Pediatric Carbamazepine Toxicity Workup

  • Author: Muhammad Waseem, MD; Chief Editor: Timothy E Corden, MD   more...
 
Updated: Apr 10, 2012
 

Laboratory Studies

  • The workup in a patient with suspected carbamazepine poisoning should include appropriate comprehensive serum and urine drug screening with 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 should also be performed 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.
    • 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.
    • 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 CBC count with a differential and platelet count should be obtained.
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Imaging Studies

  • With acute carbamazepine toxicity, ultrasonography may reveal chemical pancreatitis without accompanying pain or other signs and symptoms.
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Other Tests

  • 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.[14] 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.[15]
  • On an interesting note, carbamazepine has been detected in the environment. Significant carbamazepine levels have been found in juvenile Rainbow Trout, probably due to pharmaceuticals that were discarded and contaminated the water.[16]
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Contributor Information and Disclosures
Author

Muhammad Waseem, MD  Associate Professor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University; Consulting Staff, Department of Pediatrics, Bronx Lebanon Hospital; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center

Muhammad Waseem, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, and American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Joel R Gernsheimer, MD, FACEP  Visiting Associate Professor, Department of Emergency Medicine, Attending Physician and Director of Geriatric Emergency Medicine, State University of New York Downstate Medical Center

Joel R Gernsheimer, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians and American Geriatrics Society

Disclosure: Nothing to disclose.

Nicholas D Caputo, MD  House Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center/Weill Cornell Medical College

Nicholas D Caputo, MD is a member of the following medical societies: American College of Emergency Physicians and Emergency Medicine Residents Association

Disclosure: Nothing to disclose.

Specialty Editor Board

William T Zempsky, MD  Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center

William T Zempsky, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD  Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD  Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Girish G Deshpande, MD, to the original writing and development of this article.

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

  2. Davis AR, Westhoff CL, Stanczyk FZ. Carbamazepine coadministration with an oral contraceptive: effects on steroid pharmacokinetics, ovulation, and bleeding. Epilepsia. Feb 2011;52(2):243-7. [Medline]. [Full Text].

  3. Narita H, Ozawa T, Nishiyama T, et al. An atypical case of fulminant interstitial pneumonitis induced by carbamazepine. Curr Drug Saf. Jan 2009;4(1):30-3. [Medline].

  4. Go T. Carbamazepine-induced IgG1 and IgG2 deficiency associated with B cell maturation defect. Seizure. Apr 2004;13(3):187-90. [Medline].

  5. Sevketoglu E, Hatipoglu S, Akman M, Bicer S. Toxic epidermal necrolysis in a child after carbamazepine dosage increment. Pediatr Emerg Care. Feb 2009;25(2):93-5. [Medline].

  6. Suzuki Y, Fukuda M, Tohyama M, et al. Carbamazepine-induced drug-induced hypersensitivity syndrome in a 14-year-old Japanese boy. Epilepsia. Dec 2008;49(12):2118-21. [Medline].

  7. 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. Dec 2008;49(12):2087-91. [Medline].

  8. 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].

  9. 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].

  10. 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].

  11. Khatami A, Singh-Grewal D, Kilham H. Tendon sheath abscess and severe carbamazepine hypersensitivity. J Paediatr Child Health. Jul-Aug 2008;44(7-8):462-3. [Medline].

  12. 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].

  13. Spiller HA, Carlisle RD. Status epilepticus after massive carbamazepine overdose. J Toxicol Clin Toxicol. 2002;40(1):81-90. [Medline].

  14. De Rubeis DA, Young GB. Continuous EEG monitoring in a patient with massive carbamazepine overdose. J Clin Neurophysiol. Mar 2001;18(2):166-8. [Medline].

  15. Mantzouranis EC, Bertsias GK, Pallis EG, Tsatsakis AM. Hair analysis differentiates chronic from acute carbamazepine intoxication. Pediatr Neurol. Jul 2004;31(1):73-5. [Medline].

  16. 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].

  17. [Guideline] Vale JA, Kulig K. Position paper: gastric lavage. J Toxicol Clin Toxicol. 2004;42(7):933-43. [Medline].

  18. Deshpande G, Meert KL, Valentini RP. Repeat charcoal hemoperfusion treatments in life threatening carbamazepine overdose. Pediatr Nephrol. Nov 1999;13(9):775-7. [Medline].

  19. Askenazi DJ, Goldstein SL, Chang IF, et al. Management of a severe carbamazepine overdose using albumin-enhanced continuous venovenous hemodialysis. Pediatrics. Feb 2004;113(2):406-9. [Medline]. [Full Text].

  20. 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. Nov 2006;16(11):1176-8. [Medline].

  21. Bek K, Kocak S, Ozkaya O, et al. Carbamazepine poisoning managed with haemodialysis and haemoperfusion in three adolescents. Nephrology (Carlton). Feb 2007;12(1):33-5. [Medline].

  22. 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].

  23. 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].

  24. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. May 1 2007;146(9):657-65. [Medline].

  25. Bridge TA, Norton RL, Robertson WO. Pediatric carbamazepine overdoses. Pediatr Emerg Care. Oct 1994;10(5):260-3. [Medline].

  26. Ellenhorn MJ, Schonwald S, Ordog G. Diagnosis and treatment of human poisoning. In: Ellenhorn's Medical Toxicology. 2nd ed. 1997:597-9.

  27. Fleischman A, Chiang VW. Carbamazepine overdose recognized by a tricyclic antidepressant assay. Pediatrics. Jan 2001;107(1):176-7. [Medline]. [Full Text].

  28. Goldfrank LR, Hoffman RS. Goldfrank's Toxicologic Emergencies. 5th ed. 1994:589-600.

  29. 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). Mar 2002;14(1):89-94. [Medline].

  30. Haddad LM, Shannon MW, Winchester JF. Clinical Management of Poisoning and Drug Overdose. 3rd ed. 1998:655-61.

  31. Hardman JG, Limbird LE, Molinoff PB. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. 1996:461-86.

  32. Low CL, Haqqie SS, Desai R, Bailie GR. Treatment of acute carbamazepine poisoning by hemoperfusion [letter]. Am J Emerg Med. Sep 1996;14(5):540-1. [Medline].

  33. Macnab AJ, Birch P, Macready J. Carbamazepine poisoning in children. Pediatr Emerg Care. Aug 1993;9(4):195-8. [Medline].

  34. Marini AM, Choi JY, Labutta RJ. Transient neurologic deficits associated with carbamazepine-induced hypertension. Clin Neuropharmacol. Jul-Aug 2003;26(4):174-6. [Medline].

  35. Morselli PL, Frigerio A. Metabolism and Pharmacolinetics of Carbamazepine. Drug Metab Rev. 1975;4(1):97-113. [Medline].

  36. Spiller HA. Management of carbamazepine overdose. Pediatr Emerg Care. Dec 2001;17(6):452-6. [Medline].

  37. Stremski ES, Brady WB, Prasad K, Hennes HA. Pediatric carbamazepine intoxication. Ann Emerg Med. May 1995;25(5):624-30. [Medline].

 
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Chemical structure of carbamazepine.
 
 
 
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