Three New Drugs for Epilepsy: Levetiracetam, Oxcarbazepine, and Zonisamide

Abstract

During the last decade, nine new antiepileptic drugs were approved for use by the US Food and Drug Administration. The characteristics of three of these new antiepileptic drugs-levetiracetam, oxcarbazepine, and zonisamide--are reviewed here. Their individual characteristics, including mechanism of action, efficacy, safety, and pharmacokinetics, are compared, and their effectiveness in treating specific seizure types is noted. As with all antiepileptic drugs, the efficacy, side-effect, and pharmacokinetic profiles must be matched to each individual's clinical profile to attain the maximum benefit. All three are unique and will be useful in expanding the aggregate of therapies available to clinicians treating diverse epilepsy syndromes and seizure types. This review focuses on results in adults; pediatric experience is reported in other articles in this supplement.

Presurgical evaluation and surgical treatment of medically refractory epilepsy

“…Interestingly, the percentage of drug-resistant epilepsies has not diminished significantly, in spite of the new antiepileptic drugs [17,115,131,174]. Overall, about 30-40% of all patients with epilepsy have medically intractable seizures, and 50% of these are candidates for epilepsy surgery [2,20,44,53,80,196].…”

Newer antiepileptic drugs: Possible uses in the treatment of neuropathic pain and migraine

“…Hyponatremia (serum sodium level <125 mmol/L) has been documented in 2.7% of patients who received oxcarbazepine in 14 studies. 129 …”

“…141,142 Oxcarbazepine also inhibits CYP2C19, which alters levels of commonly used calcium channel antagonists. 129 Phenytoin, phenobarbital, and carbamazepine are all potent inducers of CYP isozymes and will lower serum levels of all AEDs mentioned in this article (except for gabapentin). 137 Valproic acid produces clinically significant decreases in the clearance of lamotrigine and thus raises lamotrigine levels.…”

“…However, the incidence of such AEs has been extremely small (46 cases of toxic dermatologic events per million patient-years of exposure; 3 cases of serious hematologic events), and the background rate of rash is 2%. 129 Zonisamide is structurally different from sulfonamide antibiotics, and there is no evidence of cross-reactivity between them. 131 It has been used with caution in patients who report allergy to sulfonamide antibiotics with no occurrence of rash or other allergic reaction.…”

“…Kidney stones were suspected clinically in 4.0% of patients receiving zonisamide in epilepsy clinical trials and were symptomatic in 1.4%. 129 Weight loss is an unexplained AE that has been associated with the use of zonisamide. In 3 randomized, placebo-controlled trials of adjunctive zonisamide therapy for the treatment of partial seizures, 132 reliable weight data were available for 314 of the 493 enrolled patients.…”