EMA’s PRAC warns of rare but severe liver injury, including hepatic failure, with Ontozry, recommending baseline and ongoing liver monitoring and updating product information
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
The Pharmacovigilance Risk Assessment Committee (PRAC), the safety committee of the European Medicines Agency, has agreed on a Direct Healthcare Professional Communication (DHPC) warning about cases of severe liver injury, including hepatic failure, reported in patients treated with Ontozry (Cenobamate). Most cases occurred when the medicine was used in combination with other anti-seizure therapies.
Monitoring Recommended Before and During Treatment
PRAC advises prescribers to perform liver function tests prior to initiating Ontozry and to continue monitoring throughout treatment. If patients develop symptoms suggestive of liver injury such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice, clinicians should promptly conduct clinical evaluation and repeat liver testing.
Patients should also be instructed to seek immediate medical attention if they experience symptoms consistent with liver injury.
Dose Adjustment or Discontinuation if Liver Injury Suspected
If liver injury is suspected or confirmed, prescribers should consider dose reduction or discontinuation of Ontozry in accordance with the summary of product characteristics. The committee noted that abrupt discontinuation should generally be avoided unless necessary, to reduce the risk of rebound seizures.
Elevated liver enzyme levels are already listed in Ontozry’s product information as a common adverse reaction, occurring in up to 1 in 10 patients. Following its review, PRAC recommended adding liver injury as a rare side effect, which may occur in up to 1 in 1,000 people, along with strengthened warnings for both healthcare professionals and patients.
Use of Ontozry in Refractory Focal Seizures
Ontozry is indicated as add-on therapy for adults with focal seizures, including those that secondarily generalize, whose seizures remain uncontrolled despite treatment with at least two other anti-seizure medications.
Next Regulatory Steps
The agreed DHPC will be forwarded to the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. Once adopted, the communication will be disseminated to healthcare professionals by the marketing authorisation holder under an agreed plan and published on EU DHPC pages and national registers across Member States.
References
Ontozry (Cenobamate): New Requirements for Liver Monitoring Due To Reports of Severe Liver Injury, 10 April 2026, European Medicines Agency (EMA) https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-7-10-april-2026
Ontozry (Cenobamate), Summary of Product Characteristics, https://www.ema.europa.eu/en/documents/product-information/ontozry-epar-product-information_en.pdf
About the Writer
Mahathi Palivela is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.
