Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases.

Abstract

As the only oral anticoagulation option available in the United States, warfarin use remains widespread. However, concerns of safety remain a substantial issue. Additional anticoagulation options include unfractionated heparin, low-molecular-weight heparins (e.g., enoxaparin, dalteparin, and tinzaparin), and the indirect-acting factor Xa inhibitor, fondaparinux. Direct thrombin inhibitors represent a newer class of anticoagulants used primarily in the treatment of heparin-induced thrombocytopenia and percutaneous coronary interventions. Three intravenous agents are currently available-lepirudin, bivalirudin, and argatroban-with an oral agent, dabigatran etexilate, undergoing clinical investigation. Dabigatran etexilate offers a rapid onset of action after oral administration, reaching peak plasma concentrations and onset of anticoagulant effect within 0.5-2 hours after administration. Studies have demonstrated linear pharmacokinetics, a linear relationship between ecarin clotting time and international normalized ratio, and no known clinically significant drug or food interactions. Dabigatran etexilate has been studied in clinical trials as prophylaxis for venous thromboembolism in patients undergoing total knee replacement or total hip replacement surgeries, as well as for stroke prevention in patients with atrial fibrillation. Dabigatran etexilate has demonstrated superiority and noninferiority to enoxaparin as prophylaxis for venous thromboembolism in patients undergoing orthopedic surgery, with the most frequent adverse effects being gastrointestinal complaints. Elevations in alanine aminotransferase concentrations were noted in small percentages of patients in both the dabigatran etexilate and enoxaparin groups, with no observed dose association. The overall rates of major bleeding were low, with minor bleeding commonly noted, often at surgical sites. Clinical trials of dabigatran etexilate in patients with atrial fibrillation are ongoing. Results of short-term efficacy and safety appear promising. Further research is needed regarding long-term safety and efficacy for other anticoagulation indications.

• Authors: Brooke E Baetz, Sarah A Spinler
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 28 Issue 11 Pg. 1354-73 (Nov 2008) ISSN: 0277-0008 [Print] United States
• PMID: 18956996 (Publication Type: Journal Article, Review)

Chemical References

• Anticoagulants
• Benzimidazoles
• Pyridines
• Thrombin
• Dabigatran

Topics

• Animals
• Anticoagulants (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Atrial Fibrillation (drug therapy, prevention & control)
• Benzimidazoles (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Clinical Trials as Topic
• Dabigatran
• Humans
• Pyridines (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
• Thrombin (antagonists & inhibitors)
• Thromboembolism (drug therapy, prevention & control)