SINTROM 4 mg Coated Tablet

Зміст інструкції

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

Sintrom 1 mg tablets, 4 mg tablets

acenocumarol

Read 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Sintrom and what is it used for

Sintrom contains the active ingredient acenocoumarol. Acenocoumarol is a substance that belongs to the
category of antithrombotic drugs, drugs used to treat blood clots in blood vessels and
prevent their formation.
Sintrom is used to prevent and treat the formation of blood clots in blood vessels.

2. What you need to know before you take Sintrom

Do not take Sintrom

• if you are allergic to acenocoumarol, to substances similar to acenocoumarol (coumarin derivatives) or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant;
• if you are a woman of childbearing potential and are not using contraceptive methods (see section “Pregnancy, breastfeeding and fertility”);
• if you are a patient unable to cooperate and are not able to be consistent with taking the medicine;
• if you have a predisposition to bleeding (haemorrhagic diathesis) or have abnormalities in the composition of the blood (blood dyscrasia);
• if you are about to undergo or have just undergone surgery on the brain or spinal cord (central nervous system), eye surgery or surgery with wide exposure of the tissues;
• if you have a stomach and duodenal ulcer or have bleeding from the stomach and/or intestines, the urogenital tract, the respiratory system or in case of bleeding in the brain (cerebrovascular), in case of acute inflammation of the membrane that externally coats the heart (pericardium), accumulation of fluid in the pericardium or inflammation caused by bacteria of the membrane that internally coats the heart (endocardium);
• if you suffer severely from high blood pressure;
• if you have severe liver failure;
• if you have severe kidney failure;
• if you have increased anticoagulant activity such as after operations on lungs, prostate, uterus etc. and in acute inflammation of the pancreas;
• if you have severe circulatory problems (circulatory insufficiency) with accumulation of blood in the liver (hepatic stasis);
• if you are taking preparations based on Hypericum perforatum (St. John's Wort). These preparations decrease the effect of this medicine (see section “Other medicines and Sintrom”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Sintrom.
During treatment with Sintrom, carry with you a card that, in case of accidents, warns rescuers
of the anticoagulant therapy you are undergoing.
Tell your doctor before taking Sintrom:

• if you have mild or moderate liver failure;
• if you have mild or moderate kidney failure or other kidney diseases;
• if you have severe heart failure, a condition in which the heart fails to provide adequate blood to the body. In this case, your doctor may adjust the dose of Sintrom and have you undergo frequent checks during treatment;
• if you have a blood disease characterized by a deficiency of protein C or protein S;
• if you suffer from a condition known as hyperthyroidism (excess hormones produced by the thyroid gland);
• if you have cancer;
• if you have an infection or inflammation;
• if you have disorders of absorption of the stomach and intestines;
• if you are about to undergo intramuscular injections because they can cause hematomas and should be avoided. Conversely, intravenous and subcutaneous injections do not entail this complication.

The doctor will prescribe frequent monitoring of blood coagulation for an increased risk of
bleeding if:

• you have variable INR values (a blood test to be performed during Sintrom therapy, to check blood coagulation);
• you have had bleeding from the stomach or intestines in the past;
• if you suffer from high blood pressure (hypertension);
• you have problems with blood circulation in the brain (cerebrovascular diseases);
• you have severe heart disease;
• you suffer from anemia (a blood disease);
• you have cancer;
• you have a trauma (an injury);
• if you have kidney problems (renal failure);
• if you are taking multiple medications;
• if you are undergoing chronic therapy with anticoagulants (medicines that slow down blood clotting).

Tell your doctor if during treatment with Sintrom you need to undergo:

• diagnostic tests (angiography, lumbar puncture);
• dental procedures;
• surgical procedures.

The doctor will perform checks to assess the speed of blood coagulation before
submitting you to one of the procedures described above.
The doctor will assess whether to reduce the dose of Sintrom or interrupt the therapy (even for a short period)
assessing the possible risks and benefits.

