Introduction: The third-generation antiseizure medications used for the treatment of focal seizures, lacosamide, eslicarbazepine acetate, perampanel, brivaracetam, and cenobamate, may elicit serious adverse reactions which could be preventable if a prescriber is acquainted with the risk factors.

Areas Covered: The literature search was conducted in MEDLINE, SCOPUS, and EBSCO databases, without time and language restrictions. Only clinical studies, observational human studies, case reports, and case series that reported serious adverse drug reactions and risk factors were considered.

Expert Opinion: In order to prevent psychiatric side effects, the use of these drugs in patients with psychiatric disorders in the past should be avoided, or intensive monitoring of patients should be undertaken in order to detect psychosis or depression as early as possible. When prescribed eslicarbazepine and perampanel, serum sodium and ammonia levels should be periodically monitored. Lacosamide is associated with rhythm and conduction disturbances in the myocardium, so caution and ECG monitoring are required in people with cardiac diseases. Eslicarbazepine, cenobamate, and lacosamide can cause Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome and other allergic manifestations, so they should be used with caution in people with allergies in medical history.

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