New evidence for oxetorone toxicity.

BACKGROUND

Oxetorone is a serotonin antagonist antimigraine drug but literature relating to its toxic properties is poor. The aim of this study is to describe the toxicological profile of oxetorone and to highlight any relationship between clinical and analytical findings.

METHODS

This is a retrospective and observational study of cases exposure to oxetorone, reported to the Angers Poison and Toxicovigilance Centre between January 2002 and May 2016. Severity was assessed using the Poisoning Severity Score (PSS). Cases where data were incomplete, where oxetorone was deemed not accountable, where clinical signs were linked mainly to a co-ingested drug or where the plasma concentration of oxetorone was negative were all excluded.

RESULTS

We included 43 cases of exposure, 31 of whom were suicide attempts. The assumed ingested dose (60-3600 mg) was correlated to severity (rs = 0.45, p = 0.01). Symptoms of moderate severity (PSS2 = drowsiness, hypertonia, myosis, convulsions, arterial hypotension, QRS widening, QTc prolongation) were observed following ingestion of more than 600 mg of oxetorone (median dose =1200 mg) and severe symptoms (PSS 3 = coma, convulsions, QTc prolongation, QRS widening, ventricular tachycardia, arterial hypotension, cardiogenic shock) were observed starting from 1800 mg (median dose =2700 mg). In four cases, a secondary worsening of symptoms 10-48 h following ingestion was observed. Plasma oxetorone was measured in four patients. Severe symptoms were observed in the event of a concentration over 0.3 mg/L and the highest measured serum oxetorone level was delayed by 20-48 h following the ingestion for two cases.

CONCLUSIONS

Several clinical and paraclinical parameters strongly point towards membrane-stabilising properties of the molecule and the risk of a delayed occurrence of symptoms or a secondary worsening.