Children and adolescents
The safety and efficacy of Sintrom in the pediatric population have not been established.

Elderly patients
If you are an elderly patient aged 65 years or older, your doctor will pay particular attention in
prescribing Sintrom and during treatment will have you undergo frequent checks to assess the speed of
blood coagulation (prothrombin time and INR).

Other medicines and Sintrom
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines:

• glucosamine (for osteoarthritis) may increase the effect of Sintrom.

There are many possible interactions between Sintrom and other medicines. If you take other medicines, your doctor will keep
you under control and have you undergo frequent blood tests to assess the speed of coagulation
(generally twice a week) when you use any medicine in
combination with Sintrom or if you need to stop a medicine administered simultaneously.
Do not take Sintrom with:

• anticoagulants (medicines that reduce blood clotting)
• antiplatelet agents (medicines that inhibit platelet aggregation)
• thrombolytics (medicines capable of dissolving a blood clot)
• non-steroidal anti-inflammatory drugs (NSAIDs)
• selective serotonin reuptake inhibitors (medicines used to treat depression)

Pay particular attention if you are taking medicines that may increase the anticoagulant effect
like:

• allopurinol (medicine used to treat gout)
• anabolic steroids (steroid hormones)
• androgens (steroid hormones)
• medicines for heart rhythm disorders: such as amiodarone or quinidine or propafenone
• antibiotics:

or clindamycin
or penicillins
or second and third generation cephalosporins
or chloramphenicol
or macrolides
or fluoroquinolones
or neomycin
or tetracyclines

• cimetidine (medicine used for the treatment of ulcers)
• disulfiram (medicine used for the treatment of alcoholism)
• ethacrynic acid (medicine that increases urine production)
• fibrates, statins (medicines that reduce triglyceride and cholesterol levels in the blood)
• glucagon (medicine used for controlling blood glucose levels)
• antifungals such as imidazole derivatives: or metronidazole or miconazole (even if administered locally)
• paracetamol (medicine that reduces fever and pain)
• medicines used for the oral treatment of type II diabetes such as sulfonylureas and derivatives: or tolbutamide or chlorpropamide
• thyroid hormones including levothyroxine
• anticancer drugs: or tamoxifen or 5-fluorouracil and similar
• tramadol (medicine that reduces pain)
• medicines that reduce stomach acidity such as proton pump inhibitors
• medicines that stimulate intestinal motor function such as prokinetic agents (cisapride)
• antacids such as magnesium hydroxide
• viloxazine (medicine used to treat depression)
• vitamin E
• hormonal type medicines used for example to reduce inflammation (corticosteroids): or dexamethasone or methylprednisolone or prednisone
• broad-spectrum antibiotics

Pay particular attention if you are taking some herbal preparations that may reduce the anticoagulant effect as:

• aminoglutethimide, a medicine for the treatment of Cushing's syndrome and breast cancer.
• anticancer drugs: or azathioprine or 6-mercaptopurine
• medicines used for the treatment of epileptic seizures: or barbiturates or carbamazepine
• cholestyramine (medicine that reduces cholesterol levels in the blood)
• medicines against HIV virus
• griseofulvin (antifungal)
• oral contraceptives
• rifampicin (antibiotic medicine)
• thiazide diuretics (medicines that promote urine production)
• bosentan (medicine for high blood pressure)

Sintrom may increase the effect of medicines used for the treatment of epileptic seizures (phenytoin),
as it may increase the concentration in the blood.
Pay particular attention if you are taking some herbal preparations that may increase
the anticoagulant effect as:

