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Fatal intoxication with ivabradine: First case report.

A Knapp-Gisclon1, M Zerah1, C Mayer-Duverneuil1

  • 1Laboratoire de Pharmacologie - Toxicologie, Centre Hospitalier Universitaire Raymond Poincaré, AP-HP, 104 boulevard Raymond Poincaré, 92380, Garches, France.

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Summary
This summary is machine-generated.

This case study details the first reported fatal overdose of ivabradine, a heart medication. Post-mortem analysis revealed high concentrations of ivabradine in blood and organs, contributing to multiple organ failure.

Keywords:
Blood concentrationFatal intoxicationIvabradineViscera concentrations

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Area of Science:

  • Forensic Toxicology
  • Clinical Pharmacology
  • Cardiology

Background:

  • Ivabradine is a widely prescribed bradycardic agent for chronic stable angina and heart failure.
  • Drug overdose cases require accurate quantification of substances in biological matrices for toxicological assessment.

Observation:

  • A 61-year-old woman presented with drowsiness, severe bradycardia (45 bpm), and hypotension following an overdose.
  • Despite medical intervention, the patient succumbed to multiple organ failure approximately ten hours after admission.

Findings:

  • A validated LC-MS/MS method quantified ivabradine in post-mortem samples.
  • Elevated ivabradine concentrations were found in blood (1210 ng/mL) and various organs, including lung (2910 ng/g) and kidney (1510 ng/g).
  • Co-ingestion of pregabalin (50 μg/mL) and zopiclone (206 ng/mL) was also detected.

Implications:

  • This case represents the first documented fatal intoxication involving ivabradine.
  • The study provides crucial reference concentrations of ivabradine in post-mortem biological samples and organs.
  • Findings highlight the potential for severe toxicity with ivabradine overdose, especially in combination with other central nervous system depressants.