Use Of Prothrombin Complex Concentrates (PCC) Or Other Procoagulant Reversal Agents Have Not Been Evaluated In Clinical Outcome Studies
(Posted by Tom Lamb at DrugInjuryWatch.com)
In relevant part, from a September 15, 2016 FDA letter to Daiichi-Sankyo, Inc.:
Prior Approval supplemental new drug application provides for changes to SAVAYSA prescribing information based on results of the Phase 1 trial DU176b-A-U158 that evaluated the effects of Prothrombin Complex Concentrate (PCCs) on reversing the pharmacologic activity of edoxaban tosylate. Sections 5.3 ‘Risk of Bleeding’ and 12.2 ‘Pharmacodynamics’ have been updated to include this information.
And here is the "new" section 5.3 Risk of Bleeding part of the Savaysa Prescribing Information document (accessed 9/27/16) -- also known as the package insert or the drug label:
Reversal of Anticoagulant Effect
There is no established way to reverse the anticoagulant effects of SAVAYSA, which can be expected to persist for approximately 24 hours after the last dose. The anticoagulant effect of SAVAYSA cannot be reliably monitored with standard laboratory testing. A specific reversal agent for edoxaban is not available. Hemodialysis does not significantly contribute to edoxaban clearance [see Clinical Pharmacology (12.3)]. Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of SAVAYSA. The use of prothrombin complex concentrates (PCC), or other procoagulant reversal agents such as activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (rFVIIa) may be considered but has not been evaluated in clinical outcome studies [see Clinical Pharmacology (12.2)]. When PCCs are used, monitoring for anticoagulation effect of edoxaban using clotting test (PT, INR, or aPTT) or anti-FXa activity is not useful and is not recommended.
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Savaysa (edoxaban) is a factor Xa inhibitor which was approved by the FDA in 2015. Savaysa has the following so-called "indications" or approved uses:
- To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; and,
- For the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5–10 days of initial therapy with parenteral anticoagulant.
For some related news as regards the FDA and Savaysa, see this article, "Xarelto / Savaysa / Eliquis: Antidote Drug AndexXa Is Rejected By FDA In August 2016".
We will continue to monitor the safety profile of Savaysa as well as Eliquis and Xarelto, especially as regards the current lack of any FDA-approved antidote which would act as a reversal agent for serious bleeding events such as intracranial hemorrhages or hemorrhagic strokes and gastrointestinal (GI) bleeds.
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