Safety and Tolerability of Zonisamide Used Concurrently with Topiramate
Abstract number :
3.131
Submission category :
Year :
2001
Submission ID :
1994
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
W.E. Rosenfeld, MD, Comprehensive Epilepsy Care Center, Chesterfield, MO
RATIONALE: Zonisamide (Zonegran[tm]) and topiramate (Topamax[reg]) are antiepilepsy drugs (AEDs) that weakly inhibit carbonic anhydrase. Zonisamide[ssquote]s carbonic anhydrase inhibition is approximately one one-hundredth that of acetazolamide. Carbonic anhydrase inhibitors are associated with an increased risk of the development of renal calculi; therefore, some concern exists regarding concurrent use of zonisamide and topiramate. The purpose of this analysis was to evaluate the safety and tolerability (including the incidence of neurocognitive adverse events and renal calculi) of concurrent use of zonisamide and topiramate in patients with refractory partial seizures.
METHODS: Data from a multicenter, open-label, low-dose, titration study of zonisamide were analyzed. Subjects receiving zonisamide and topiramate concurrently were identified. Adverse events were recorded throughout the study.
RESULTS: Thirty-five subjects who received zonisamide and topiramate concurrently were identified. Among these, 24 subjects (68%) were also receiving other AEDs. Six subjects (17%) prematurely discontinued the study: 1 for lack of efficacy, 1 for an adverse event, 2 for noncompliance, and 2 for other/unknown reasons. Adverse events occurring in [gte]10% of subjects included somnolence (26%), headache (20%), nausea (20%), asthenia (14%), dizziness (14%), nervousness (14%), and amnesia (11%). One subject who was receiving 100 mg/d of zonisamide and 450 mg/d of topiramate reported renal calculus. This subject had received zonisamide for approximately 3 months and topiramate for approximately 5 months. The incidence of neurocognitive adverse events was not different from clinical trials of zonisamide and of topiramate.
CONCLUSIONS: Incidence of neurocognitive adverse events and renal calculi in this analysis of patients receiving zonisamide and topiramate concurrently was similar to previous clinical trials of each drug. Though these data represent patients who have received zonisamide and topiramate concurrently for only a brief time period, increased risk of developing renal calculi was not noted.
Support: Elan Pharmaceuticals.
Disclosure: Grant - Elan Pharmaceuticals. Honoraria - Elan Pharmaceuticals.