Abstracts

RATIONALE: The objective of this study was to assess safety and tolerability of 25/50mg capsules used in initial titration of zonisamide. Zonisamide 100mg capsule is commercially available and recommended as a starting daily dose with biweekly 100mg/day increments to reach a maintenance dose of 400mg qhs. Since adverse events (AEs) may result from the initial 100mg dose, slower titration with 25 and 50mg capsules is tested in this study.
METHODS: 25 subjects (F:M=10:15) [gte]12 years old participated. Zonisamide, one 25mg capsule qhs x1 week, then one 50mg capsule qhs x1 week, followed by two 50mg capsules qhs (1-5 weeks).
RESULTS: Six subjects dropped due to UTI (n=1), rash (n=1), increased heartbeat (n=1), tinnitus (n=1), and two never took study drug. AEs reported by [gte]4% of subjects included: decreased appetite (n=2), diarrhea (n=2), hyperactivity (n=2), UTI (n=1), insomnia (n=1), double vision (n=1), rash (n=1), increased depression (n=1), nightmares (n=1), increased arthritic pain (n=1), tinnitus (n=1), and headache worsening (n=1). Diarrhea, grogginess, and forgetfulness were reported by one subject. Tachycardia and difficulty walking occurred in one subject. Six subjects reported [gte]75% reduction in seizure frequency compared to retrospective baseline (four had complex partial seizures, one had partial, and one had atonic) seizures. Of the 19 subjects who completed the study, 15 continued to a maintenance dose of 400mg qhs.
CONCLUSIONS: Slow initial titration of zonisamide using 25 and 50mg capsules was safe and well tolerated by the majority of subjects (19 of 23). AEs were mild to moderate in severity.
Support: Elan Pharmaceuticals
Disclosure: Grant - Elan Pharmaceuticals research grants (2) for clinical studies.