Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 38-20: Anticonvulsants Overdose + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Drowsiness, somnolence with all Phenytoin: ataxia, slurred speech, nystagmus Carbamazepine: atrioventricular block, coma, seizures, dilated pupils, tachycardia Valproic acid: encephalopathy, hypernatremia, metabolic acidosis, hyperammonemia +++ General Considerations ++ 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) Phenytoin intoxication can occur with only slightly increased doses because of the small toxic-therapeutic window and zero-order kinetics + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs +++ Phenytoin ++ In overdose, often only mild symptoms even with high serum levels Most common manifestations Ataxia Nystagmus Drowsiness Occasionally, choreoathetoid movements +++ Carbamazepine ++ Most common manifestations Drowsiness, stupor Coma and seizures (with high levels) Dilated pupils Tachycardia +++ Valproic acid ++ Most common manifestations Encephalopathy Hyperammonemia 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, 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 Download Section PDF Listen +++ +++ Laboratory Tests ++ Phenytoin toxicity Levels > 20 mg/L associated with ataxia, nystagmus, drowsiness 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 Valproic acid toxicity Obtain frequent repeated levels to rule out delayed absorption from sustained-release formulations (eg, Depakote ER) + Treatment Download Section PDF Listen +++ +++ Medications +++ Activated charcoal ++ For recent ingestions, give activated charcoal orally or by gastric tube +++ Whole-bowel irrigation ++ Indicated for large ingestions of carbamazepine or valproic acid, especially of sustained-release formulations Administer the balanced polyethylene glycol-electrolyte solution (CoLyte, GoLYTELY) into the stomach via gastric tube at a rate of 1–2 L/h until the rectal effluent is clear +++ Specific treatment ++ There are no specific antidotes Carnitine (and possibly L-arginine) may be useful in patients with valproic acid–induced hyperammonemia Naloxone has been reported to reverse valproic acid overdose in a few anecdotal case reports +++ Therapeutic Procedures ++ Consider hemodialysis for massive intoxication (eg, carbamazepine levels > 60 mg/L [254 mcmol/L] or valproic acid levels > 800 mg/L [5544 mcmol/L]) + Outcome Download Section PDF Listen +++ +++ When to Admit ++ For phenytoin-induced ataxia if adequate home care is not available After symptomatic overdose of any anticonvulsant + References Download Section PDF Listen +++ + +Alyahya B et al. Acute lamotrigine overdose: a systematic review of published adult and pediatric cases. Clin Toxicol (Phila). 2018 Feb;56(2):81–9. [PubMed: 28862044] + +Kalogera V et al. Patient survival after acute voluntary poisoning with a huge dose of oxcarbazepine and olanzapine. Med Arch. 2018 Oct;72(4):303–5. [PubMed: 30515002] + +Mahmoud SH. Antiepileptic drug removal by continuous renal replacement therapy: a review of the literature. Clin Drug Investig. 2017 Jan;37(1):7–23. [PubMed: 27587068] + +Schrettl V et al. L-Arginine in the treatment of valproate overdose—five clinical cases. Clin Toxicol (Phila). 2017 Apr;55(4):260–6. [PubMed: 28152637]