Sintrom

Italy
Brand name Sintrom
Form tablets
Active substance / Dosage
ACENOCOUMAROL
Prescription type Prescription only
ATC code
B01AA07
Registration number 011782
Manufacturer Merus Labs Luxco II S.a.r.l.
Sintrom tablets

Table of Contents

Patient Information Leaflet

Sintrom 1 mg tablets, 4 mg tablets

acenocoumarol
Please read this entire 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 or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are similar to yours, as it could be harmful.
  • If you experience any adverse reaction, including those not listed in this leaflet, contact 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 taking 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 Sintrom is and what it is used for

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

2. What you should know before taking Sintrom

Do not take Sintrom

  • if you are allergic to acenocoumarol, to substances similar to acenocoumarol (cumarin 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 age and are not using contraceptive methods (see section “Pregnancy, breastfeeding and fertility”);
  • if you are a patient unable to cooperate and unable to consistently adhere to taking the medicine;
  • if you have a tendency to bleed (haemorrhagic diathesis) or have blood composition abnormalities (haematological dyscrasia);
  • if you are scheduled for, or have recently undergone, surgery on the brain or spinal cord (central nervous system), eye surgery, or surgery involving extensive tissue exposure;
  • if you have a stomach or duodenal ulcer, or are experiencing gastrointestinal bleeding, bleeding of the urogenital tract, respiratory tract bleeding, or cerebral haemorrhage (cerebrovascular), acute inflammation of the membrane lining the outside of the heart (pericardium), fluid accumulation in the pericardium, or bacterial inflammation of the membrane lining the inside of the heart (endocardium);
  • if you suffer from severe high blood pressure;
  • if you have severe liver failure;
  • if you have severe kidney failure;
  • if you have increased anticoagulant activity, such as after surgery on the lungs, prostate, uterus, etc., or during acute pancreatitis;
  • if you have severe circulatory problems (circulatory insufficiency) with blood pooling in the liver (hepatic congestion);
  • if you are taking Hypericum perforatum (St. John's Wort) preparations. These preparations reduce 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 an identification card that alerts emergency responders
to your anticoagulant therapy in case of accidents.
Inform your doctor before taking Sintrom:

  • if you have mild or moderate liver impairment;
  • if you have mild or moderate kidney impairment or other kidney diseases;
  • if you have severe heart failure, a condition in which the heart cannot supply adequate blood to the body. In this case, your doctor may adjust your Sintrom dose and perform frequent monitoring during treatment;
  • if you have a blood disorder characterized by deficiency of protein C or protein S;
  • if you have a condition known as thyrotoxicosis (excess thyroid hormones);
  • if you have a tumour;
  • if you have an infection or inflammation;
  • if you have gastrointestinal malabsorption disorders;
  • if you need intramuscular injections, as they may cause haematomas and should be avoided. In contrast, intravenous and subcutaneous injections do not carry this risk.

Your doctor will prescribe frequent blood coagulation tests if you are at increased risk of
bleeding due to:

  • variable INR values (a blood test performed during Sintrom treatment to monitor blood clotting);
  • a history of gastrointestinal bleeding;
  • high blood pressure (hypertension);
  • cerebrovascular disorders (blood circulation problems in the brain);
  • severe heart disease;
  • anaemia (a blood disorder);
  • a tumour;
  • trauma (injury);
  • kidney problems (renal insufficiency);
  • concomitant use of multiple medications;
  • chronic treatment with anticoagulants (medicines that delay blood clotting).

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

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

Your doctor will perform tests to assess your blood clotting speed before
any of the procedures listed above.
Your doctor will evaluate whether to reduce your Sintrom dose or temporarily interrupt treatment,
weighing potential risks and benefits.

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

Elderly patients
If you are an elderly patient aged 65 years or older, your doctor will exercise particular caution when
prescribing Sintrom and will perform frequent blood clotting tests (prothrombin time and INR) during treatment.

