Zonisamide is a benzisoxazole derivative that is chemically unrelated to other anti-epileptic drugs (see the summary of product characteristics for Zonegran). The mechanism of action of zonisamide is not fully understood. It appears to act on voltage-sensitive sodium and calcium channels, disrupting synchronised neuronal firing and reducing the spread of abnormal electrical activity in the brain and disturbing subsequent epileptic activity. Zonisamide also has a modulatory effect on gamma-aminobutyric acid (GABA)-mediated neuronal inhibition (see the European public assessment report (EPAR) for Zonegran).
In October 2013, the approved licence for zonisamide (Zonegran, Eisai Limited; adjunctive treatment of partial seizures, with or without secondary generalisation, in adults) was extended to include 'adolescents' and children aged 6 years and over (see the EPAR for Zonegran).
Zonisamide (Zonegran, Eisai Limited) is also licensed for monotherapy treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy (see the summary of product characteristics for Zonegran).
When used as adjunctive therapy in children aged 6 years and over, the summary of product characteristics for Zonegran advises that zonisamide should be initiated at a dose of 1 mg/kg/day, titrated upwards according to clinical response in increments of 1 mg/kg at weekly intervals in those taking CYP3A4-inducing agents, and at 2-weekly intervals in those who are not taking CYP3A4-inducing agents. The usual maintenance dose for children weighing from 20 kg to 55 kg is 6–8 mg/kg taken once daily up to a maximum of 500 mg daily. To ensure a therapeutic dose is maintained, the child's weight should be monitored and the dose reviewed as weight changes occur, up to a weight of 55 kg. For children weighing more than 55 kg, the usual maintenance dose is 300–500 mg taken once daily. Some children, especially those not taking CYP3A4-inducing agents, may respond to lower doses.
The current NHS cost of zonisamide (excluding VAT; costs taken from Drug Tariff, February 2014) is:
£8.82 for 14×25 mg capsules
£47.04 for 56×50 mg capsules
£62.72 for 56×100 mg capsules.
The cost per year for a child weighing between 20 and 55 kg taking 6–8 mg/kg once daily as a maintenance dose is estimated to be between £638.75 and £1941.80 depending on the dose and child's weight. The cost per year for a child weighing more than 55 kg taking 300–500 mg once daily as a maintenance dose is estimated to be £1226.40 to £2044. Comparison costs with other treatment alternatives are given in the Costs of treatment alternatives section.