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For further information, see CMDT Part 40-20: Anticonvulsants Overdose

KEY FEATURES

  • Rapid intravenous injection of phenytoin can cause acute myocardial depression and cardiac arrest owing to the solvent propylene glycol (does not occur with fosphenytoin injection)

  • Chronic phenytoin intoxication can occur following only slightly increased doses because of zero-order kinetics and a small toxic-therapeutic window

  • Phenytoin intoxication can also occur following acute intentional or accidental overdose

CLINICAL FINDINGS

Symptoms and Signs

Phenytoin

  • In overdose, often only mild symptoms even with high serum levels

  • Most common manifestations

    • Ataxia

    • Nystagmus

    • Drowsiness

  • Choreoathetoid movements have been described

Carbamazepine

  • Most common manifestations

    • Drowsiness, stupor

    • Atrioventricular (AV) block, coma, and seizures (with high levels)

    • Dilated pupils

    • Tachycardia

Valproic Acid

  • Most common manifestations

    • Encephalopathy

    • Elevated serum ammonia

    • Metabolic acidosis

    • Hypernatremia (from the sodium component of the salt)

    • Hypocalcemia

    • Mild liver aminotransferase elevations

    • Cerebral edema

  • Hypoglycemia, as a result of hepatic metabolic dysfunction

  • Coma with small pupils, can mimic opioid poisoning

Gabapentin, Levetiracetam, Lacosamide, Vigabatrin, and Zonisamide

  • Generally cause somnolence, confusion, and dizziness

  • One case report of hypotension and bradycardia after a large overdose of levetiracetam

Felbamate

  • Can cause crystalluria and kidney dysfunction after overdose

  • May cause idiosyncratic aplastic anemia with therapeutic use

Tiagabine, Lamotrigine, Topiramate

  • Seizures after overdose

  • Lamotrigine

    • Has sodium-channel blocking properties

    • May cause QRS prolongation and heart block

Differential Diagnosis

  • Opioid intoxication

  • Sedative-hypnotic overdose

DIAGNOSIS

  • Phenytoin toxicity

    • Levels > 20 mg/L associated with ataxia, nystagmus, drowsiness; severe poisoning associated with concentrations > 35 mg/L

  • Carbamazepine toxicity

    • May be seen with serum levels > 20 mg/L (85 mcmol/L), though severe poisoning is usually associated with concentrations > 30–40 mg/L (127–169 mcmol/L)

    • Because of erratic and slow absorption, intoxication may progress over several hours to a day

TREATMENT

  • Emergency and supportive measures

    • For recent ingestions, give activated charcoal orally or by gastric tube

      • Repeated doses of activated charcoal, 20–30 g every 3–4 hours, are indicated for massive ingestions of valproic acid or carbamazepine

      • Sorbitol or other cathartics should not be used with each dose, or resulting large stool volumes may lead to dehydration or hypernatremia

    • For large ingestions of carbamazepine or valproic acid (especially of sustained-release formulations) consider whole bowel irrigation

  • Specific treatment

    • There are no specific antidotes

    • Carnitine may be useful in patients with valproic acid–induced hyperammonemia

    • Carbapenem antibiotics can reduce serum valproic acid concentrations and have been used in some cases of acute toxicity

    • Consider hemodialysis for massive intoxication with valproic acid or carbamazepine

      • Carbamazepine levels > 60 mg/L (254 mcmol/L)

      • Valproic acid levels > 800 mg/L ...

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