- Spencer Greene, MD, MS, FACEP
Spencer Greene, MD, MS, FACEP
- Assistant Professor of Medicine
- Baylor College of Medicine
- Director of Medical Toxicology
- Section of Emergency Medicine
- Ayrn O'Connor, MD
Ayrn O'Connor, MD
- Clinical Associate Professor of Emergency Medicine
- University of Arizona College of Medicine
- Section Editors
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics
- Harvard Medical School
Carbamazepine has been used for many years for the treatment of both partial and generalized seizures, as well as trigeminal neuralgia. It has also been used as a mood stabilizer and for treatment of neuropathic pain syndromes.
In 2010, the American Association of Poison Control Centers reported 4282 toxic exposures to carbamazepine . Of these, 2248 were reportedly isolated ingestions. Among the 1489 patients who sought treatment, there was one death and 538 patients who experienced moderate or major toxicity .
The toxicology, diagnosis, and management of acute carbamazepine poisoning are discussed here. The clinical use of carbamazepine and chronic complications related to its use are reviewed separately. (See "Overview of the management of epilepsy in adults" and "Seizures and epilepsy in children: Initial treatment and monitoring" and "Antiepileptic drugs: Mechanism of action, pharmacology, and adverse effects".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
Carbamazepine interacts with multiple receptors and ion channels. Its therapeutic effect results from binding to sodium channels in their inactivated state, which inhibits neuron depolarization and decreases glutamate release . It is also anticholinergic, a property that is more relative in overdose than the therapeutic setting . (See "Anticholinergic poisoning".)
In carbamazepine toxicity, sodium channel blockade may manifest as cardiovascular toxicity, particularly prolongation of the QRS interval. This conduction abnormality predisposes patients to ventricular arrhythmias and hypotension .
- Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2010 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th Annual Report. Clin Toxicol (Phila) 2011; 49:910.
- Novartis Pharmaceuticals USA. Prescribing information for Tegretol CR400(R) tablets www.pharma.us.novartis.com/product/pi/pdf/tegretol.pdf (Accessed on August 27, 2008).
- Spiller HA. Management of carbamazepine overdose. Pediatr Emerg Care 2001; 17:452.
- Starmer CF, Lastra AA, Nesterenko VV, Grant AO. Proarrhythmic response to sodium channel blockade. Theoretical model and numerical experiments. Circulation 1991; 84:1364.
- Fujiwara Y, Sato M, Otsuki S. Interaction of carbamazepine and other drugs with adenosine (A1 and A2) receptors. Psychopharmacology (Berl) 1986; 90:332.
- Van Calker D, Steber R, Klotz KN, Greil W. Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses. Eur J Pharmacol 1991; 206:285.
- Kanarkowski R, Rybakowski J. [Clinical pharmacokinetics of carbamazepine]. Psychiatr Pol 1989; 23:379.
- Graudins A, Peden G, Dowsett RP. Massive overdose with controlled-release carbamazepine resulting in delayed peak serum concentrations and life-threatening toxicity. Emerg Med (Fremantle) 2002; 14:89.
- Vree TB, Janssen TJ, Hekster YA, et al. Clinical pharmacokinetics of carbamazepine and its epoxy and hydroxy metabolites in humans after an overdose. Ther Drug Monit 1986; 8:297.
- Spina E, Martines C, Fazio A, et al. Effect of phenobarbital on the pharmacokinetics of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine. Ther Drug Monit 1991; 13:109.
- Kanarkowski R, Wankiewicz G, Lehmann W, Rybakowski J. Pharmacokinetics of carbamazepine in psychiatric patients. Pol J Pharmacol Pharm 1988; 40:55.
- Yoo JH, Kang DS, Chun WH, et al. Anticonvulsant hypersensitivity syndrome with an epoxide hydrolase defect. Br J Dermatol 1999; 140:181.
- Hundt HK, Aucamp AK, Müller FO. Pharmacokinetic aspects of carbamazepine and its two major metabolites in plasma during overdosage. Hum Toxicol 1983; 2:607.
- Goulden KJ, Camfield P, Dooley JM, et al. Severe carbamazepine intoxication after coadministration of erythromycin. J Pediatr 1986; 109:135.
- Tagawa T, Mimaki T, Ono J, et al. Erythromycin-induced carbamazepine intoxication in two epileptic children. Jpn J Psychiatry Neurol 1989; 43:513.
- Jerling M, Lindström L, Bondesson U, Bertilsson L. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 1994; 16:368.
