Antidote for eliquis5/28/2023 With or without simultaneous food administration, levels peak at 3 to 4 hours. Courtney Broaddus MD, in Murray & Nadel's Textbook of Respiratory Medicine, 2022 Apixaban (a Direct Oral Anticoagulant)Īnother anti–factor Xa drug, apixaban, is begun 12 to 24 hours after hip or knee replacement surgery at 2.5 mg every 12 hours and is continued for 35 days (hip) and 12 days (knee). There was major bleeding or non-major clinically relevant bleeding in 28 (7.3%) of the 385 patients who received apixaban and in 10 (7.9%) of the 126 who received conventional anticoagulants. In a dose-ranging study 520 patients with deep vein thrombosis were randomized to apixaban 5 mg bd, 10 mg bd, or 20 mg/day, or to low-molecular-weight heparin for 84–91 days followed by a coumarin. Apixaban was less effective than the comparators, but there were significant and similar dose-related increases in the incidence of total bleeding events with once- and twice-daily apixaban. Adverse effects were assessed in 1217 patients and efficacy in 856. Treatment lasted for 10–14 days and started 12–24 hours after surgery. They were randomized to 5, 10, or 20 mg/day given as a single dose or twice-daily divided doses, enoxaparin 30 mg bd, or warfarin (titrated to an INR of 1.8–3.0). In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016 Comparative studiesĪpixaban has been evaluated in a double-blind study in 1238 patients after total knee replacement. 162 Larger studies are currently underway to further evaluate the effectiveness and safety of andexanet alfa. In this small study, there were no serious adverse events and no cases of inappropriate thrombosis. In the rivaroxaban group (41 participants) a 92% reduction in anti-Xa activity was seen in the andexanet alfa–treated group ( n = 27), compared to 18% in the placebo group ( n = 14). Thrombin generation was fully restored in 100% of the treatment group and 11% of the placebo group. In the apixaban group (33 participants), anti–factor Xa activity was reduced by 94% in the andexanet alfa–treated group ( n = 24) compared to 21% among those who received a placebo ( n = 9). The end point was measurement of anti–factor Xa activity and thrombin generation. Both arms of the study first looked at a bolus dose of andexanet alfa and then a bolus followed by a continuous 2-hour infusion. The NEJM study had two different arms each looked at andexanet alfa reversal of either apixaban or rivaroxaban compared to a placebo. In humans, the drug has been shown to reverse markers of anticoagulation, including anti–factor Xa activity. Andexanet alfa acts as an inactive factor Xa decoy that binds both direct and indirect factor Xa inhibitors and makes them unavailable to inhibit native factor Xa. 162 This drug, which is scheduled for release in the fall of 2016, is capable of reversing the effect of all direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) and indirect factor Xa inhibitors (low-molecular-weight heparins and fondaparinux). 161 The risks and benefits must be thoroughly weighed when choosing to reverse anticoagulation with agents that could cause thrombosis.Ī 2015 study published in the New England Journal of Medicine (NEJM) looked at a novel reversal agent, andexanet alfa. According to the Hemostasis and Thrombosis Research Society, the use of four-factor PCCs seems to be a reasonable approach to reversing the effects of direct Xa inhibitors. 160 Although the effectiveness is suggested in animal bleeding models, there have been no studies evaluating the effect of PCCs on clinical bleeding in humans receiving factor Xa inhibitors. Four-factor PCCs also seem effective at reversing abnormal coagulation parameters in healthy humans taking these medications. 157–159 As a result, FEIBA is an acceptable agent to reverse the effects of direct Xa inhibitors. In contrast, FEIBA was effective in reversing abnormal coagulation studies in rivaroxaban-treated healthy volunteers and seemed to be effective at reversing bleeding in two animal models. At the present time, rFVIIa is not recommended as a reversal agent for direct factor Xa inhibitors. 156 rFVIIa failed, however, to reverse active bleeding in a rivaroxaban animal model. In an ex vivo study of healthy volunteers, rFVIIa reversed abnormal coagulation studies in patients who were given rivaroxaban. A variety of strategies using rFVIIa, PCC, and FEIBA have been tried in the treatment of these patients. Roberts MD, FACEP, FAAEM, FACMT, in Roberts and Hedges’ Clinical Procedures in Emergency Medicine and Acute Care, 2019 Direct Factor Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)ĭirect factor Xa inhibitors also present a challenge to reversal in the setting of acute hemorrhage.
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