Patient Information Leaflet

Apo-Flutam, 250 mg, film-coated tablets
Flutamide
Please read all of this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not share it with others. It may harm them, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of Contents

What Apo-Flutam is and what it is used for
Important information before taking Apo-Flutam
How to take Apo-Flutam
Possible side effects
How to store Apo-Flutam
Contents of the pack and other information

1. What Apo-Flutam is and what it is used for

Flutamide – the active substance in this medicine – is an oral, non-steroidal, non-hormonal androgen (male sex hormone) antagonist used in the treatment of metastatic prostate cancer. Prostate cancer develops due to excessive growth of prostate cells, a process promoted by androgens.
Flutamide inhibits the transport and/or binding of dihydrotestosterone in the nuclei of prostate tissue cells. As a result, the growth and division of prostate cells are suppressed.
The drug shows the greatest therapeutic efficacy when used in combination with luteinizing hormone-releasing hormone (LHRH) agonists, e.g. leuprorelin acetate, and in patients who have not previously been treated with hormones.
Flutamide is not effective in the treatment of other hormone-dependent tumours, such as breast cancer or benign prostatic hyperplasia.
Apo-Flutam is indicated:

for the treatment of metastatic prostate cancer (stage D), in combination with luteinizing hormone-releasing hormone (LHRH) agonists, e.g. leuprorelin acetate. To achieve optimal effectiveness in combined therapy, both medicines should be administered simultaneously (see section 3);
as an adjunctive treatment following surgical castration, to achieve complete androgen blockade;
prior to and during radiotherapy in patients with bulky, locally advanced prostate cancer (stage B and stage C), in combination with luteinizing hormone-releasing hormone (LHRH) agonists.

2. Information before taking Apo-Flutam

When not to take Apo-Flutam

if the patient is allergic to flutamide or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Apo-Flutam, discuss the following with your doctor or pharmacist:

if gynecomastia (excessive growth of breast tissue in males) has occurred. If this adverse effect occurs, inform your doctor;
if methemoglobinemia (increased levels of reduced hemoglobin in red blood cells, causing cyanosis with a gray-blue hue), hemolytic anemia, or cholestatic jaundice (due to impaired bile flow) occur. In patients with hypersensitivity to aniline derivatives (glucose-6-phosphate dehydrogenase deficiency, methemoglobinemia, or smokers), methemoglobin levels should be monitored regularly;
if long-term treatment with Apo-Flutam is required. Liver function and semen should then be monitored periodically;
if patients with liver impairment develop changes in aminotransferase activity (so-called liver enzymes in blood), cholestatic jaundice, liver necrosis, or hepatic encephalopathy (brain disturbances). Your doctor may recommend liver function tests if any symptoms of liver dysfunction occur, such as itching, dark urine, prolonged loss of appetite, jaundice (yellowing of eyes and skin), tenderness upon pressure in the upper right abdominal area, or unexplained flu-like symptoms. If laboratory tests confirm liver dysfunction or jaundice and show that it is not due to liver metastases (liver biopsy is recommended), dose reduction or discontinuation of Apo-Flutam may be necessary. If symptoms of liver dysfunction occur, inform your doctor immediately. Severe liver damage due to flutamide may require hospitalization and can even lead to death;
if increased serum levels of testosterone and estradiol occur, leading to fluid retention and edema, especially in patients with cardiac insufficiency;
if patients with a tendency to thrombosis experience prolonged blood clotting time;
if the patient has any heart or blood vessel disorders, including cardiac arrhythmias, or is being treated with medications for these conditions. Treatment with Apo-Flutam may increase the risk of developing cardiac rhythm disturbances.

Dose adjustment of flutamide is not necessary in patients with renal impairment.
Note: During treatment, urine may turn amber or yellow-green in color due to the presence of flutamide and its metabolites in urine.
Apo-Flutam and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.
No interactions have been observed between flutamide and leuprorelin acetate.
In patients on long-term warfarin therapy, flutamide may enhance the anticoagulant effect of warfarin and prolong blood clotting time. Your doctor may recommend monitoring prothrombin time and possibly reducing the dose of the anticoagulant.
Apo-Flutam and leuprorelin acetate should be used simultaneously and according to the recommended dosing schedule. Do not discontinue flutamide without consulting your doctor.
Apo-Flutam may affect the action of certain drugs used to treat cardiac arrhythmias (e.g., quinidine, procainamide, amiodarone, and sotalol) or may increase the risk of cardiac arrhythmias when used concomitantly with certain other drugs [e.g., methadone (used for pain relief and as part of opioid detoxification), moxifloxacin (an antibiotic), antipsychotics used in severe psychiatric disorders].
Apo-Flutam with food and drink
Flutamide is rapidly and completely absorbed from the gastrointestinal tract. Apo-Flutam may be taken independently of meals.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Flutamide is indicated for use in males only. However, its use in females has been reported. Well-controlled studies in pregnant women have not been conducted. Flutamide is likely to have harmful effects on the fetus. Use of Apo-Flutam is not recommended in pregnant women.
Breastfeeding
There are no data from well-controlled clinical studies on the use of flutamide in women during breastfeeding. Flutamide may pass into breast milk. Due to the risk of adverse effects in infants, women taking Apo-Flutam (as reported in medical literature) should discontinue breastfeeding.
Driving and operating machinery
Some patients may experience adverse effects such as drowsiness, disorientation, fatigue, dizziness, or blurred vision. In such cases, do not drive or operate machinery.
Apo-Flutam contains lactose monohydrate
If the patient has previously been diagnosed with an intolerance to certain sugars, they should consult their doctor before taking this medicine.
Apo-Flutam contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Apo-Flutam

