Haemorrhagic risk

As with all anticoagulants, dabigatran etexilate should be used with caution in conditions with an increased risk of bleeding. Bleeding can occur at any site during therapy with dabigatran. An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to a search for a bleeding site.

Factors, such as decreased renal function (30-50 ml/min CrCL), age  75 years, low body weight < 50 kg, or strong P-gp inhibitor co-medication (e.g. amiodarone, quinidine or verapamil) are associated with increased dabigatran plasma levels (see sections 4.2, 4.5 and 5.2).

Use of acetylsalicylic acid (ASA), clopidogrel or non steroidal antiinflammatory drug (NSAID), as well as the presence of esophagitis, gastritis or gastroesophageal reflux requiring proton pump inhibitors (PPI) or histamine 2 (H2)-blocker treatment increase the risk of GI bleeding. The administration of a PPI can be considered to prevent GI bleeding.

Close clinical surveillance (looking for signs of bleeding or anaemia) is recommended throughout the treatment period, especially if risk factors are combined (see section 5.1).

Table 1 summarises factors which may increase the haemorrhagic risk.

Pharmacodynamic and kinetic factors
 Age  75 years
 
Factors increasing dabigatran plasma levels
 Major:

• Moderate renal impairment (30-50 ml/min CrCL)

• P-gp inhibitor co-medication

Minor:

Low body weight (< 50 kg)
 
Pharmacodynamic interactions
 • ASA

• NSAID

• Clopidogrel
 
Diseases / procedures with special haemorrhagic risks
 • Congenital or acquired coagulation disorders

• Thrombocytopenia or functional platelet defects

• Active ulcerative GI disease

• Recent GI bleeding

• Recent biopsy or major trauma

• Recent ICH

• Brain, spinal or ophthalmic surgery

• Bacterial endocarditis
The measurement of dabigatran related anticoagulation may be helpful to avoid excessive high exposure to dabigatran in the presence of additional risk factors.

The activated partial thromboplastin time (aPTT) test is widely available and provides an approximate indication of the anticoagulation intensity achieved with dabigatran. In patients who are bleeding or at risk of bleeding, the aPTT test may be useful to assist in determining an excess of anticoagulant activity. However, the aPTT test has limited sensitivity and is not suitable for precise quantification of anticoagulant effect, especially at high plasma concentrations of dabigatran. High aPTT values should be interpreted with caution.

If required, more sensitive quantitative tests such as calibrated diluted Thrombin Time (dTT) should be performed (see section 5.1).

Patients who develop acute renal failure must discontinue Pradaxa (see section 4.3).

Limited data is available in patients < 50 kg (see section 5.2).

When severe bleedings occur treatment must be discontinued and the source of bleeding investigated (see se