Reversibility of the anti‐FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion

Abstract

Summary. Background: Idraparinux is an inhibitor of activated factor X (FXa) with a long half-life allowing once-weekly dosing. Idrabiotaparinux is a biotinylated version of idraparinux; its activity can be reversed with avidin. Objective: To investigate the tolerability, safety and pharmacodynamics of avidin in healthy subjects and patients with deep vein thrombosis (DVT) receiving idrabiotaparinux. Patients and Methods: In a placebo-controlled, randomized, double-blind Phase I study, 41 healthy males received subcutaneous idrabiotaparinux before being randomized to a 30-min intravenous avidin infusion or placebo. Idrabiotaparinux plus avidin were re-administered 10-14 months later in eight subjects. In addition, in a prospective substudy of the Phase III EQUINOX trial, 55 patients who received weekly idrabiotaparinux for 6 months were randomized to receive either 100 mg avidin (n = 33) or placebo (n = 22). The primary activity outcome was anti-FXa activity calculated immediately before and after avidin infusion. Adverse events were recorded to assess safety and tolerability. Results: Avidin rapidly reversed the anti-FXa activity of idrabiotaparinux, ranging from 66.1 to 90.3% in healthy subjects and from 67 to 97% (mean 78%) in DVT patients. Avidin was well tolerated, with a similar nature and frequency of adverse events to placebo. No venous thromboembolism recurrence occurred in the 3-month post-avidin infusion. Conclusion: A 30-min intravenous infusion of avidin 100 mg is well tolerated, safe, and offers immediate and specific reversibility both after single and repeated doses of idrabiotaparinux in healthy subjects, and in DVT patients following a 6-month treatment period.

Current approaches in atrial fibrillation treatment

“…AME-DEUS çalışmasına 4576 hasta alınmış olup inme ve emboli oranı warfarinde %1.3 idraparinux'ta %0.9 bulunmuştur (p=0.0007). Kanama oranları warfarine göre fazla olması nedeniyle %19.7 vs %11.3 (p=0.0001) nötralize edilebilen formu biotinylated idraparinux üretilmiştir ve en son hasta alımı Eylül 2010 olan BOREALİS-AF çalışmasında warfarin ile karşılaştırılmaktadır [40,41]. Direk FXa inhibitörle-rinden rivoraxaban 1100 merkezde 14.000 den fazla hasta alınan ROCKET-AF çalışmasında nonvalvu-ler AF'de tek doz kullanımı warfarinle karşılaştırıl-mış olup non inferior bulunmuştur [42].…”

New Antithrombotic Drugs

“…The primary end point, thrombus burden, as assessed by measuring changes in compression ultrasound and perfusion lung scan fi ndings, Reversibility of idraparinux was demonstrated in two studies. 94 First, in a double-blind phase 1 study, 41 healthy males received idrabiotaparinux prior to being randomized to a 30-min infusion of either 100 mg of avidin or placebo. In eight of these subjects, idrabiotaparinux plus avidin was readministered 10 to 14 months later.…”

Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte

“…O idraparinux e idrobiotaparinux são formas hipermetiladas do fondaparinux, têm meias-vidas mais prolongadas (80 a 130 horas), de modo que podem ser usados em intervalos de 1 semana, ministradas por via SC 28 . O idrabiotaparinux tem biotina incorporada à molécula, de modo que sua ação anticoagulante pode ser revertida com injeção de avidina 40 . Entretanto, devido ao maior risco de sangramento observado em estudo de tratamento do TEV 41 e à inferioridade em relação à enoxaparina + varfarina no tratamento da embolia pulmonar (EP) 42 , aparentemente ambas não são mais desenvolvidas pelo fabricante.…”