 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 Midamid

Do not take Midamid

• 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 Midamid’ 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 Midamid', below).
If you have a seizure during treatment:
Contact your doctor as soon as possible. Your doctor may decide that you should stop taking Midamid.
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 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 Midamid.
Talk to your doctor before taking Midamid:

• If you have previously developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking Midamid or other medicines
• If you are taking medicines to prevent blood clots (e.g. warfarin, acenocoumarol, clopidogrel)
• If you are using a chemotherapy medicine 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 Midamid.
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 Midamid.
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 Midamid 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 Midamid
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 talking to the doctor who prescribed Midamid for you.
Tell your doctor if you are taking any of the following medicines. If taken together with Midamid, 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 Midamid, or Midamid 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 diseases 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)

Midamid 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 to relieve pain and in drug addiction detoxification programmes), moxifloxacin (an antibiotic), antipsychotics (used for severe mental illnesses)].
Tell your doctor if you are taking any of the medicines listed above. It may be necessary to adjust the dose of Midamid or of any other medicine you are taking.
Pregnancy, breastfeeding and fertility

• Midamid 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.
• This medicine may affect male fertility.
• If you have sexual intercourse with a woman who could 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, 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 Midamid” for instructions on use and handling.

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

Take this medicine exactly as directed by your doctor. If you have any doubts, 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 Midamid

• Swallow the tablets whole with water.
• Do not cut, crush, or chew the tablets before swallowing.
• Midamid may be taken with or without food.
• Midamid 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 Midamid tablets without wearing protective equipment, such as gloves.

Your doctor may prescribe other medicines during treatment with Midamid.

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

If you forget to take Midamid

• If you forget to take Midamid at your usual time, take your usual dose as soon as you remember.
• If you forget to take Midamid for a whole day, take your usual dose the next day.
• If you forget to take Midamid 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 Midamid
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 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 greater than the recommended dose, if you take other medicines, or if you have an above-normal risk of seizures.
If you have a seizure, contact your doctor as soon as possible. Your doctor may decide that you should stop treatment with Midamid.
Reversible posterior encephalopathy syndrome (PRES)
Rare cases of PRES (up to 1 in 1,000 people may be affected) have been reported in patients treated with enzalutamide, a rare reversible condition affecting the brain. If you have seizures, worsening headaches, confusion, blindness, or other vision problems, contact your doctor as soon as possible.
Other possible side effects are:
Very common side effects (may affect more than 1 in 10 people)
Fatigue, falls, bone fractures, hot flushes, high blood pressure
Common side effects (may affect up to 1 in 10 people)
Headache, anxiety, dry skin, itching, memory disturbances, blockage of the 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 side effects (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)
Side effects of unknown frequency (frequency cannot be estimated from the available data)
Muscle pain, muscle cramps, muscle weakness, back pain, changes in the electrocardiogram (ECG) (QT prolongation), stomach discomfort 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 serious skin reaction presenting as flat reddish spots on the trunk, resembling targets or circular shapes, often with central blisters, skin peeling, mouth ulcers, ulcers in the throat, nose, genitals and eyes, which may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), rash, malaise (vomiting), swelling of the face, lips, tongue and/or throat, reduced number of blood platelets (increased risk of bleeding or bruising), diarrhoea.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You may 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 Midamid

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 blister and carton after Exp.
The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of medicines 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 Midamid contains

• The active substance is enzalutamide.
• Each 40 mg film-coated tablet contains 40 mg of enzalutamide.
• Each 80 mg film-coated tablet contains 80 mg of enzalutamide.

The other components of the film-coated tablets are:

• Tablet core: Methacrylic acid-ethyl acrylate copolymer (1:1) Type A (containing sodium lauryl sulfate and polysorbate 80), anhydrous colloidal silica (E551), microcrystalline cellulose (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 Midamid and packaging contents
Midamid 40 mg film-coated tablets are yellow, round, film-coated tablets (tablets) with "40" engraved on one side, 10 mm in diameter.
Each pack contains 112 film-coated tablets in Aluminio-OPA/Alu/PVC blisters.
Midamid 80 mg film-coated tablets are yellow, oval, film-coated tablets (tablets) with "80" engraved on one side, sized 17 mm x 9 mm.
Each pack contains 56 film-coated tablets in Aluminio-OPA/Alu/PVC blisters.
Not all pack sizes may be marketed.

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

Manufacturer
Pharos MT Limited
Hf62x
Qasam Industrijali Hal Far
BBG 3000 Hal Far, Birzebbuga
Malta

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Netherlands: Midamid 40 mg filmomhulde tabletten; Midamid 80 mg filmomhulde tabletten
Italy: Midamid