SINTHROME

Posology General target population Sensitivity to anticoagulants varies from patient to patient and may also fluctuate during the course of treatment. Therefore, it is essential to perform regular testing of prothrombin time (PT)/International Normalised Ratio (INR) and to adjust the patient’s dosage accordingly.

If this is not possible, Sinthrome should not be used. Sinthrome should be given in a single oral dose.

Initial dosage:

The dosing of Sinthrome must be individualised. If the PT/INR value is within the normal range before starting treatment, the following dosage schedule is recommended: The usual starting dose is between 2 mg/day to 4 mg/day without administration of a loading dose.

Treatment may also be initiated with a loading dose regimen, usually 6 mg on the first day followed by 4 mg on the second day. If the initial thromboplastin time is abnormal, treatment should be instituted with caution. 4). Measurement of the thromboplastin time should be carried out daily in hospital starting from second or third dose of Sinthrome and up to the time when the coagulation status is stabilized within the target range.

The interval between tests can later be extended, depending on the stability of PT/INR results. Blood samples for laboratory tests should always be taken at the same time of day. Maintenance therapy and coagulation tests The maintenance dose of Sinthrome varies from patient to patient and must be checked individually on the basis of PT/INR values.

e. at least once a month. The maintenance dose generally lies between 1 to 8mg daily depending on the individual patient, the underlying disease, clinical indication and desired intensity of anticoagulation. 5 (see Table 1). 5 may be required in individual cases.

5 *The PT, which reflects the reduction of Vitamin K dependent clotting factors VII, X and II, is dependent on the responsiveness of the thrombosplastin used for PT-testing. The responsiveness of the respective local thromboplastin compared to World Health Organisation international reference preparations is reflected by its International Sensitivity Index (ISI).

The “International Normalised Ratio” (INR) was introduced for the purpose of standardisation of the PT. The INR is the ratio of the patient’s anticoagulated plasma PT to the normal plasma PT using the same thromboplastin in the same test system raised to the power of a value defined by the International Sensitivity Index.

Undesirable effects are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000), including isolated reports.

Haemorrhage, in various organs, is the most common side-effect associated with Sinthrome; its occurrence is related to the dosage of the drug, the patient’s age and the nature of the underlying disease. Fatalities have been reported.

Possible sites of haemorrhage include the gastro-intestinal tract, brain, urogenital tract, uterus, liver, gall bladder and the eye. If haemorrhage occurs in a patient with a thromboplastin time within the therapeutic range, diagnosis of their condition must be clarified.

g. 4) *Usually associated with congenital deficiency of protein C or its cofactor protein S. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

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2). Renal impairment Due to the possibility of accumulation of metabolites in impaired renal function, caution should be exercised in patients with mild to moderate renal impairment. 2). Anticoagulant-related nephropathy In patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur, possibly in relation to episodes of excessive anticoagulation and hematuria.

A few cases have been reported in patients with no pre-existing kidney disease. Close monitoring including renal function evaluation is advised in patients with a supratherapeutic INR and hematuria (including microscopic). Heart failure In severe heart failure, a very cautious dosage schedule must be adopted, since hepatic congestion may reduce the activation of gamma-carboxylation of coagulation factors.

However, with reversal of the hepatic congestion, it may be necessary to raise the dosage. g. 8). Calciphylaxis Calciphylaxis is a rare syndrome of vascular calcification with cutaneous necrosis, associated with high mortality. The condition is mainly observed in patients with end- stage renal disease on dialysis or in patients with known risk factors such as protein C or S deficiency, hyperphosphataemia, hypercalcaemia or hypoalbuminaemia.

Rare cases of calciphylaxis have been reported in patients taking vitamin K antagonists including Sinthrome also in the absence of renal disease. In case calciphylaxis is diagnosed, appropriate treatment should be started and consideration should be given to stopping treatment with Sinthrome.

Hemorrhage Sinthrome can cause major (including hemorrhagic and hypovolemic shock) or fatal bleeding. 5 ),. Regular monitoring of INR should be performed on all treated patients [138]. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy.

2 Pharmacokinetic properties). g. thyrotoxicosis, tumours, renal disease, infections and inflammation). Disorders affecting gastro-intestinal absorption may alter the anticoagulant activity of Sinthrome. During treatment with anticoagulants, intramuscular injections may cause haematomas and should be avoided.

g. unsupervised patients with dementia, alcoholics and patients with psychiatric disorders). g. 2 Posology and method of administration) and in cases of increased fibrinolytic activity following operations on the lung, prostate or uterus etc.