Tagant

Package leaflet: Information for the user

Tagant, 40 mg, coated tablets
Tagant, 80 mg, coated tablets
Enzalutamide
Please read all of 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 further questions, ask your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of the leaflet

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

1. What Tagant is and what it is used for

Tagant contains the active substance enzalutamide. Tagant is used in adult men for the treatment of prostate cancer that:

• no longer responds to hormonal therapy or surgical treatment aimed at reducing testosterone levels, or
• has spread to other parts of the body and responds to hormonal therapy or surgical treatment aimed at reducing testosterone levels, or
• in men who previously underwent prostatectomy or radiation therapy and have rapidly rising PSA levels, but in whom the cancer has not spread to other parts of the body and who respond to hormonal therapy aimed at reducing testosterone levels.

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

2. Important information before taking Tagant

When not to take Tagant:

• if the patient is allergic to enzalutamide or any of the other ingredients of this medicine (listed in section 6.);
• during pregnancy or if there is a possibility of becoming pregnant (see "Pregnancy, breastfeeding and effect on fertility").

Warnings and precautions
Seizures
Seizures have been reported in 5 out of 1000 individuals taking Tagant and in fewer than 3 out of 1000 individuals taking placebo (see "Tagant and other medicines" below and section 4. "Possible side effects").
If the patient is taking medicines that may cause seizures or increase susceptibility to seizures (see below "Tagant and other medicines").
If the patient experiences a seizure during treatment:
Contact the doctor as soon as possible. The doctor may decide whether the patient should discontinue treatment with Tagant.

Posterior Reversible Encephalopathy Syndrome (PRES)
PRES (a rare, reversible condition affecting the brain) has been rarely reported in patients treated with Tagant. If the patient develops seizures, worsening headache, altered consciousness, blindness, or other visual disturbances, seek immediate medical attention (also see section 4. "Possible side effects").

Risk of new tumours (second primary malignant tumours)
There have been reports of new (second) cancers in patients treated with Tagant, including bladder and colorectal cancer.
If gastrointestinal bleeding, blood in the urine, or frequent urgent need to urinate occur while taking Tagant, contact the doctor immediately.

Swallowing difficulties related to the medicine formulation
Difficulty swallowing enzalutamide, including choking incidents, has been reported in patients. Swallowing difficulties and choking events have been observed more frequently in patients taking the medicine in capsule form, which may be related to the larger capsule size. Capsules should be swallowed whole with an adequate amount of water.

Before starting Tagant, discuss with the doctor:

• if the patient has ever experienced severe rash, skin peeling, blisters and/or oral ulcers after taking Tagant or other medicines;
• if the patient is taking anticoagulant medicines (e.g. warfarin, acenocoumarol, clopidogrel);
• if the patient is receiving chemotherapy, e.g. docetaxel;
• if the patient has liver disease;
• if the patient has kidney disease.

Inform the doctor if the patient has any of the following conditions:
any heart or blood vessel disease, including heart rhythm disorders (arrhythmia), or if the patient is being treated for such conditions. The risk of heart rhythm disturbances may increase during treatment with Tagant.
If the patient is allergic to enzalutamide, a rash or swelling of the face, tongue, lips or throat may occur. If the patient has been diagnosed with allergy to enzalutamide or any of the other ingredients of this medicine, Tagant must not be taken.
Serious skin reactions, including Stevens-Johnson syndrome, such as severe rash, skin peeling, blisters and/or oral ulcers, have been reported during treatment with Tagant. If any of these symptoms associated with serious skin reactions, described in section 4, occur, contact the doctor immediately and discontinue treatment with Tagant.
If any of the above situations apply or if in doubt, consult the doctor before taking this medicine.

Children and adolescents
This medicine is not intended for use in children and adolescents.

Tagant and other medicines
Inform the doctor about all medicines currently taken or recently taken, as well as any medicines the patient plans to take. Be aware of the names of the medicines being taken. Keep a list of these medicines to show the doctor when a new prescription is issued. Do not start or stop taking any medicine without consulting the doctor who prescribed Tagant.

