The content of this evidence summary was up-to-date in April 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Key points from the evidence

In June 2012, the approved licence for zonisamide (Zonegran; adjunctive treatment of partial seizures, with or without secondary generalisation, in adults) was extended to include monotherapy for treating partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.

One randomised, double blind, non-inferiority trial assessed the efficacy and tolerability of zonisamide in 583 patients with newly diagnosed partial seizures. The response rates were consistently lower with zonisamide compared with carbamazepine controlled release. In the per-protocol population, 79.4% of patients taking zonisamide were seizure free for at least 26 weeks (the primary outcome) compared with 83.7% of patients taking carbamazepine, an absolute difference of 4.5% in favour of carbamazepine. Zonisamide was not shown to be non-inferior to carbamazepine because the lower confidence interval of 12.2% was outside the pre-defined absolute non-inferiority margin of 12%. However, in its assessment of zonisamide, the European Medicines Agency concluded that a lower level of efficacy was acceptable because, overall, the response rates were high in both study groups (around 80%); the difference in absolute and relative point estimates was less than 5%; and retention rates were similar in both groups.

The incidence of adverse events that were considered to be treatment related was similar for zonisamide and carbamazepine (36% compared with 38% respectively). The most frequently reported treatment-emergent adverse events (5% or more in either group) were headache, decreased appetite, somnolence, dizziness and weight loss. The adverse events reported for each drug were consistent with their established safety profiles.

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care (NICE clinical guideline 137) advises that people with newly diagnosed partial-onset seizures (also known as 'focal' seizures) should be offered monotherapy with carbamazepine or lamotrigine as first-line treatment. If carbamazepine and lamotrigine are unsuitable or not tolerated, levetiracetam, oxcarbazepine or sodium valproate is the next treatment option. If the first anti-epileptic drug tried is ineffective, an alternative from these 5 anti-epileptic drugs should be offered.

Zonisamide could offer an alternative to other anti-epileptic drugs in some people because of its different mechanism of action, once-daily dosing, and adverse event and interaction profiles (unlike some other anti-epileptic drugs, zonisamide is not thought to affect the pharmacokinetics of other medicines, such as oral contraceptives, through cytochrome P450-mediated mechanisms).

When making decisions about using zonisamide, localities will need to consider the available evidence suggesting similar efficacy and tolerability to carbamazepine alongside its less well established safety profile compared with other treatment options. Furthermore, the acquisition cost of zonisamide is generally, considerably higher than the other potential treatment options.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.