PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Warning! Keep the leaflet. Information on the outer packaging in a foreign language!
Sintrom, 4 mg, tablets
Acenocoumarolum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

Keep this leaflet for future reference.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are similar.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Sintrom is and what it is used for

What Sintrom is
Sintrom contains the active substance acenocoumarol.
Acenocoumarol belongs to a group of anticoagulant substances that reduce the blood's ability to clot, thereby preventing the formation of blood clots in blood vessels.
What Sintrom is used for
Sintrom is indicated for the treatment and prevention of thromboembolic disorders.
How Sintrom works
Sintrom works by inhibiting the formation of blood clots. It does not dissolve existing blood clots but may prevent clots from growing larger and causing more serious problems.
Control tests during Sintrom treatment
During treatment with Sintrom, your doctor will order regular blood tests and adjust the dose accordingly.
Consult your doctor if you have any questions about how Sintrom works or why it has been prescribed.

2. Important information before using Sintrom

Sintrom must only be taken after consultation with a doctor. Sintrom is not suitable for every patient.
You must strictly follow your doctor's instructions, which may differ from the information contained in this leaflet.
When not to use Sintrom:

If the patient is allergic (hypersensitive) to acenocoumarol and similar coumarin derivatives, or to any of the other ingredients of this medicine (listed in section 6 of the leaflet). In such a case, contact your doctor before using Sintrom. If you are unsure which medicines to avoid, ask your doctor or pharmacist.
If the patient is unable to cooperate (e.g. unsupervised elderly patients, alcoholics, or patients with psychiatric disorders).
If the patient has congenital or acquired bleeding disorders (e.g. haemophilia).
Shortly after eye surgery, central nervous system surgery, dental procedures, or after surgical procedures involving the lungs, prostate gland, uterus, those associated with significant blood loss, or shortly before surgery when significant blood loss is expected.
If the patient has peptic ulcer disease of the stomach and/or duodenum, gastrointestinal bleeding, bleeding from the urinary or genital tract, brain, or lungs.
If the patient has acute infection or inflammatory conditions affecting the heart, or pericardial effusion.
If the patient has uncontrolled arterial hypertension.
If the patient has severe liver or kidney disease.
If the patient is pregnant or if pregnancy is suspected.

If any of the above situations apply, contact your doctor before using
Sintrom.
Consult your doctor for advice if the patient has an allergy.
Warnings and precautions:
Before starting Sintrom, discuss the following with your doctor:

If the patient has liver function disorders.
If the patient has kidney or thyroid function disorders, cancer, inflammatory conditions, or malabsorption syndromes of the gastrointestinal tract. These conditions may lead to abnormal levels of the active substance in the blood.
If the patient has severe heart failure.
If the patient has been diagnosed with protein C or protein S deficiency (types of proteins affecting blood coagulation).
If diagnostic or therapeutic procedures are planned, e.g. minor surgery, tooth extraction, lumbar puncture, angiography.
If the patient is receiving intramuscular injections. During treatment with Sintrom or similar medicines, intramuscular injections should be avoided, as they may cause haematomas.
If the patient has an increased risk of bleeding, for example, patients with a history of fluctuating international normalized ratio (INR) test results, current or past gastric or duodenal ulcers, high blood pressure, cerebral circulation disorders (cerebrovascular disease), anaemia, recent wounds or injuries, or if the patient is currently taking or has recently taken any of the medicines listed below, or has been taking Sintrom for a long time.
In patients taking anticoagulant medicines known as vitamin K antagonists, including Sintrom, rare cases of calciphylaxis have been reported, a condition in which calcium accumulates in the blood vessels of the skin. This causes painful nodules or ulcers, which may lead to severe infection, often fatal. This usually occurs only when the person has severe kidney disease or abnormal levels of calcium, albumin, phosphorus, or certain proteins in the blood. If this condition is diagnosed, the doctor will initiate appropriate treatment and may discontinue Sintrom therapy.

