Zonisamide

Source: UK SPC for Zonisamide 100 mg capsules (§4.2). Dose must be titrated on the basis of clinical effect; some patients, especially those not taking CYP3A4-inducing agents, may respond to lower doses. TITRATION — Monotherapy (newly diagnosed adults): 100 mg/day once daily in weeks 1+2, 200 mg/day in weeks 3+4, 300 mg/day in weeks 5+6; if a higher dose is required, increase at two-weekly intervals in increments of 100 mg up to a maximum of 500 mg. Adjunctive therapy WITH CYP3A4-inducing agents: 50 mg/day in two divided doses in week 1, 100 mg/day in two divided doses in week 2, then increase at weekly intervals in increments of 100 mg over weeks 3 to 5 to 300–500 mg/day. Adjunctive therapy WITHOUT CYP3A4-inducing agents, or with renal or hepatic impairment: 50 mg/day in two divided doses in weeks 1+2, 100 mg/day in two divided doses in weeks 3+4, then increase at two-weekly intervals in increments of up to 100 mg over weeks 5 to 10 to 300–500 mg/day. WITHDRAWAL: withdraw gradually — in adult clinical studies, dose reductions of 100 mg at weekly intervals were used, with concurrent adjustment of other antiepileptic doses where necessary. May be taken with or without food. Capsule strengths available are 25 mg, 50 mg and 100 mg. Elderly: exercise caution at initiation as information is limited. Hepatic impairment: not studied — use in severe hepatic impairment is not recommended; caution and slower titration in mild to moderate impairment. Contains a sulphonamide group — see contraindications. Note: the US label (openFDA) differs — it recommends zonisamide only as adjunctive therapy for partial seizures in adults over age 16, starting at 100 mg daily and increasing at 2-weekly intervals to 200, 300 then 400 mg/day, stating 100–600 mg/day were effective with no suggestion of increasing response above 400 mg/day. The UK SPC has been used for this draft.

UK SPC §4.2, paediatric population aged 6 years and above, ADJUNCTIVE THERAPY ONLY (must be added to existing therapy). Usual maintenance is 6 to 8 mg/kg/day once daily for patients weighing 20 to 55 kg — a RANGE, so no single per-kg figure is given and dosePerKg is left null deliberately; the SPC states the dose regime is 6–8 mg/kg/day up to a maximum dose of 500 mg/day. Patients weighing more than 55 kg: 300–500 mg/day once daily (not weight-based). TITRATION — with CYP3A4-inducing agents: 1 mg/kg/day once daily in week 1, then increase at weekly intervals in increments of 1 mg/kg over weeks 2 to 8. Without CYP3A4-inducing agents: 1 mg/kg/day once daily in weeks 1+2, then increase at two-weekly intervals in increments of 1 mg/kg from week 3. Monitor the child's weight and review the dose as weight changes occur, up to a weight of 55 kg. Safety and efficacy have NOT been established in children aged below 6 years or below 20 kg; there are limited data below 20 kg, so children aged 6 years and above weighing less than 20 kg should be treated with caution. Round the total dose up or down to the nearest dose achievable with the available capsule strengths (25 mg, 50 mg, 100 mg). Withdrawal: down-titrate at weekly intervals — 20–28 kg: 25 to 50 mg/day decrements; 29–41 kg: 50 to 75 mg/day; 42–55 kg and >55 kg: 100 mg/day (all once daily). Verify all paediatric dosing against a children's formulary before prescribing.