Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions

Abstract Oral anticoagulants are commonly prescribed but high risk to cause adverse events. Skilled drug interaction management is essential to ensure safe and effective use of these therapies. Clinically relevant interactions with warfarin include drugs that modify cytochrome 2C9, 3A4, or both. Drugs that modify p-glycoprotein may interact with all direct oral anticoagulants, and modifiers of cytochrome 3A4 may interact with rivaroxaban and apixaban. Antiplatelet agents, nonsteroidal anti-inflammatory drugs, and serotonergic agents, such as selective serotonin reuptake inhibitors, can increase risk of bleeding when combined with any oral anticoagulant, and concomitant use should be routinely assessed. New data on anticoagulant drug interactions are available almost daily, and therefore, it is vital that clinicians regularly search interaction databases and the literature for updated management strategies. Skilled drug interaction management will improve outcomes and prevent adverse events in patients taking oral anticoagulants.

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THU-130-Management strategies for drug drug interactions between direct oral anticoagulants and hepatitis C directly acting agents: A multicentre review

Journal of Hepatology ◽

10.1016/s0618-8278(19)30405-0 ◽

2019 ◽

Vol 70 (1) ◽

pp. e216-e217 ◽

Cited By ~ 1

Author(s):

Alison Boyle ◽

Katherine Davidson ◽

Caroline Cassidy ◽

Aniqa Afzal ◽

Anthony Pratt ◽

...

Keyword(s):

Hepatitis C ◽

Drug Interactions ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Management Strategies

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Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review

Thrombosis Research ◽

10.1016/j.thromres.2020.08.016 ◽

2020 ◽

Vol 194 ◽

pp. 240-245

Author(s):

Allen Li ◽

Ming K. Li ◽

Mark Crowther ◽

Sara R. Vazquez

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Drug Interactions ◽

Real World ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The Real

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Evaluation of the efficacy and safety of apixaban and rivaroxaban in cancer patients receiving concomitant active anti-neoplastic therapy at an outpatient cancer setting

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220901777 ◽

2020 ◽

Vol 26 (7) ◽

pp. 1650-1656

Author(s):

Darin Yassine ◽

Erika N Brown ◽

David Putney ◽

Oyejoke Fasoranti

Keyword(s):

Drug Interaction ◽

Venous Thromboembolism ◽

Drug Interactions ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Minor Bleeding ◽

Bleeding Events ◽

Venous Thromboembolism Recurrence ◽

Drug Drug Interaction

Introduction Venous thromboembolism is a common complication among cancer patients with an estimated risk of 20%. American Society of Clinical Oncology guidelines recommend direct oral anticoagulants for long-term anticoagulation but caution the use of direct oral anticoagulants because of drug–drug interactions with antineoplastic therapies. The clinical impact of these drug–drug interactions is yet to be studied in clinical trials. This study aims to evaluate the effect of the drug–drug interactions on venous thromboembolism recurrence and bleeding. Methods This is a retrospective cohort study that included cancer patients with venous thromboembolism receiving apixaban or rivaroxaban with antineoplastic therapy. The impact of the drug–drug interaction was determined by its effect on the rates of venous thromboembolism recurrence and bleeding in patients with a drug–drug interaction compared to patients with no drug–drug interaction. Results The primary composite endpoint of venous thromboembolism recurrence and bleeding events occurred in 65% versus 62% of patients in drug–drug interaction and non-drug–drug interaction groups accordingly. There was a higher rate of venous thromboembolism recurrence and minor bleeding events with anti-mitotic microtubule inhibitors and a higher rate of minor bleeding events with hormonal therapy and alkylating agents. Among the drug–drug interaction group, there were no major bleeding events reported with mild drug–drug interactions when compared to moderate-to-severe drug–drug interactions. There was no difference in time to venous thromboembolism recurrence between rivaroxaban and apixaban. Conclusion Due to small sample size, our study results could not confirm a higher risk of bleeding or venous thromboembolism recurrence with the drug–drug interactions. Further prospective study is warranted, but clinicians should be aware of these drug–drug interactions and identify them using available literature.

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Haematological factors in the management of adult epistaxis: systematic review

The Journal of Laryngology & Otology ◽

10.1017/s0022215117002067 ◽

2017 ◽

Vol 131 (12) ◽

pp. 1093-1107 ◽

Cited By ~ 10

Author(s):

A Williams ◽

A Biffen ◽

N Pilkington ◽

L Arrick ◽

R J Williams ◽

...

Keyword(s):

Systematic Review ◽

Tranexamic Acid ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Management Strategies ◽

Significant Risk ◽

Antiplatelet Agents ◽

Transfusion Practice ◽

Small Sample ◽

Multiple Sources

AbstractBackground:The management of epistaxis requires an understanding of haematological factors that may complicate its treatment. This systematic review includes six distinct reviews examining the evidence supporting epistaxis-specific management strategies relating to warfarin, direct oral anticoagulants, heparin, antiplatelet agents, tranexamic acid and transfusion.Method:A systematic review of the literature was performed using a standardised methodology and search strategy.Results:Limited numbers of articles were identified in each systematic review, with level 1 evidence only regarding the use of tranexamic acid. No studies met the inclusion criteria within the heparin, direct oral anticoagulants or transfusion systematic reviews. Many studies were limited by small sample sizes and significant risk of bias.Conclusion:The management of major bleeding and transfusion practice is well documented in national guidance from multiple sources. The guidelines include advice on anticoagulants, antiplatelet agents and tranexamic acid. In the absence of more specific evidence, these guidelines should be applied in the management of epistaxis.

