An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers

Spiller, Henry A.; Mowry, James B.; Aleguas, Alfred; Griffith, Jill R. K.; Goetz, Robert; Ryan, Mark L.; Bangh, Stacey A.; Klein‐Schwartz, Wendy; Schaeffer, Scott; Casavant, Marcel J.

doi:10.1016/j.annemergmed.2015.07.014

Cited by 33 publications

(27 citation statements)

References 21 publications

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“…First, the apixaban-induced toxicity profile, represented by elevation in liver enzymes (particularly ALT), occurred within 2–3 days of initiation of apixaban, which is a significantly shorter time than the other published cases 2 8. Second, a rapid and remarkable clinical and laboratory improvement was encountered in a relatively short time (1–2 days) after discontinuation of apixaban.…”

Section: Discussionmentioning

confidence: 82%

“…Few case reports have described drug-induced hepatotoxicity in patients receiving DOACs such as apixaban and rivaroxaban 2 8. A meta-analysis of 152 116 patients in 29 stage III clinical trials concluded that there was no increased risk of hepatotoxicity with DOACs 10.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of 152 116 patients in 29 stage III clinical trials concluded that there was no increased risk of hepatotoxicity with DOACs 10. However, case reports, pharmacovigilance data and patient series reveal hepatotoxicity associated with DOACs in patients with normal and impaired liver function 2 8 10 11. Of all available DOACs, apixaban is less frequently associated with hepatotoxicity 12 13.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetic and pharmacodynamics of apixaban are predictable; thus, no blood level monitoring is generally required when treatment is initiated or maintained with this novel oral anticoagulant 1. Apixaban has been approved by the United States Food and Drugs Administration (FDA) since October 2012 and is used to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation 2. Between 2.7 and 6.1 million people in the USA are diagnosed with atrial fibrillation each year, many of whom will be prescribed apixaban 3.…”

Section: Introductionmentioning

confidence: 99%

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Apixaban-induced liver injury

Clarke

Alsaad²,

Mack

et al. 2016

BMJ Case Reports

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An 81-year-old woman with well-controlled hypertension presented to the emergency department with new-onset atrial fibrillation with rapid ventricular response. Treatment for atrial fibrillation was initiated, including rate control and anticoagulation with 5 mg of apixaban two times per day for primary stroke prophylaxis. Three days after initiation of apixaban, the patient noted new-onset abdominal pain, worsening shortness of breath and weakness. Laboratory results showed elevated liver enzymes. Workup for elevated transaminase did not reveal any underlying infectious or autoimmune process. Apixaban, a probable cause for the hepatocellular injury, was discontinued and replaced with intravenous unfractionated heparin to bridge anticoagulation with warfarin. The patient's symptoms resolved as her transaminases improved by discontinuation of apixaban. We illustrate this case of drug-induced hepatotoxicity secondary to treatment with apixaban. It is important for physicians to be aware of this rare adverse effect caused by a widely used novel oral anticoagulant.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apixaban-induced liver injury

Clarke

Alsaad²,

Mack

et al. 2016

BMJ Case Reports

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“…46 In contrast, it still remains controversial as to whether PT is the best predictive marker of event risks in patients receiving treatment with FXa inhibitors. 46,47 Other clotting markers, such as activated partial thromboplastin time and anti-FXa activity, are also known to correlate with plasma concentrations of FXa inhibitors. 26 The use of these clotting markers might be an alternative.…”

Section: 10mentioning

confidence: 99%

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

et al. 2018

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Key Points• Simulations suggested that the dose reduction of rivaroxaban would decrease fatal events associated with major bleeding.• Dose optimization of FXa inhibitors might further enhance their therapeutic benefit.The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding. By using the models, we simulated the optimal therapeutic doses for each FXa For apixaban and edoxaban, no distinct change in the overall mortality was simulated by dose modification. This study suggested that the current dose of rivaroxaban might be excessive and would need to be reduced to decrease the excess risk of major bleeding.

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Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Cuker

Burnett

Triller³

et al. 2019

American J Hematol

257

263

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Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non‐specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

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An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers

Cited by 33 publications

References 21 publications

Apixaban-induced liver injury

Apixaban-induced liver injury

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

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