Drug Interactions

This drug is mainly metabolized by the drug-metabolizing enzyme CYP3A. ZONISAMIDE (ZONEGRAN®) should be administered with care when co-administered with the following drugs.

Drugs Clinical Symptoms & Treatment Mechanisms & Risk Factors
Anti-epileptic drugs Phenytoin, Carbamazepine, Sodium valproate, etc. When the dose i s reduced or the
administration is discontinued in other
anti-epileptic agents used with
zonisamide concomitantly, zonisamide
blood concentration may be increased.
It is suggested that hepatic cytochrome
P450 is induced by phenytoin and
carbamazepine, and then zonisamide
blood concentration is decreased.
Phenytoin Since toxic symptoms caused by phenytoin such as nystagmus, dyslalia and ataxia may occur, the blood concentration should be measured as much as possible and appropriate measures taken such as reduction of the dose.  It is suggested that zonisamide inhibits
metabolism of phenytoin and increases
its blood concentration.


An in vitro study shows that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 267 μmol/L and there is the theoretical potential for zonisamide to affect the pharmacokinetics of drugs which are P-gp substrates. Caution is advised when starting or stopping zonisamide treatment or changing the zonisamide dose in patients who are also receiving drugs which are P-gp substrates (e.g. digoxin, quinidine).

Zonisamide is metabolised partly by CYP3A4 (reductive cleavage), and also by N-acetyl transferases and conjugation with glucuronic acid; therefore, substances that can induce or inhibit these enzymes may affect the pharmacokinetics of zonisamide.