Clinical Features of Carbamazepine Overdose

where:

• The molecular weight of carbamazepine is 236.27.

• Factor to convert from µg/mL to µmol/L: 4.23.

• The anticholinergic effect of carbamazepine reduces GI motility in stages I to III.

The half-life of carbamazepine is:

(1) longer on initial exposure, but decreases with continued use due to self-induced metabolism

(2) longer in an overdose, possibly because of continued absorption and/or delayed excretion associated with saturated metabolic pathways

Carbamazepine 10,11-epoxide is the major metabolic product that may have toxic effects if it accumulates. Accumulation of the epoxide may be detected by an increase in the ratio of metabolite to parent drug:

ratio of carbamzepine 10,11-epoxide to carbamazepine =

= (serum epoxide concentration in µg/mL) / (serum carbamazepine in µg/mL)

Management:

(1) Repeated gastric lavage with administration of activated charcoal at 2 hour intervals via a nasogastric tube. Catharsis has little benefit.

(2) If an insoluble tablet coagulum is found within the stomach on upper GI series or with ultrasound, then consider gastrostomy to remove it. The coagulum can result in GI obstruction and serve as a reservoir for later drug release.

(3) Cardiac monitoring in the intensive care unit.

(4) Monitoring of electrolytes, with management of hyponatremia or other electrolyte disturbances.

(5) Periodic monitoring of hepatic function tests.

(6) Monitoring of serum carbamazepine and carbamazepine epoxide levels to document declining serum levels and detect accumulation.

(7) Avoidance of cathartics, which may distribute tablets along the GI tract and result in increased drug absorption.

(8) If seizures occur then treat with diazepam and phenytoin.

(9) Respiratory support may be necessary if respiratory depression occurs.

(10) Consider hemoperfusion if cardiac arrhythmias or severe hypotension develop.

(12) Continue active monitoring during Stage IV until completely recovered.