Basics
Description
- Therapeutic uses of carbamazepine:
- Anticonvulsant
- Treatment of chronic pain
- Migraine prophylaxis
- Mood stabilizer
- Mechanism:
- Anticholinergic
- Similarities to phenytoin and tricyclic antidepressants (TCAs)
- Sodium channel blocker
- Decreases synaptic transmission
Etiology
Toxicity may occur from:
- Suicide attempt
- Accidental ingestion
- Supratherapeutic dosing
- Drug-drug interaction
Diagnosis
Signs and Symptoms
- Neurologic manifestations common
- Cardiotoxicity rare, except in massive overdose
- CNS:
- Ataxia
- Dizziness
- Drowsiness
- Nystagmus
- Hallucinations
- Combativeness
- Coma
- Seizures
- Respiratory system:
- Respiratory depression
- Aspiration pneumonia
- Cardiovascular system:
- Hypotension
- Conduction disturbances (mostly in elderly)
- Supraventricular tachycardia
- Sinus tachycardia or bradycardia
- ECG changes:
- Prolongation of PR, QRS, and QTc intervals
- T-wave changes
Higher incidence of neurologic manifestations
History
- Overdose of carbamazepine or extended-release versions
- Time of ingestion
- Is the bottle available
- Accidental or intentional ingestion
- Coingestions
Physical Exam
- May present with seizures or altered mental status
- May be combative or drowsy
- Sinus tachycardia (massive carbamazepine overdose)
- Bradydysrhythmia (often seen in elderly with mild increase in carbamazepine level)
- Anticholinergic manifestations:
- Decreased bowel sounds
- Mydriasis
- Flushing
- Urinary retention
- Neuromuscular changes:
- Tremor
- Slurred speech
- Myoclonus
- Choreiform and choreoathetoid movements
Essential Workup
- Continuous cardiac monitor
- Serum carbamazepine level:
- Therapeutic, 6-12 μg/L
- Levels >25-40 μg/mL associated with serious toxicity:
- Coma
- Seizures
- Respiratory failure
- Conduction defects
- Serum levels do not clearly predict clinical toxicity:
- Active metabolite carbamazepine 10, 11 epoxide not measured
- Neurologic manifestations depend on CNS (not serum) level
- Serial levels may be needed owing to erratic absorption of carbamazepine.
- ECG:
- Conduction delays:
- Increased QRS interval
- Increased PR interval
- QTc prolongation
- Dysrhythmias
- Serum acetaminophen level (to evaluate for coingestion in a suicide attempt)
Diagnosis Tests & Interpretation
Lab
- CBC:
- Leukopenia or leukocytosis
- Electrolytes, BUN/creatinine, glucose:
- Hyperglycemia
- Hypokalemia
- Hyponatremia
- Arterial blood gases (ABGs)
- Urinalysis:
- Pregnancy test
- ALT, AST, bilirubin, alkaline phosphatase:
- May be mildly elevated
- Usually not clinically significant
Imaging
CXR:
- Aspiration pneumonia
- Pulmonary edema
Differential Diagnosis
- Drugs that cause decreased mental status:
- Alcohol
- Anticholinergics
- Barbiturates
- Benzodiazepines
- Lithium
- Opiates
- Phenothiazines
- Drugs that cause seizures:
- Alcohol withdrawal
- Anticholinergics
- Camphor
- Isoniazid
- Lithium
- Phenothiazines
- Sympathomimetics:
- TCAs
- Drugs that cause abnormal movement:
- Antihistamines
- Butyrophenones
- Caffeine
- Cocaine
- Levodopa
- Meperidine
- Phencyclidine
- Phenothiazines
- Phenytoin
- TCAs
Treatment
Pre-Hospital
- Do not administer ipecac.
- Intubate if significant respiratory depression or airway compromise.
- Secure IV access.
- Get complete information about all products potentially ingested.
Initial Stabilization/Therapy
- ABCs
- IV access and fluid resuscitation if hypotensive
- Oxygen
- Cardiac monitor
- Naloxone, thiamine, D50W (or Accu-Chek) if altered mental status
Ed Treatment/Procedures
- General management:
- Activated charcoal:
- Administer sorbitol with 1st dose (only) of activated charcoal.
