Case report
Fatal flecainide intoxication

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Abstract

A fatal case attributed to flecainide acetate (Tambocor®), a class Ic antiarrythmic drug, is presented. Flecainide was detected by GC/MS in gastric contents, blood and liver as well. The urine analysis revealed the presence of its dealkylated metabolite. Body fluids and tissue concentrations determined by GC/ECD were 7.7 mg/kg in femoral blood, 0.26 mg/kg in bile, 18 mg/kg in liver, 0.17 mg/kg in cerebrospinal fluid, 0.22 mg/kg in brain cortex and 28.9 mg/kg in urine. The total amount of flecainide in gastric contents was about 43 mg. Even taking into account the postmortem redistribution of flecainide, its blood level still remains in the toxic range.

Introduction

Flecainide acetate (Tambocor®) is a class Ic antiarrythmic. Intoxications with this drug are seldom in Switzerland. During the past 15 years, only eight cases were reported to the Swiss Toxicological Information Centre in Zurich [1]. None was fatal. Moreover, to our knowledge only a few cases of lethal intoxications have been published.

Flecainide is used to treat symptomatic ventricular arrythmias when other treatment is ineffective. After oral administration, its absorption is rapid and almost complete with minimal first-pass effect (95% oral bioavailability) [2]. Its apparent volume of distribution is high, about 8.7 l/kg, and its plasma protein binding is ∼40%. The therapeutic levels in serum range between 0.2 and 1.0 mg/l with possible toxicity over 1.0 mg/l. Serious cardiac adverse effects include ventricular tachyarrhythmias and severe bradycardia [2]. Flecainide undergoes biotransformation via O-dealkylation in two main metabolites: meta-O-dealkylated flecainide and meta-O-dealkylated lactam of flecainide (see Fig. 1). Both can be further conjugated. None of the metabolites exhibit significant therapeutic activity. Fifty percent of a single oral dose is excreted in the 24-h-urine, with the parent drug representing ∼10% of the dose [3], [4].

Section snippets

Case history

A 65-year-old man was found dead by his wife in their residence. They both had spent the day with their family but he had gone back home alone. After that, he had called his wife several times requesting her to return. At the scene, an empty package of 20 Tambocor® 100-mg tablets was discovered. Moreover, a tape on which he had recorded some time before the music he wanted for his funeral was placed on evidence. The man was a retired representative in pharmaceutical products. According to his

Chemicals and reagents

Flecainide was obtained from Health Care 3M (Tambocor®). All other chemicals and solvents were analytical reagent grade. Opiates were obtained from Radian and deuterated opiates from Lipomed (Arlesheim, Switzerland). Sylon BFT (BSTFA+TMCS, 99:1, v/v) was purchased from Supelco.

Equipment and chromatographic conditions

For screening investigations, a Hewlett-Packard (HP) Series 6890 gas chromatograph was used in combination with a HP MSD Series 5973 mass spectrometer, a HP 6890 Series injector and a HP Vectra XM Series 4 workstation

Results and discussion

An ethanol concentration of 1.75 g‰ was determined in femoral blood. Immunoassays and color tests in urine detected opiates only. The basic drug screens of the main body fluids and tissues performed by GC/MS revealed the presence of several xenobiotics (Table 1). Flecainide was detected in blood, gastric contents and liver as well. In urine, flecainide was present as its O-dealkyl metabolite. Formal identification of flecainide was achieved by comparing its underivatized and acetylated mass

Conclusion

The circumstances surrounding the death pointed to a self-poisoning with flecainide. The toxicological analyses revealed that the blood concentration of flecainide was in the range of those previously reported in case of fatal flecainide intoxications and led us to confirm our hypothesis. The previous cardiopathy could have increased the cardiac adverse effects of flecainide.

Acknowledgments

The skilled technical assistance of Ms Carine Rotondo is gratefully acknowledged. We are also grateful to Ms Anne Tricot for her assistance in the preparation of this manuscript.

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