Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs)

Gelosa, Paolo; Castiglioni, Laura; Tenconi, Marco; Baldessin, Ludovico; Racagni, Giorgio; Corsini, Alberto; Bellosta, Stefano

doi:10.1016/j.phrs.2018.07.016

Cited by 91 publications

(71 citation statements)

References 149 publications

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“…Even though no direct trauma is involved in spontaneous spinal hematomas, some activities have been associated with onset such as stretch exercises [19] and Valsalva maneuvers during trumpet playing [20] and defecation [3], for example, which might have been the case in our patient as well. Even though new reversal agents have been recently approved for dabigatran, apixaban, and rivaroxaban [16], the lack of their widespread use makes it essential to identify the best evidence-supported choice for surgical timing of evacuation. Based on the few case reports that have been published so far, it seems that the benefit of earlier intervention outweighs the risk of surgical bleed.…”

Section: Discussionmentioning

confidence: 99%

“…Despite reports of successful medical management [13,14], surgical decompression remains the cornerstone of management of these patients with earlier intervention correlating with better outcome [15]. However, even with the recent FDA approval of idarucizumab as a reversal agent for dabigatran and andexanet alfa for apixaban and rivaroxaban [16], the limited availability and experience with these agents complicates the timing of surgery. We hope that this case report and literature review will help in establishing a better idea about the optimal management of these patients and raise awareness about the importance of having a high index of suspicion for this condition when encountering a patient on DOACs.…”

Section: Introductionmentioning

confidence: 99%

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Spontaneous Spinal Epidural Hematoma in a Patient on Apixaban for Nonvalvular Atrial Fibrillation

Alayli

Neelakandan

Krayem

2020

Case Reports in Hematology

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Background. With the rise in the use of direct oral anticoagulants (DOACs), more hemorrhagic complications are being encountered. Since the first description of a case of spontaneous spinal epidural hematoma (SSEH) related to the utilization of DOACs in 2012, there have been few reports describing a similar association. However, no cases so far have reported an association between SSEHs and apixaban. Case Description: A 76-year-old lady, with a history of nonvalvular atrial fibrillation, presented with a new onset of progressive left lower and upper extremity weakness. She reported back pain and numbness in the left leg up to the knee along with numbness in the left arm up to the shoulder. A CT scan of the neck was suggestive of an epidural hematoma extending from C2-C3 level to C6-C7. As the patient was on apixaban at the time, surgical treatment was delayed for two days to decrease the risk of intraoperative bleeding. Nine days later, she was discharged. Her physical exam was almost unchanged from that on presentation, except for resolution of pain and minimal improvement in motor power in her left lower extremity from 1/5 to 2/5 distally. Conclusions. Spinal hematomas represent surgical emergencies with earlier intervention portending better outcome. Based on the few case reports that point to DOACs as a potential culprit, it appears that a high suspicion index resulting in earlier SSEH diagnosis and intervention is crucial for improved neurological outcome and recovery. Prompt diagnosis remains a challenge, especially that SSEH can mimic cerebrovascular accidents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spontaneous Spinal Epidural Hematoma in a Patient on Apixaban for Nonvalvular Atrial Fibrillation

Alayli

Neelakandan

Krayem

2020

Case Reports in Hematology

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“…Stosowanie tego typu leków wiążę się z wieloma korzyściami dla pacjenta, m.in. stałym dziennym dawkowaniem, brakiem konieczności rutynowej kontroli krzepnięcia krwi, lepszą tolerancją, mniej restrykcyjną dietą oraz niewielką ilością interakcji z innymi lekami w porównaniu z antagonistami witaminy K [1,6].…”

Section: Wstępunclassified

“…Prescription volume for non-vitamin K antagonists (including warfarin) has been gradually surpassed by direct oral anticoagulants (NOAC-Non-Vitamin K antagonist Oral Anticoagulants) like dabigatran and rivaroxaban (since 2008), apixaban (since 2011), edoxaban (since 2015) [4] and betrixaban (currently available only in the United States) since January 2018 [5]. Reported patient benefits from therapy of NOAC include fixed daily dosage regimen, eliminated need for routine coagulation check, better tolerance, more relaxed diet precautions and fewer drug interactions when compared with non-vitamin K antagonists [1,6].…”