Other medicines and Sintrom
Inform 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 are taking other medicines, your doctor will monitor you closely and perform frequent blood tests to assess blood clotting speed (usually twice weekly) when starting any new medicine in combination with Sintrom, or when discontinuing a concomitantly administered medicine.

Do not take Sintrom with:

  • anticoagulants (medicines that reduce blood clotting)
  • antiplatelet agents (medicines that inhibit platelet aggregation)
  • thrombolytics (medicines that dissolve blood clots)
  • non-steroidal anti-inflammatory drugs (NSAIDs)
  • serotonin reuptake inhibitors (medicines used to treat depression)

Use particular caution if you are taking medicines that may increase the anticoagulant effect, such as:

  • allopurinol (a medicine used to treat gout)

  • anabolic steroids (steroid hormones)

  • androgens (steroid hormones)

  • medicines for heart rhythm disorders: amiodarone, quinidine, or propafenone

  • antibiotics:

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

  • cimetidine (a medicine used to treat ulcers)

  • disulfiram (a medicine used to treat alcoholism)

  • ethacrynic acid (a medicine that increases urine production)

  • fibrates, statins (medicines that reduce triglyceride and cholesterol levels in the blood)

  • glucagon (a medicine used to control blood glucose levels)

  • antifungal medicines such as imidazole derivatives: metronidazole or miconazole (even if administered locally)

  • paracetamol (a medicine that reduces fever and pain)

  • oral medicines for type II diabetes such as sulfonylureas and derivatives: tolbutamide or chlorpropamide

  • thyroid hormones including levothyroxine

  • anticancer medicines: tamoxifen, 5-fluorouracil, and similar agents

  • tramadol (a pain-relieving medicine)

  • medicines that reduce gastric acidity such as proton pump inhibitors

  • medicines that stimulate intestinal motility such as prokinetic agents (cisapride)

  • antacids such as magnesium hydroxide

  • viloxazine (a medicine used to treat depression)

  • vitamin E

  • hormonal medicines used, for example, to reduce inflammation (corticosteroids): dexamethasone, methylprednisolone, or prednisone

  • broad-spectrum antibiotics

Use particular caution if you are taking medicines that may reduce the anticoagulant effect, such as:

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

Sintrom may increase the effect of medicines used to treat epileptic seizures (phenytoin), as it may increase their blood concentration.

Use particular caution if you are taking certain herbal preparations that may increase the anticoagulant effect, such as:

  • agrimony
  • Chinese angelica (Angelica sinensis)
  • anise
  • arnica
  • asafoetida (Ferula assa-foetida)
  • bogbean (Menyanthes trifoliata)
  • boldo
  • buchu (Agathosma betulina)
  • capsicum
  • cassia
  • celery
  • chamomile (German and Roman)
  • dandelion
  • fenugreek
  • horse chestnut
  • horseradish
  • liquorice
  • meadowsweet (Filipendula ulmaria)
  • nettle
  • passionflower
  • prickly ash (northern)
  • quassia
  • red clover
  • sweet clover
  • sweet woodruff (Asperula odorata)
  • Dipteryx odorata
  • Fucus vesiculosus
  • Pau d'Arco
  • agrimony
  • trembling poplar
  • Cimicifuga rubifolia
  • clove
  • red cranberry
  • feverfew (Tanacetum parthenium)
  • ginger
  • ginkgo biloba
  • meadowsweet (Filipendula ulmaria)
  • policosanol
  • tamarind
  • willow
  • Canadian tea
  • yarrow
  • bromelain
  • Salvia miltiorrhiza
  • garlic
  • ginseng (Panax spp)

Use particular caution if you are taking certain herbal preparations that may counteract the anticoagulant action of Sintrom:

  • alfalfa (Medicago sativa)
  • agrimony
  • green vegetables (broccoli, cabbage, spinach, turnip tops, Brussels sprouts)
  • St. John's Wort (Hypericum perforatum). The therapeutic efficacy of Sintrom may be reduced if taken concurrently with St. John's Wort (Hypericum perforatum) preparations. This 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,
as they may reduce the medicine's effects.
Limit alcohol and grapefruit juice consumption while taking Sintrom.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take Sintrom if you are pregnant or planning to become pregnant, as it may cause fetal malformations.