Inform the doctor if the patient is taking any of the following medicines. These medicines, when taken concomitantly with Tagant, may increase the risk of seizure:

• 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).

Inform the doctor if the patient is taking any of the following medicines. These medicines may affect the action of Tagant or Tagant may affect their action.
This includes medicines used for:

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

Tagant may affect the action of certain medicines used to treat heart rhythm disorders (e.g. quinidine, procainamide, amiodarone, sotalol) or increase the risk of heart rhythm disturbances when taken with certain other medicines [e.g. methadone (used for pain relief and as part of detoxification in drug addiction), moxifloxacin (an antibiotic), antipsychotic medicines (used to treat severe mental illnesses)].
Inform the doctor if taking any of the medicines listed above. The dose of Tagant or any other medicine the patient is taking may need to be adjusted.

Pregnancy, breastfeeding and effect on fertility

• Tagant is not indicated for use in women. This medicine, if taken by pregnant women, may harm the unborn child or cause loss of pregnancy. This medicine must not be used by pregnant women, women who may become pregnant, or women who are breastfeeding.
• This medicine may possibly affect fertility in men.
• If the patient has sexual intercourse with a woman of reproductive age during treatment and for 3 months after treatment ends, a condom and another effective method of contraception must be used. If the patient has sexual intercourse with a pregnant woman, a condom must be used to protect the unborn child during treatment and for 3 months after treatment ends.
• Caregivers – see section 3 "How to take Tagant", which describes how to handle the medicine.

Driving and operating machinery
Tagant may have a moderate effect on the ability to drive and operate machinery. Seizures have been reported in patients taking Tagant.
If there is an increased risk of seizures, consult the doctor.

Tagant contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per coated tablet, meaning the medicine is considered "sodium-free".

3. How to take Tagant

This medicine should always be taken as directed by the physician. In case of doubt, consult
your doctor.
The recommended dose is 160 mg (four 40 mg coated tablets or two 80 mg coated tablets), taken once daily at the same time each day.
Taking Tagant

• Swallow the tablets whole with water.
• Do not cut, crush, or chew the tablets before swallowing.
• Tagant may be taken with or without food.
• Individuals other than the patient or their caregivers should not come into contact with Tagant. Women who are pregnant or may become pregnant should not handle damaged or crushed Tagant tablets without protective gloves.

Your doctor may also prescribe other medicines during treatment with Tagant.
Overdose of Tagant
If the patient has taken more tablets than prescribed, stop taking Tagant and contact your doctor immediately. This may increase the risk of seizures or other adverse effects.
Missed dose of Tagant
If the patient forgets to take Tagant at the usual time, the usual dose should be taken as soon as possible.

• If the patient forgets to take Tagant on a given day, take the usual dose the next day.
• If the patient forgets to take Tagant for more than one day, contact the doctor immediately.
• Do not take a double dose to make up for a missed dose.

