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PubMed2004

Effects of zonisamide monotherapy in children with epilepsy.

This study examined the efficacy and safety of zonisamide as monotherapy in pediatric patients with epilepsy. Seventy-seven children with epilepsy (ages 8 months-15 years) were treated with zonisamide. Nine patients were withdrawn early because of side effects; these patients were included in side effect but not efficacy analyses. Zonisamide dosages were initiated at approximately 2 mg/kg per day and adjusted for each patient individually to a maximum of 12 mg/kg per day. Among 44 patients with cryptogenic/symptomatic partial epilepsy, 36 (82%) became seizure free; 4 (9%) had a > or =50% reduction in seizure frequency; and 4 (9%) had no change in seizures with zonisamide treatment. Of 11 patients with cryptogenic/symptomatic generalized epilepsy, 10 (91%) became seizure free, and 1 experienced no change with zonisamide treatment. Similarly, 4 patients (100%) with idiopathic partial epilepsy, and 8 of 9 patients (89%) with idiopathic generalized epilepsy became seizure free with zonisamide treatment; in the last group, 1 experienced no change. Thirty patients (39%) reported side effects, including somnolence (11.7%), decreased spontaneity (7.8%), anorexia (6.5%), and rash (6.5%). Thus, zonisamide is effective for partial seizures with or without secondarily generalized seizures in children and should be considered a broad-spectrum antiepilepsy agent.

Adolescent↗
PubMed2004

Safety of zonisamide therapy: prospective follow-up survey.

Zonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1-3 years. Nine hundred twenty-eight children and 584 adults (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1008 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (5.8%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hypohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis.

Abnormalities, Drug-Induced↗
PubMed2004

Review of United States and European clinical trials of zonisamide in the treatment of refractory partial-onset seizures.

Zonisamide is an antiepilepsy drug (AED) with both sodium and calcium channel-blocking properties. This dual mechanism may predict efficacy in some refractory patients, and a broad spectrum of action against different seizure types. Zonisamide has been commercially available in Japan since 1989, and became available in the United States for treatment of adults over the age of 12 with partial-onset seizures in March 2000. Several multicenter clinical trials have been conducted in the United States over the past 15 years. These have included three double-blind, placebo-controlled trials as well as long-term open-label studies. Zonisamide was characterized in these studies as a safe and effective adjunctive treatment for partial-onset seizures. Zonisamide has not yet been studied in the United States as an initial monotherapy, but in one long-term study, some patients were able to discontinue other AEDs and successfully transition to monotherapy. The most frequently reported adverse events were somnolence, dizziness, and anorexia. Current United States labeling states that 12 patients with epilepsy receiving zonisamide had symptomatic kidney stones; however, after more than a dozen years of zonisamide use in Japan, the incidence of kidney stones associated with zonisamide remains low.

Anticonvulsants↗
PubMed2003

Oligohydrosis and fever in pediatric patients treated with zonisamide.

Zonisamide is an antiepileptic drug developed and first marketed in Japan in 1989. Cases of oligohydrosis, characterized by deficient production and secretion of sweat, were reported in children treated with zonisamide in Japan during development and in the postmarketing period. Zonisamide was approved in the United States in March 2000 for adjunctive treatment of partial seizures in adults. Searching the Food and Drug Administration's Adverse Events Reporting System, we identified six domestic cases of zonisamide-associated oligohydrosis and/or fever, all in patients </= 18 years of age. The calculated reporting rate was 13 cases per 10,000 pediatric-years of exposure, approximately 10-fold the reporting rate in Japan. A possible risk factor for the development of oligohydrosis in these cases was pediatric age, leading to exposure to elevated zonisamide blood levels relative to patient size. Although the mechanism for zonisamide-associated oligohydrosis has not been fully elucidated, the drug may mediate its effect on eccrine sweat glands by inhibiting carbonic anhydrase, thereby influencing pH dynamics, hydrogen ion concentration, and available calcium transients. Awareness of zonisamide-associated oligohydrosis may prevent morbidity, especially in the pediatric population.

Adolescent↗
PubMed2002

Selective mutism and obsessive compulsive disorders associated with zonisamide.

