Dose tailoring of dabigatran etexilate: obvious or excessive?

Abstract

Introduction: Dabigatran etexilate is used for preventing blood clots and tends to replace older anticoagulants in many of their indications. However, the ‘one dose fits all’ policy is subject to criticism. Recent findings assert the anxiety of the scientific community concerning the pharmacokinetic properties of dabigatran etexilate, that is, an important interindividual variability including an important genetic variant with a significant dependence of the renal function as route of elimination.

Areas covered: This meta-opinion provides an overview of the current knowledge and evidence on the dose tailoring of dabigatran etexilate. It also discusses the remaining challenges to benefit from this perspective strategy to enhance the benefit–risk balance of dabigatran etexilate. Data were searched in the published literature and on regulatory agencies’ websites. Additionally, unpublished data were searched and discussed.

Expert opinion: Causality between dabigatran exposure and bleeding risk is now established and recommendations on how to best estimate the drug exposure are published. Additionally, simulating studies revealed that a dose adaptation based on dabigatran plasma concentration estimations could improve the benefit–risk profile of the drug. This accumulating evidence suggests that some patients under dabigatran etexilate may benefit from a tailoring of the dose beyond the ones already proposed by the manufacturer.

Keywords:

• anticoagulant drugs
• benefit–risk assessment
• dabigatran etexilate
• drug monitoring

Acknowledgment

J Douxfils, F Mullier and J-M Dogné are contributed equally to this work.

Declaration of interests

F Mullier has acted as consultant for Boehringer Ingelheim, Bayer Healthcare, Bristol Meyers Squibb and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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