Zonisamide 100 mg Capsule, 100-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Anti-epileptic Agent class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
Zonisamide is used in combination with other medications to treat certain types of seizures. Zonisamide is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
Read the full MedlinePlus article ↗- Zonisamide is used to help control partial seizures — seizures that start in one specific area of the brain. It's always used as an add-on to other seizure medications, not on its...
- Because zonisamide stays in your body for a long time — with a half-life of about 63 hours — it takes roughly two weeks after each dose change to reach a stable level. Your doctor...
- How long does it take before zonisamide starts working?
- The most common ones are drowsiness, dizziness, loss of appetite, nausea, and trouble concentrating or remembering things — especially as the dose goes up. These are often manageab...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Zonisamide — tap one for details:
Zonisamide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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A synthetic red dye used to color medicines and products. It helps make pills, liquids, and capsules visually distinct and easier to identify.
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A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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Hydrogenated cottonseed oil is a solid fat made by adding hydrogen to cottonseed oil. It's used in medicines as a binder and lubricant to help hold ingredients together and make tablets easier to compress and release.
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Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
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Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
11 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.107 | $10.67 / 100 capsules |
| Medicaid paysCMS SDUD · 12 mo | $0.1971 | $19.71 / 100 capsules |
| Medicare drug plans payPart D · Q2 2026 | $0.1678 | $16.78 / 100 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zonisamide 100 mg 29300-0430-01 | Unichem | 100 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mg 50268-0816-15 | AvPAK | 50 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mg 59651-0380-01 | Aurobindo | 100 capsules | $0.107 | — | Availability likely | — |
| Zonisamide 100 mg 60687-0230-01 | American | 100 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mg 68001-0244-00 | BluePoint | 100 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mg 68462-0130-01 | Glenmark | 100 capsules | $0.107 | AB | Availability likely | — |
| zonisamide 100 mg 69097-0861-07 | Cipla | 100 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mgthis 72578-0042-01 | Viona | 100 capsules | $0.107 | AB | Availability likely | — |
| Zonisamide 100 mg 76282-0228-01 | Exelan | 100 capsules | $0.107 | AB | Availability likely | — |
| zonisamide 100 mg 00615-8266-39 | NCS | 30 capsules | — | AB | FDA listed | — |
| Zonegran 100 mg 59212-0680-10 | Advanz | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 62756-0260-01 | Sun | 30 capsules | — | — | FDA listed | — |
| Zonisamide 100 mg 63187-0583-30 | Proficient | 30 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 63187-0897-30 | Proficient | 30 capsules | — | — | FDA listed | — |
| Zonisamide 100 mg 63629-3293-01 | Bryant | 100 capsules | — | — | FDA listed | — |
| Zonisamide 100 mg 68788-4004-06 | Preferred | 60 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 68788-7438-01 | Preferred | 100 capsules | — | — | FDA listed | — |
| Zonisamide 100 mg 70518-3224-00 | REMEDYREPACK | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 70518-3903-00 | REMEDYREPACK | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 70771-1144-00 | Zydus | 1000 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 71205-0727-30 | Proficient | 30 capsules | — | AB | FDA listed | — |
| zonisamide 100 mg 71335-0486-01 | Bryant | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 71335-2797-01 | Bryant | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 71335-9679-01 | Bryant | 100 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 80425-0370-01 | Advanced | 30 capsules | — | AB | FDA listed | — |
| Zonisamide 100 mg 80425-0392-01 | Advanced | 30 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 72578-0042-01 You're viewing this | 100 CAPSULE in 1 BOTTLE (72578-042-01) | $0.1067 / ea | $10.67 | 2022-07-04 | Active |
| 72578-0042-05 | 500 CAPSULE in 1 BOTTLE (72578-042-05) | $0.1067 / ea | $53.34 | 2022-07-04 | Active |
| 72578-0042-10 | 1000 CAPSULE in 1 BOTTLE (72578-042-10) | — | — | 2022-07-04 | Active |
You're viewing the smallest of 3 pack sizes for this product.
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.1067 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 83% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 72578-0042-01?
What is the difference between NDC 72578-0042-01 and NDC 72578-0042-05?
What NDC number is used to bill for this package of Zonisamide 100 mg Capsule?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Zonisamide capsules are indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Zonisamide capsules are recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Zonisamide capsules should be administered once or twice daily, using 25 mg, 50 mg or 100 mg capsules.
Zonisamide capsules are given orally and can be taken with or without food. Capsules should be swallowed whole. Adults over Age 16 The prescriber should be aware that, because of the long half-life of zonisamide, up to two weeks may be required to achieve steady state levels upon reaching a stable dose or following dosage adjustment.
Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of zonisamide at steady state, noting that many of the side effects of zonisamide are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100-200 mg/day, the increase appears small and formal dose-response studies have not been conducted. The initial dose of zonisamide should be 100 mg daily.
After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that zonisamide doses of 100-600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day (see CLINICAL PHARMACOLOGY, Clinical Studies subsection ).
There is little experience with doses greater than 600 mg/day. Patients with Renal or Hepatic Disease Because zonisamide is metabolized in the liver and excreted by the kidneys, patients with renal or hepatic disease should be treated with caution, and might require slower titration and more frequent monitoring (see CLINICAL PHARMACOLOGY and PRECAUTIONS ).
⛔ Contraindications ▾
CONTRAINDICATIONS Zonisamide capsules are contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
⚠️ Warnings ▾
WARNINGS Potentially Fatal Reactions to Sulfonamides: Fatalities have occurred, although rarely, as a result of severe reactions to sulfonamides (zonisamide is a sulfonamide) including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Such reactions may occur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue zonisamide immediately.
Specific experience with sulfonamide-type adverse reaction to zonisamide is described below. Serious Skin Reactions Consideration should be given to discontinuing zonisamide in patients who develop an otherwise unexplained rash. If the drug is not discontinued, patients should be observed frequently.
Seven deaths from severe rash [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)] were reported in the first 11 years of marketing in Japan. All of the patients were receiving other drugs in addition to zonisamide. In post-marketing experience from Japan, a total of 49 cases of SJS or TEN have been reported, a reporting rate of 46 per million patient-years of exposure.
Although this rate is greater than background, it is probably an underestimate of the true incidence because of under-reporting. There were no confirmed cases of SJS or TEN in the U.S., European, or Japanese development programs. In the U.S. and European randomized controlled trials, 6 of 269 (2.2%) zonisamide patients discontinued treatment because of rash compared to none on placebo.
Across all trials during the U.S. and European development, rash that led to discontinuation of zonisamide was reported in 1.4% of patients (12 events per 1,000 patient-years of exposure). During Japanese development, serious rash or rash that led to study drug discontinuation was reported in 2% of patients (27.8 events per 1,000 patient years). Rash usually occurred early in treatment, with 85% reported within 16 weeks in the U.S. and European studies and 90% reported within two weeks in the Japanese studies.
There was no apparent relationship of dose to the occurrence of rash. Serious Hematologic Events Two confirmed cases of aplastic anemia and one confirmed case of agranulocytosis were reported in the first 11 years of marketing in Japan, rates greater than generally accepted background rates. There were no cases of aplastic anemia and two confirmed cases of agranulocytosis in the U.S., European, or Japanese development programs.
There is inadequate information to assess the relationship, if any, between dose and duration of treatment and these events. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with zonisamide. Some of these events have been fatal or life-threatening.
DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved.
It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Zonisamide should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Oligohidrosis and Hyperthermia in Pediatric Patients Oligohidrosis, sometimes resulting in heat stroke and hospitalization, is seen in association with zonisamide in pediatric patients. During the pre-approval development program in Japan, one case of…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS The most common adverse reactions with zonisamide (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration. In controlled clinical trials, 12% of patients receiving zonisamide as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received zonisamide in clinical studies discontinued treatment because of an adverse reaction.
The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were dose-related (see WARNINGS and PRECAUTIONS ) . Adverse Reaction Incidence in Controlled Clinical Trials Table 4 lists adverse reactions that occurred in at least 2% of patients treated with zonisamide in controlled clinical trials that were numerically more common in the zonisamide group.
