Zonisamide (Zonegran®)

Zonisamide (Zonegran®) is characterized by a half-life of approximately 20-40 hrs in dogs (unknown in the cat) variability among animals is likely to be marked. As such, during a 24 hr dosing interval, drug concentrations will decline by approximately 50%. We recommend, therefore, that a 12 hr dosing interval be implemented to avoid inappropriate fluctuation during the dosing interval. “Steady-state” should occur in 3 to 5 drug half-lives, or 60 to 100 hrs (3 to 5 days). However, we have commonly measured half-lives longer than 150 hrs, suggesting that drug metabolism in dogs might “saturate” (the drug is acetylated, which is an enzyme in which the dog is deficient). As such zonisamide recommendations are very similar to phenobarbital in terms of when and what.

The therapeutic range recommended in animals is currently that recommended in humans, that is, 10 to 40 mcg/ml. Assuming that this therapeutic range is appropriate for dogs or cats, we suggest that doses be designed to achieve a “low” concentration of 15 to 20 mcg/ml as therapy is begun. We have measured (often) concentrations well above 60 mcg/ml or higher; dogs appear to tolerate this concentration well, although safety has not been confirmed.

When: Baseline steady-state concentrations can be determined at 7 to 14 days. Steady-state will thus take longer than 10 to 14 days in those patients. The half-life is likely to be shorter in dogs simultaneously receiving Phenobarbital; up to a 30% decrease in half-life or drug concentrations may occur. However, this is not consistent.

Sampling times: For routine monitoring, either a peak (2 hr) or trough (just before the next dose) is reasonable, although we suggest a trough sample such that the lowest concentrations can be determined for the patient and so that concentrations can be compared across time. Peak and trough samples are necessary only for animals in which a half-life less than 20 hrs is suspected such that a shorter dosing interval might be recommended. However, for some patients, a peak and trough might be prudent to detect longer half-lives that might lead to marked drug accumulation.

Other considerations: We are concerned that the oral bioavailability of zonisamide varies among the generic human products, meaning that one product may be absorbed differently than another product in the same dog. Accordingly, clients may want to ask the pharmacist to let them know when the pharmacy has changed the manufacturer of the generic product; monitoring might be implemented after the change has been made in the patient.

Thyroid gland suppression may be more likely at this concentration. Baseline thyroid function testing is recommended as you begin zonisamide and repeated as concentrations reach the maximum.

Phenobarbital will substantively decrease the half-life of zonisamide. If phenobarbital is discontinued in an animal, note that zonisamide concentrations will likely increase.