Hypersensitivity reaction risk when restarting cenobamate after discontinuation: Insights from a prolonged...

To evaluate the risk of hypersensitivity reactions, including dermatological rashes, when cenobamate (CNB) is restarted at maintenance doses after temporary discontinuation.

We leveraged the natural experiment of long antiseizure medication discontinuation during intracranial EEG evaluation and conducted a retrospective cohort study of these patients at a tertiary epilepsy center who were taking CNB at admission. Clinical data, including duration of interruption, restart dose, and occurrence of dermatologic or hypersensitivity adverse events, were extracted from electronic health records. Patients were followed during hospitalization and for 2 weeks postdischarge.

Thirty-two patients (53% female; median age 29 years) were included. CNB was withheld for a median of 7 days (IQR 5-8) and restarted at a median dose of 200 mg/day (IQR 193.75-250), including 25% restarted at ≥300 mg/day. Four patients had interruptions ≥10 days. Fourteen patients (44%) had a history of rash. No hypersensitivity reactions attributable to CNB, including rash, were observed during hospitalization or follow-up.

These findings provide the first evidence that short-term CNB interruptions may not require retitration in previously tolerant patients. This has direct implications for managing nonadherence in routine clinical care. Prospective studies are needed to confirm safety across larger cohorts and longer interruptions.

Many people with epilepsy miss doses of their seizure medicines, but it is unclear whether cenobamate needs to be slowly restarted after a short break. We studied 32 hospitalized patients who stopped cenobamate for about a week and then restarted their usual dose, and none developed a drug-related rash or allergic reaction, even those at higher doses or with prior rash history. These findings suggest that short interruptions of cenobamate may be safely restarted without retitration in patients who previously tolerated the medication, though larger studies are needed to confirm this.