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 micrograms/ml [105 mumol/l]); II--combativeness, hallucinations, choreiform movements (15 to 25 micrograms/ml [65 to 105 mumol/l]); III--drowsiness, ataxia (11 to 15 micrograms/ml [45 to 65 mumol/l]); and IV--potentially catastrophic relapse (less than 11 micrograms/ml [45 mumol/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.