A case of lacosamide and mirtazapine self-poisoning.

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 µg/mL and a mirtazapine concentration of 12.0 µg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

Α Simple Method for the Determination of Lacosamide in Blood by GC-MS.

Lacosamide is a functionalized amino acid with antiepileptic function. Therapeutic drug monitoring (TDM) in patients for lacosamide is critical as it allows clinicians to control epileptic seizures. A single liquid-liquid extraction step was applied for the extraction of lacosamide from whole blood samples which were thereafter analyzed by GC-MS. Optimum extraction conditions were selected on the basis of experiments with various solvents at different pHs, indicating ethyl acetate at pH 12 as the most efficient parameters for the extraction of lacosamide. Method exhibited linearity from 2 to 100 µg/mL with R2  = 0.998. Accuracy and precision were evaluated at three concentrations and found to be within acceptable limits. LOD and LOQ were determined at 0.1 and 0.5 µg/mL, respectively. Lacosamide was found to be stable at storage conditions. The developed method was applied successfully in clinical samples and postmortem blood sample from an overdose case.

Lacosamide: a Study of Exposures Reported to US Poison Centers over a 9-Year Period.

BACKGROUND: Lacosamide (Vimpat®) is an anticonvulsant used to treat partial-onset seizures. Little is known about the characteristics and outcomes of patients exposed to lacosamide. OBJECTIVE: To characterize lacosamide exposures reported to US poison centers with regard to patient demographics, clinical effects, and outcomes. METHODS: This retrospective observational study queried the National Poison Data System (NPDS) for single substance lacosamide exposures from January 2008 to December 2016. Variables of interest included age, gender, medical outcome, management site, level of healthcare facility, reason for exposure, and clinical effects. RESULTS: Lacosamide exposures were identified in 1124 patients, ranging from ages 2 months to 99 years. Six hundred and twenty-two patients (55.3%) were female. Nine hundred and seventy-six patients (86.8%) had minimal or no toxic effects. Life-threatening exposures numbered 30 cases (2.7%). There was one death. Five hundred and forty-eight patients (48.8%) did not require healthcare management while 537 (47.7%) were either referred to or already at a hospital. Among those treated at a healthcare facility, 269 (50.1%) did not require admission. Thirty-three patients (6.1%) were admitted to a psychiatric facility, 68 (12.7%) to a non-critical care unit, and 93 (17.3%) to a critical care unit. Six hundred and thirty-two exposures (56.2%) were due to therapeutic error. Suicide attempts numbered 168 (14.9%). Neurologic, gastrointestinal, and cardiovascular symptoms were commonly encountered. CONCLUSION: Lacosamide exposures infrequently cause death or disability; however, a considerable proportion of the study population required intensive care. Exposed patients with symptoms require healthcare evaluation.