Carbamazepine Toxicity

Updated: Dec 13, 2016
  • Author: Nidhi Kapoor, MD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Practice Essentials

Carbamazepine (5H-dibenzazepine-5-carboxamide) is an iminostilbene derivative with a tricyclic structure. It is an antiepileptic drug widely used for treatment of simple partial seizures and complex partial seizures, trigeminal neuralgia, and bipolar affective disorder.

Carbamazepine selectively inhibits high frequency epileptic foci while normal neuronal activity remains undisturbed. Carbamazepine is absorbed erratically after oral administration because of its lipophilic nature. It has a large volume of distribution; peak plasma levels occur 4-8 hours postingestion but may take up to 24 hours to peak. The primary site of metabolism is the liver; its metabolite also is active, which may increase duration of the symptoms of toxicity.

Patients with carbamazepine toxicity may present with neurologic, ocular, cardiovascular, and cutaneous signs and symptoms (see Presentation). In addition to measurement of the serum carbamazepine level, the workup should include testing to detect organ system complications and rule out alternative diagnoses (see Workup). Treatment focuses on decontamination and supportive care (see Treatment and Medication).



Carbamazepine reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potentials in the epileptic focus. Carbamazepine is absorbed slowly and distributed erratically following oral administration. It enters the brain rapidly because of its high lipid solubility.

Carbamazepine is metabolized primarily in the liver by oxidative enzymes, then is conjugated with glucuronic acid, and finally is excreted in the urine. Its metabolite, carbamazepine-10,11-epoxide, is active and may achieve up to 50% concentration of the parent compound.

The elimination of carbamazepine increases over the first few weeks because of autoinduction. Carbamazepine also enhances the metabolism of phenytoin, causing its levels to fall. Erythromycin, isoniazid, and propoxyphene (withdrawn from the US market) inhibit the hepatic metabolism of carbamazepine; therefore, the dose of carbamazepine may need to be adjusted in patients taking multiple medications.

Carbamazepine induces the hepatic cytochrome P-450 system and its half-life decreases with chronic administration. The enhanced cytochrome P-450 system increases metabolism of other antiepileptic drugs.




United States

According to the American Association of Poison Control Centers' National Poison Data System, 1880 carbamazepine single exposures were reported in 2014. Of these, 1336 were treated in a health care facility. [1]


Of the single exposures to carbamazepine reported to the AAPCC in 2014, 300 resulted in no significant outcome and 62 had a major outcome. No deaths were reported. [1]

Montgomery et al reports that severity of symptoms at the time of initial contact with the poison control center correlates with outcome severity for children and adults. [2] However, the amount of time between ingestion and poison control center contact did not alter the correlation between initial severity of symptoms and final outcome severity.

Far more exposures to the drug are unintentional (57.2%) than intentional (37.6%). A small number of people experienced the effects of toxicity secondary to adverse reactions rather than true poisonings (4%). Montgomery et al found that the reason for ingestion was correlated significantly with outcome. Carbamazepine levels greater than 85 mg/L were associated with severe toxicity. [2]

Oxcarbazepine is structural derivative of carbamazepine. It is metabolized to 10-monohydrate derivate (MHD), which is the pharmacologically effective compound. van Optstal et al reported a case in which a patient ingested more than 100 tablets of oxcarbazepine. [3] The serum level of the parent compound was 10-fold higher than the therapeutic dosage of 31.6 mg/L. However, the concentration of MHD was only 2-fold higher. MHD levels peaked 7 hours after intake. The patient survived without an adverse outcome. The authors concluded that since oxcarbazepine is a prodrug, formation of the active MHD metabolite is a rate-limiting process contributing to low overall toxicity of this drug.

A review of oxcarbazepine exposures reported to National Poison Data System from 2000 to 2012 found that less than 1% of cases resulted in severe outcomes. Of the 18,867 total cases, 68% of those with major outcomes, and all five deaths, were due to intentional exposure (ie, suicide attempt). [4]


In 2014, 253 of the 1880 reported cases of carbamazepine exposures occurred in children younger than 6 years. Pediatric patients with carbamazepine ingestion are at higher risk for dystonic reactions, coma, and apnea if serum levels exceed 28 mg/L. Children eliminate the drug more rapidly than adults.


Increased risk for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis has been linked to carriage of the HLA-B*1502, which is common in Han-Chinese, Thai, and Malaysian populations.The US Food and Drug Administration has recommended screening for the HLA-B*1502 allele before starting carbamazepine therapy in patients of Asian ancestry, [5]