We treated 27 children with idiopathic epilepsy with zonisamide monotherapy over a period of 2 years and observed behaviour disturbances in a prospective study. In all cases, seizure control was excellent; however, two cases (7.4%) had behaviour disturbances. The first (Case 1) was a 14-year-old girl with partial epilepsy which began at age 4 years. Zonisamide was administered at age 6 years, which was effective against her seizures, but selective mutism, violent behaviour, and lack of concentration developed at age 10 years. The second (Case 2) was a 15-year-old girl with generalized tonic-clonic seizures which began at age 10 years. Zonisamide was also effective against her seizures, but obsessive compulsive disorders (OCD) developed at age 13 years. The patients have had no other physical or mental problems and decreasing the dosage of zonisamide reduced the problems. There are few reports of behaviour disturbances provoked by zonisamide monotherapy in epileptic children who are neither physically nor mentally disturbed. While problems can develop several years later, in the present study, decreasing the zonisamide dosage maintained adequate prevention of seizures and eliminated the behaviour disturbances. Zonisamide is still a useful anticonvulsant for epileptic seizures, but physicians should be wary of its adverse behavioural side effects, which may arise several years later.

Adolescent↗
PubMedDate not supplied

Open-label zonisamide for refractory migraine.

OBJECTIVES: Zonisamide is a novel anticonvulsant drug with multiple mechanisms of action, many of which may confer efficacy in the treatment of migraine headaches. This study investigated the use of open-label zonisamide in treating patients with refractory migraine headaches. METHODS: Thirty-four migraine patients were initiated on a 100-mg/day zonisamide dosage, which was titrated to 400 mg/day as tolerated. Mean headache severity, frequency, and duration were assessed before and 1, 2, and 3 months after initiation of zonisamide therapy. RESULTS: Statistically significant improvements in headache severity (P <0.01), duration (P <0.05), and frequency (P <0.05) were evident after 1 month of zonisamide therapy and were carried through month 3 of treatment. Zonisamide was well tolerated, with only 4 patients (11.8%) discontinuing for adverse events, including dysphoria (n=2) and difficulty concentrating (n=2). Other adverse events were transient and tolerable. CONCLUSIONS: : These results suggest that zonisamide may be a safe and effective adjunctive agent for migraine prevention. Double-blind studies are warranted to confirm these findings.

Adolescent↗
PubMed2006

A long-term follow-up of zonisamide monotherapy.

OBJECTIVES: Several studies have reported the safety and efficacy of zonisamide monotherapy, but studies on its long-term outcomes are limited. This chart review was conducted to evaluate the long-term outcomes of zonisamide monotherapy. METHODS: The charts were reviewed for 77 patients treated with zonisamide as monotherapy for 6-180 months between May 1985 and December 2003. Outcomes were analyzed by the following subcategories: patients with newly diagnosed epilepsy or with antiepileptic drug-resistant epilepsy, the type of epilepsy, patient age, and treatment period. RESULTS: Of a total of 77 patients, 49 patients (64%) attained 50% or more reduction of seizure frequency and of those patients 38 (49%) attained 75% or more reduction, with 18 patients (24%) becoming seizure-free from 6 to 180 (median 80.6 +/- 43.6) months of follow-up. Thirty-eight patients (49%) continued zonisamide monotherapy as of December 2003. Proportions of patients having 75% or more reduction in seizure frequency in subcategories were as follows; 56% in patients with newly diagnosed epilepsy and 48% in patients whose treatment was switched to zonisamide monotherapy owing to lack of efficacy of or adverse reaction to previous antiepileptic drugs; 60% in patients with localization-related epilepsies and 38% in patients with generalized epilepsies; and 49% in pediatric patients and 50% in adult patients. CONCLUSION: Long-term zonisamide monotherapy was efficacious in a wide range of patients with epilepsy. Zonisamide did not seem to exhibit a reduction in efficacy during long-term use of up to 180 months.

Adolescent↗
PubMed1996

Pharmacokinetic study of zonisamide in patients undergoing brain surgery.

To test whether the concentration of the anticonvulsant zonisamide in erythrocytes reflects the brain concentration and the clinical response of the drug, its pharmacokinetics were studied in nine patients undergoing surgery for brain tumour. Erythrocyte, total and free serum concentrations in samples drawn on the day of brain surgery were compared with levels on a day after the operation. In three patients zonisamide and its major metabolite, 2-sulphamoylacetylphenol, were also analysed in urine. The area under the curve of the free and the erythrocyte concentration did not differ between the two study phases whereas the area under the curve of the total serum concentration was significantly lower on the day of the operation, and this was associated with significant increases in total clearance (15.4 compared with 12.7 mL kg-1 h-1, P < 0.05, n = 9) and renal clearance (5.4 compared with 3.3 mL kg-1 h-1, P < 0.05, n = 3), and non-significant change in non-renal clearance (7.7 on the day of operation compared with 8.4 mL kg-1 h-1 on the post-operation day, n = 3). Zonisamide distribution was also altered by the operative procedure, as evidenced by a higher volume of distribution (1.48 compared with 0.87 L kg-1, P < 0.05, n = 9). The binding of zonisamide was characterized on both days. Zonisamide binding to erythrocytes seemed to occur by two processes: a saturable process and a non-saturable linear process. The maximum binding capacity to erythrocytes (31.6 vs 29.7 micrograms mL-1) did not differ on the two days; however, increases in the dissociation binding constant (+28%) and the proportionality constant (+24%) were observed on the day of the operation, suggesting that the zonisamide concentration in erythrocytes was greater on the day of the operation. Brain surgery appears to be one of the possible factors altering the rate of elimination of zonisamide and the uptake of the drug by erythrocytes.