Stopping Tagant
Do not stop taking this medicine unless instructed by your doctor.
If you have any further questions about the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Seizure
Seizures have been reported in 6 out of 1,000 people taking Tagant and in fewer than 3 out of 1,000 people taking placebo.
The occurrence of seizures is more likely when taking a higher than recommended dose of this medicine, when taking certain other medicines, or when there is a higher than usual risk of seizure.
If a patient experiences a seizure, contact a doctor as soon as possible.
The doctor will decide whether to discontinue treatment with Tagant.
Posterior reversible encephalopathy syndrome (PRES)
PRES has been rarely reported in patients treated with Tagant (may occur in fewer than 1 in 1,000 people); this is a rare, reversible brain condition. If a patient develops seizures, worsening headache, disturbances of consciousness, blindness, or other vision disturbances, contact a doctor immediately.
Other adverse reactions include:
Very common (may affect more than 1 in 10 people)
Fatigue, fall, bone fracture, hot flush, high blood pressure.
Common (may affect up to 1 in 10 people)
Headache, feeling of anxiety, dry skin, itching, memory impairment, blockage of arteries in the heart (ischaemic heart disease), breast enlargement in men (gynaecomastia), nipple pain, breast tenderness, restless legs syndrome (uncontrollable urge to move part of the body, usually the leg), reduced concentration, forgetfulness, change in taste sensation, 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 (indicating liver problems).
Frequency not known (frequency cannot be estimated from the available data)
Muscle pain, muscle cramps, muscle weakness, back pain, changes in ECG (prolongation of QT interval), difficulty swallowing this medicine, including choking, stomach discomfort including 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 lighter red rings (erythema multiforme), or other serious skin reaction appearing as reddish, flat, disc-shaped or round patches on the trunk, often with central blisters, skin peeling, ulceration of the mouth, throat, nose, genital organs and eyes, which may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), rash, vomiting, swelling of the face, lips, tongue and (or) throat, reduced platelet count (increasing the risk of bleeding or bruising), diarrhoea, decreased appetite.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor, pharmacist or nurse. Adverse reactions can be reported directly to:
Department of Monitoring Adverse Reactions of Medicinal Products
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Tagant

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister, bottle, and outer carton following: EXP. The expiry date refers to the last day of the stated month.
This medicine does not require any special storage conditions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Tagant contains

• The active substance is enzalutamide.
• Each Tagant 40 mg coated tablet contains 40 mg of enzalutamide.
• Each Tagant 80 mg coated tablet contains 80 mg of enzalutamide.
• The other ingredients are:
  • Tablet core: methacrylic acid-ethyl acrylate copolymer (1:1), colloidal anhydrous silica (E551), microcrystalline cellulose (E 460), sodium croscarmellose (E468), magnesium stearate.
  • Tablet coating: hypromellose (E464), macrogol (E1521), titanium dioxide (E171), yellow iron oxide (E172), talc (E553b).

What Tagant looks like and contents of the pack
Tagant 40 mg, coated tablets, are yellow, round coated tablets (tablets) with a diameter of 10.1 mm ± 5%, imprinted with the number "40" on one side.
Each box contains 112 coated tablets in blisters made of Aluminium-OPA/Aluminium/PVC film or in blisters made of Aluminium-OPA/Aluminium/PVC film with perforations containing single doses of 112 x 1 coated tablet, packed in a cardboard box.
Tagant is also available in high-density polyethylene (HDPE) bottles with a polypropylene (PP) container containing an oxygen-absorbing agent and a child-resistant PP cap, containing 112 coated tablets, packed in a cardboard box.
Tagant 80 mg, coated tablets, are yellow, oval coated tablets (tablets) measuring 17.1 mm x 9.1 mm ± 5%, imprinted with the number "80" on one side.
Each box contains 56 coated tablets in blisters made of Aluminium-OPA/Aluminium/PVC film or in blisters made of Aluminium-OPA/Aluminium/PVC film with perforations containing single doses of 56 x 1 coated tablets.
Tagant is also available in high-density polyethylene (HDPE) bottles with a polypropylene (PP) container containing an oxygen-absorbing agent and a child-resistant PP cap, containing 56 coated tablets, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Egis Pharmaceuticals PLC
Keresztúri út 30-38,
1106 Budapest
Hungary

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00

This medicinal product is authorised in the European Economic Area under the following names:
Netherlands: Tagant 40 mg, filmomhulde tabletten, Tagant 80 mg, filmomhulde tabletten
Czech Republic: Tagant
Hungary: Tagant 40 mg, filmtabletta, Tagant 80 mg, filmtabletta
Poland: Tagant
Romania: Tagant, 40 mg, comprimate filmate, Tagant, 80 mg, comprimate filmate
Slovakia: Tagant, 40 mg, Tagant, 80 mg