Abstracts

RATIONALE: Zonisamide (ZNS) is a broad-spectrum antiepileptic drug (AED) structurally classified as a sulfonamide. It was approved in the United States in early 2000 for the treatment of partial seizures with or without secondary generalization in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established for FDA approval in the United States. There has been extensive clinical experience with Japanese children indicating safety, tolerability, and effectiveness in the treatment of both partial and generalized onset seizures. As reported by Wirrell et al., the initial AED is successful in only 60% of children with Absence Epilepsy (AE). In their study valproic acid (VPA) was the most successful initial drug (Wirrel, et al., Epilepsia 2001; 42: 760-763). Children with AE refractory to valproic acid (VPA) or ethosuximide (ESM) or with unacceptable side effects may benefit from ZNS. We assessed the response to ZNS as adjunctive and monotherapy in a small group of children with AE.
METHODS: A retrospective data base analysis revealed four children who were sucessfully treated with ZNS for AE. All children carried the diagnosis of primary generalized epilepsy confirmed on routine EEG or video EEG monitoring and had normal MRIs. Ages ranged from 8 to 12 years. All four were incompletely controlled on VPA and/or ESM at therapeutic drug serum levels. Three were started on ZNS as an adjunctive AED. One child was off all AEDs because of unacceptable gastrointestinal side effects from VPA, ESM and LMT and began ZNS as monontherapy. Weights ranged from 31 to 40 kilos. All began ZNS dosing at 100 mg per day administered at bedtime. Parents reported on seizure frequency, seizure severity, adverse events, and any side effect at a one month follow-up visit and every two to three months thereafter.
RESULTS: Three children tolerated the medication well with 100% reduction in seizures reported at the one month follow-up evaluation. They remained on their 100 mg per day original dose and experienced complete seizure control thereafter. The only side effects were reported in the fourth child, a pre-adolescent, with a 5 lb weight loss (6%) and complaints of feeling tired after 2 months on ZNS. Her dosing was lowered by allowing her to skip every third day of 100 mg per day dosing. She also experienced a possible brief seizure related to hyperventilation while running for a school bus after 2 months on the drug. No other side effects or seizure like sypmptoms have been reported in the three children who are on ZNS for 6 months and one who is on for 18 months. High therapeutic dosing of VPA was reduced in two children while on ZNS adjunctive therapy. One child has continued on ZNS monotherapy for 6 months. All parents report ease of ZNS administration with once a day dosing.
CONCLUSIONS: ZNS provided seizure control without significant side effects in the study subjects. These findings suggest that ZNS is effective and well tolerated as an adjunctive and possible monotherapy for AE. Smaller dosing formulations as anticipated shortly will facilitate administration in the younger child.
[Supported by: Elan Pharmaceuticals]; (Disclosure: Salary - no, Grant - no, Equity - no, Consulting - no, Ownership - no, Materials - no, Stock - no, Royalties - no, Honoraria - Dr. Andriola receives honoraria from Elan Pharmaceuticals for speaking)