Abstracts

RATIONALE: This presentation alerts prescribers of antiepileptc drugs to a potentially life-threatening side effect of the recently approved antiepileptic drug (AED) zonisamide. Zonisamide (ZNS) is an AED developed and first marketed in Japan. It was approved in the U.S. in March 2000 for adjunctive treatment of partial seizures in adults. ZNS has a sulfonamide side chain in common with the protypical carbonic anhydrase inhibitor, acetazolamide. In addition to its ability to inhibit carbonic anhydrase, ZNS exhibits in vitro, both sodium and calcium (T-type) channel-blocking properties. In 11 years of development and marketing in Japan, more than 50 cases of the potentially serious adverse event oligohydrosis/fever have been reported with ZNS use in pediatric patients, some resulting in heat stroke and hospitalization. ZNS is not approved in the United States (U.S.) for pediatric use. Nevertheless, considerable off-label use exists. The purpose of this study was to determine whether cases of oligohydrosis/fever have been reported in the U.S., and if so, to characterize them.
METHODS: We conducted a search of the Food and Drug Administration[ssquote]s (FDA) Adverse Event Reporting System for reports of oligohydrosis/fever associated with ZNS use. Patient demographics, concomitant drugs, and ZNS dosing and duration of treatment were summarized from the identified cases. The U.S. reporting rate for oligohydrosis was calculated using prescription data compiled from IMS Health[ssquote]s National Prescription Audit and patient demographic data from IMS Health[ssquote]s National Disease and Therapeutic Index.
RESULTS: Five patients were identified as having oligohydrosis with or without fever. The three U.S. reports described a 6-month old male, a 9-month old male, and a 4-year old female. These children were receiving ZNS as monotherapy in doses ranging from 5.7-17mg/kg (mean=11.5mg/kg). The duration of therapy to onset of oligohydrosis ranged from 10 days to 4 months. The 6-month old boy was reported to have a temperature of 41[degree]C. Body temperature was not specified in the other cases. Two of three patients improved upon discontinuation of ZNS. The 6-month old male improved after ZNS discontinuation but had not recovered completely. The estimated number of ZNS prescriptions dispensed by retail pharmacies in the U.S. (March 2000-May 2001) was 77,000, of which 27% appeared in the [lt]16 year-old group. Therefore, the U.S. reporting rate for oligohydrosis for this age group is calculated as 1.8/1,000 pediatric-years.
CONCLUSIONS: Children may develop oligohydrosis and fever during ZNS use. This potentially serious adverse event must be considered in the differential diagnosis of fever in a child being treated with ZNS. Discontinuation of ZNS may be the only necessary intervention.