Dabigatran (Pradaxa): risk of bleeding relating to use
Safety advisory
3 November 2011
Pradaxa (dabigatran) is an oral anticoagulant medicine originally used for the prevention of clots in the legs after major orthopaedic surgery (such as hip or knee replacement). In April 2011, the Therapeutic Goods Administration (TGA) approved the use of Pradaxa to prevent stroke and other blood clots in people with atrial fibrillation (AF), a commonly occurring abnormal heart rhythm. As with warfarin, another oral anticoagulant, there is a risk of bleeding when using this medicine.
Risk factors for bleeding
Age ≥ 75 years
Moderate renal failure (creatinine clearance 30 - 50 mL/min)
Use with aspririn, clopidogrel, non-steroidal anti-inflammatory drugs, warfarin
Please refer to additional safety information about monitoring renal (kidney) function while using Pradaxa on the TGA website at Dabigatran (Pradaxa) & the risk of bleeding: new recommendations for monitoring kidney function.
Increased incidence of reported adverse events
Since more people have started to use Pradaxa the TGA has received an increase in the number of bleeding-related adverse events reports.
Adverse events reported to the TGA for Pradaxa from 14 June 2009 to 14 October 2011
| Type of adverse event | Number since 2009 |
|---|---|
| Total adverse events | 297 |
| Serious adverse events | 196 |
| Serious bleeding adverse events | 70 |
| Serious gastrointestinal bleeding | 48 |
| Serious intracranial bleeding | 6 |
| Events in patients aged 75 years or older | |
| Total adverse events | 166 |
| Serious adverse events | 108 |
The TGA analysis of these reports shows that:
- Some of the bleeding adverse events occurred during the transition from warfarin to dabigatran.
- Many of the adverse events are occurring in patients on the reduced dosage regimen.
- The most common site of serious bleeding for Pradaxa is the gastrointestinal tract, whereas for warfarin it is intracranial.
In clinical trials the risk of bleeding per year of treatment with Pradaxa was 16.6% (1 in 6 patients) when taking 150 mg twice daily, and 14.7% (1 in 6.8 patients) taking 110 mg twice daily) compared to 18.4% (1 in 5.4 patients) for warfarin.
Information for health professionals
As a result of the TGA investigation, the TGA would like to remind clinicians of factors to be considered when prescribing Pradaxa. It is strongly recommended that clinicians read the Product Information before prescribing Pradaxa.
- Clinicians are urged to give careful consideration to the suitability of their patients for Pradaxa, particularly with regard to the risks of bleeding and their current stability on warfarin or other anticoagulants.
- Special consideration should be given to the perioperative management of patients taking Pradaxa. Clinicians are directed to the Product Information for guidance.
Australian experts are currently developing Australian guidelines for the management of bleeding in patients taking Pradaxa. In the meantime, clinicians are referred to the New Zealand guidelines for management of bleeding with dabigatran.
Information for consumers
If you are taking Pradaxa:
- You should not suddenly stop taking Pradaxa or lower the dose without consulting your doctor.
- You should see your doctor immediately if you notice bleeding, red or brown urine, or red or black bowel motions.
- Remember to tell all doctors, dentists and pharmacists who are treating you that you are taking Pradaxa.
Laboratory tests for dabigatran
Existing standard laboratory tests are not validated for use with dabigatran. In cases of emergency, the most accessible qualitative tests are:
- Thrombin Time (TT)
- activated Partial Thromboplastin Time (aPTT). An aPTT >80 seconds is associated with a higher bleeding risk.
Prothrombin time (INR) should not be used. Interpretation of coagulation assay results should consider time of dabigatran administration relative to time of blood sampling.
How to report an adverse event
Consumers and healthcare professionals are encouraged to report adverse reactions associated with Pradaxa to the TGA. Your report will be acknowledged, and will contribute to our continued monitoring of this medicine.
The TGA cannot give personal advice about an individual's medical condition. Consumers are strongly encouraged to talk with a health professional if they are concerned about a possible adverse reaction to any medication.
Information about dabigatran
Dabigatran is a direct thrombin inhibitor that inhibits free and clot-bound thrombin. It has a mean half life of 12-17 hours and is excreted by the kidneys; the rate of elimination is related to kidney function.
The TGA approved dabigatran was approved for the prevention of venous thromboembolic events in adult patients who have undergone major orthopaedic surgery of the lower limb (elective total hip or knee replacement) in November 2008. It is currently listed on the Pharmaceutical Benefits Scheme (PBS) for this indication, with limited usage.
In April 2011 the approved indications for Pradaxa were extended to include the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and at least one risk factor for stroke. An increase in adverse event reports occurred after this extension of indications.
For more detailed information regarding the considerations of the TGA in approving Pradaxa, please see the Australian Public Assessment Report (AusPAR) for Pradaxa.
Content last updated: Thursday, 3 November 2011
Web page last updated: Tuesday, 14 February 2012
URL: http://www.tga.gov.au/safety/alerts-medicine-dabigatran-111005.htm