Massive carbamazepine overdose: Clinical and pharmacologic observations in five episodes

We report five episodes of carbamazepine (CBZ) intoxication in four patients. Clinically, there were four distinct stages: I—coma, seizures (CBZ levels more than 25 μg/ml [105 μmol/l]); II—combativeness, hallucinations, choreiform movements (15 to 25 μg/ml [65 to 105 μmol/l]); III—drowsiness, ataxia (11 to 15 μg/ml [45 to 65 μmol/l]); and IV—potentially catastrophic relapse (less than 11 μg/ml [45 μmol/l]). Pharmacokinetic studies revealed a prolongation of the CBZ half-life, elevation of the CBZ-epoxide/CBZ ratio, and emergence of CBZ-epoxide as a significant toxic metabolite. A treatment approach is proposed including repeated gastric lavage, detection of an insoluble tablet coagulum, electrolyte monitoring, avoidance of cathartics, and treatment of seizures with diazepam and phenytoin.