Bleeding

The table 4 shows the number (%) of patients experiencing bleeding events during the treatment period in the VTE prevention in the two pivotal clinical trials, according to dose.

  Dabigatran etexilate

150 mg

N (%)
 Dabigatran etexilate

220 mg

N (%)
 Enoxaparin
N (%)
 
Treated
 1866 (100.0)
 1825 (100.0)
 1848 (100.0)
 
Major Bleeding
 24 (1.3)
 33 (1.8)
 27 (1.5)
 
Any bleeding
 258 (13.8)
 251 (13.8)
 247 (13.4)
The definition of major bleeding events in the RE-NOVATE and RE-MODEL studies were as follows:

• fatal bleeding

• clinically overt bleeding in excess of what was expected and associated with  20 g/l (corresponds to 1.24 mmol/l) fall in haemoglobin in excess of what was expected

• clinically overt bleeding in excess of what was expected and leading to transfusion of  2 units packed cells or whole blood in excess of what was expected

• symptomatic retroperitoneal, intracranial, intraocular or intraspinal bleeding

• bleeding requiring treatment cessation

• bleeding leading to re-operation

Objective testing was required for a retroperitoneal bleed (ultrasound or Computer Tomography (CT) scan) and for an intracranial and intraspinal bleed (CT scan or Magnetic Resonance Imaging).

4.9 Overdose

 Doses of dabigatran etexilate beyond those recommended, expose the patient to increased risk of bleeding.
In case of an overdose suspicion, coagulation tests can help to determine a bleeding risk (see sections 4.4 and 5.1). A calibrated quantitative dTT test or repetitive dTT measurements allow prediction of the time by when certain dabigatran levels will be reached (see section 5.1), also in case additional measures e.g. dialysis have been initiated.

Excessive anticoagulation may require interruption of Pradaxa treatment. There is no specific antidote to dabigatran. In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. Since dabigatran is excreted predominantly by the renal route adequate diuresis must be maintained. Appropriate supportive treatment, such as surgical haemostasis and blood volume replacement, should be undertaken at the prescribers discretion.

As protein binding is low, dabigatran can be dialysed; there is limited clinical experience to demonstrate the utility of this approach in clinical studies.
5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

 Pharmacotherapeutic group: direct thrombine inhibitors, ATC code: B01AE07

Dabigatran etexilate is a small molecule prodrug which does not exhibit any pharmacological activity. After oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by esterase-catalysed hydrolysis in plasma and in the liver. Dabigatran is a potent, competitive, reversible direct throm