Zonisamide is a substrate of CYP 3A4 and contains a sulfonamide group, motivating caution in its use in acute porphyria. It does not, however,contain the 4-aminobenzene group characteristic for the strongly porphyrogenic sulfanilamide. In spite of careful studies there are no in vitro or clinical evidence of capacity for CYP inhibition or CYP induction.

1-(1,2-Benzoxazol-3-yl)methanesulphonamide(M= 212).

Zonisamide is a benzisoxazole derivative, used as an adjunctive antiepileptic in the treatment of partial seizures, with or without secondary generalisation. In contrast to fenytoin and carbamazepine, zonisamide is mainly effective against seizures of cortical origin. The effect may be due to action on voltage sensitive sodium and calcium channels, thereby interfering with synchronized neuronal activity. There is also a limited effect on GABA-mediated neuronal inhibition. Adverse effects are more common and severe in doses above 300 mg/d. In higher doses there is an increased risk for side effects such as restlessness, irritability, confusion, depression, nausea, abdominal pain and diarrhoea. Note! Renal calculi has been noted in patients treated by zonisamide and may be the cause for severe pain and red urine. This should not be mistaken as porphyria symptom.

Possibly significant.

Insignificant first pass metabolism, largely distributed to tissues. Metabolized by acetylation via acetyltransferases, and CYP 3A4 mediated reductive cleavage of the benzioxazole ring to 2-sulfamoylacetylphenol(SMAP). Excretion mainly in urine, 15-30 per cent as unchanged drug, 15 per cent as the acetyl metabolite and 50 per cent as the glucuronide of SMAP. In human in vitro system no inhibition of CYPs 1A2, 2A6, 2C9, 2B6, 2C8, 2C19, 2D6, 2E1 or 3A4, in clinically relevant doses. In repeated doses no clinically relevant effects on CYP metabolism of other drugs, including CYP 3A4 substrates.