Precautions for co-administration [ZONISAMIDE (ZONEGRAN) should be administered with care when co-administered with the following drugs)]: (See Table 5.)

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.