A Welcome New Option in Epilepsy Therapy

Andrew N. Wilner, MD


January 05, 2012

Clobazam: A New (Old) Drug Approved to Treat Seizures

On October 21, 2011, the US Food and Drug Administration (FDA) approved clobazam (Onfi®)* as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in adults and children aged 2 and older.[1] This is good news for people with Lennox-Gastaut syndrome, and their families and physicians, because successful treatment of seizures associated with Lennox-Gastaut syndrome has been an elusive goal.

Lennox-Gastaut Syndrome

People with Lennox-Gastaut syndrome typically have mixed seizure types, developmental delay, and a specific pattern of slow spike and wave (< 2.5 Hz) on the electroencephalogram (EEG). Seizures usually begin in childhood before the age of 8 years and may follow infantile spasms. In Lennox-Gastaut syndrome, multiple seizure types such as atypical absence seizures, drop attacks, and nocturnal tonic seizures are often accompanied by disabilities such as blindness, cerebral palsy, hearing impairment, and mental retardation, culminating in its designation as a "catastrophic epilepsy." Many etiologies may be responsible, including anoxic, cryptogenic, infectious, malformations of cortical development, metabolic, and post-traumatic. Although Lennox-Gastaut syndrome accounts for only about 4% of cases of childhood epilepsy, affected children are overrepresented in neurology clinics because of treatment-resistant seizures, behavioral problems, and multiple comorbidities. Drop attacks, which occur in at least 50% of patients, are particularly problematic because the sudden falls may result in facial and head injuries, often requiring the child to wear a protective, but stigmatizing helmet.[2] Episodes of status epilepticus require frequent visits to the emergency department.

A Look at Clobazam

Clobazam, a 1,5-benzodiazepine, was approved for adjunctive therapy of epilepsy in children over 3 years old in Europe in 1975[3] and is available in over 100 countries.[1] Clobazam is a benzodiazepine, the same family that includes familiar drugs used for acute seizure control such as diazepam (Valium®) and lorazepam (Ativan®). Clobazam acts as a gamma-aminobutyric acid alpha (GABAA)receptor agonist. It is primarily metabolized in the liver by cytochrome P450 (CYP)3A4, which produces an active metabolite, N-desmethylclobazam. N-desmethylclobazam has a long half-life of 30-65 hours and is metabolized by CYP2C19.[3]

*Manufactured by Catalent Pharma Solutions, Winchester, KY, and distributed by Lundbeck, Inc.


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