Adult↗
PubMed2004

Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital.

OBJECTIVES: Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) is a novel anti-seizure medication approved for use in the United States as adjunct therapy in the treatment of partial seizures in adults with epilepsy. It has also been used to treat other conditions including intractable pain. The aim of this study was to determine the usefulness of zonisamide in patients whose seizures were not controlled after having been treated with at least three other currently available anticonvulsant medications or in patients whose pain control was suboptimal despite the use of commonly used drug regimens. METHODS: This was a retrospective study documenting the efficacy of zonisamide in 48 consecutive patients who presented at an outpatient neurology clinic at a Veterans Administration hospital. The patients were diagnosed with refractory partial seizures (n = 21) or a variety of intractable neuropathic pain syndromes (n = 27). RESULTS: Sixteen out of 21 seizure patients (76%) experienced a 50% or greater reduction in seizure frequency when zonisamide (100-200 mg daily) was added to their existing anticonvulsant medication regimen. Of 27 patients with neuropathic pain, 17 (59%) responded to zonisamide, reporting subjective reduction in pain by at least 50%. The most common adverse events were gastrointestinal upset, somnolence, and one case of skin rash. CONCLUSIONS: In this study, zonisamide appeared to be an effective adjunct therapy in the treatment of partial seizures in adults who continued to experience frequent episodes while taking other anticonvulsant medications, and in adults whose neuropathic pain was not well controlled with analgesics. These promising results must be tempered by the fact that this investigation included a small patient population in an uncontrolled study design. Further research into the efficacy and tolerability of zonisamide in these areas is warranted.

Aged↗
PubMed2003

Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.

We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg/kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D(3) metabolite, at a dose of 0.1 microg/kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol.

Animals↗
PubMed2004

Zonisamide in the treatment of binge-eating disorder: an open-label, prospective trial.

BACKGROUND: Binge-eating disorder is characterized by recurrent episodes of uncontrollable overeating without compensatory weight-loss behaviors. It commonly co-occurs with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to preliminarily assess zonisamide in the treatment of binge-eating disorder. METHOD: Fifteen outpatients with DSM-IV-TR binge-eating disorder were enrolled from Jan. 25, 2002, through Sept. 10, 2002, in an open-label, prospective, 12-week, flexible dose (100-600 mg/day) study of zonisamide. The primary outcome measure was binge-eating episode frequency. Secondary measures included binge day frequency, body mass index (BMI), weight, Clinical Global Impressions-Severity of Illness scale (CGI-S) scores, Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (YBOCS-BE) scores, Three Factor Eating Questionnaire (TFEQ) scores, and Hamilton Rating Scale for Depression scores. Safety measures included adverse events, routine blood chemical and hematology laboratory values, urinalyses, plasma zonisamide levels, physical examination findings, and electrocardiograms. Outcome measures were analyzed by a repeated-measures random regression analysis using all data and an endpoint analysis using last observation carried forward. RESULTS: Eight subjects completed the 12 weeks of treatment. The mean (SD) zonisamide daily dose at endpoint evaluation was 513 (103) mg/day. Both the random regression and endpoint analyses found a highly significant decrease in binge-eating episode frequency, binge day frequency, BMI, weight, CGI-S scores, YBOCS-BE total scores, and TFEQ hunger and disinhibition scores (p <.0001 for all measures in both analyses except p =.001 for endpoint analysis of binge eating frequency, p =.0001 for endpoint analysis of TFEQ disinhibition, and p =.0008 for endpoint analysis of TFEQ hunger). The 7 subjects who discontinued zonisamide prematurely did so due to lack of response (N = 1), protocol non-adherence (N = 2), and adverse events (N = 4). CONCLUSION: Zonisamide was effective in reducing binge-eating frequency, severity of illness, and weight and was generally well tolerated in an open trial of binge-eating disorder. Controlled trials appear warranted.

