Cenobamat is a medication indicated for the treatment of partial-onset seizures in adult patients. While it demonstrates significant efficacy in seizure control, like other antiepileptic drugs, it may be associated with a range of adverse reactions.

Adverse Reactions of Cenobamat

Common Adverse Reactions

Somnolence and Fatigue: This is one of the most common adverse reactions. Patients may experience abnormal drowsiness, lassitude, lack of energy or asthenia.

Dizziness and Balance Disorders: Including sensations such as dizziness, vertigo, unsteady gait and ataxia (impaired physical coordination).

Visual Disturbances: Mainly manifested as diplopia (double vision); blurred vision may also occur.

Headache: Headache may develop in some patients.

Serious Adverse Reactions of Cenobamat

Severe Hypersensitivity Reactions (DRESS/Multiorgan Hypersensitivity Reaction)

This is a rare but life-threatening systemic hypersensitivity reaction that may involve multiple organs including the skin, lymph nodes, liver, kidneys and heart.

Clinical features may include: skin rash (though not always present).

Fever, lymphadenopathy, and swelling of the face or eyes.

Unexplained severe fatigue, myalgia and sore throat.

Important Warning: If fever, skin rash or any of the aforementioned symptoms occur during treatment, discontinue the medication immediately and seek emergency medical assistance.

QT Interval Shortening

Cenobamat may cause QT interval shortening on electrocardiogram (ECG).

The drug is contraindicated in patients with familial short QT syndrome, as this condition itself is associated with a high risk of sudden cardiac death and ventricular fibrillation.

For other patients, although no dangerous cases of QT interval shortening to less than 300 milliseconds were observed in clinical studies, caution should still be exercised.

Precautions: Concomitant use with other drugs that also prolong QT interval should be avoided to prevent additive effects. Patients who experience prolonged palpitations or syncope should inform their physician promptly.

Risk of Suicidal Ideation and Behavior

Like all antiepileptic drugs, cenobamat may slightly increase the risk of suicidal thoughts or behaviors.

Monitoring Requirements: Patients, their family members and caregivers should closely monitor for changes in mood and behavior, particularly the emergence or exacerbation of depression, anxiety, agitation, aggressiveness, significant mood swings, or any thoughts of self-harm or suicide.

If any of these signs appear, contact a physician immediately.

Withdrawal Reactions and Discontinuation Precautions

Prolonged use of cenobamat may lead to physical dependence.

Abrupt discontinuation is strictly prohibited, as it may trigger a rebound increase in seizure frequency or even status epilepticus (a life-threatening emergency).

If discontinuation is necessary, the dosage must be tapered gradually over a period of at least two weeks under the guidance of a physician.

Immediate discontinuation should only be considered when life-threatening adverse reactions such as severe hypersensitivity occur.

Precautions for Cenobamat Administration

Patients with Hepatic or Renal Impairment

Hepatic Impairment: Caution is advised in patients with mild to moderate hepatic impairment, with the maximum recommended daily dosage not exceeding 200 mg. The use of cenobamat is not recommended in patients with severe hepatic impairment.

Renal Impairment: Caution is required in patients with mild, moderate or severe renal impairment, and dosage adjustment may be necessary. The drug is not recommended for use in end-stage renal disease patients undergoing dialysis.

Contraception

Cenobamat may reduce the efficacy of hormonal oral contraceptives.

During cenobamat treatment, patients must use additional or alternative non-hormonal contraceptive methods (e.g., condoms, intrauterine devices) to prevent unintended pregnancy.

Drug Interactions

Drugs that increase cenobamat concentration: For example, phenytoin. When co-administered, the dosage of phenytoin usually needs to be reduced by up to 50%.

Drugs whose concentration is decreased by cenobamat: For example, lamotrigine, carbamazepine, and certain drugs metabolized via CYP2B6 and CYP3A enzymes (including some oral contraceptives). Dosage adjustment of these drugs may be required.

Drugs whose concentration is increased by cenobamat: For example, phenobarbital, clobazam, and certain drugs metabolized via the CYP2C19 enzyme. Dosage reduction of these drugs may be needed.