Pediatric Carbamazepine Toxicity Workup
- Author: Muhammad Waseem, MD, MS; Chief Editor: Timothy E Corden, MD more...
The workup in a patient with suspected carbamazepine poisoning should include appropriate comprehensive serum and urine drug screening, plus analysis of the following:
Alcohol level, if alcohol toxicity is suspected, particularly in adolescents
Serum electrolyte levels, including glucose, calcium, magnesium, phosphate, serum bicarbonate, BUN, and serum creatinine levels
Liver function tests, because elevated liver enzyme levels, hepatitis, and hyperammonemia may be noted with chronic toxicity
Serum drug testing should be based on the history of ingestion and/or the patient’s toxidrome.
A serum and urine drug screen may not detect carbamazepine; therefore, the serum carbamazepine level should also be determined if the patient has access to carbamazepine. Structural similarity between carbamazepine and tricyclic antidepressants (TCAs) may cause false-positive results with immunoassay for TCAs. Patients who are taking carbamazepine should have therapeutic drug monitoring using serum carbamazepine levels.
Because carbamazepine absorption varies, the serum concentration may not peak for as long as 24-72 hours. With controlled-release formulation, levels may continue to rise until 4 days postingestion. In fact, the initial carbamazepine level may be misleading. For this reason, serial measurements documenting a declining carbamazepine level and prolonged observation are recommended when managing these overdoses.
Initial serum levels of more than 35 mg/L (127 µmol/L) suggest serious toxicity. However, lower initial serum levels do not necessarily indicate a benign course and the patient still needs to be closely monitored for signs and symptoms of significant toxicity.
The serum concentration may not always directly correlate with the clinical picture. The severity of toxicity is assessed on the basis of the clinical status and not only the serum carbamazepine concentration.
Toxicity may result from carbamazepine itself or its active epoxide metabolite. However, measuring epoxide levels along with the carbamazepine level provides no additional advantage.
The complete blood cell count (CBC) with a differential should be obtained.
Although in utero exposure to carbamazepine has not been associated with adverse neuropsychological function, it has been associated with reduced verbal abilities.Therefore, a urine pregnancy test should be obtained on adolescent girls and if they are pregnant they should be counseled as to the possible effects of carbamazepine on the development of the fetus.
With acute carbamazepine toxicity, ultrasonography may reveal chemical pancreatitis. These patients may have no accompanying pain or other signs and symptoms.
Other tests to consider include the following:
Perform a 12-lead ECG in patients with suspected poisoning.
Continuous EEG recordings in a case with unconsciousness, absent brainstem reflexes, and stimulus-sensitive multifocal myoclonus revealed a burst-suppression pattern, with bursts containing only generalized spikes accompanying myoclonic activity.  After treatment, EEG became more continuous and rhythmic without epileptiform discharges and with declining serum carbamazepine levels.
Carbamazepine is incorporated and retained in hair, depending on the blood levels. Sectional hair analysis helps investigators determine if chronic poisoning is an issue. 
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015 Dec. 53 (10):962-1147. [Medline]. [Full Text].
Brodie MJ, Mintzer S, Pack AM, Gidal BE, Vecht CJ, Schmidt D. Enzyme induction with antiepileptic drugs: cause for concern?. Epilepsia. 2013 Jan. 54(1):11-27. [Medline].
Davis AR, Westhoff CL, Stanczyk FZ. Carbamazepine coadministration with an oral contraceptive: effects on steroid pharmacokinetics, ovulation, and bleeding. Epilepsia. 2011 Feb. 52(2):243-7. [Medline]. [Full Text].
Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P Jr. Evaluation of the potential for pharmacokinetic drug-drug interaction between armodafinil and carbamazepine in healthy adults. Clin Ther. 2015 Feb 1. 37 (2):325-37. [Medline].
Li ZH, Zlabek V, Velisek J, et al. Acute toxicity of carbamazepine to juvenile rainbow trout (Oncorhynchus mykiss): effects on antioxidant responses, hematological parameters and hepatic EROD. Ecotoxicol Environ Saf. March 2011. 74(3):319-27. [Medline].
Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Omslaer JC, et al. 2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2001 Sep. 19(5):337-95. [Medline].
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). 2008 Dec. 46(10):927-1057. [Medline].
Dogan M, Yilmaz C, Temel H, Çaksen H, Taskin G. A case of carbamazepine intoxication in a young boy. J Emerg Med. 2010 Nov. 39(5):655-6. [Medline].
Narita H, Ozawa T, Nishiyama T, et al. An atypical case of fulminant interstitial pneumonitis induced by carbamazepine. Curr Drug Saf. 2009 Jan. 4(1):30-3. [Medline].
Celik IE, Akyel A, Colgecen M, Ozeke O. A rare cause of 2:1 atrioventricular block: carbamazepine. Am J Emerg Med. 2015 Oct. 33 (10):1541.e3-4. [Medline].