Administration, Oral↗
PubMed1990

Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain.

The effects of zonisamide on [3H]flunitrazepam binding and [3H]muscimol binding were studied in Sprague-Dawley rat brain. Specific [3H]flunitrazepam bound was decreased to 64.6 +/- 5.6% (mean +/- SD, n = 5, p < 0.002) and 91.9 +/- 4.0% (p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Scatchard plot analysis of [3H]flunitrazepam binding with 10(-3) M of zonisamide revealed an increased Kd value with no change in Bmax. No inhibitory effect of zonisamide was seen on the enhancement of specific [3H]flunitrazepam binding by GABA. As for the effects on GABA receptors, specific [3H]muscimol bound was decreased to 27.7 +/- 10.4% (mean +/- SD, n = 4, p < 0.005) and 68.3 +/- 3.7% (mean +/- SD, n = 4, p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Since therapeutic serum level of zonisamide are around 10(-4) M, these results suggest that zonisamide neuropharmacologically interacts with the GABA/benzodiazepine receptor ionophore complex in a manner similar to phenytoin.

Animals↗
PubMedDate not supplied

Metabolism of the anticonvulsant agent zonisamide in the rat.

The metabolism of zonisamide [3-(sulfamoylmethyl)-1,2-benzisoxazole], a new anticonvulsant, has been studied. In rats dosed with [14C]zonisamide (100 mg/kg, ip) 86.5% of the radioactive dose was excreted in the urine over 72 hr. The remainder of the radioactive dose (13.5%) was excreted in the feces over the same time period. Unchanged drug and eight metabolites were isolated from the urine, and the structures of five metabolites were assigned by physicochemical methods. metabolism of zonisamide primarily involves reductive and conjugative mechanisms, with oxidation of this compound being of minor metabolic significance. The percentage of urinary radioactivity accounted for by unmetabolized zonisamide and metabolites is as follows: unmetabolized zonisamide (metabolite 9), 32.8%; metabolite 8 [N-acetyl-3-(sulfamoylmethyl)-1,2-benzisoxazole], 7.7%; unidentified metabolite 7, 2.4%; metabolite 6 (zonisamide glucuronide), 7.6%; metabolite 5 [3-(carboxy)-1,2-benzisoxazole], 5.4%; unidentified metabolite 4, 13.1%; metabolite 3 [2-(sulfamoylacetyl)-phenol glucuronide], 12.6%; unidentified metabolite 2, 3.8%; and metabolite 1 (2-[1-(amino)sulfamoylethyl]phenol sulfate), 2.3%. A total of 87.7% of the 0-24 hr urinary radioactivity was accounted for by unchanged zonisamide and metabolites.

Animals↗
PubMed1994

Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects.

To clarify whether the inhibitory effect of zonisamide (Excegran, CAS 68291-97-4) on carbonic anhydrase contributes to its anticonvulsant activity, the anticonvulsant activity of 7-methylated zonisamide, a zonisamide analogue which has the same potency of activity as zonisamide in inhibiting carbonic anhydrase in vitro, has been examined. The study using mice did not reveal 7-methylated zonisamide to have any anticonvulsant activity even though its brain concentration level was more than two times the minimal effective concentration of zonisamide. These findings indicate that the anticonvulsant effect of zonisamide is derived from a mechanism(s) other than inhibition of carbonic anhydrase.

Animals↗
PubMed1996

Involvement of mammalian liver cytosols and aldehyde oxidase in reductive metabolism of zonisamide.

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide), an anticonvulsant agent, is primarily metabolized to 2-sulfamoylacetylphenol by reductive cleavage of the 1,2-benzisoxazole ring. Rabbit liver cytosol with an electron donor of aldehyde oxidase exhibited a significant zonisamide reductase activity that was sensitive to inhibition by menadione, an inhibitor of aldehyde oxidase. The result suggested that the cytosolic activity is caused by aldehyde oxidase, a cytosolic enzyme. In fact, rabbit and rat liver aldehyde oxidase had the ability to reduce zonisamide when supplemented with its electron donor. Apparent KM and Vmax values of aldehyde oxidase for zonisamide were 217 microM and 42 nmol/10 min/mg protein in the case of the rabbit liver enzyme, and 542 microM and 382 nmol/10 min/mg protein in the case of the rat liver enzyme, respectively. In rabbits, hamsters, mice, and guinea pigs, zonisamide reductase activity of the liver cytosols with 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, was much higher than that of the liver microsomes with NADPH. In rats, zonisamide reductase activity was examined with liver microsomes and cytosols from seven strains. The 2-hydroxypyrimidine-dependent cytosolic activity exhibited marked strain differences, unlike the NADPH-dependent microsomal activity. 1,2-Benzisoxazole was also reduced to salicylaldehyde by rabbit liver cytosol and aldehyde oxidase in the presence of 2-hydroxypyrimidine. Stoichiometric studies showed that 2-sulfamoylacetylphenol was formed accompanying nearly equimolar ammonia from zonisamide.

Aldehyde Oxidase↗
PubMed1999

Monitoring of zonisamide in human breast milk and maternal plasma by solid-phase extraction HPLC method.

An HPLC method was developed for the determination of zonisamide in human breast milk and plasma. Chromatographic separation was achieved using a Develosil CN analytical column with potassium dihydrogenphosphate buffer (pH 3.5 with milk, pH 2.5 with plasma)-acetonitrile as the mobile phase. Zonisamide and 1, 2-benzisoxazole-3-methansulfonamine acetate as internal standard were detected by ultraviolet absorbance at 240 nm. Zonisamide in breast milk and plasma was extracted by a rapid and simple procedure based on C(18) bonded-phase extraction. Determination of zonisamide in human breast milk and plasma was possible in the concentration range 0.05-20.0 microg/mL. The recoveries of zonisamide added to human breast milk and plasma were 79.5-85.0% and 86.3-93.1%, respectively, with coefficients of variation of less than 8.3% and 11.4% respectively. The mean concentrations of zonisamide in breast milk and plasma were 9.41 +/- 0.95 and 10.13 +/- 0.45 microg/mL, respectively. The average ratio between the breast milk concentration and plasma concentration (M/P ratio) was 0.93 +/- 0.09.

Adult↗
PubMed1988

Chronic toxicity of the anticonvulsant zonisamide in beagle dogs.

The chronic toxicity of the new anticonvulsant drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was evaluated in a detailed 52-week study in which dose levels of 0, 10, 30 and 75 mg/kg/day were administered orally in gelatin capsules to groups of five Beagle dogs per sex. Potential toxicity was based on the effects of zonisamide on body weight and food consumption; clinical and ophthalmic examinations; electrocardiography and heart rates; clinical biochemistry, hematology and urinalysis determinations; organ weights and gross and histopathologic evaluations; electron microscopy of high dose and control male dogs; and plasma zonisamide concentrations. Zonisamide was relatively well tolerated during the study. In animals given 75 mg/kg/day, early body weight losses occurred and therefore, from Weeks 2 and 3 until study termination, for males and females respectively, the high dose was given as two equal portions (i.e., 37.5 mg/kg each) approximately 3-4 hr apart. Clinical laboratory analyses in the dogs given 75 mg/kg revealed a small but statistically significant decrease in plasma albumin concentration and a small increase in alkaline phosphatase activity. In animals given 75 mg/kg, liver weights were increased and a brownish discoloration of the liver was noted grossly at necropsy. No significant light microscopic changes were evident; however, electron microscopic evaluation of the liver tissue from the 5 male dogs given 75 mg/kg revealed the presence of concentric lamellae of paired smooth membranes which were not seen in control animals. At the 10 and 30 mg/kg dose levels, plasma zonisamide concentrations reached steady-state and were proportional to dose, but at 75 mg/kg, plasma levels were disproportionately higher and never achieved steady-state. The results of this study indicated that at the high dose level of 75 mg/kg, chronic administration of zonisamide had a mild effect on the liver, particularly the endoplasmic reticulum.

Administration, Oral↗
PubMed1994

The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania.

1. Zonisamide, an anticonvulsant developed in Japan, is structurally similar to serotonin. Zonisamide has been proven to have a pharmacological profile that is very similar to that of carbamazepine. Thus, the effect of zonisamide was examined in 24 psychiatric patients: 15 with bipolar manic state, 6 with schizoaffective manic state, and 3 schizophrenic excitement. 2. Approximately 25% of all the patients and 33% of the bipolar manic patients showed remarkable global improvement with the addition of zonisamide. Approximately 71% of all the patients and 80% of the bipolar group had more than moderate global improvement. 3. No serious adverse reactions were found and no patients required zonisamide withdrawal. One patient developed both leukocytosis and mildly abnormal liver function test. One developed leukocytosis and another reported mild sleepiness. These reactions disappeared when zonisamide was discontinued.

Adult↗