ACUTE OVERDOSE OF ZOLPIDEM (STILNOX(R))

Zolpidem (Stilnox(R)), an imidazopyridine derivative, is a strong seda tive with minor myorelaxant and anticonvulsant properties which exhibi ts high-affinity binding at a benzodiazepine-receptor subtype. Althoug h the structure of zolpidem differs from the benzodiazepines, the acut e toxicity of zolpidem has generally been compared to triazolam (Halci on(R)) and midazolam (Dormicum(R)). 5 years after introduction of zolp idem to the Swiss market we have therefore retrospectively analyzed 91 well documented cases of acute zolpidem intoxication reported to the Swiss Toxicological Information Center. Furthermore, 54 monointoxicati ons with zolpidem were compared with 53 triazolam and 55 midazolam int oxications observed over the same time period. 0.01-0.02 g of zolpidem is the recommended therapeutic dose. But only mild symptoms were obse rved in acute monointoxications with zolpidem up to 0.6 g. Patients ma inly suffered from somnolence. Only one anorectic patient became comat ose after ingestion of 0.6 g zolpidem. The acute toxicity of zolpidem was markedly less pronounced than that of the short-acting benzodiazep ines triazolam and midazolam. With forty-fold the therapeutic dose no severe symptoms occurred in patients with zolpidem monointoxications, while coma was encountered in 4 cases with triazolam (11% of patients) and 4 cases with midazolam (10%). While only the patient mentioned ab ove was reported to be comatose after over-dosing with zolpidem, 6 (11 %) and 8 (15%) comatose patients were observed in triazolam and midazo lam monointoxications, respectively. On the other hand, in combined in toxications with other CNS active drugs or ethanol a zolpidem dose as low as 0.1-0.15 g induced coma in some patients, even if the amount of the additionally ingested drugs in itself would not have caused a com atose state. Flumazenil (Anexate(R)) was an effective antidote in mono - and combined intoxications involving zolpidem. In conclusion, our re sults indicate that zolpidem monointoxications are generally benign an d require no specific therapeutic measures. In combined intoxications, however, patients may develop coma at relatively low zolpidem doses a nd should therefore be monitored for approximately 24 hours. If necess ary, disturbances of consciousness can be successfully treated with fl umazenil.