The recommended daily dose of zonisamide to start is 100 to 200 milligrams (mg) for adults. For children, the amount is calculated according to child's weight. Children usually start at 2 to 4 mg per kilogram (kg, about 2.2 pounds) per day, divided into two doses.

Dosages should be increased at 2-week intervals to a target maintenance dose of 400 to 600 mg per day for adults and 4 to 8 mg per kg per day for children. Some people may need (and be able to tolerate) higher dosages.

The doctor occasionally may suggest checking the level of zonisamide in the blood to see whether it falls within the range that is usually considered appropriate for treatment ("therapeutic level"). For zonisamide, this range is 10-40 mcg/mL. Whether the amount prescribed needs to be adjusted generally depends on whether seizures or side effects are occurring, however. When the level in the blood is fairly high, a small increase in the dose may produce a large increase in the level in the blood (often causing side effects).