Diphenhydramine overdose can be fatal. Peak serum levels of DPH are reached approximately 2–3 h after ingestion, and elimination half‐life is approximately 4 h. Because DPH is liposoluble and its volume of distribution is large (3–7 L/kg), its elimination by hemodialysis and hemoperfusion is difficult. Although DPH is considered as a relatively safe drug with a large therapeutic range, it causes dose‐dependent toxicity. Eckes et al . have reported serum DPH concentration of >5 μg/mL as fatal.
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In previous reports, DPH overdose resulted in severe symptoms within several hours. Symptoms are dose‐dependent. Severe symptoms (delirium/psychosis, seizures, and coma) can occur with ingestion of >1.0 g DPH. The frequency of coma and seizures may increase with ingestion of >1.5 g DPH, and electrocardiographic disturbances may occur with ingestion of >3.0 g DPH. Although the serum DPH concentration was thought to have peaked about 13 h before arriving at the hospital in this case because peak serum DPH concentration is usually reached 2–3 h after ingestion, the patient's serum DPH concentration at the time of arrival was >5 μg/mL, which is considered to be a fatal dose.
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Although the patient ingested a fatal dose of DPH, it is estimated that it took approximately 16 h for symptoms to appear. Therefore, caution should be exercised when symptoms occur long after DPH ingestion.