title: Dose tailoring of dabigatran etexilate: obvious or excessive?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 Additionally, unpublished data were searched and discussed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Namur, Faculty of Medicine, Department of Pharmacy, Namur Research Institute for LIfe Sciences (NARILIS), Namur Thrombosis and Hemostasis Center (NTHC) , rue de Bruxelles, 61, B-5000 Namur, Belgium , Europe +32 81 72 42 92 ; +32 81 72 42 99 ; jonathan.douxfils@unamur.be.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069604:Dabigatran / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D014644:Genetic Variation; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: anticoagulant drugs; benefit–risk assessment; dabigatran etexilate; drug monitoring