Section: Introductionmentioning

confidence: 99%

Safety of concomitant treatment with Non-Vitamin K Oral Anticoagulants and SSRI/SNRI antidepressants

Boguta

Juchnowicz

Wróbel-Knybel

et al. 2018

Curr Probl Psychiatry

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Introduction: Warfarin has been considered as a “gold standard” in the prevention and treatment of thromboembolic events since 1954. Since the introduction of direct oral anticoagulants in the last few years (NOAC-Non-Vitamin K antagonist Oral Anticoagulants) prescriptions volume for apixaban, edoxaban, dabigatran and rivaroxaban have been gradually surpassing warfarin. The benefits include: anticoagulation from day one, fixed daily dosing, elimination for the need of international normalised ratio (INR) monitoring, fewer interactions with food and co-administered medicines with reduced risk of bleeding and better overall life quality. Objectives: Assessing evidence for the safe use of Non-vitamin K Oral Anticoagulants (NOAC) with Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRI). Method: Review of literature published between 2014 and 2016 was made using the key words: Selective Serotonin Reuptake Inhibitor, Serotonin and Noradrenaline Reuptake Inhibitors, apixaban, dabigatran, edoxaban, rivaroxaban, bleeding, interaction, depression with time description from 2014 to 2018. Evidence within the literature was then compared with guidelines from the National Institute for Health and Care Excellence (UK), British National Formulary (UK), Clinical Excellence Commission (Australia), Thrombophilia and Anticoagulation Clinic (USA) and Summaries of Product Characteristics (SPC). Results: 1. Serotonin plays a critical role in maintaining homeostasis. Use of SSRI/SNRI compromises its platelet reuptake increasing risk of bleeding. 2. Increased tolerability and safety of NOAC over Warfarin, although caution is advised when NOAC is used with SSRI/SNRI with less evidence suggesting pharmacodynamic interactions. 3. It is not recommended to use NOAC with strong CYP and P-gp inhibitors. Conclusions: With limited literature evidence, caution is advised when co-prescribed NOACs with SSRI/SNRI, especially with other cofactors and interacting medicines further increasing risk of bleeding.

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“…However, the clinical administration to anticoagulant therapy has changed recently due to several limitations of warfarin, including slow onset and offset of effect, a narrow therapeutic window, and variable dose-response relations, which necessitate frequent monitoring using International Normalized Ratio (INR) and dose adjustments [9]. Therefore, many countries selected LMWH, rivaroxaban or aspirin as the main methods of VTE prophylaxis after major orthopedic surgery, while warfarin was rarely used [10,11].…”

Section: Introductionmentioning

confidence: 99%

The timing of symptomatic pulmonary embolism in patients with non-warfarin following elective primary total joint arthroplasty

Hu¹,

C²,

Wang³

et al. 2019

Preprint

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Background: The purpose of this study was to investigate the incidence and timing of postoperative symptomatic pulmonary embolism (PE) in patients receiving non-warfarin following primary total joint arthroplasty (TJA), to clarify the appropriate duration of postoperative VTE prophylaxis. Methods: We retrospectively reviewed the medical records of 11148 patients who underwent primary TJA, including total knee arthroplasty (TKA) and total hip arthroplasty (THA) at our institution from January 2012 to March 2019. The median postoperative day of diagnosis of symptomatic PE and interquartile range for day of diagnosis were determined. Multivariate Cox proportional hazards modeling was used to test the difference of timing for PE based on demographics and comorbidities. Results: The overall 90-day rate of symptomatic PE was 0.71%. The median day of diagnosis for symptomatic PE was 3 day postoperatively (interquartile: 2–7 day). Factors that showed statistical significance on multivariate analysis in association with earlier timing of PE occurrence in patients with atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke. Conclusion: The vast majority symptomatic PE occurs in the early postoperative period after TJA, and atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke were independent factors affecting the timing of symptomatic PE.

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Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs)

Cited by 91 publications

References 149 publications

Spontaneous Spinal Epidural Hematoma in a Patient on Apixaban for Nonvalvular Atrial Fibrillation

Spontaneous Spinal Epidural Hematoma in a Patient on Apixaban for Nonvalvular Atrial Fibrillation

Safety of concomitant treatment with Non-Vitamin K Oral Anticoagulants and SSRI/SNRI antidepressants

The timing of symptomatic pulmonary embolism in patients with non-warfarin following elective primary total joint arthroplasty

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