Boehringer Ingelheim implements additional guidance supporting appropriate use of Pradaxa® (dabigatran etexilate) in Europe

Boehringer Ingelheim has agreed with the European Medicines Agency (EMA) to update healthcare professionals across Europe on Pradaxa® (dabigatran etexilate) regarding the importance of renal function assessment. Pradaxa® is approved in Europe for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors* and for the primary prevention of venous thromboembolic (VTE) events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery. 1

The communication to be sent to healthcare professionals strengthens that patients taking Pradaxa® should have their renal function evaluated prior to treatment initiation. While on treatment, renal function should be assessed in clinical situations where a decline in renal function is suspected (e.g. hypovolemia, dehydration and with certain comedications). In patients older than 75 or with renal impairment renal function should be assessed at least yearly whilst on treatment. Given Pradaxa® is mainly excreted renally, the treatment should not be prescribed to patients with severe renal impairment (creatinine clearance less than 30 ml/min).

Further to the healthcare professional communication, Boehringer Ingelheim has agreed with the EMA to strengthen the Summary of Product Characteristics (SmPC) and the prescriber guides accordingly. It is of critical importance that healthcare professionals abide by the information regarding the appropriate and safe use of Pradaxa® as provided in the label, and report any adverse events suspected to be associated with the use of the treatment to Boehringer Ingelheim in their respective countries or to their national health authority.

The main reason for using an anticoagulant such as Pradaxa® is to prevent blood clots which can lead to stroke or VTE events. Caution is however warranted with the use of all anticoagulants since they increase the risk of bleeding. It is well established that this risk increases with age or when multiple risk factors for bleeding are combined in an individual patient such as renal impairment, prior history of bleeding or concomitant treatment with other antithrombotics (e.g. aspirin or clopidogrel). 2 While Pradaxa® does not require routine international normalized ratio (INR) monitoring like the long-time standard of care warfarin, clinical surveillance including the assessment of renal function needs to be undertaken by treating physicians before initiation and over the course of the therapy as appropriate.

The effectiveness and favourable safety profile of Pradaxa® has been proven within an extensive clinical trial programme 3-7, passing independent regulatory scrutiny and approval worldwide.

Compared to well-controlled warfarin (median time in therapeutic range (TTR) 67.3%), the following results were seen with Pradaxa® in the landmark RE-LY® trial: 3,4

• Pradaxa® 150mg bid significantly reduced the risk of stroke and systemic embolism by 35%, providing clinically important stroke prevention in non-valvular AF
• Pradaxa® 150mg bid significantly reduced both ischaemic (RRR 25 %) and haemorrhagic stroke (RRR 74%)
• Pradaxa® 110mg bid showed similar rates of stroke and systemic embolism as well-controlled warfarin
• Both doses of Pradaxa® significantly reduced intracranial and life threatening bleeding compared to warfarin
• Pradaxa® 110mg bid also significantly reduced major bleeds.

The RE-LY® trial was a PROBE trial (prospective, randomized, open-label with blinded endpoint evaluation), comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin. 3

Boehringer Ingelheim closely monitors the use of all its medicines including Pradaxa® and will continue to work with health authorities to ensure that usage of the product appropriately reflects the label. Boehringer Ingelheim is confident that the additional guidance supports the correct use of Pradaxa® in clinical practice, enabling healthcare professionals and patients

References

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4. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY® trial. N Engl J Med 2010;363(19):1875-1876.
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*Previous stroke, transient ischemic attack, or systemic embolism (SEE); Left ventricular ejection fraction < 40 %; Symptomatic heart failure, ≥ New York Heart Association (NYHA) Class 2; Age ≥ 75 years; Age ≥ 65 years associated with one of the following: diabetes mellitus, coronary artery disease, or hypertension.