ation activation. Table 1 Pharmacological profile of new oral anticoagulants: direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban and direct thrombin inhibitor dabigatran Drug Rivaroxaban Apixaban Edoxaban Dabigatran Target Xa Xa Xa IIa VTE prophylaxis dose 10 mg OD 2.5 mg BID VX-680 MK-0457 220 mg OD 1 4 h, 110 mg Bioavailability Up to 100% 66% 50% 6% Half life 5 13 h 8 15 h 9 11 h 12 17 h Renal elimination 40% 25% 35% 85% Interactions CYP3A4/p Gp inhibitors CYP3A4/p Gp inhibitors CYP3A4/p Gp inhibitors p Gp inhibitors Abbreviations: BID, twice daily, CrCl, creatinine clearance, CYP, cytochrome P450, OD, once daily, p Gp, p glycoprotein, VTE, venous thromboembolism. submit your manuscript | www.dovepress.
com Dovepress Dovepress 141 VTE prophylaxis MLN8237 in major orthopedic surgery Therapeutics and Clinical Risk Management 2012:8 or clarithromycin leads to higher plasma concentrations of dabigatran, requiring a dose reduction. Furthermore, the combination of dabigatran and ketoconazole, ciclosporin, itraconazol, and tacrolimus is prohibited. Due to the reduction of dabigatran plasma concentrations, concomitant therapy with St Johns wort or rifampicin is not recommended. Clinical trials of apixaban in major orthopedic surgery Dose response relationship and the safety of escalating doses of apixaban were tested in a trial comparing enoxaparin twice daily 30 mg subcutaneously, open label warfarin target international normalized ratio 1.8 3.0, and six double blind apixaban doses 5 mg,10 mg, and 20 mg daily as once or twice daily divided dose in patients undergoing total knee replacement.
43 Treatment lasted 10 14 days, commencing 12 24 hours after surgery with apixaban and enoxaparin and on the evening of surgery with warfarin. Usual exclusion criteria applied, and a mandatory bilateral venography was scheduled for Day 12 after the last study drug dose. Primary efficacy outcome was a composite of VTE and all cause mortality during treatment. Primary safety outcome was major bleeding, defined as reduction of hemoglobin. 2 g/dL and/or requirement of two units of packed red blood cells, need for discontinuing study medication, intracranial, retroperitoneal, intraspinal, or necessitating reoperation or intervention, intrapericardial or fatal. Minor bleeding were all events not meeting these criteria. A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis.
In all apixaban treatment arms, patients had lower primary efficacy event rates than either comparator. The primary outcome decreased with increasing apixaban dose. Efficacy outcome was 9.0% for 2.5 mg apixaban twice daily and 11.3% for 5 mg apixaban once daily, compared with 15.6% in the enoxaparin and 26.6% in the warfarin group. Total VTE rates were lower in the twice daily group than in the once daily regimen. For the composite outcome of proximal DVT or PE and allcause mortality, each apixaban group had a lower event rate compared with the enoxaparin group, which was not statistically significant. For both once daily and twice daily apixaban regimens, a significant dose related increase in the incidence of bleeding events was noted. Incidence ranged from 0% to 3.3%. No major bleeding was observed in either the enoxaparin group or the warfarin group. Minor bleeding incidences during apixaban, enoxaparin, and warfarin treatment were 0.7% 7.2%, 4.0%, and 5.3%, respectively. For patients receiving apixaban, rates of myocardial infarction and stroke were in line with ot
Related posts:
- Pazopanib GW786034 patients with deep leg vein thrombosis or PE in which study treatment
- VX-680 MK-0457 of GSH or restore vitro susceptibility to increased hen
- 5-HT Receptor mutations all appear to constitutive activation of the kinase
- Dyphylline p38 MAPK activation by TGF-beta1 increases MLC
- Sunitinib Sutent increased Hte signaling through NTAL improved activation of ERK