Safety and tolerability of an oral zonisamide loading dose

There are a limited number of anticonvulsant medications that can be administered with an oral loading dose in order to rapidly achieve an effective serum level, and most of these have associated adverse effects. Zonisamide is approved for the treatment of partial onset epilepsy, and is used in practice for both generalized and partial onset epilepsy. It is generally well-tolerated, has a long half-life, and can be administered once daily. Unfortunately, the recommended titration schedule for initiating therapy takes several weeks to reach target dose and therapeutic serum levels.

We initiated zonisamide therapy using a large initial dose of zonisamide in 32 patients in our epilepsy monitoring unit over the past four years.

Adverse effects were rare and involved nausea/vomiting (9.4%) or drowsiness (6.3%). In patients where serum levels were available for review, therapeutic or near-therapeutic levels were achieved after an oral load of 600-900 mg given as divided doses over a 6-12h period.

This report is the first to suggest a method of rapidly initiating zonisamide therapy, achieving therapeutic serum levels in a shorter time frame, with an adverse effect profile similar to the recommended titration schedule.