Novel oral anticoagulants: pharmacology, coagulation measures, and considerations for reversal

Abstract

Novel oral anticoagulants (NOAC) provide an effective and, in some cases, superior alternative to traditional, oral vitamin K antagonists such as warfarin. These drugs differ in their pharmacokinetic and pharmacodynamics profiles, which is important for selecting the right drug for the right patient. A concern among clinicians is a virtual absence of guidance from clinical trials for reversing the anticoagulant effects of these drugs in clinical settings such as life-threatening bleeding or a need for emergent procedures that carry bleeding risk. In this review, we discuss NOAC, the role of coagulation assays to assess their systemic anticoagulants effects, and the available data supporting strategies designed to reverse or attenuate these effects.

New antithrombotic therapies and complementary and alternative medicine (CAM): Chartering into unknown territory

“…Dabigatran etexilate is the pro-drug of dabigatran, which selectively and reversibly inhibits both free and clot-bound thrombin by binding to the active site of thrombin molecule [1,38]. As a prodrug, dabigatran etexilate is cleaved by a hydrolytic reaction involving serum and liver serine esterases to the active form [38].…”

“…As a prodrug, dabigatran etexilate is cleaved by a hydrolytic reaction involving serum and liver serine esterases to the active form [38]. This reaction occurs rapidly after intestinal absorption with peak plasma dabigatran concentrations occurring approximately 0.5 -2 hours after oral ingestion.…”

“…This reaction occurs rapidly after intestinal absorption with peak plasma dabigatran concentrations occurring approximately 0.5 -2 hours after oral ingestion. Dabigatran has a half-life of 12-14 hours [1,4,22,39] and given its hydrophilic nature has a poor intestinal absorption and a low oral bioavailability of 6.5% [38]. Dabigatran is unique in that it is not metabolised, induced or inhibited by the cytochrome P450 (CYP450) drug metabolising enzymes [1].…”

“…Dabigatran is unique in that it is not metabolised, induced or inhibited by the cytochrome P450 (CYP450) drug metabolising enzymes [1]. Dabigatran is a substrate for the p-glycoprotein (P-gp) efflux reverse transporter, an ATP-dependant pump that transports numerous substrates, including drugs across cell membranes [38]. Elimination of dabigatran after hepatic activation occurs predominately in the kidneys (up to 80%) [12].…”

“…The bioavailability of rivaroxaban is between 80 and 100% and has a half-life of approximately 5-9 hours, which is increased to 11-13hrs for individuals greater than 75 years of age [12,38] . Rivaroxaban is metabolised by CYP3A4 in the CYP450 system with 70% of the drug excreted in the urine and the remaining 30% excreted through the faeces [1,38]. Rivaroxaban does interact with the CY450 system with specific interactions with CYP3A4 and CYP2J2 [40].…”