The X factor: Lack of bleeding after an acute apixaban overdose

Leikin, Scott M.; Patel, Hina; Welker, Katherine L.; Leikin, Jerrold B.

doi:10.1016/j.ajem.2016.11.035

Cited by 13 publications

(16 citation statements)

References 5 publications

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“…In cases of acute poisoning, apixaban concentrations were up to 2,700 ng mL À1 [21,22]. Using this method one sample with apixaban concentrations above linearity range was analyzed (1,500 ng mL À1 ) while among analyzed patients' samples there were no apixaban concentrations out of linearity range.…”

Section: Discussion Of Validated Methodsmentioning

confidence: 99%

Development and validation of LC-MS/MS method for determination of plasma apixaban

Džudović

Sakač

Antunović

et al. 2022

AChrom

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Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.

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Section: Discussion Of Validated Methodsmentioning

confidence: 99%

Development and validation of LC-MS/MS method for determination of plasma apixaban

Džudović

Sakač

Antunović

et al. 2022

AChrom

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“…Similarly, absorption was prolonged in two apixaban-poisoned patients (ingested 280 and 300 mg) with observed peak concentrations at 6 h and 17 h, respectively. 22,25 Prolonged absorption may be related to either bezoar formation, saturation of intestinal transporters or gastrointestinal transit slowing induced by co-intoxicants.…”

Section: Discussionmentioning

confidence: 99%

“…T 1/2 were prolonged in two apixaban patients with marked cardiovascular failure resulting from co-ingested cardiotoxicants (patients 9 and 10) and in one rivaroxaban patient (patient 7), despite no obvious explanation. Studies suggested saturable clearance in overdose, 13,22 which may have occurred in patient 7 due to individual variability. By contrast, t 1/2 was shortened in one rivaroxaban patient (patient 4), possibly due to massive fluid administration to restore blood pressure, since one-third of the rivaroxaban dose is known to be eliminated as unchanged drug in urine and rivaroxaban has no active liver metabolites and no in vivo metabolism of the metabolites back to the parent drug.…”

Section: Discussionmentioning

confidence: 99%

Case series of massive direct oral anticoagulant ingestion—Treatment and pharmacokinetics data

Delrue

Chevillard

Stépanian

et al. 2022

Eur J Clin Investigation

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Background Direct oral anticoagulants (DOAC) are widely used due to favourable benefit/risk ratio. However, consequences of massive ingestion have been poorly investigated. Objectives We aimed to report outcome and pharmacokinetic parameters in patients who massively ingested DOACs. Methods We conducted a 5‐year cohort study including consecutive massive DOAC ingestion patients admitted to two critical care departments. Patients were managed in accordance with standards of care. We collected the main history, clinical, laboratory, management and outcome data. The time‐course of plasma DOAC concentrations measured using specific assays was modelled. Results Twelve patients (3F/9M; age, 55 years [41–63], median [25th–75th percentiles]) were included. Ingestions involved rivaroxaban (n = 7), apixaban (n = 3) and dabigatran (n = 2), with presumed doses of 9.4‐fold [5.0–22.0] the full daily dose. Six patients received activated charcoal but no antidote nor blood‐derived product. No bleeding was observed. One patient died due to refractory cardiogenic shock related to bisoprolol co‐intoxication. Highest observed peak plasma concentrations were 1720 ng/ml (rivaroxaban), 750 ng/ml (apixaban) and 644 ng/ml (dabigatran). Times to reach DOAC concentration below 50 ng/ml were ~20–45 h (rivaroxaban), ~125 h (apixaban) and ~30–50 h (dabigatran). Elimination half‐lives were 2.5–25.5 h (rivaroxaban), 22.0 and 36.5 h (apixaban), and 5.8 and 15.5 h (dabigatran), with substantial interindividual variability and prolongation in case of cardiovascular failure related to co‐intoxicants. Charcoal administration, even if delayed, may have contributed to limit toxicity, possibly by reducing absorption and/or enteroenteric recycling. Conclusion No bleeding was observed in this series of massive DOAC ingestions despite elevated plasma concentrations. No patient required specific haemostatic agents. Charcoal administration should be considered to limit toxicity.

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“…As previously reported, the apixaban plasma concentration vs. time profile exhibited a multiphasic elimination profile, with an initial rapid decline followed by a more gradual terminal phase [ 4 ]. Apixaban was eliminated with a terminal half-life of 8.2 h. The half-life described in adults overdose was between 6 h and 15 h depending on the patient and other co-administered drugs [ 6 – 9 ]. The rapid elimination may explain the absence of bleeding despite high concentrations.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Apixaban has linear pharmacokinetics, and concentration-related pharmacodynamic effects have been described in adults [4]. Many clinical cases reported severe self-poisoning with apixaban among adult patients [5][6][7][8][9]. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described.…”

Section: Introductionmentioning

confidence: 99%

Accidental apixaban intoxication in a 23-month-old child: a case report

et al. 2020

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Background Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described. Case presentation A 23-month-old boy, with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 40 mg apixaban and 0.75 mg digoxin. No adverse event was observed. Digoxin trough level was within therapeutic values. Apixaban blood concentration increased up to 1712 μg/L at H + 6 (1000–2750 μg/L using 2–5 mg/kg of apixaban in adults). The terminal half-life was 8.2 h (6–15 h in adults). The rapid elimination may explain the absence of bleeding despite high concentrations. Conclusions Despite an important intake of apixaban and a real disturbance in routine coagulation assays, no clinical sign of bleeding was observed, perhaps due to wide therapeutic range of apixaban. It may also be explained by its rapid elimination. Considering the high Cmax and a possible enteroenteric recycling, the use of activated charcoal should be considered in such situations in order to prevent eventual bleeding.

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The X factor: Lack of bleeding after an acute apixaban overdose

Cited by 13 publications

References 5 publications

Development and validation of LC-MS/MS method for determination of plasma apixaban

Development and validation of LC-MS/MS method for determination of plasma apixaban

Case series of massive direct oral anticoagulant ingestion—Treatment and pharmacokinetics data

Accidental apixaban intoxication in a 23-month-old child: a case report

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