- Iwahashi K, Miyatake R, Suwaki H, et al. The drug-drug interaction effects of haloperidol on plasma carbamazepine levels. Clin Neuropharmacol 1995; 18:233.
- Winnicka RI, Topaciński B, Szymczak WM, Szymańska B. Carbamazepine poisoning: elimination kinetics and quantitative relationship with carbamazepine 10,11-epoxide. J Toxicol Clin Toxicol 2002; 40:759.
- Perez A, Wiley JF. Pediatric carbamazepine suspension overdose-clinical manifestations and toxicokinetics. Pediatr Emerg Care 2005; 21:252.
- Durelli L, Massazza U, Cavallo R. Carbamazepine toxicity and poisoning. Incidence, clinical features and management. Med Toxicol Adverse Drug Exp 1989; 4:95.
- Spiller HA, Carlisle RD. Status epilepticus after massive carbamazepine overdose. J Toxicol Clin Toxicol 2002; 40:81.
- Tibballs J. Acute toxic reaction to carbamazepine: clinical effects and serum concentrations. J Pediatr 1992; 121:295.
- O'Neal W Jr, Whitten KM, Baumann RJ, et al. Lack of serious toxicity following carbamazepine overdosage. Clin Pharm 1984; 3:545.
- Fisher RS, Cysyk B. A fatal overdose of carbamazepine: case report and review of literature. J Toxicol Clin Toxicol 1988; 26:477.
- Hojer J, Malmlund HO, Berg A. Clinical features in 28 consecutive cases of laboratory confirmed massive poisoning with carbamazepine alone. J Toxicol Clin Toxicol 1993; 31:449.
- Seymour JF. Carbamazepine overdose. Features of 33 cases. Drug Saf 1993; 8:81.
- Stremski ES, Brady WB, Prasad K, Hennes HA. Pediatric carbamazepine intoxication. Ann Emerg Med 1995; 25:624.
- de la Cruz M, Bance M. Carbamazepine-induced sensorineural hearing loss. Arch Otolaryngol Head Neck Surg 1999; 125:225.
- Tsao CY, Wright FS. Acute chemical pancreatitis associated with carbamazepine intoxication. Epilepsia 1993; 34:174.
- Godden DJ, McPhie JL. Bullous skin eruption associated with carbamazepine overdosage. Postgrad Med J 1983; 59:336.
- Brahmi N, Kouraichi N, Abderrazek H, et al. Clinical experience with carbamazepine overdose: relationship between serum concentration and neurological severity. J Clin Psychopharmacol 2008; 28:241.
- George S, Braithwaite RA. A preliminary evaluation of five rapid detection kits for on site drugs of abuse screening. Addiction 1995; 90:227.
- Fleischman A, Chiang VW. Carbamazepine overdose recognized by a tricyclic antidepressant assay. Pediatrics 2001; 107:176.
- Saidinejad M, Law T, Ewald MB. Interference by carbamazepine and oxcarbazepine with serum- and urine-screening assays for tricyclic antidepressants. Pediatrics 2007; 120:e504.
- Sobotka JL, Alexander B, Cook BL. A review of carbamazepine's hematologic reactions and monitoring recommendations. DICP 1990; 24:1214.
- Kuz GM, Manssourian A. Carbamazepine-induced hyponatremia: assessment of risk factors. Ann Pharmacother 2005; 39:1943.
- Mayoral W, Lewis JH. Drug-induced liver disease. Curr Opin Gastroenterol 2000; 16:231.
- Bradberry SM, Thanacoody HK, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate. Toxicol Rev 2005; 24:195.
- Liebelt EL. Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal role for alkalinization and sodium loading. Pediatr Emerg Care 1998; 14:293.
- Cave G, Sleigh JW. ECG features of sodium channel blockade in rodent phenytoin toxicity and effect of hypertonic saline. Vet Hum Toxicol 2003; 45:254.
- Mise S, Jukić I, Tonkić A, et al. Multidose activated charcoal in the treatment of carbamazepine overdose with seizures: a case report. Arh Hig Rada Toksikol 2005; 56:333.
- Chyka PA, Seger D, Krenzelok EP, et al. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43:61.
- Greene S, Harris C, Singer J. Gastrointestinal decontamination of the poisoned patient. Pediatr Emerg Care 2008; 24:176.
- Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1999; 37:731.
