Clinical toxicity of daridorexant: a retrospective analysis of poison centre data
Katharina von Fabeck1, Jean-Paul Boudsocq2, Matthieu Boye2
1Institut de Neurosciences de la Timone, UMR7289 CNRS, Hop Sainte Marguerite, Department of Clinical Pharmacology, CAP-TV, Aix Marseille Univ, APHM, Marseille, France.
Introduction:
Daridorexant is a dual orexin receptor antagonist approved for insomnia treatment. While clinical trials suggest a favourable safety profile, real-world data on acute toxicity and overdose are scarce. This study aimed to characterize the clinical presentation, severity, and outcomes of daridorexant exposures reported to French National Poison Centre network, focusing on co-ingested substances and sex-specific differences.
Methods:
A retrospective review of all daridorexant-related cases reported between March 2024 and May 2025 was conducted. Demographic, clinical, and toxicological data were extracted and classified using standardized criteria. Poisoning severity was graded with Poisoning Severity Score. Ordinal logistic regression assessed the association between co-intoxication and Poisoning Severity Score.
Results:
Fifty-one cases were identified (70.6% female, age range eight months-89 years): 30 were suicide attempts, seven therapeutic errors, five adverse drug reactions, and three pediatric unintentional ingestions. Seventeen mono-intoxications presented mainly with somnolence (n = 7), vertigo (n = 1), and nausea (n = 1). Median ingested dose was 200 mg (IQR 100-362.5 mg). Co-intoxications occurred primarily with benzodiazepines, antidepressants, analgesics, antidiabetics, neuroleptics, or alcohol, producing symptoms such as somnolence, confusion, hallucinations, tachycardia, hypoglycaemia, and in severe cases coma (lowest Glasgow Coma Scale was seven). Regression analysis showed that co-intoxication was significantly associated with increased severity in females (β = 1.95, SE = 0.74, P = 0.0086), whereas no significant effect was observed in males. Severe outcomes occurred exclusively in cases with co-intoxications, particularly among women.
Discussion:
Daridorexant overdoses were generally of low severity, with no fatalities. Most patients recovered with supportive care. Co-intoxication may increase toxicity, particularly in females, but findings should be interpreted cautiously due to small subgroups.
Conclusion:
While daridorexant appears safe when taken alone, clinicians should remain vigilant in polypharmacy scenarios involving central nervous system depressants. Further studies are needed to confirm sex-related differences and refine risk stratification in overdose management.
Insights
Daridorexant overdose cases showed low severity, with no fatalities. Co-ingestion with other substances, especially in females, increased toxicity risk, highlighting the need for caution in polypharmacy.
Area of Science:
- Pharmacology
- Toxicology
- Clinical Medicine
Background:
- Daridorexant is a dual orexin receptor antagonist used for insomnia.
- Real-world data on daridorexant acute toxicity and overdose are limited.
- Understanding overdose characteristics is crucial for patient safety.
Purpose of the Study:
- To characterize clinical presentation, severity, and outcomes of daridorexant exposures.
- To investigate the role of co-ingested substances in overdose severity.
- To identify potential sex-specific differences in daridorexant toxicity.
Main Methods:
- Retrospective review of daridorexant exposure cases reported to a French Poison Centre network (March 2024 - May 2025).
- Data extraction included demographics, clinical, and toxicological information.
- Poisoning Severity Score (PSS) was used to grade severity; logistic regression analyzed co-intoxication effects.
Main Results:
- Fifty-one cases were analyzed, with 70.6% being female.
- Mono-intoxications primarily caused somnolence; co-intoxications involved CNS depressants and led to severe symptoms like coma.
- Co-intoxication was significantly associated with increased severity in females (P=0.0086).
Conclusions:
- Daridorexant overdose is generally low severity when taken alone.
- Co-ingestion significantly increases toxicity, particularly in females.
- Clinical vigilance is advised in polypharmacy cases involving daridorexant and CNS depressants.
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