Acute seizures in a patient receiving divalproex sodium after starting ertapenem therapy

Divalproex sodium is an anticonvulsant widely prescribed to treat several types of seizure disorders, including tonic-clonic and simple or complex partial seizures. We describe a 41-year-old man who experienced recurring tonic-clonic seizures after a drug interaction between divalproex sodium and ertapenem, a carbapenem antibiotic. The patient's valproic acid serum concentration was 130 mu g/ml approximately 3 months before he started ertapenem 2000 mg/day (20.6 mg/kg/day). On day 7 of ertapenem therapy, the patient was brought to the emergency department with tonic-clonic seizures; his valproic acid serum concentration was 70 mu g/ml. His divalproex sodium dosage was increased, and he was released from the emergency department only to return 4 days later with recurring seizures. This time his valproic acid serum concentration was 10.7 mu g/ml. Ertapenem was discontinued, and his divalproex sodium dosage was increased further. The patient's valproic acid level rapidly returned to a therapeutic level 2 days after ertapenem discontinuation, and he had no further seizures. Using the Naranjo adverse drug reaction probability scale to determine the probability of the drug interaction, we found that the likelihood of the interaction was probable (score of 7). Similar interactions have been reported between other carbapenern antibiotics and valproic acid. Clinicians should be aware of this potential interaction between divalproex sodium and ertapenem; concurrent administration of these two drugs should be approached with caution. In patients prescribed this combination, the valproic acid serum concentration should be carefully monitored to prevent recurring seizures.