Immediately inform your doctor if any of the above situations occur.
Children and adolescents
Data on use in children and adolescents are limited; therefore, more frequent monitoring is required.
Elderly patients (over 65 years of age)
Patients over 65 years of age may be more sensitive to acenocoumarol; therefore, more frequent monitoring and, if necessary, dose reduction of the medicine may be required.
Other medicines and Sintrom
Inform your doctor about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
The effect of Sintrom may influence the action of other medicines and vice versa.
Concomitant use of Sintrom with the following medicines is not recommended:

heparin (anticoagulant),
antibiotics (e.g. clindamycin),
salicylic acid and its derivatives, e.g. acetylsalicylic acid, aminosalicylic acid, diflunisal (analgesic),
clopidogrel, prasugrel, ticagrelor, ticlopidine, phenylbutazone and other pyrazolone derivatives, non-steroidal anti-inflammatory drugs (including celecoxib),
pyrazolone (sulfinpyrazone), other non-steroidal anti-inflammatory drugs (medicines affecting platelets and involved in the blood coagulation process).

Exercise caution when concomitant use of Sintrom with other medicines is necessary, particularly with:

glucosamine (used in osteoarthritis) – may enhance the effect of Sintrom,
certain types of medicines used to prevent blood clotting (e.g. warfarin, dicoumarol, phenprocoumon, acenocoumarol, and fluindione). The effect of these medicines may be stronger when used concomitantly with glucosamine. Patients treated with such combinations should be monitored particularly carefully when starting and stopping glucosamine therapy.

It is recommended that Sintrom not be taken simultaneously with any of the above-mentioned medicines. If taking any of these medicines becomes necessary during Sintrom therapy, your doctor will monitor blood coagulation parameters more frequently.
Other medicines that may increase the effect of Sintrom include:

allopurinol (used in the treatment of gout),
androgens, anabolic steroids,
antiarrhythmic agents (e.g. amiodarone, quinidine) (medicines preventing irregular heart rhythm),
antibiotics (e.g. erythromycin, tetracyclines, neomycin, chloramphenicol, amoxicillin, certain cephalosporins, and certain fluoroquinolones) (medicines used to treat infections),
selected antidepressants (serotonin reuptake inhibitors, SSRIs: e.g. citalopram, fluoxetine, sertraline),
cimetidine (used for dyspepsia and gastrointestinal ulcers),
clofibrate and its derivatives (used to reduce cholesterol levels),
corticosteroids, e.g. methylprednisolone, prednisone (anti-inflammatory medicines),
disulfiram (used in the treatment of alcoholism),
ethacrynic acid (used to increase urine output),
glucagon (used to maintain normal blood glucose levels),
imidazole derivatives (e.g. metronidazole, and even topically applied miconazole) (medicines used to treat infections),
paracetamol (antipyretic),
sulfonamides including co-trimoxazole (sulfamethoxazole and trimethoprim) (medicines used to treat infections),
sulfonylurea derivatives (tolbutamide, chlorpropamide) (medicines used to treat diabetes),
thyroid hormones (including levothyroxine) (used to treat hypothyroidism),
medicines that reduce the activity of the liver enzyme called CYP2C9 (e.g. valproic acid)
ask your doctor or pharmacist whether any of the medicines you are taking have such an effect.
statins (e.g. fluvastatin, atorvastatin, simvastatin) (medicines used to reduce cholesterol levels),
tamoxifen (used in breast cancer treatment),
tramadol (analgesic),
proton pump inhibitors (e.g. omeprazole),
plasminogen activators (e.g. urokinase, streptokinase, and alteplase), thrombin inhibitors (e.g. argatroban) (medicines used to dissolve blood clots during angina),
prokinetic agents (e.g. cisapride) (medicines used to treat gastrointestinal disorders),
gastric acid neutralizing agents (e.g. magnesium hydroxide),
viloxazine (antidepressant),
vitamin E.

