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Pediatric Carbamazepine Toxicity Clinical Presentation

  • Author: Muhammad Waseem, MD, MS; Chief Editor: Timothy E Corden, MD  more...
 
Updated: Apr 22, 2016
 

History

Ingestion history

In children younger than 6 years, ingestions of carbamazepine are commonly unintentional. Suicidal ingestions typically occur in adolescents.

Other causes of carbamazepine poisoning include iatrogenic overdose; dosage errors; and interactions with drugs such as erythromycin, cimetidine, and isoniazid. All these drugs increase the levels of carbamazepine by competitively inhibiting its metabolism.

The medication source is usually the patient or another family member who is taking carbamazepine for seizure control or the treatment of other illness.

An important cause of toxicity in children who are using the suspension is failure to adequately shake the bottle. Because the drug settles to the bottom of the bottle, if the full bottle is not shaken, the patient actually receives a low dose of the drug, which may lead to subtherapeutic levels and seizures. However, if the child is subsequently given doses of the drug from the bottom of the unshaken bottle, the patient may develop toxicity because the active drug has been concentrated there.

Symptom history

Symptoms usually appear within 6 hours of ingestion but may be delayed as long as 24 hours after the ingestion. Case reports indicate the possibility of delayed absorption, which causes levels to peak as late as 72 hours.

Mild toxic ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations.

Severe intoxications may produce coma, seizures, respiratory depression, and hypotension. Neurologic symptoms are the most common symptoms seen with severe overdoses. In a letter to the Editor of the Journal of Emergency Medicine, the case of a 7 year-old boy who took an overdose of carbamazepine that was equivalent to 100 mg/kg and presented to the emergency department in a coma is reported.[8]

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Physical

Carbamazepine toxicity should be considered in any child who presents with seizures, apnea, or an unexplained change in mental status, particularly when the child has access to the drug. 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 the serum carbamazepine concentration.

Vital signs

Hypothermia may occur after an acute overdose and may last as long as 10 hours. Hyperthermia may occur as part of a neuroleptic malignant syndrome.

Neurologic effects

Common neurologic effects include ataxia, slurred speech, nystagmus, dystonia and other extrapyramidal movements, and various degrees of CNS depression. Seizures are common in children with an underlying epileptic disorder. In severe cases, coma and status epilepticus may occur.

Neuroleptic malignant syndrome and transient ophthalmoplegia are also associated with carbamazepine overdose. Syndrome of inappropriate antidiuretic hormone secretion has also been reported.

Respiratory effects

Respiratory depression or apnea that requires mechanical ventilation may be observed within first 24 hours of the patient's presentation. Pulmonary edema or aspiration pneumonia may occur. Fulminant interstitial pneumonitis may also be noted.[9]

Cardiovascular effects

Cardiovascular effects are rarely observed in children. Hypotension, bradycardia, and conduction disorders may occur in patients with an abnormal myocardium or a preexisting conduction defect. A 2:1 atrioventricular (AV) block due to carbamazepine has been reported, which may occur even in therapeutic serum carbamazepine levels, and can be reversible after discontinuation of carbamazepine therapy. [10]

GI and hepatic effects

Anticholinergic effects include delayed gastric emptying and decreased intestinal motility.

With acute carbamazepine toxicity, chemical pancreatitis without accompanying pain or abnormalities may be present.

Hepatitis and, rarely, hepatic failure may occur. This is usually due to an idiosyncratic reaction rather than an overdose. Studies in mice demonstrate that liver injury due to carbamazepine is probably due to metabolic activation of enzymes followed by the stimulation of immune responses. Prostaglandin E administration appeared to ameliorate the liver toxicity caused by carbamazepine in mice.[11]

Hematologic effects

Neutropenia, agranulocytosis, thrombocytopenia, and aplastic anemia may occur with therapeutic doses or chronic intoxication but not after an acute overdose. Carbamazepine has also been reported to have induced immunoglobulin deficiency in some cases in therapeutic doses;[12] however, this has not been reported in acute intoxication.

Thrombocytopenia or aplastic anemia can result in bleeding. However, this effect is rarely seen with acute poisoning.

Dermatologic effects

Dermatologic effects are due to idiosyncratic reactions rather than to an overdose of carbamazepine. Severe cutaneous adverse reactions (SCARS) such as the following may occur:

Patients of Asian descent, especially Han Chinese, are particularly at risk for SCARS. This sensitivity is linked to having the HLA-B*1502 allele.[16] Some authorities recommend that patients of Asian descent be screened for this allele before being started on carbamazepine.[17] In Europeans, the HLA-A*3101 allele has been associated with carbamazepine-induced hypersensitivity reactions, but this is much less common than that seen in Asians who have the HLA-B*1502 allele.[18]

Endocrine effects

Long-term use of carbamazepine may decrease free T4 levels. Usually this is compensated for by increasing thyrotropin levels. Therefore, thyroid function tests should be monitored in patients on carbamazepine, and thyroid hormone supplementation can be given if clinically indicated.[19]

Fatalities

Death may result from any of the following:

  • Apnea
  • Status epilepticus [20]
  • Aspiration pneumonitis
  • Severe hepatitis
  • Aplastic anemia
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Contributor Information and Disclosures
Author

Muhammad Waseem, MD, MS Associate Professor of Emergency Medicine in Clinical Pediatrics, Associate Professor of Clinical Healthcare Policy and Research, Weill Medical College of Cornell University; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center

Muhammad Waseem, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, Society of Critical Care Medicine, Society for Simulation in Healthcare, 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, 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, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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: Received salary from Merck for employment.

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, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

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.

Acknowledgements

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.

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