Supratherapeutic carbamazepine concentration following a recent SARS-CoV-2 infection

Student discussion

Maxwell L. Harsha and Mark A. Marzinke

Case description

A 29-year-old male presented to the emergency department after a dizziness episode and drop attack followed by impaired ambulation, nausea, and vomiting. Prior to this episode, the patient had experienced multiple days of coughing, general malaise, and poor oral intake. His medical history was notable for genetically confirmed Coffin-Lowry syndrome, which is characterized by intellectual disability, motor dysfunction, and frequent drop attacks without epilepsy. Additionally, he tested positive for SARS-CoV-2 (COVID-19) via at-home testing 2 days prior to his presentation. At the time of presentation, his medications included carbamazepine extended release (600 mg twice a day), clonazepam (0.5 mg twice a day), fluoxetine (20 mg daily), and recently initiated (2 days prior to presentation) Paxlovid^TM (nirmatrelvir 300 mg/ritonavir 100 mg twice a day).

A workup was initiated to determine the cause of the patient’s presentation with primary concern for seizure activity and head injury. His physical exam indicated no acute focal neurologic deficits. Laboratory results were largely unremarkable. Mild anemia was noted, indicated by decreased hemoglobin and hematocrit levels. A slightly increased serum total CO₂ concentration was suggestive of metabolic alkalosis, likely induced by emesis. Additionally, the patient had an elevated D-dimer and tested positive for SARS-CoV-2 via RNA analysis. Imaging studies showed no evidence of acute injury, ischemia, pulmonary embolism, or infection. Given the inconclusive workup, the patient was admitted for treatment with intravenous fluids, antiemetics, and reassessment of his baseline ambulation.

The following day, a serum total carbamazepine level was measured using the Roche Cobas Pro c503 homogenous KIMS immunoassay with a supratherapeutic result of 26.8 mg/L (therapeutic range: 4.0–12.0 mg/L). While the exact timing of his last carbamazepine dose was unknown, it is suspected to have occurred sometime the day prior. Carbamazepine administration was withheld, and levels were monitored serially every 24 hours. Twenty-four hours after the initial supratherapeutic measurement, concentrations declined to 14.6 mg/L and, 48 hours later, decreased to 8.0 mg/L. His ambulation, nausea, and vomiting improved, and he was subsequently discharged with instructions to resume his regular carbamazepine dosing the following morning.