• agrimony
• Chinese angelica (Angelica sinensis)
• anise
• arnica
• asafoetida (Ferula assa-foetida)
• water clover (Menyanthes trifoliata)
• boldo
• buchu (Agathosma Betulina)
• capsicum
• cassia
• celery
• chamomile (German and Roman)
• dandelion
• fenugreek
• horse chestnut
• horseradish
• licorice
• ulmaria (Filipendula ulmaria)
• nettle
• passionflower
• northern prickly ash (Zanthoxylum americanum)
• quassia
• red clover
• sweet clover
• asperula (Asperula odorata)
• dipteryx odorata
• fucus vesiculosus
• pau d'Arco
• agrimony
• trembling poplar
• black cohosh
• clove
• cranberry
• parthenium (Tanacetum parthenium)
• ginger
• ginkgo biloba
• ulmaria (Filipendula ulmaria)
• policosanol
• tamarind
• willow
• Canadian tea
• yarrow
• bromelain
• salvia miltiorrhiza
• garlic
• ginseng (Panax spp)

Pay particular attention if you are taking some herbal preparations that may counteract
the anticoagulant action of Sintrom:

• alfalfa (Medicago sativa)
• agrimony
• green vegetables (broccoli, cabbage, spinach, turnip tops and Brussels sprouts)
• St. John's wort (Hypericum perforatum) The therapeutic efficacy of Sintrom may be reduced if you take St. John's wort (Hypericum perforatum) preparations at the same time. The effect may persist for at least 2 weeks after stopping treatment with Hypericum perforatum products.

Sintrom with food, drinks and alcohol
Avoid consuming large amounts of foods (such as leafy green vegetables) or drinks rich in vitamin K,
because the effects of the medicine may decrease.
Limit alcohol consumption and grapefruit juice if you are taking Sintrom.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take Sintrom if you are pregnant or think you may become pregnant as it may cause
birth defects.
Breastfeeding
Sintrom passes into breast milk in small amounts. Therefore, the doctor will assess whether it is appropriate for you
to breastfeed during treatment with Sintrom. If you are breastfeeding, the doctor may perform coagulation tests
on the newborn and may administer 1 mg of vitamin K1 prophylactically for a week.
Fertility
Women of childbearing potential must use effective contraceptive measures during treatment with Sintrom.

Driving and operating machinery
Sintrom does not impair the ability to drive vehicles or operate machinery.
During treatment with Sintrom, carry with you a card that, in case of accidents, warns rescuers
of the anticoagulant therapy you are undergoing.

Sintrom contains lactose
If you have been diagnosed with intolerance to some sugars, contact your doctor before taking this
medicine.

3. How to take Sintrom

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
Sensitivity to therapy with Sintrom varies from patient to patient and may also vary during the
treatment.
Therefore, your doctor will have you undergo regular tests to check blood coagulation (prothrombin time (PT)/International Normalised Ratio (INR)) to
adjust the dose based on the results.
Initial dose
The recommended initial dose is between 2 mg and 4 mg of Sintrom per day. In some cases the dose may
be 6 mg on the first day followed by 4 mg on the second day.
If you are an elderly patient (aged 65 years or older), if you have liver problems or severe heart failure or if you are a malnourished patient, a lower dose may be necessary both at the beginning of treatment
and during maintenance therapy.
Your doctor will have you undergo daily checks, starting from the second or third dose of Sintrom, to
check the speed of blood coagulation. Subsequently, the interval between tests may be
extended. Perform these checks always at the same time of day.
Maintenance dose
The recommended maintenance dose is between 1 mg and 8 mg per day based on the doctor's assessment.
Switching from heparin therapy to Sintrom therapy
The anticoagulant effect of Sintrom is not immediate. If you need a rapid anticoagulant effect, your
doctor will start you on treatment with heparin. Switching to therapy with Sintrom can begin
concurrently with heparin therapy for at least 4 days, all to ensure continuous anticoagulant action. During the transition phase to therapy with Sintrom, you will need to undergo more frequent checks to assess the speed at which the blood coagulates.
Treatment during dental care and surgical procedures
The doctor will carefully monitor the state of coagulation of your blood.
The doctor, after a careful evaluation of your conditions, will decide whether to suspend Sintrom, even for a
short period or whether to introduce another temporary anticoagulant therapy (e.g. with heparin).

How to take Sintrom:

• take the recommended daily dose always at the same time of day.
• swallow the tablet whole with a glass of water

The score line on the 4 mg tablet is to facilitate breaking it to make it easier to swallow and not to divide it into equal doses.

