Self‐poisoning with 60 tablets of Apixaban, a pharmacokinetics case report

Abstract

A 67‐year‐old man was admitted to the emergency department about 5 h after deliberate self‐poisoning with 300 mg of Apixaban. The clinical examination did not show any organ dysfunctions or haemorrhagic signs, and the patient's life was not in danger. The first analysis, upon admission, showed a concentration of 2655 μg l−1 of Apixaban. The Cmax was observed 17 h after the intake (3654 μg l−1), about four times the classical Tmax value (median [range]: 4 h [2–4]). The Apixaban was then eliminated following a first order elimination with a calculated half‐life of 10.8 h. The anti‐Xa activity seems to be linearly related to concentration up to 4000 μg l−1. This report suggests that the use of activated charcoal should be effective up to 17 h after a massive intake.

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

“…Apixaban blood concentration increased up to a high level of 1712 μg/L at H + 6 after ingesting 40 mg of apixaban (3.1 mg/Kg). Cmax was consistent with data in adults overdose (between 1000 and 2750 μg/L after ingesting 2 to 5 mg/kg of apixaban) [ 5 , 6 ].…”

“…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.…”

“…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.…”

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

“…Overdose resulting from DOAC self‐ingestion has been poorly reported, mostly as single cases, limited series and PCC reports, representing ~100 cases, with serum/plasma concentration assessment in <20 cases (Table 3). 12–35 Overall, suicidal ingestion does not seem to result in notable bleeding despite high‐ingested amounts and high peak plasma concentrations in most patients. Of note, peak DOAC concentrations in patients included in clinical trials evaluating DOAC for stroke prevention in atrial fibrillation or venous thromboembolism treatment (ie at regular doses) showed a wide inter‐individual variability 3,36 .…”

“…Overall, 29 additional cases mostly involving intentional exposure to dabigatran ( n = 15), rivaroxaban ( n = 8) and apixaban ( n = 6) were published (Table 3). 12–35 Only 10 of these 29 cases presented bleeding. A 53‐year‐old man who co‐ingested 200 mg apixaban presented minor oozing from his femoral venous line insertion site, easily controlled with direct pressure and prothrombin complex concentrate 13 .…”