Background: Amantadine has been used in the treatment of the influenza virus, Parkinson's disease, and drug-induced extrapyramidal symptoms. Toxic doses have produced cardiac arrhythmias and neuropsychiatric effects in animal studies and have also been demonstrated in human case reports. We report a case of amantadine toxicity resulting in ventricular tachycardia, status epilepticus, and death.
Case Report: An asymptomatic 33 year-old woman with a history of bipolar disorder and multiple sclerosis presented to the ED 1.5 hours after ingesting 6.2 g of amantadine in an attempt at self-harm. Four hours post-ingestion, she became acutely disoriented, developed ventricular tachycardia, seized, and had a cardiac arrest treated successfully with CPR, intubation, lidocaine and amiodarone. Her potassium was 2.5 mEq/L, sodium 135 mEq/L, glucose 88 mg/dL, bicarbonate 26 mEq/L, and creatinine 0.58 mg/dL. Supplemental magnesium and potassium were administered. Her amantadine concentration 1.5 hours post-ingestion was 3,960 ng/mL, 10.5 hours post-ingestion was 20,508 ng/mL, and 21.8 hours post-ingestion was 15,508 ng/mL. She was extubated on hospital day (HD) 2, but remained confused and was hallucinating. Due to hypoxia and concern for airway compromise, she was re-intubated on HD 3. She developed acute respiratory distress syndrome and septic shock with positive urine (Escherichia coli), blood (Staphylococcus epidermidis), and sputum (Haemophilus influenza) cultures. Levofloxacin and continuous infusions of norepinephrine, propofol, midazolam and vecuronium were administered during hospitalization. Due to refractory seizure activity confirmed by electroencephalogram (EEG), pentobarbital was administered on HD 14. On HD 21 life support was withdrawn after EEG monitoring revealed 252 hours of persistent seizure activity.
Discussion: A therapeutic range of amantadine has not been established, however the expected steady state concentration in patients receiving therapeutic doses is thought to be 200-1,000 ng/mL. Time to peak serum concentrations is 3.3 hours, which approximated the onset of toxicity in this case. Reported effects in overdose are cardiac dysrhythmias (including arrest), hypertension, and CNS toxicity. Much of the acute toxicity is attributed to antimuscarinic effects and usually observed when serum concentrations exceed 2,000 ng/mL. This case highlights the rare occurrence of refractory status epilepticus following an acute overdose of amantadine.
Conclusion: Toxicologists and emergency providers should be aware that amantadine toxicity may result in lethal cardiac dysrhythmias and refractory seizure activity.