Carbamazepine Toxicity in Emergency Medicine Clinical Presentation

  • Author: Nidhi Kapoor, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Mar 29, 2012
 

History

Carbamazepine toxicity should be considered in differential diagnosis of patients presenting with ataxia. Query about whether the patient has been taking carbamazepine on an acute or chronic basis, the time of ingestion, formulation (immediate vs extended release) and the approximate dose ingested. The symptoms of carbamazepine toxicity may include the following:

  • Drowsiness
  • Slurred speech
  • Ataxia
  • Hallucinations
  • Nausea, vomiting
  • Tremors
  • Seizures
  • Oliguria
  • Blurred vision
  • Bullous skin formations
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Physical

Physical examination findings may include the following:

  • Ocular
    • Mydriasis
    • Nystagmus
    • Ophthalmoplegia
  • Cardiovascular
    • Tachycardia
    • Hypotension
  • Neurologic
    • Ataxia
    • Slurred speech
    • Dystonia, myoclonic activity
    • Varying degrees of CNS depression progressing to coma
    • Seizures, headache, confusion, and athetosis
    • Increased or decreased deep tendon reflexes
  • Respiratory depression, apnea
  • Delayed gastric emptying, abdominal pain
  • Oliguria, urinary retention
  • Skin
    • Bullous skin eruptions: Toxic epidermal necrolysis (TEN) has been reported with use of this drug. Severe drug eruptions are rare, and life-threatening events occur in 4 per million persons a year. TEN can trigger a life-threatening systemic inflammatory reaction leading to respiratory failure.[4]
    • Rash, dermatitis: Drug rash with eosinophilia and systemic symptoms, also known as DRESS syndrome, reflects a serious hypersensitivity reaction to drugs. Clinically, a diffuse maculopapular rash, exfoliative dermatitis, facial edema, lymphadenopathy, fever, and multivisceral involvement may be observed. All of these symptoms are associated with a high mortality rate.[5] A cross-reactivity between carbamazepine and phenytoin occurs, which may lead to or worsen DRESS syndrome. Discontinuation of the anticonvulsants and topical steroids should ameliorate the rash.
    • Stevens-Johnson syndrome
  • Blood dyscrasias
    • Pancytopenia
    • Splenomegaly
    • Lymphadenopathy
    • Vasculitis
    • Aplastic anemia
    • Agranulocytosis
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Causes

  • Carbamazepine toxicity may result from acute overdose or chronic therapy.
  • Therapeutic levels are 4-12 mg/L, but individual variation exists.
  • Patients on multiple anticonvulsants may not tolerate high levels and can be maintained at 4-8 mg/L, while others can achieve levels of 8-12 mg/L without adverse effects.
  • Ataxia and nystagmus may occur at levels greater than 10 mg/L.
  • Cardiovascular effects are usually seen at levels greater than 12 mg/L. The drug interferes with action potentials in Purkinje fibers and the His bundle, which may lead to atrioventricular blocks and arrhythmias.
  • Peak serum levels with controlled-release formulations of carbamazepine can result in delayed presentations of toxicity. Levels may not peak for 96 hours from the time of ingestion. Continuing repeat dosing of activated charcoal and whole-bowel irrigation is important. Hemoperfusion may be necessary if end-organ toxicity becomes evident.
  • Drug-drug interactions are known to occur. Vander et al reported a case of carbamazepine toxicity that occurred after administration of oxybutynin and an increase in the dose of dantrolene.[6] The combination of these drugs elevated the level of carbamazepine leading to toxicity.
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Contributor Information and Disclosures
Author

Nidhi Kapoor, MD  Clinical Assistant Professor, Department of Emergency Medicine, The Warren Alpert Medical School of Brown University

Nidhi Kapoor, MD is a member of the following medical societies: American College of Emergency Physicians, Rhode Island Medical Society, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Richard J Hamilton, MD, FAAEM, FACMT  Professor and Chair, Department of Emergency Medicine, Drexel University College of Medicine

Richard J Hamilton, MD, FAAEM, FACMT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

David C Lee, MD  Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

John G Benitez, MD, MPH  Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD  Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). Dec 2009;47(10):911-1084. [Medline].

  2. Montgomery VL, Richman BJ, Goldsmith LJ, Rodgers GC Jr. Severity and carbamazepine level at time of initial poison center contact correlate with outcome in carbamazepine poisoning. J Toxicol Clin Toxicol. 1995;33(4):311-23. [Medline].

  3. van Opstal JM, Janknegt R, Cilissen J, L'Ortije WH, Nel JE, De Heer F. Severe overdosage with the antiepileptic drug oxcarbazepine. Br J Clin Pharmacol. Sep 2004;58(3):329-31. [Medline]. [Full Text].

  4. Fischer M, Hamm H, Wirbelauer J. [Severe drug-related skin reaction: toxic epidermal necrolysis caused by carbamazepine]. Klin Padiatr. Sep-Oct 2004;216(5):288-93. [Medline].

  5. Allam JP, Paus T, Reichel C, Bieber T, Novak N. DRESS syndrome associated with carbamazepine and phenytoin. Eur J Dermatol. Sep-Oct 2004;14(5):339-42. [Medline].

  6. Vander T, Odi H, Bluvstein V, Ronen J, Catz A. Carbamazepine toxicity following Oxybutynin and Dantrolene administration: a case report. Spinal Cord. Apr 2005;43(4):252-5. [Medline].

  7. Apfelbaum JD, Caravati EM, Kerns WP 2nd, Bossart PJ, Larsen G. Cardiovascular effects of carbamazepine toxicity. Ann Emerg Med. May 1995;25(5):631-5. [Medline].

  8. Bass J, Miles MV, Tennison MB, Holcombe BJ, Thorn MD. Effects of enteral tube feeding on the absorption and pharmacokinetic profile of carbamazepine suspension. Epilepsia. May-Jun 1989;30(3):364-9. [Medline].

  9. Goldfrank L, Flomenbaum NE, Lewin NA. Carbamazepine. In: Goldfrank's Toxicologic Emergencies. Appleton & Lange; 1994:594-5.

  10. 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].

  11. Klimaszyk D, Lukasik-GLebocka M. [Cardiac toxicity of carbamazepine]. Przegl Lek. 2002;59(4-5):384-5. [Medline].

  12. Micromedex. Toxicologic Managements of Carbamazepine. Healthcare Series Micromedex. 95.

  13. Miles MV, Lawless ST, Tennison MB, Zaritsky AL, Greenwood RS. Rapid loading of critically ill patients with carbamazepine suspension. Pediatrics. Aug 1990;86(2):263-6. [Medline].

  14. Riva R, Contin M, Albani F, et al. Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: diurnal fluctuations and relationship with side effects. Ther Drug Monit. 1984;6(4):408-13. [Medline].

  15. Romero Maldonado N, Sendra Tello J, Raboso Garcia-Baquero E, Harto Castano A. Anticonvulsant hypersensitivity syndrome with fatal outcome. Eur J Dermatol. Sep-Oct 2002;12(5):503-5. [Medline].

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

  17. Van Der Meyden CH, Kruger AJ, Muller FO, Rabie W, Schall R. Acute oral loading of carbamazepine-CR and phenytoin in a double-blind randomized study of patients at risk of seizures. Epilepsia. Jan-Feb 1994;35(1):189-94. [Medline].

  18. Wada JA, Troupin AS, Friel P, Remick R, Leal K, Pearmain J. Pharmacokinetic comparison of tablet and suspension dosage forms of carbamazepine. Epilepsia. Jun 1978;19(3):251-5. [Medline].

 
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