Breastfeeding
Sintrom passes into breast milk in small amounts. Therefore, your doctor will assess whether you should breastfeed during Sintrom treatment. If you breastfeed, your doctor may perform coagulation tests on the newborn and may administer 1 mg of vitamin K1 weekly as a preventive measure.

Fertility
Women of childbearing age must use effective contraceptive methods during Sintrom treatment.

Driving and using machines
Sintrom does not affect the ability to drive or operate machinery.
During treatment with Sintrom, carry an identification card that alerts emergency responders
to your anticoagulant therapy in case of accidents.

Sintrom contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Sintrom

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Sensitivity to Sintrom therapy varies from patient to patient and may also change during the
course of treatment.
Therefore, your doctor will regularly perform blood tests to monitor blood clotting (prothrombin time (PT)/International Normalised Ratio (INR)) in order to adjust the dose according to the results.
Initial dose
The recommended initial dose ranges between 2 mg and 4 mg of Sintrom daily. 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 malnourished, a lower dose may be required both at the beginning of treatment and during maintenance therapy.
Starting from the second or third dose of Sintrom, your doctor will have you undergo daily checks to monitor the speed of blood clotting. Afterwards, the interval between tests may be extended. Always perform these checks at the same time of day.
Maintenance dose
The recommended maintenance dose ranges between 1 mg and 8 mg daily, according to your doctor's assessment.
Switching from heparin therapy to Sintrom therapy
The anticoagulant effect of Sintrom is not immediate. If you require a rapid anticoagulant effect, your doctor will start your treatment with heparin. The switch to Sintrom therapy may begin simultaneously with heparin therapy for at least 4 days, to ensure continuous anticoagulant action. During the transition phase to Sintrom therapy, you will need more frequent monitoring to assess the rate of blood clotting.
Treatment during dental procedures and surgical interventions
Your doctor will carefully monitor your blood's coagulation status.
After carefully evaluating your condition, your doctor will decide whether to discontinue Sintrom, even temporarily, or whether to introduce a temporary alternative anticoagulant therapy (e.g. with heparin).
How to take Sintrom:

  • Take the recommended daily dose at the same time each day.
  • Swallow the tablet whole with a glass of water.

The score line on the 4 mg tablet is intended to facilitate breaking the tablet for easier swallowing and does not serve to divide the tablet into equal doses.
If you take more Sintrom than you should
If you take more Sintrom than prescribed, you may experience:

  • skin bleeding
  • blood in the urine (haematuria)
  • nosebleeds (epistaxis)
  • vomiting blood (haematemesis)
  • stomach or intestinal bleeding
  • vaginal bleeding
  • joint bleeding
  • bruising (haematomas)
  • bleeding gums
  • rapid heartbeat
  • low blood pressure
  • circulatory disturbances due to blood loss
  • nausea
  • vomiting
  • diarrhoea
  • abdominal pain

In case of accidental ingestion of an excessive dose of Sintrom, contact your doctor immediately or go to the nearest hospital.
If you forget to take Sintrom
Take the missed dose as soon as possible on the same day. Do not take a double dose to make up for the missed dose. Consult your doctor if you have any doubts.
If you stop taking Sintrom
Your doctor will advise you on how and when to discontinue treatment.
If you are a high-risk patient (e.g. after a heart attack), you must gradually reduce the dose before stopping completely.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

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

  • Bleeding (haemorrhages)

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

  • Allergic reactions: or urticaria or skin rash or skin inflammation (dermatitis)
  • Decreased 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 skin necrosis), often associated with congenital deficiency of protein C or protein S

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Pack contents and other information

What Sintrom contains
Sintrom 1 mg tablets

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

Sintrom 4 mg tablets

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

Description of the appearance of Sintrom and pack contents
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 Authorization 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 1 mg and 4 mg tablets
Rovi Pharma Industrial Services, S.A.,
Vía Complutense, 140,
Alcalá de Henares,
Madrid,
28805, Spain