Carbamazepine Overdose: A Prospective Study of Serum Levels and Toxicity

Abstract

A cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age, chronic exposure, or previous disorder or cardiovascular disease could be used as prognostic indicators. Seventy-three consecutive cases were collected from two regional certified poison control centers from January 1989 to August 1989. There were 25 exposures in children less than 6 yrs., 11 exposures in adolescents, and 37 exposures in adults. Ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information. Peak measured serum levels ranged from 0.3 to 56 mcg/ml. Using the presence of coma, seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity, we found poor correlation between rising serum levels of carbamazepine and toxicity. Increased serum levels of carbamazepine did appear to correlate with increased hospital stay, but not with ICU stay. History of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose. In this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect. Serum levels below 40 mcg/ml do not appear to accurately predict the severity of toxicity. Cardiac conduction defects were rare (one child). Anticholinergic findings, as evidence by decreased bowel motility and sinus tachycardia were common. Previous cardiovascular disease and age did not appear to be important prognostic indicators.

Antiepileptic Drugs as a Cause of Worsening Seizures

“…Outside the therapeutic setting as well, precipitation of seizures has been described in association with deliberate or accidental acute overdosage: seizures and status epilepticus may complicate acute CBZ poisoning (33)(34)(35); status epilepticus and myoclonus have been reported after TBG overdose (36); nonconclusive status has been seen after phenobarbital (PB) poisoning (37); and myoclonic seizures have occurred following VPA overdose (38).…”

False-Positive Tricyclic Antidepressant Drug Screen Results Leading to the Diagnosis of Carbamazepine Intoxication

“…[3][4][5][6][7][8][9][10][11][12] Seizures can occur, most often in patients with a known seizure disorder 11 ; 1 study described seizures as an indicator of fatal outcome. 4 Patients with coma may develop respiratory depression requiring mechanical ventilation.…”

Carbamazepine toxicity following Oxybutynin and Dantrolene administration: a case report

“…3,4 Carbamazepine is less frequently used in patients with SCL, but it may be required when patients have concomitant posttraumatic or postoperative epilepsy, or more frequently for the treatment of painful or paraesthetic phenomena. 9,10 Carbamazepine intoxication includes nausea, vomiting, dizziness, ataxia, confusion, dysarthria, and nystagmus, 11 and it may also cause liver dysfunction. 12 Administration of the three drugs at the same time exposes the patient with SCL to their combined side effects.…”

“…It is eliminated through the hepatic pathway and catalyzed by cytochrome P450 (CYP3A subfamily), 13 so drugs that inhibit the activity of this cytochrome may elevate Carbamazepine blood level and cause toxicity. 11 These drugs include itriconazole, ketokonazole, clarythromycin, erythromycin, nefazodone, ritonavir, 14 isoniazide, propoxyphene, cimetidine, 15 fluvoxamine, fluoxetine, 16 and acetazolamide. 17 Here we present a case of Carbamazepine toxicity related to a pharmacokinetic interaction with either Oxybutynin or Dantrolene.…”