Medicines that may reduce the effect of Sintrom include:

certain anticancer medicines (aminoglutethimide, azathioprine, 6-mercaptopurine),
certain antiviral medicines (ritonavir, nelfinavir) (used in HIV therapy),
barbiturates, carbamazepine (antiepileptic medicines),
cholestyramine (used to reduce cholesterol levels),
griseofulvin (used to treat fungal infections),
oral contraceptives,
rifampicin (used to treat infections),
St. John's wort preparations ( Hypericum perforatum ) (herbal medicine used to treat depression),
foods rich in vitamin K.

Effect of Sintrom on other medicines:

Sintrom may increase the risk of toxicity when used concomitantly with hydantoin derivatives, such as phenytoin (used to treat epilepsy).
Sintrom may enhance the blood glucose-lowering effect of antidiabetic medicines known as sulfonylurea derivatives (e.g. glibenclamide, glimepiride).

Sintrom with food, drink, and alcohol
Limit consumption of large amounts of alcohol and foods rich in vitamin K, such as green leafy vegetables, spinach, cabbage, kale, peas, soybean oil, walnuts, broccoli, turnip, alfalfa, avocado, etc. Alcohol may alter the effect of Sintrom. If in doubt, consult your doctor.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Use during pregnancy is contraindicated. Sintrom, like other anticoagulants, may cause serious harm to the unborn child.
It is recommended that a pregnancy test be performed in women of childbearing age before starting Sintrom to exclude pregnancy. An effective method of contraception should be used during treatment with Sintrom.
The potential risks and benefits of the therapy should be discussed with the patient by the doctor.
In case of breastfeeding, consult your doctor. Both mother and child require special medical monitoring, and the child should receive prophylactic vitamin K.
Driving and operating machinery
Sintrom has no effect on the ability to drive or operate machinery. In case of an accident, inform the doctor or hospital staff about taking this medicine.
Given the risk of injury, e.g. in an accident, it is recommended to carry a card with information about anticoagulant therapy.
The medicine contains lactose monohydrate
Sintrom contains lactose (milk sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact their doctor before taking the medicine.

