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Clobazam is a benzodiazepine; it is chemically substituted as the 1 and 5 positions, in contrast to the 1,4-benzodiazepines. The drug is under evaluation in Canada as an add-on drug for epileptic seizures which do not respond to conventional antiepileptic treatments. Clobazam produces fewer cognitive side effects than the 1,4-benzodiazepines, and is generally well tolerated. Three cases are now reported, however, in which the addition of clobazam to a phenytoin-based (the drug, Dilantin) regimen resulted in the development of phenytoin toxicity. All three patients developed lethargy within a few weeks of the introduction of clobazam, in two cases the patients also became ataxic. However, seizure activity improved in all three cases. Blood analysis revealed that the phenytoin levels for the three patients were 29.0, 31.6, and 33.1 milligrams per liter, well above the therapeutic level for this drug. The phenytoin dose was reduced or eliminated and the symptoms resolved. In two cases, the dose of clobazam was eventually increased without ill effect. The results suggest that the introduction of clobazam may have adversely affected the patients' abilities to metabolize the phenytoin. The molar levels of clobazam are thought to be too small to replace phenytoin bound to plasma proteins and produce higher blood levels in this fashion. Rather, it seems likely that the clobazam interfered with the breakdown of phenytoin in the liver, a process which may already have been close to saturation in these patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Reports in the medical literature have suggested that the cerebellum may be particularly sensitive to toxic effects of the antiepileptic drug phenytoin (Dilantin). Cerebellar atrophy may occur after long-term use of the drug. Now, however, a different sort of case adds evidence to the apparent susceptibility of the cerebellum to phenytoin toxicity. The patient had attempted suicide by ingesting 7 grams of phenytoin. Magnetic resonance imaging revealed cerebellar atrophy which was similar in appearance to that observed after long-term phenytoin use. The atrophy progressed slightly for the first year, and has not progressed further; the most recent follow-up is 4.5 years after the initial suicide attempt. During the first year, the patient's clinical condition improved slowly and incompletely. However, on the most recent examination, the patient's only symptom was dysmetria, or failure to estimate distance accurately in movement tasks. (Consumer Summary produced by Reliance Medical Information, Inc.)