Higuchi S, Yano A, Takai S, Tsuneyama K, Fukami T, Nakajima M, et al. Metabolic activation and inflammation reactions involved in carbamazepine-induced liver injury. Toxicol Sci. 2012 Nov. 130(1):4-16. [Medline].
Go T. Carbamazepine-induced IgG1 and IgG2 deficiency associated with B cell maturation defect. Seizure. 2004 Apr. 13(3):187-90. [Medline].
Sevketoglu E, Hatipoglu S, Akman M, Bicer S. Toxic epidermal necrolysis in a child after carbamazepine dosage increment. Pediatr Emerg Care. 2009 Feb. 25(2):93-5. [Medline].
Suzuki Y, Fukuda M, Tohyama M, et al. Carbamazepine-induced drug-induced hypersensitivity syndrome in a 14-year-old Japanese boy. Epilepsia. 2008 Dec. 49(12):2118-21. [Medline].
Locharernkul C, Loplumlert J, Limotai C, et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008 Dec. 49(12):2087-91. [Medline].
Zhang Y, Wang J, Zhao LM, Peng W, Shen GQ, Xue L, et al. Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. Eur J Clin Pharmacol. September 2011. 67(9):885-887. [Medline].
Chen P, Lin JJ, Lu CS, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. March 2011. 364(12):1126-33. [Medline].
McCormack M, Alfirevic A, Bourgeois S et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. March 2011. 364(12):1134-43. [Medline].
Aggarwal A, Rastogi N, Mittal H, et al. Thyroid hormone levels in children receiving carbamazepine or valproate. Pediatr Neurol. Sep 2011. 45(3):159-62. [Medline].
Spiller HA, Carlisle RD. Status epilepticus after massive carbamazepine overdose. J Toxicol Clin Toxicol. 2002. 40(1):81-90. [Medline].
Lucas C, Donovan P. Just a repeat' - When drug monitoring is indicated. Aust Fam Physician. Jan-Feb 2013. 42(1-2):18-22. [Medline].
Patel VH, Schindlbeck MA, Bryant SM. Delayed elevation in carbamazepine concentrations after overdose: a retrospective poison center study. Am J Ther. Nov-Dec 2013. 20(6):602-6. [Medline].
Baker GA, Bromley RL, Briggs M, Cheyne CP, Cohen MJ, García-Fiñana M, et al. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology. 2015 Jan 27. 84 (4):382-90. [Medline].
De Rubeis DA, Young GB. Continuous EEG monitoring in a patient with massive carbamazepine overdose. J Clin Neurophysiol. 2001 Mar. 18(2):166-8. [Medline].
Mantzouranis EC, Bertsias GK, Pallis EG, Tsatsakis AM. Hair analysis differentiates chronic from acute carbamazepine intoxication. Pediatr Neurol. 2004 Jul. 31(1):73-5. [Medline].
Doyon S. Antiepileptics. Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank's Toxicologic Emergencies. 10th ed. New York, NY: McGraw-Hill Education; 2015.
[Guideline] Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J, et al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila). 2013 Mar. 51 (3):140-6. [Medline].
Deshpande G, Meert KL, Valentini RP. Repeat charcoal hemoperfusion treatments in life threatening carbamazepine overdose. Pediatr Nephrol. 1999 Nov. 13(9):775-7. [Medline].
Askenazi DJ, Goldstein SL, Chang IF, et al. Management of a severe carbamazepine overdose using albumin-enhanced continuous venovenous hemodialysis. Pediatrics. 2004 Feb. 113(2):406-9. [Medline]. [Full Text].
Yildiz TS, Toprak DG, Arisoy ES, Solak M, Toker K. Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine overdose in a pediatric patient. Paediatr Anaesth. 2006 Nov. 16(11):1176-8. [Medline].
Bek K, Kocak S, Ozkaya O, et al. Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents. Nephrology (Carlton). 2007 Feb. 12(1):33-5. [Medline].
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. July 2011. 15(3):412-5. [Medline].
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. July 2011. 15(3):407-11. [Medline].
Ghannoum M, Yates C, Galvao TF, Sowinski KM, Vo TH, Coogan A, et al. Extracorporeal treatment for carbamazepine poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila). 2014 Dec. 52 (10):993-1004. [Medline].
Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007 May 1. 146(9):657-65. [Medline].
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 Mar. 14(1):89-94. [Medline].
Marini AM, Choi JY, Labutta RJ. Transient neurologic deficits associated with carbamazepine-induced hypertension. Clin Neuropharmacol. 2003 Jul-Aug. 26(4):174-6. [Medline].
Morselli PL, Frigerio A. Metabolism and Pharmacolinetics of Carbamazepine. Drug Metab Rev. 1975. 4(1):97-113. [Medline].
Spiller HA. Management of carbamazepine overdose. Pediatr Emerg Care. 2001 Dec. 17(6):452-6. [Medline].
Spiller HA, Strauch J, Essing-Spiller SJ, Burns G. Thirteen years of oxcarbazepine exposures reported to US poison centers: 2000 to 2012. Hum Exp Toxicol. 2015 Nov 26. [Medline].