Acute amiodarone poisoning occurring twice in the same subject

To the Editor:

Bonati et al.¹ reported that a 20-year-old female, who was not on the drug, ingested 8 g of amiodarone with a QTc of 500 ms on days 2 and 3 after admission following the peak serum concentration of amiodarone on day 1. In contrast, a 67-year-old female receiving amiodarone ingested 2.6 g, and QTc was prolonged up to 680 ms;² a 57-year-old woman on a 5-year amiodarone therapy ingested 5 g, and developed prolonged QT interval, atrial flutter, atrioventricular block and severe hypotension, requiring administration of epinephrine.³

We now report a 71-year-old male with bipolar disorder treated with sertraline and clotiazepam but not on amiodarone who was admitted following ingestion of 4 g of amiodarone. One year later, he again attempted suicide by ingesting 11.4 g of amiodarone with phenobarbital. Renal and hepatic function as normal.

In the first episode, 10 g of activated charcoal was administered 3 hours after ingestion. In the second, 50 g of activated charcoal was administered 8.5 hours after ingestion (0.5 hour after presentation) and 20 g at 2 and 6 hours subsequently. QTc was 446 ms on days 3 and 4 after admission in the first episode, whereas it was 447 ms on day 2 in the second episode (Fig. 1A). In the first episode, the concentration of amiodarone peaked on day 2 after admission while that of desethylamiodarone continued to increase until at least day 6 (Fig. 1B). In contrast, in the second episode, the concentration of amiodarone decreased rapidly while that of desethylamiodarone did not increase. The area under the curves (AUCs) for amiodarone concentration from admission till day 6 in both episodes were 21.5 and 25.9 mgh/L, and those for desethylamiodarone were 10.6 and 13.3 mgh/L. No adverse events were observed during the clinical course.

Fig. 1. A) Corrected QT interval (QTc); B) Serum concentrations of amiodarone (AMI) and desethylamiodarone (DEA) during the 1st and 2nd episodes.

Management after a single large dose of amiodarone includes reducing its bioavailability by multiple-dose administration of cholestyramine or activated charcoal (e.g. 25 g 4-hourly for 12 hours).⁴ Although administration of 25 g of activated charcoal 1.5 hours after a single oral dose of amiodarone resulted in a 50% reduction in bioavailability in healthy volunteers,⁵ effect of delayed and repeated administration of activated charcoal on patients with massive oral overdose of amiodarone is unknown. In this case, multiple-dose activated charcoal seems to have resulted in a more rapid decrease in amiodarone in the second episode. However, it is also possible that co-ingested phenobarbital may have had some effect on the concentration curves of amiodarone and desethylamiodarone on the second occasion.

Caution should be exercised especially when amiodarone overdose occurred in patients receiving chronic therapy, and because QTc correlates with the myocardial concentration of amiodarone in such patients.⁶

In conclusion, we wish to highlight differences in acute ingestion in drug-naïve patients from those on chronic therapy by describing two ingestions in the same patient, and emphasize the use of monitoring of plasma concentrations after acute overdose in better understanding toxico-kinetics in overdose.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.