- Administer with caution if GI activity is decreased.
- Contraindicated if bowel sounds are absent
- Multidose activated charcoal:
- Decreases mean half-life of carbamazepine
- Binds unabsorbed drug in GI tract
- Interrupts enterohepatic circulation
- Do not give additional sorbitol
- Charcoal hemoperfusion/hemodialysis:
- Removes small to moderate amount of ingested dose
- Patients usually do well with supportive care without hemoperfusion or dialysis
- Indicated in cases of clinical deterioration or lack of improvement with good supportive care
- Respiratory depression:
- Intubation
- Ventilatory support
- Hypotension:
- Bolus with IV isotonic crystalloid solution
- Norepinephrine if unresponsive to IV fluids
- Seizures:
- Diazepam (drug of choice)
- Phenobarbital (if diazepam ineffective)
- Phenytoin not effective in most toxic seizures
- Cardiac conduction delay:
- QRS widening (>100 msec):
- Sodium bicarbonate (to overcome sodium channel blockade)
- Psychiatric consultation if suicide attempt
Medication
First Line
- Activated charcoal (initial bolus): Slurry 1-2 g/kg up to 100 g PO
- Multidose activated charcoal: 25 g (peds: 0.25 g/kg) q2h PO after bolus dose (above); can also use 50 g q6h PO/NG
Second Line
- Dextrose: D50W 1 ampule: 50 mL or 25 g (peds: D25W 2-4 mL/kg) IV
- Diazepam: 5-10 mg (peds: 0.2-0.5 mg/kg) IV
- Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV/IM initial dose
- Norepinephrine: 2-4 μg/min (peds: 0.05-0.1 μg/kg/min) IV titrated to effect
- Sodium bicarbonate: 1 or 2 amps IV push (peds: 1-2 mEq/kg)
Follow-Up
Disposition
Admission Criteria
- Decreased mental status at any time, even if resolving (tends to recur with fluctuating drug levels):
- Observe at least 24 hr for late relapse.
- Seizures
- Cardiac dysrhythmias
- Lack of psychiatric clearance after suicidal ingestion
Discharge Criteria
- Asymptomatic after 6 hr of observation
- Normal mental status
- Normal or baseline ECG
- GI motility present
- Psychiatric clearance (after suicidal ingestion)
Issues for Referral
Suicidal patients need psychiatric evaluation referral.
Followup Recommendations
Supratherapeutic dosing will need ongoing monitoring by physician treating underlying disorder.
Pearls and Pitfalls
- Carbamazepine levels commonly rebound to higher levels during treatment. Obtain serial measurements for severe ingestions.
- Monitor closely for arrhythmias.
- Multidose charcoal may be needed for more serious ingestions.
- Paradoxical seizures may occur, use benzodiazepines to treat initially (diazepam is the drug of choice).
Additional Reading
- Brahmi N, Kouraichi N, Thabet H, et al. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning. Am J Emerg Med. 2006;24:440-443.
- Perez A, Wiley JF. Pediatric carbamazepine suspension overdose-Clinical manifestations and toxicokinetics. Pediatr Emerg Care. 2005;21(4):252-254.
- Pilapil M, Peterson J. Efficacy of hemodialysis and charcoal hemoperfusion in carbamazepine overdose. Clin Toxicol (Phila). 2008;46(4):342-343.
- Schmidt S, Schmitz-Buhl M. Signs and symptoms of carbamazepine overdose. J Neurol. 1995;242:169-173.
Codes
ICD9
966.3 Poisoning by other and unspecified anticonvulsants
ICD10
- T42.1X1A Poisoning by iminostilbenes, accidental, init
- T42.1X2A Poisoning by iminostilbenes, intentional self-harm, init
- T42.1X4A Poisoning by iminostilbenes, undetermined, initial encounter
SNOMED
- 241753006 Poisoning by carbamazepine (disorder)
- 290962008 Intentional poisoning by carbamazepine (disorder)
- 290961001 Accidental poisoning by carbamazepine (disorder)
- 290963003 Poisoning by carbamazepine of undetermined intent (disorder)