3. How to use Sintrom

This medicine must always be taken as directed by the doctor. In case of any doubts, consult
your doctor.
The dosage of this medicine is determined by the doctor. Regular blood clotting tests allow the
doctor to appropriately adjust the dose of Sintrom, which must be taken daily. Follow your
doctor's instructions carefully and do not exceed the recommended doses.
Recommended dose of Sintrom
Your doctor will inform you exactly how many Sintrom tablets you should take. Depending
on your response to treatment, your doctor may recommend increasing or decreasing the dose.
Individual sensitivity to the medicine varies and may change during the course of treatment or
when dietary changes occur, especially if foods rich in vitamin K (spinach, cruciferous vegetables)
are introduced. You must strictly follow your doctor's instructions, who will determine the
appropriate dose based on laboratory tests and your individual needs.
Do not suddenly stop taking this medicine or change the dose on your own initiative.
Dosage:
Adults
The usual recommended initial dose is 2 mg/day to 4 mg/day.
The maintenance dose usually ranges between 1 mg/day and 8 mg/day.
Elderly patients, patients with liver disease or severe heart failure (which slows blood flow through
the liver and may damage it), or undernourished patients may require a lower dose at the start
and during maintenance treatment with Sintrom.
Use in children and adolescents
The doctor will decide whether to use this medicine in children and adolescents.
During every visit to the doctor or dentist, inform them about taking this medicine.
How and when to take Sintrom
Take the tablets regularly every day at the same time (e.g. in the evening with a meal, with a
glass of water). Swallow the tablets whole.
The tablet may be divided into equal doses.
The doctor should assess whether the patient is able to divide the Sintrom 4 mg tablet into four
equal parts.
How long to take Sintrom
Your doctor will clearly inform you how long you should continue taking Sintrom.
Taking more than the recommended dose of Sintrom
If you accidentally take more than the recommended amount of Sintrom tablets, you must
contact your doctor immediately. Overdosing on Sintrom may lead to bleeding. If bleeding occurs,
stop taking Sintrom and start appropriate treatment for bleeding.
Missing a dose of Sintrom
If you miss a dose at the usual time, take it as soon as possible. If it is almost time for your next
dose, do not take the missed dose; instead, take the next dose at the regular time.
Do not take a double dose to make up for a missed dose. At your next visit to the doctor, inform
them about any missed doses.
Stopping treatment with Sintrom
If you have any further doubts about using this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious:
Common (less than 1 case in 10 people): bleeding (symptoms may include: unexplained
nosebleeds or bleeding gums during tooth brushing; unexplained bruising; unusual, heavy bleeding or oozing from cuts or wounds; abnormally heavy or unexpected menstrual bleeding; blood in urine; bloody or black, tarry stools; coughing up blood or bloody sputum or vomiting blood; sudden, severe or persistent headache). If any of the above bleeding symptoms occur, this may indicate that the patient has received more medicine than needed.
Rare (less than 1 case in 1,000 people): Allergic reactions such as rash or itching.
Very rare (less than 1 case in 10,000 people): Skin hemorrhagic lesions forming blisters, with or without scarring, usually located on cheeks, buttocks, abdomen, breasts and sometimes on toes; hemorrhagic skin lesions or subcutaneous hematomas (a sign suggesting possible vasculitis); jaundice (symptoms of possible liver damage).
If any of the above adverse symptoms occur, you must immediately inform your doctor.
Other adverse reactions:
Rare (less than 1 case in 1,000 people): hair loss, decreased appetite, vomiting, nausea.
If any of the above symptoms occur, you should inform your doctor.
Frequency unknown (frequency cannot be determined from available data): Painful skin rash. Sintrom may cause serious skin disorders, including so-called calciphylaxis, which may initially present as painful skin rash but may lead to other serious complications. This adverse reaction occurs more frequently in patients with chronic kidney disease.
Lower than normal number of red blood cells or reduced hemoglobin concentration
(anemia).
If any adverse reactions not listed in this leaflet occur, you should inform your doctor.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the 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
Reporting adverse reactions allows further information on the safety of the medicine to be collected.

5. How to store Sintrom

No special storage instructions are required.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Sintrom contains

The active substance is acenocoumarol. Each tablet contains 4 mg of acenocoumarol.
The other ingredients are: monohydrate lactose, magnesium stearate, corn starch, gelatinized corn starch, and anhydrous colloidal silicon dioxide.

What Sintrom looks like and contents of the pack
Sintrom is a white, round, flat tablet with rounded edges. On one side it is embossed with "CG", and on the other side has a cross-shaped score line allowing division into four equal parts, each embossed with the letter "A".
Sintrom is available in packs containing 20 tablets.
For more detailed information, please contact the responsible party or the parallel importer.

Responsible party in Romania, country of export:
Merus Labs Luxco II S.à.R.L.
26-28, rue Edward Steichen
L-2540 Luxembourg
Luxembourg

Manufacturer:
FAMAR A.V.E.
Anthoussa Avenue 7
Anthoussa Attiki, 15349
Greece
NORGINE B.V.
Antonio Vivaldistraat 150
1083 HP, Amsterdam
The Netherlands
ROVI PHARMA INDUSTRIAL SERVICES, S.A.
FROSST IBÉRICA, S.A.
Via Complutense, 140
Alcalá de Henares
28805 Madrid
Spain

Parallel importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
Poland
SHIRAZ PRODUCTIONS Sp. z o.o.
ul. Tymiankowa 24/28
95-054 Ksawerów
Poland
CANPOLAND SPÓŁKA AKCYJNA
ul. Beskidzka 190
91-610 Łódź
Poland

Romania (country of export) marketing authorization number: 2606/2010/01
Parallel import authorization number: 155/18