Accidental apixaban intoxication in a 23-month-old child: a case report
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CASE REPORT
Open Access
Accidental apixaban intoxication in a 23month-old child: a case report Manon Launay1* , Yara Nasser1, Isabelle Maubert2, Anne-Cécile Chaux3 and Xavier Delavenne1,4
Abstract 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. Keywords: Apixaban, DOAC, Pediatrics, Intoxication, Pharmacokinetics, Child, Overdose, Digoxin, Case report
Background Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases [1, 2]. Apixaban is a reversible and selective FXa inhibitor (activated factor X) and inhibits free, clot-bound FXa, and prothrombinase activity [3]. 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 [5–9]. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described. Digoxin, on * Correspondence: [email protected] 1 Laboratoire de Pharmacologie-Toxicologie-Gaz du Sang, CHU Saint-Etienne, Albert Raimond avenue, Saint-Etienne, France Full list of author information is available at the end of the article
the other hand, is better known in pediatrics as it is commonly used for arrhythmias and heart failure treatment.
Case presentation A 23-month-old boy (12.9 Kg), with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 8 pills of apixaban 5 mg (40 mg) and 3 pills of digoxin 0.25 mg (0.75 mg). His clinical exam was normal. No hemorrhagic sign was identified. His heart rate (105 pulsations/minute) and the ECG were normal. The child remained under medical supervision for 48 h. Four blood tests were withdrawn during hospitalization at 2, 6, 21.5 and 48 h after the ingestion (H +
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