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Drug-drug interactions with direct oral anticoagulants: practical recommendations for clinicians

The American Journal of Medicine ◽

10.1016/j.amjmed.2021.04.003 ◽

2021 ◽

Author(s):

Terrier Jean ◽

Gaspar Frédéric ◽

Fontana Pierre ◽

Daali Youssef ◽

Reny Jean-Luc ◽

...

Keyword(s):

Drug Interactions ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Practical Recommendations

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Underdosed Direct Oral Anticoagulants in Atrial Fibrillation Patients Reduce Stroke Severity and Improve Outcome

Cerebrovascular Diseases ◽

10.1159/000520857 ◽

2021 ◽

pp. 1-8

Author(s):

Masaki Naganuma ◽

Yuichiro Inatomi ◽

Toshiro Yonehara ◽

Makoto Nakajima ◽

Mitsuharu Ueda

Keyword(s):

Atrial Fibrillation ◽

Functional Outcomes ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

National Institutes Of Health ◽

Stroke Severity ◽

Anticoagulant Drugs ◽

Scale Scores ◽

Anticoagulant Drug ◽

Ischemic Attack

Background and Purpose: Anticoagulant drugs, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs), can reduce stroke severity and are associated with good functional outcomes. Some patients are prescribed lower-than-recommended doses of DOACs; whether these have similar effects has not been clarified. Methods: We retrospectively evaluated 1,139 consecutive ischemic stroke and transient ischemic attack patients with atrial fibrillation. Patients were divided into 5 groups according to their preceding anticoagulant drug therapies: no anticoagulant therapy (ACn), undercontrolling VKA doses (VKAuc), recommended, controlling VKA doses (VKArec), prescribed underdoses of DOAC (DOACud), and recommended doses of DOAC (DOACrec). We investigated the associations between these anticoagulant drug therapies and patients’ initial stroke severity and 3-month outcomes. Results: Median National Institutes of Health Stroke Scale scores at admission were as follows: ACn: 16, VKAuc: 15, VKArec: 9, DOACud: 5, and DOACrec: 7. When the ACn group was used as a reference, regression analysis showed that VKArec (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.01–2.21), DOACud (OR 2.84, 95% CI: 1.47–5.66), and DOACrec (OR 1.83, 95% CI: 1.23–2.74) were associated with milder stroke severity, while VKAuc was not. Median 3-month modified Rankin Scale scores were 2 in the DOACud and DOACrec groups and 4 in all other groups. After adjusting for confounding factors, DOACud (OR 3.14, 95% CI: 1.50–6.57) and DOACrec (OR 1.67, 95% CI: 1.05–2.64) were associated with good 3-month outcomes while VKAuc and VKArec were not. Conclusions: In patients with atrial fibrillation, recommended doses and underdoses of DOACs reduced stroke severity on admission and were associated with good 3-month outcomes.

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Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection

BMC Gastroenterology ◽

10.1186/s12876-019-1124-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Shoko Ono ◽

Marin Ishikawa ◽

Kana Matsuda ◽

Momoko Tsuda ◽

Keiko Yamamoto ◽

...

Keyword(s):

Endoscopic Mucosal Resection ◽

Perioperative Management ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Multivariate Logistic Regression Analysis ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Clinical Impact ◽

Antithrombotic Agents ◽

Mucosal Resection

Abstract Background Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR. Methods From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding. Results A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs. Conclusions The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

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Rates and Determinants for the Use of Anticoagulation Treatment before Stroke in Patients with Known Atrial Fibrillation

Cerebrovascular Diseases Extra ◽

10.1159/000506923 ◽

2020 ◽

Vol 10 (2) ◽

pp. 44-49

Author(s):

Michela Giustozzi ◽

Giancarlo Agnelli ◽

Silvia Quattrocchi ◽

Monica Acciarresi ◽

Andrea Alberti ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Medical Information ◽

Treatment Guidelines ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Antiplatelet Agents ◽

Anticoagulant Treatment ◽

Anticoagulation Treatment

Introduction and Objective: Even though the introduction of less cumbersome anticoagulant agents has improved, the rates ofoverall anticoagulant treatment in eligible patients with atrial fibrillation (AF) remain to be defined. We aimed to assess the rates of and determinants for the use of anticoagulation treatment before stroke in patients with known AF since the introduction of direct oral anticoagulants (DOAC) in clinical practice. Methods: Consecutive patients admitted to an individual stroke unit, from September 2013 through July 2019, for acute ischemic stroke or transient ischemic attack (TIA) with known AF before the event were included in the study. Logistic regression analysis was used to identify independent predictors of the use of anticoagulant treatment. Results: Overall, 155 patients with ischemic stroke/TIA and known AF were included in this study. Among 152 patients with a CHA2DS2-VASc score >1, 43 patients were not receiving any treatment, 47 patients were receiving antiplatelet agents, and the remaining 62 patients were on oral anticoagulants. Among 34 patients on DOAC, 13 were receiving a nonlabeled reduced dose and 18 out of 34 patients on vitamin K antagonists had an INR value <2 at the time of admission. Before stroke, only 34 out of 155 patients (21.9%) were adequately treated according to current guidelines. Previous stroke/TIA was the only independent predictor of the use of anticoagulant therapy. Conclusions: Only 21.9% of the patients hospitalized for a stroke or TIA with known AF before the event were adequately treated according to recent treatment guidelines. It is important to improve medical information about the risk of AF and the efficacy of anticoagulants in stroke prevention.

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