Case reportFatal flecainide intoxication
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: -O-dealkylated flecainide and -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.
References (16)
Systematic toxicological analysis of drugs and their metabolites by gas chromatography-mass spectrometry
J. Chromatogr.
(1992)- Swiss Toxicological Information Centre in Zürich=Centre suisse d’information toxicologique (CSIT), Klosbachstr. 107,...
- et al.
- et al.
Biotransformation and elimination of 14C-flecainide in humans
Drug Metab. Dispos.
(1984) - et al.
High-performance liquid chromatographic procedure with fluorescence detection for the m-O-dealkylated lactam metabolite of flecainide acetate in human
J. Chromatogr.
(1988) - et al.
The tragedy of the sect of the Ordre du temple solaire (Cheiry-Salvan, Switzerland, 48 deaths): analytical strategy and main toxicological findings
- et al.
Cited by (36)
Flecainide poisoning and prolongation of elimination due to alkalinization
2022, American Journal of Emergency MedicineCitation Excerpt :There have been rare cases of flecainide toxicity reported in the medical literature with quantitative findings and we found none with serial measurements. Cases of fatalities due to flecainide overdose were found to have serum concentrations between 7.3 and 94 μg/ml with urine concentrations between 54 and 117 μg/ml [10-15] and another fatality had a postmortem flecainide serum concentration of 5.4 μg/ml. [16] In cases of survival in the setting of flecainide toxicity, accidental acute overdoses in children were found to have serum flecainide concentrations between 0.7 and 2.0 μg/ml in symptomatic patients. [17-20]
Summary statistics for drugs and alcohol concentration recovered in post-mortem femoral blood in Western Switzerland
2021, Forensic Science InternationalCitation Excerpt :A systematic toxicological analysis (STA) of therapeutic drugs, drugs of abuse, volatiles, cyanide, and pesticides are performed using validated analytical procedures. The STA used is based on screening procedures and quantification analyses as described in previous publications [15–18] and relies on toxicological literature [14,19,20]. Screening procedures include immunoassays (Siemens; Specialty Diagnostics; Randox) using the manufacturer’s recommended cut-off, colour tests (Fujiwara; Cyantesmo), and chromatographic analyses which consist of: gas chromatography coupled to mass spectrometry (GC-MS, Agilent), liquid chromatography coupled to diode array detectors (HPLC-DAD, Agilent), and head-space gas chromatography coupled to flame ionisation detectors (HS-GC-FID, Agilent).
State of the art in bile analysis in forensic toxicology
2017, Toxicologie Analytique et CliniqueState of the art in bile analysis in forensic toxicology
2016, Forensic Science InternationalFlecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial
2015, EBioMedicineCitation Excerpt :However, in the current study, all patients were on steady state riluzole treatment throughout, which may contribute to the lack of changes pre- and post-flecainide in cortical excitability. Further, while therapeutic dose levels for the cardiac setting were achieved in the present study, flecainide levels in cerebrospinal fluid may be lower than serum levels (Romain et al., 1999), suggesting that higher doses may be required to impact cortical excitability. Further studies with increased dosing ranges may be required to comment on clinical efficacy.
A case of near-fatal flecainide overdose in a neonate successfully treated with sodium bicarbonate
2013, Journal of Emergency Medicine