Agents that may enhance the risk of haemorrhage should not be administered concomitantly or should be administered with caution with Pradaxa (see section 4.5).
Interaction with P-gp inducers

Concomitant administration of P-gp inducers (such as rifampicin, St. John`s wort (Hypericum perforatum), carbamazepine, or phenytoin) is expected to result in decreased dabigatran plasma concentrations, and should be avoided (see sections 4.5 and 5.2).
Surgery and interventions

Patients on dabigatran etexilate who undergo surgery or invasive procedures are at increased risk for bleeding. Therefore surgical interventions may require the temporary discontinuation of dabigatran etexilate.

Caution should be exercised when treatment is temporarily discontinued for interventions and anticoagulant monitoring is warranted. Clearance of dabigatran in patients with renal insufficiency may take longer (see section 5.2). This should be considered in advance of any procedures. In such cases a coagulation test (see sections 4.4 and 5.1) may help to determine whether haemostasis is still impaired.
Preoperative phase
Table 2 summarizes discontinuation rules before invasive or surgical procedures.
Renal function

(CrCL in ml/min)
 Estimated half-life

(hours)
 Stop dabigatran before elective surgery
 
High risk of bleeding or major surgery
 Standard risk
 
 80
 ~ 13
 2 days before
 24 hours before
 
 50-< 80
 ~ 15
 2-3 days before
 1-2 days before
 
 30-< 50
 ~ 18
 4 days before
 2-3 days before (> 48 hours)
If an acute intervention is required, dabigatran etexilate should be temporarily discontinued. A surgery / intervention should be delayed if possible until at least 12 hours after the last dose. If surgery cannot be delayed the risk of bleeding may be increased. This risk of bleeding should be weighed against the urgency of intervention.

Spinal anaesthesia/epidural anaesthesia/lumbar puncture

Procedures such as spinal anaesthesia may require complete haemostatic function.

The risk of spinal or epidural haematoma may be increased in cases of traumatic or repeated puncture and by the prolonged use of epidural catheters. After removal of a catheter, an interval of at least 2 hours should elapse before the administration of the first dose of dabigatran etexilate. These patients require frequent observation for neurological signs and symptoms of spinal or epidural haematoma.

Post-surgical patients with an increased risk for bleeding

Patients at risk for bleeding or patients at risk of overexposure, notably patients with moderate renal impairment (CrCL 30-50 ml/min), should be treated with caution (see sections 4.4 and 5.1). Resume treatment after complete haemostasis is achieved.

Patients at high surgical mortality risk and with intrinsic risk factors for thromboembolic events

There are limited efficacy and safety data for dabigatran available in these patients and therefore they should be treated with caution.

Hip fracture surgery

There is no data on the use of Pradaxa in patients undergoing hip fracture surgery. Therefore treatment is not recommended.

Colorants

Pradaxa hard capsules contain the colorant sunset yellow (E110), which may cause allergic reactions.