If you take more Sintrom than you should
If you take more Sintrom than you should, you may experience:

• skin bleeding
• presence of blood in the urine (hematuria)
• nosebleeds (epistaxis)
• emission of blood with vomiting (hematemesis)
• bleeding of the stomach and intestines
• vaginal bleeding
• bleeding of the joints
• bruises
• bleeding of the gums
• rapid heartbeat
• low blood pressure
• circulatory disorders due to blood loss
• nausea
• vomiting
• diarrhea
• abdominal pain

In case of accidental ingestion of an excessive dose of Sintrom, immediately inform your doctor or
go to the nearest hospital.

If you forget to take Sintrom
Take the forgotten dose as soon as possible on the same day. Do not take a double dose to
compensate for the missed dose. Consult your doctor for any doubts.

If you stop taking Sintrom
The doctor will tell you how and when to stop treatment.
If you are a patient at risk (e.g. after a heart attack), you will need to gradually reduce the dose until
discontinuation.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately inform your doctor if you experience any of the following side effects:
painful skin rash. In rare cases, Sintrom may cause serious skin conditions, including so-called
calciphylaxis, which may initially manifest as a painful skin rash but may lead to other
serious complications. This side effect occurs more frequently in patients with chronic
kidney disease.
The most frequent complications are bleeding in various parts of the body; these have been correlated with the dosage,
the patient's age and the nature of the underlying disease (but not the duration of treatment).

Common side effects (may affect up to 1 in 10 people)

• bleeding (haemorrhage)

Rare side effects (may affect up to 1 in 1,000 people)

• allergic reactions: or hives or skin rash or skin inflammation (dermatitis)
• loss of appetite
• nausea
• vomiting
• hair loss (alopecia)

Very rare side effects (may affect up to 1 in 10,000 people)

• inflammation of blood vessels (vasculitis)
• liver damage
• severe skin degeneration due to haemorrhage (haemorrhagic cutaneous necrosis) often associated with a congenital deficiency of protein C or protein S

Frequency not known:Serious skin problems (appearance of painful and itchy spots or nodules). These
lesions may worsen to ulceration and infection of the affected area (calciphylaxis). This
syndrome occurs more frequently in patients with chronic kidney disorders and may lead to
serious and sometimes fatal complications.

• Reduced number of red blood cells or low levels of haemoglobin (anaemia).

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national
reporting system at https://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 Sintrom

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after Expires. The date of
expiry refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Sintrom contains
Sintrom 1 mg tablets

• The active ingredient is acenocoumarol. Each tablet contains 1 mg of acenocoumarol.
• The other ingredients are: anhydrous colloidal silica, hypromellose, lactose, magnesium stearate, corn starch, talc.

Sintrom 4 mg tablets

• The active ingredient is acenocoumarol. Each tablet contains 4 mg of acenocoumarol.
• The other ingredients are: anhydrous colloidal silica, lactose, magnesium stearate, corn starch, pregelatinized corn starch.

Description of the appearance of Sintrom and contents of the pack
Sintrom 1 mg tablets
Each pack of Sintrom 1 mg tablets contains 20 or 100 tablets.
Sintrom 4 mg tablets
Each pack of Sintrom 4 mg tablets contains 20 tablets.

Marketing Authorisation Holder
MERUS LABS LUXCO II SARL
26-28 Rue Edward Steinchen,
L-2540 Luxembourg

Manufacturer
Sintrom 1 mg tablets
FAMAR A.V.E
Anthousa Avenue 7,
Anthousa Attiki, 15344,
Greece
Sintrom 4 mg tablets
FAMAR A.V.E
Anthousa Avenue 7,
Anthousa Attiki, 15349,
Greece
Sintrom 1mg and 4mg tablets
Rovi Pharma Industrial Services, S.A.,
Vía Complutense, 140,
Alcalá de Henares,
Madrid,
28805, Spain