- Wason S, Baker RC, Carolan P, et al. Carbamazepine overdose--the effects of multiple dose activated charcoal. J Toxicol Clin Toxicol 1992; 30:39.
- Brahmi N, Kouraichi N, Thabet H, Amamou M. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning. Am J Emerg Med 2006; 24:440.
- Montoya-Cabrera MA, Sauceda-García JM, Escalante-Galindo P, et al. Carbamazepine poisoning in adolescent suicide attempters. Effectiveness of multiple-dose activated charcoal in enhancing carbamazepine elimination. Arch Med Res 1996; 27:485.
- Thanacoody R, Caravati EM, Troutman B, et al. Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol (Phila) 2015; 53:5.
- Lurie Y, Bentur Y, Levy Y, et al. Limited efficacy of gastrointestinal decontamination in severe slow-release carbamazepine overdose. Ann Pharmacother 2007; 41:1539.
- Vale JA, Kulig K, American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position paper: gastric lavage. J Toxicol Clin Toxicol 2004; 42:933.
- Position paper: Ipecac syrup. J Toxicol Clin Toxicol 2004; 42:133.
- Ghannoum M, Yates C, Galvao TF, et al. Extracorporeal treatment for carbamazepine poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2014; 52:993.
- Harder JL, Heung M, Vilay AM, et al. Carbamazepine and the active epoxide metabolite are effectively cleared by hemodialysis followed by continuous venovenous hemodialysis in an acute overdose. Hemodial Int 2011; 15:412.
- Choi JS, Kim CS, Bae EH, et al. Enhanced clearance of carbamazepine using albumin-containing dialysate during CVVHDF. Intensive Care Med 2013; 39:159.
- Bek K, Koçak S, Ozkaya O, et al. Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents. Nephrology (Carlton) 2007; 12:33.
- Deshpande G, Meert KL, Valentini RP. Repeat charcoal hemoperfusion treatments in life threatening carbamazepine overdose. Pediatr Nephrol 1999; 13:775.
- Leslie PJ, Heyworth R, Prescott LF. Cardiac complications of carbamazepine intoxication: treatment by haemoperfusion. Br Med J (Clin Res Ed) 1983; 286:1018.
- Cameron RJ, Hungerford P, Dawson AH. Efficacy of charcoal hemoperfusion in massive carbamazepine poisoning. J Toxicol Clin Toxicol 2002; 40:507.
- Pilapil M, Petersen J. Efficacy of hemodialysis and charcoal hemoperfusion in carbamazepine overdose. Clin Toxicol (Phila) 2008; 46:342.
- Duzova A, Baskin E, Usta Y, Ozen S. Carbamazepine poisoning: treatment with plasma exchange. Hum Exp Toxicol 2001; 20:175.
- Ram Prabahar M, Raja Karthik K, Singh M, et al. Successful treatment of carbamazepine poisoning with hemodialysis: a case report and review of the literature. Hemodial Int 2011; 15:407.
- Chetty M, Sarkar P, Aggarwal A, Sakhuja V. Carbamazepine poisoning: treatment with haemodialysis. Nephrol Dial Transplant 2003; 18:220.
- Schuerer DJ, Brophy PD, Maxvold NJ, et al. High-efficiency dialysis for carbamazepine overdose. J Toxicol Clin Toxicol 2000; 38:321.
- Li TG, Yan Y, Wang NN, Zhao M. Acute carbamazepine poisoning treated with resin hemoperfusion successfully. Am J Emerg Med 2011; 29:518.
- Garlich FM, Goldfarb DS. Have advances in extracorporeal removal techniques changed the indications for their use in poisonings? Adv Chronic Kidney Dis 2011; 18:172.
- Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000; 35:374.
- Macnab AJ, Birch P, Macready J. Carbamazepine poisoning in children. Pediatr Emerg Care 1993; 9:195.
- Lifshitz M, Gavrilov V, Sofer S. Signs and symptoms of carbamazepine overdose in young children. Pediatr Emerg Care 2000; 16:26.
- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES
- Examination and clinical manifestations
- DIFFERENTIAL DIAGNOSIS
- LABORATORY EVALUATION
- General diagnostic testing in overdose
- Serum carbamazepine concentration
- Ancillary testing
- Airway, breathing, and circulation
- QRS interval prolongation
- Gastrointestinal decontamination
- - Activated charcoal
- - Multidose activated charcoal
- - Other methods
- Extracorporeal elimination
- Other complications
- PEDIATRIC CONSIDERATIONS
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS