Zonisamide (zonisamide)

The initial dosage of zonisamide as adjunctive therapy for partial seizures in adults and children older than 16 years of age is 100 mg daily. After 2 weeks, the dosage may be increased to 200 mg daily for at least 2 weeks. Dosage can further be increased to 300 and 400 mg daily with at least 2 weeks between dosage changes to achieve steady state at each dosage level. Results of controlled clinical trials suggest that zonisamide dosages of 100-600 mg daily are effective; however, dosages exceeding 400 mg daily may not be associated with increased therapeutic benefit. There is only limited experience with zonisamide dosages exceeding 600 mg daily. The manufacturer states that although this dosage regimen has been shown to be tolerated, some clinicians may prefer to administer lower dosages of zonisamide for longer periods in order to fully assess safety of zonisamide at steady state, since adverse effects occur more frequently at dosages of 300 mg daily and higher.

Zonisamide is administered orally once or twice daily (except the initial daily dosage of 100 mg, which is administered once daily), without regard to meals. The capsules should be swallowed intact. Patients should be encouraged to drink plenty of fluids while taking the drug to reduce the risk of kidney stones.

Zonisamide therapy should not be discontinued abruptly; dosage reduction or discontinuance of the drug should be done gradually.

Patients currently receiving or beginning therapy with zonisamide and/or any other anticonvulsant should be closely monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression. (See Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Known hypersensitivity to zonisamide, sulfonamides, or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Abdominal pain, anorexia, diarrhea, nausea, dyspepsia, constipation, dry mouth, taste perversion, headache, dizziness, ataxia, nystagmus, paresthesia, confusion, difficulty concentrating, impaired memory, mental slowing, speech abnormalities, difficulty in verbal expression, agitation and/or irritability, depression, insomnia, anxiety, nervousness, schizophrenic and/or schizophreniform behavior, somnolence, fatigue, tiredness, flu-like syndrome, ecchymosis, rhinitis, weight loss, rash, and diplopia were reported in 2% or more patients in clinical studies in which zonisamide was administered in conjunction with other anticonvulsants.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Safety and efficacy of zonisamide in children younger than 16 years of age have not been established. However, the drug has been used for the treatment of epilepsy in some pediatric patients+; studies conducted with pediatric patients indicate that the frequency of some adverse effects (e.g., metabolic acidosis, oligohidrosis and hyperthermia) may be increased compared with adults.

Oligohidrosis and hyperthermia, characterized by decreased sweating and abnormally high body temperatures, have been reported in pediatric patients (1.6-17 years of age) receiving zonisamide and have sometimes resulted in heat stroke and hospitalization. (See Oligohidrosis and Hyperthermia under Warnings/Precautions: Warnings, in Cautions.) As of December 31, 2001, there were 40 reported cases of oligohidrosis and hyperthermia in patients receiving zonisamide, including 38 in the first 11 years of marketing in Japan (approximately one case per 10,000 patient-years of exposure) and 2 in the first year of marketing in the US (approximately 12 cases per 10,000 patient-years of exposure). However, it generally is recognized that postmarketing data are subject to underreporting. In many of the reported cases, oligohidrosis and hyperthermia occurred after exposure to elevated environmental temperatures; in some cases, heat stroke requiring hospitalization resulted. There have been no reported deaths associated with these adverse effects thus far.

If zonisamide is used in pediatric patients (not an FDA-labeled population), they should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather or when other drugs that predispose patients to heat-related disorders (e.g., carbonic anhydrase inhibitors) are used concomitantly. (See Drug Interactions: Drugs Predisposing to Heat-related Disorders.)

Pediatric patients may be at increased risk for zonisamide-induced metabolic acidosis and the condition may be more severe in younger patients. In an open-label trial evaluating adjunctive zonisamide therapy in pediatric patients 3-16 years of age with partial epilepsy, the incidence of a persistent decrease in serum bicarbonate to levels less than 20 mEq/L was up to 90% and generally increased with higher dosages. The incidence of persistent and abnormally low serum bicarbonate values (less than 17 mEq/L and more than 5 mEq/L decrease from pretreatment value of at least 20 mEq/L) was as high as 18% and appeared to increase with higher dosages. Although the specific effects of zonisamide on growth and bone have not been studied, chronic metabolic acidosis in pediatric patients can reduce growth rates, resulting in a reduction in the maximal height achieved. (See Metabolic Acidosis under Warnings/Precautions: Warnings, in Cautions and see also Advice to Patients.)

Zonisamide may cause fetal harm; the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should be advised to use effective contraception during zonisamide therapy. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Women who are pregnant while receiving zonisamide should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; patients can enroll by calling 888-233-2334. Information on the registry also can be found on the website https://www.aedpregnancyregistry.org.

Zonisamide therapy can cause metabolic acidosis. (See Metabolic Acidosis under Warnings/Precautions: Warnings, in Cautions.) The effect of zonisamide-induced metabolic acidosis has not been specifically studied during pregnancy; however, metabolic acidosis from other causes during pregnancy can result in decreased fetal growth, decreased fetal oxygenation, and fetal death, and also may affect the ability of the fetus to tolerate labor. Therefore, pregnant women receiving zonisamide should be monitored and treated for metabolic acidosis in the same manner as nonpregnant patients. In addition, neonates born to women treated with zonisamide should be monitored for metabolic acidosis because of possible drug transfer to the fetus and possible occurrence of transient metabolic acidosis following birth.

Some clinicians recommend closely monitoring plasma zonisamide concentrations and adjusting zonisamide dosage as necessary in pregnant women.

Zonisamide is distributed into milk. Because of the potential for serious adverse reactions to zonisamide in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Clinical studies of zonisamide did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adults. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Pharmacokinetics were similar in geriatric and young healthy volunteers in single-dose studies. (See Dosage and Administration: Special Populations.)