The shorter elimination half-life of diphenhydramine (4–8 hours) may give it an advantage over doxylamine in this regard. Unlike with diphenhydramine, case reports of coma and rhabdomyolysis have been reported with doxylamine. Doxylamine succinate is generally safe for administration to healthy adults. The median lethal dose () is estimated to be 50–500 mg/kg in humans. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic (or grand mal) seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3-year-old child died 18 hours after ingesting 1000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis and acute kidney injury. Studies of doxylamine's carcinogenicity in mice and rats have produced positive results for both liver and thyroid cancer, especially in the mouse. The carcinogenicity of the drug in humans is not well studied, and the IARC lists the drug as "not classifiable as to its carcinogenicity to humans". Doxylamine acts primarily as an antagonist or inverse agonist of the histamine H1 receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of the muscarinic acetylcholine receptors, an action responsible for its minor hypnotic, anticholinergic, and (at high doses) deliriant effects. The bioavailability of doxylamine is 24.7% for oral administration and 70.8% for intranasal administration. The Tmax of doxylamine is 1.5 to 2.5 hours. Its elimination half-life is 10 to 12 hours. Doxylamine is metabolized in the liver primarily by the cytochrome P450 enzymes CYP2D6, CYP1A2, and CYP2C9. The main metabolites are "N"-desmethyldoxylamine, "N","N"-didesmethyldoxylamine, and doxylamine "N"-oxide.