Current drug discovery technologies
-
For more than 50 years, heparin(s) and warfarin have been the most important anticoagulant agents, and clinicians are accustomed to their specific antidotes (protamine sulfate and vitamin K/plasma [or factor concentrates], respectively). Recently, there has been an explosion of novel anticoagulant development: ideally, these newer agents should have advantages over traditional anticoagulants, such as fewer side effects, a more predictable pharmacokinetic profile (and potentially no need for monitoring), minimal drug-drug interactions, and so forth. But, unlike the older agents, the newer anticoagulants do not have specific antidotes. ⋯ Based on extrapolation from animal models, clinical anecdote, and an understanding of their mechanism of action, we recommend treating major bleeding complications of DTIs, as follows (in descending order of preference): activated PCCs; rFVIIa; and (non-activated) PCCs. For management of fondaparinux-associated bleeding, rFVIIa has some rationale (for which we provide an illustrative case). The increasing use of novel anticoagulants will require physicians to have an understanding of rational approaches to "reverse" their anticoagulant effects when true antidotes do not exist.
-
Curr Drug Discov Technol · Jun 2012
ReviewNew oral anticoagulants for venous thromboembolism: focus on factor Xa and thrombin inhibitors.
Several oral direct anti-Xa agents and one antithrombin agent are currently under clinical development for the prevention and treatment of venous thromboembolism (VTE). The anti-Xa inhibitors rivaroxaban (10 mg once daily) and apixaban (2.5 mg twice daily) as well as the thrombin inhibitor dabigatran (150 or 220 mg once daily) have been recently licensed for the prevention of VTE in total hip or knee replacement. The publication of the results of studies with rivaroxaban and apixaban in the prevention of VTE in medical patients are awaited. ⋯ The incidence of major or clinically relevant non-major bleeding was similar in patients receiving standard treatment and rivaroxaban or dabigatran. Clinical trials on VTE treatment are currently ongoing with apixaban and edoxaban. A number of phase II clinical trials are currently ongoing with several other antiXa agents in the prophylaxis and treatment of VTE.