Posts Tagged ‘Edoxaban’
Stephan Moll, MD writes (on Nov 7th, 2014)… A publication this week in the New England Journal of Medicine reports on a new reversal agent (PER977 = Aripazine = ciraparantag) that may be effective against a number of different new oral anticoagulants [ref 1]. Read the rest of this entry »
Stephan Moll, MD writes… Today the FDA approved Pradaxa (dabigatran) for the treatment of DVT and PE. Thus, two of the new oral blood thinners are now FDA-approved for the treatment of DVT and PE: Xarelto (rivaroxaban) and Pradaxa (dabigatran). Due to the design of the clinical trials that lead to the FDA approval, Pradaxa should NOT be given immediately when DVT or PE are diagnosed, but rather after 5-10 days of treatment with an injectable blood thinner (into the skin or a vein; such as Lovenox = enoxaparin; Fragmin = dalteparin; Innohep = tinzaparin; or heparin). A Clot Connect summary of the FDA approval status of the four big new oral blood thinners for the various indications is in this table. Pradaxa’s full medication package insert is here. Today’s press release from Boehringer-Ingelheim about the FA approval is here.
Disclosures: I have been a consultant for Boehringer-Ingelheim, Daiichi, and Janssen.
Last updated: April 7th, 2014
Stephan Moll, MD writes… This week (Sept 1st 2013) the New England Journal of Medicine published the phase 3 clinical trial of the new oral blood thinner edoxaban compared with warfarin in the treatment of DVT and PE [ref 1]. It showed that edoxaban was as effective as warfarin and led to less clinically relevant bleeding.
- Edoxaban is one of the new oral blood thinners (anti-Xa anticoagulant) that does not require routine m0nitoring for its blood thinning effect and does not interact with vitamin K in the diet like warfarin.
- At this point it is not FDA approved for any indication.
- It is dosed once daily.
- It reaches its peak blood thinning effect within 1 to 2 hours of oral intake.
- Its half-life is 9-11 hours, which means that it is mostly out of the system in 48 hours after stopping it.
- 35 % of the drug is cleared by the kidney, which means that it needs to be dose reduced or avoided in patients with significant impairment of kidney disease.
- This is a randomized, double-blind study.
- All patients received initial therapy with open-label enoxaparin into the skin (subcutaneous) or intravenous heparin for at least 5 days, before edoxaban or warfarin were started.
- Edoxaban was dosed 60 mg once daily. The dose was reduced to 30 mg once daily in patients with impaired kidney function or a body weight less than 60 kg (132 pounds).
- Length of treatment with blood thinners was 3 to 12 months.
- A total of 8292 patients were enrolled (4143 into the edoxaban treatment arm, 4149 into the warfarin arm).
- Recurrent DVT or PE occured in 3.2 % of patients in the edoxaban group and 3.5 % in the warfarin group. Conclusion: edoxaban is not worse than warfarin.
- “Clinically relevant bleeding” occured in 8.5 % of patients in the edoxaban group and 10.3 % in the warfarin group. Conclusion: edoxaban is better than warfarin from a bleeding point of view.
- “Major bleeding” was the same in both groups, 1.4 % in the edoxaban group, 1.6 % in the warfarin group. Conclusion: edoxaban is not worse than warfarin in respect to major bleeding.
The study concludes that edoxaban (a) is as effective as high quality standard therapy with warfarin, and (b) causes less clinically relevant bleeding.
My perspective – Edoxaban compared to the other new oral blood thinners
- This table lists the key differences of the 4 new oral blood thinners in the treatment of VTE.
- Edoxaban is the 4th of the big new oral blood thinners. Its development lags behind the other 3 drugs, which are, at least for the irregular heart beat (atrial fibrillation) indication, already FDA-approved and on the market. For DVT and PE treatment, only rivaroxaban (Xarelto) is FDA-approved; Xarelto is, therefore, the only one of the new oral blood thinners I would use at this time for DVT and PE treatment.
- The main downside of the edoxaban study design is that edoxaban was not started right off the bat once the diagnosis of VTE was made in a patient, but that patients were first treated for at least 5 days with la ow molecular weight heparin (LMWH) blood thinner into the skin or i.v. heparin before edoxaban or warfarin were started. This is similar to the dabigatran study design. The Xarelto and Pradaxa studies, on the other hand, gave the new oral blood thinner immediately after diagnosis, without the need for initial LMWH. Thus, from a clinical-practical point of view, treatment of an acute DT or PE with edoxaban would be more cumbersome (cost of LMWH; teaching of self injections) than treatment with Xarelto or Eliquis.
- Edoxaban is given once daily. This is more convenient for patients than a twice daily regimen, such as with Pradaxa and Eliquis.
- It is good to see data of DVT and PE trials on these various drugs published and the drugs making their way through the FDA approval process and, hopefully, eventually onto the market. It is good to see data on a variety of different patients treated with these drugs, as there are a number of different types of patients which we need to learn more about as to how they fare on the new oral blood thinners: patients who are obese, have kidney impairment, have large PEs, have cancer, etc. The data published in today’s New England Journal of Medicine are a very helpful addition to our knowledge-base.
- HOKUSAI-Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013;Sept 1.
- Agnelli G et al. Oral Apixaban for the Treatment of acute venous thromboembolism. N Engl J Med, 369:799-808.
- The Einstein Investigators: Oral Rivaroxaban for symptomatic venous thromboembolism. New Engl J Med 2010;363:2499-510.
- The Einstein Investigators: Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism. New Engl J Med 2012;366:1287-97.
- Schulman s et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim and Daiichi.
Last updated: Sept 2nd, 2013
Stephan Moll, MD writes…
1. Pradaxa (Dabigatran)
- Today, August 28th, 2013, it was announced that the FDA is reviewing the application by Boehringer-Ingelheim to get Pradaxa (dabigatran) approved for use in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) – details here.
- At present, in the US, Pradaxa is only FDA-approved for prevention of stroke and other arterial clots in patients with irregular heart beat.
2. Eliquis (Apixaban)
- On July 11th , 2013 the company making Eliquis applied for FDA approval of their drug for DVT and PE prevention after hip and knee replacement surgery – details here.
- The company has not yet filed for approval of the drug for DVT and PE treatment.
- At present, in the US, Eliquis is only FDA-approved for prevention of stroke and other arterial clots in patients with irregular heart beat.
3. Xarelto (Rivaroxaban)
- Xarelto is, at present the only one of the new oral anticoagulants that is FDA-approved for the treatment of DVT and PE. It is also approved for (a) DVT and PE prevention after hip and knee replacement surgery, and (b) for prevention of stroke and other arterial clots in patients with irregular heart beat.
- This new oral anticoagulant by the Japanese company Daiichi is not FDA-approved at this time and no FDA review of data is pending, as far as I know, for any indication.
Disclosure: I have consulted for Janssen, Daiichi, Boehringer Ingelheim.
Last updated: Aug 28th, 2013
Stephan Moll writes…
Savaysa® (Edoxaban), the 4th of the big new oral blood thinners in development (the other big 3 being Dabigatran = Pradaxa, Rivaroxaban = Xarelto, and Apixaban = Eliquis), is now commercially available in Japan (July 19th, 2011 press release here). It is available as once daily dosing for prevention of blood clots in the legs and lungs (DVT and PE) Read the rest of this entry »