A 17-year-old female developed hyperammonemic
encephalopathy 2 weeks after
valproic acid (VPA), 500 mg twice a day, was added to her regimen of
topiramate (TPM), 200 mg twice a day. She presented to the emergency department (ED) with altered mental status,
hypotension,
bradycardia, and
lethargy. Laboratory analysis showed mild non-anion gap hyperchloremic
acidosis, serum VPA concentration of 86 mg/L, and urine
drug screen result that was positive for marijuana. She was admitted to the pediatric intensive care unit for persistent symptoms, prolonged QTc, and medical history. Blood
ammonia concentrations were obtained because of her persistent altered mental status, initially 94 μmol/L and a peak of 252 μmol/L. A serum
carnitine profile was obtained at the time of
hyperammonemia and was found to be normal (results were available postdischarge). VPA and TPM were discontinued on day 1 and day 2, respectively, as the patient's blood
ammonia concentration remained elevated. On day 3, her mental status had returned to baseline, and blood
ammonia concentrations trended downward; by day 4 her blood
ammonia concentration was 23 μmol/L. VPA has been associated with numerous side effects including
hyperammonemia and
encephalopathy. Recently, drug interactions with TPM and VPA have been reported; however, serum
carnitine concentrations have not been available. We discuss the possible mechanisms that VPA and TPM may affect serum
ammonia and
carnitine concentrations and the use of
levocarnitine for patients or treating toxicity.