Introduction. Most cases of methemoglobinemia result from exposure to certain medications and chemicals such as nitrates, nitrites, aniline, dapsone, phenazopyridine, benzocaine, and chlorates which oxidize the iron from the ferrous state. Intoxication with zopiclone is expected to produce drowsiness, confusion and coma but not methemoglobinemia. We report two cases of zopiclone overdose with methemoglobinemia. Case Reports. Case one: A 43-year-old woman presented to the emergency department two hours after ingesting 100 tablets of 7.5 mg zopiclone. Her initial vital signs, physical examination, chest x-ray, and electrocardiogram were normal. Two hours post-ingestion her methemoglobin level was 9.8%; 14 hours post-arrival she showed cyanosis of the lips and extremities and dyspnea after walking. The blood sample 16 hours post-ingestion was dark brown in color and the methemoglobin was 23.8%. Shortly after the second of two doses of methylene blue (1 mg/kg each) her methemoglobin was 3.6%. Case two: A 30-year-old woman came to the emergency department 50 hours after ingesting 150 to 200 tablets of 7.5 mg zopiclone. Her vital signs and physical examination were normal. Her methemoglobin level was 5.2% at 52 hours post-ingestion and it peaked at 10.4% one hour later. She recovered following symptomatic care. Discussion and Conclusions. Methemoglobinemia has not previously been reported following acute zopiclone overdose. In our patients, there were no identifiable alternative causes explaining the methemoglobinemia and zopiclone was confirmed in both patients by laboratory analysis. These two cases suggest that zopiclone overdose is capable of producing delayed methemoglobinemia, which may be related to formation of a sufficient quantity of the N-oxide metabolite.

In zopiclone overdose, there may be oxidative stress rendering the development of not only methemoglobinemia but also hemolysis.