The anticonvulsant phenacemide (phenylacetylurea), discarded for 30 years because of serious toxicity, has been resurrected and used in the treatment of 13 children with refractory complex seizures at Loyola University, Maywood, and Christ Hospital, Oak Lawn, Illinois. Twelve responded, nine were seizure free for 2-12 months, and one developed nausea and vomiting necessitating drug withdrawal. Other side-effects included aggressive behavior in 1, drowsiness (2) ataxia (2), headache (1), and elevated SGPT and GGT in one child aged 3 yrs with tuberous sclerosis. A liquid chromatography assay developed to determine plasma phenacemide concentrations showed a linear relationship between drug peak height and plasma concentration over a range of 0-150 ug/ml. After a single oral dose the peak concentration in a 16 year old patient was at 1 to 2 hours and in a 40 year old volunteer, at 5 hours.

Phenacemide half-life in the adult was 25 hours and was estimated at 25 and 22 hours in two children. A twice-daily dosage regimen seemed appropriate. Therapeutic levels ranged from 16-75 ug/ml (median, 52 ug/ml). [1]

COMMENT. The authors rationalize their re-evaluation of phenacemide as monotherapy, stating that the majority of phenacemide-related deaths from liver failure or aplastic anemia had occurred in adults receiving polytherapy. After 30 years of dormancy, it is surprising that the drug had not been withdrawn from the market, having regard to its well established toxicity. The efficacy of phenacemide in partial complex (temporal-lobe) seizures has been demonstrated repeatedly in earlier studies and reconfirmed in this re-evaluation. Fortunately, none developed liver failure but one patient taking 4 gm daily had symptoms of nausea and vomiting suggestive of liver involvement and sufficient to warrant phenacemide withdrawal. Another showed a behavior or personality disorder, a common and troublesome side effect in previous trials. Is the reactivation of this drug necessary or advisable?