Zonisamide ( Zonegran ) is a sulphonamide derivative that inhibits carbonic anhydrase; it resembles Topiramate ( Topamax ).

The main clinical trial, a double-blind study lasting 36 weeks, compared the addition of Zonisamide or placebo to ongoing treatment in 351 patients with refractory partial epilepsy.
The response rate ( the proportion of patients with at least a 50% reduction in the frequency of seizures ) was significantly higher with Zonisamide plus the previous treatment than with placebo plus the previous treatment ( 46.6% versus 17.6% ).
An indirect comparison suggests that this is no better than treatment with a second-line antiepileptic drug.

The main adverse effects of Zonisamide are those typically seen with Topiramate: neuropsychological disorders and disorders due to carbonic anhydrase inhibition ( kidney stones, reduced perspiration, and hyperthermia ).

Serious immune based adverse reactions that have been associated with medicinal products containing a sulphonamide group include rash, allergic reaction and major haematological disturbances including aplastic anaemia.
Consideration must be given to discontinuing Zonisamide in patients who develop an otherwise unexplained rash. All patients who develop a rash while taking Zonisamide must be closely supervised, with additional levels of caution applied to those patients receiving concomitant anti-epileptic agents that may independently induce skin rashes.

Cases of agranulocytosis, thrombocytopenia, leukopenia, aplastic anaemia, pancytopenia and leucocytosis have been reported.

Zonisamide should be used with caution in patients who have risk factors for nephrolithiasis, including prior stone formation, a family history of nephrolithiasis and hypercalcuria. Such patients may be at increased risk for renal stone formation and associated signs and symptoms such as renal colic, renal pain or flank pain. In addition, patients taking other medications associated with nephrolithiasis may be at increased risk. Increasing fluid intake and urine output may help reduce the risk of stone formation, particularly in those with predisposing risk factors.

The profile of interactions is complex. There is a risk of pharmacokinetic interactions, and of pharmacodynamic interactions with other carbonic anhydrase inhibitors.

According to authors, Zonisamide has no therapeutic advantages over other antiepileptics available for combination therapy of partial epilepsy.

Source: Prescrire International, 2007

XagenaMedicine2007


Link: Xapedia - Medical Encyclopedia