Xonimide ODT is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.
The precise mechanism(s) by which zonisamide exerts its antiseizure effect is unknown. Zonisamide demonstrated anticonvulsant activity in several experimental models. In animals, zonisamide was effective against tonic extension seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol. Zonisamide raised the threshold for generalized seizures in the kindled rat model and reduced the duration of cortical focal seizures induced by electrical stimulation of the visual cortex in cats. Furthermore, zonisamide suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human epilepsy is unknown. Zonisamide may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that zonisamide blocks sodium channels and reduces voltagedependent, transient inward currents (T-type Ca2+ currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that zonisamide binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux. Other in vitro studies have demonstrated that zonisamide (10–30 μg/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [3H]-GABA (rat hippocampal slices). Thus, zonisamide does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that zonisamide facilitates both dopaminergic and serotonergic neurotransmission. Zonisamide is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of zonisamide is unknown. However, as a carbonic anhydrase inhibitor, zonisamide may cause metabolic acidosis
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Zonisamide is recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Zonisamide should be administered once or twice daily, using 25 mg or 100 mg capsules. Zonisamide is given orally and can be taken with or without food. Capsules should be swallowed whole. Adults Over Age 16 : The prescriber should be aware that, because of the long half-life of zonisamide, up to two weeks may be required to achieve steady state levels upon reaching a stable dose or following dosage adjustment. Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of zonisamide at steady state, noting that many of the side effects of zonisamide are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100-200 mg/day, the increase appears small and formal dose-response studies have not been conducted. The initial dose of Zonisamide should be 100 mg daily. After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that Zonisamide doses of 100-600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day. There is little experience with doses greater than 600 mg/day.
The most common adverse reactions with Xonimide ODT (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration. In controlled clinical trials, 12% of patients receiving Xonimide ODT as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received Xonimide ODT in clinical studies discontinued treatment because of an adverse reaction. The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were doserelated
Zonisamide is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
Somnolence is commonly reported, especially at higher doses of Xonimide ODT. Xonimide ODT is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering Xonimide ODT to patients with hepatic and renal dysfunction