This medicine should always be taken as prescribed by the doctor. In case of doubt, consult a
physician or pharmacist.
Recommended dose
For the treatment of prostate cancer (stage D ), in combination with gonadotropin-releasing hormone
(GnRH) agonists ( LHRH ) and as adjuvant therapy following orchidectomy: 250 mg
(1 coated tablet) three times daily every eight hours.
If Apo-Flutam is to be used in combination with an LHRH agonist, flutamide treatment should
be initiated 3 days before starting the LHRH agonist.
In patients with bulky, locally advanced prostate cancer (stage B and stage
C): 250 mg (1 coated tablet) three times daily every eight hours. Flutamide treatment should
be initiated 3 days before starting the LHRH agonist.
Flutamide treatment should begin eight weeks before starting radiotherapy. Flutamide treatment
should continue during radiotherapy.
Do not extend the duration of treatment without consulting the physician.
Use of a higher than recommended dose of Apo-Flutam
In case of ingestion of a higher than recommended dose, seek immediate medical advice from a
physician or pharmacist.
Symptoms of overdose: reduced vital activity, slowed breathing, flaccidity, lacrimation, somnolence,
vomiting, methemoglobinemia, and even liver failure. The single daily dose causing overdose symptoms or
indicating life-threatening risk has not been established. If vomiting does not occur spontaneously, it should
be induced.
Hemodialysis is ineffective in flutamide overdose.
Missed dose of Apo-Flutam
Do not take a double dose to make up for a missed tablet. Continue following the prescribed treatment regimen.
Discontinuation of Apo-Flutam
The physician may recommend discontinuation of flutamide treatment in case of jaundice or a 2–3-fold
increase in aminotransferase activity (without clinical symptoms). Usually, after dose reduction or withdrawal of
flutamide, liver function returns to pre-treatment levels.
In case of any further doubts regarding the use of this medicine, consult a physician or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although not everybody gets them.
You should tell your doctor if any of the following symptoms occur:

Very common adverse reactions (may occur in more than 1 in 10 people):

nausea, vomiting, diarrhoea, decreased appetite;
feeling tired, muscle pain.

Common adverse reactions (may occur in less than 1 in 10 people):

hypertension;
drowsiness, disorientation, depression, anxiety, nervousness;
adverse reactions affecting the lungs;
gynaecomastia (enlargement of the breasts);
other gastrointestinal disorders;
oedema;
haemolytic or macrocytic anaemia, decreased number of white blood cells in peripheral blood, thrombocytopenia, methemoglobinemia (abnormal haemoglobin structure).

Uncommon adverse reactions (may occur in less than 1 in 100 people):

hepatitis, jaundice, cholestatic jaundice, hepatic encephalopathy, liver necrosis (reversible upon discontinuation of the medicine).

Rare adverse reactions (may occur in less than 1 in 1,000 people):

myocardial infarction;
pulmonary embolism;
insomnia, fatigue, headache, dizziness, weakness, malaise, blurred vision;
breast tenderness, sometimes associated with galactorrhea, reduced semen volume;
increased appetite, dyspepsia, constipation;
haematuria;
in long-term treatment: pruritus, purpura, herpes zoster, increased thirst, lymphoedema, lupus-like syndrome.

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

changes in ECG findings (prolongation of QT interval);
cases of patient death due to severe liver damage resulting from flutamide intolerance; photosensitivity, erythema, ulceration, bullous rash, skin necrolysis.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, PL-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 Authorisation Holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Apo-Flutam

Keep this medicine out of sight and reach of children.
Do not use Apo-Flutam after the expiry date stated on the packaging after the words "Expiry date:". The expiry date refers to the last day of the specified month. The first two digits indicate the month, and the following four digits indicate the year.
Store below 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Apo-Flutam contains

The active substance is flutamide. Each coated tablet contains 250 mg of flutamide.
Other ingredients are:
- Tablet core: magnesium stearate, anhydrous colloidal silicon dioxide, lactose monohydrate, microcrystalline cellulose, sodium croscarmellose.
- Tablet coating: hypromellose 2910 E5, hydroxypropylcellulose 470 CPS, macrogol 3350, titanium dioxide (E 171), carnauba wax.

What Apo-Flutam looks like and contents of the pack
White or almost white, round, biconvex coated tablet, with a score line and engraved marking
"FLUT" above "250" on one side and "APL" on the other side.
Pack contents: 30, 60, 90 or 100 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Aurovitas Pharma Polska Sp. z o.o.
ul. Sokratesa 13D lok.27
01-909 Warsaw
Poland
Importer:
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate
Hal Far, Birzebbugia, BBG 3000
Malta