In these studies, either zonisamide or placebo was added to the patient's current AED therapy. Table 4 Adverse Reactions in Placebo-Controlled, Add-On Trials (Events that occurred in at least 2% of zonisamide capsules-treated patients and occurred more frequently in zonisamide capsules-treated than placebo-treated patients) BODY SYSTEM/PREFERRED TERM ZONISAMIDE CAPSULES (N=269) % PLACEBO (N=230) % BODY AS A WHOLE Headache 10 8 Abdominal Pain 6 3 Flu Syndrome 4 3 DIGESTIVE Anorexia 13 6 Nausea 9 6 Diarrhea 5 2 Dyspepsia 3 1 Constipation 2 1 Dry Mouth 2 1 HEMATOLOGIS AND LYMPHATIC Ecchymosis 2 1 METABOLIC AND NUTRITIONAL Weight Loss 3 2 NERVOUS SYSTEM Dizziness 13 7 Ataxia 6 1 Nystagmus 4 2 Paresthesia 4 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-ALTERED COGNITIVE FUNCTION Confusion 6 3 Difficulty Concentrating 6 2 Difficulty with Memory 6 2 Mental Slowing 4 2 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES(NON - PSYCHOSIS- RELATED) Agitation/Irritability 9 4 Depression 6 3 Insomnia 6 3 Anxiety 3 2 Nervousness 2 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES (PSYCHOSIS - RELATED) Schizophrenic/Schizophreniform Behavior 2 0 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-CNS DEPRESSION Somnolence 17 7 Fatigue 8 6 Tiredness 7 5 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-SPEECH AND LANGUAGE ABNORMALITIES Speech Abnormalities 5 2 Difficulties in Verbal Expression 2 <1 RESPIRATORY Rhinitis 2 1 SKIN AND APPENDAGES Rash 3 2 SPECIAL SENSES Diplopia 6 3 Taste Perversion 2 0 Other Adverse Reactions in Clinical Trials Zonisamide has been administered to 1,598 individuals during all clinical trials, only some of which were placebo-controlled.
The frequencies represent the proportion of the 1,598 individuals exposed to zonisamide who experienced an event on at least one occasion. All events are included except those already listed in the previous table or discussed in WARNINGS or PRECAUTIONS , trivial events, those too general to be informative, and those not reasonably associated with zonisamide. Events are further classified within each category and listed in order of decreasing frequency as follows: frequent occurring in at least 1:100 patients; infrequent occurring in 1:100 to 1:1000 patients; rare occurring in fewer than 1:1000 patients.
Body as a Whole: Frequent: Accidental injury, asthenia. Infrequent: Chest pain, flank pain, malaise, allergic reaction, face edema, neck rigidity. Rare: Lupus erythematosus.
Cardiovascular: Infrequent: Palpitation, tachycardia, vascular insufficiency, hypotension, hypertension, thrombophlebitis, syncope, bradycardia. Rare: Atrial fibrillation, heart failure, pulmonary embolus, ventricular extrasystoles. Digestive: Frequent: Vomiting.
Infrequent: Flatulence, gingivitis, gum hyperplasia, gastritis, ga…
🔄 Drug Interactions ▾
Drug Interactions Drug Interactions with CNS Depressants: Concomitant administration of zonisamide and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants. Other Carbonic Anhydrase Inhibitors: Concomitant use of zonisamide, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., topiramate, acetazolamide or dichlorphenamide), may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation or the risk of hyperammonemia.
Therefore, if zonisamide is given concomitantly with another carbonic anhydrase inhibitor, the patient should be monitored for the appearance or worsening of metabolic acidosis (see CLINICAL PHARMACOLOGY, Interactions of Zonisamide with Other Carbonic Anhydrase Inhibitors subsection and WARNINGS, Metabolic Acidosis subsection and Hyperammonemia and Encephalopathy subsection).
🤰 Pregnancy ▾
Pregnancy: (see WARNINGS, Teratogenicity subsection): Zonisamide may cause serious adverse fetal effects, based on clinical and nonclinical data. Zonisamide was teratogenic in multiple animal species. Zonisamide treatment causes metabolic acidosis in humans.
The effect of zonisamide induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) may be associated with decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus's ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state (see WARNINGS, Metabolic Acidosis subsection). Newborns of mothers treated with zonisamide should be monitored for metabolic acidosis because of transfer of zonisamide to the fetus and possible occurrence of transient metabolic acidosis following birth.
Transient metabolic acidosis has been reported in neonates born to mothers treated during pregnancy with a different carbonic anhydrase inhibitor. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis. Fetal abnormalities or embryo-fetal deaths occurred in these species at zonisamide dosage and maternal plasma levels similar to or lower than therapeutic levels in humans, indicating that use of this drug in pregnancy entails a significant risk to the fetus.
A variety of external, visceral, and skeletal malformations was produced in animals by prenatal exposure to zonisamide. Cardiovascular defects were prominent in both rats and dogs. Following administration of zonisamide (10 mg/kg/day, 30 mg/kg/day or 60 mg/kg/day) to pregnant dogs during organogenesis, increased incidences of fetal cardiovascular malformations (ventricular septal defects, cardiomegaly, various valvular and arterial anomalies) were found at doses of 30 mg/kg/day or greater.
The low effect dose for malformations produced peak maternal plasma zonisamide levels (25 mcg/mL) about 0.5 times the highest plasma levels measured in patients receiving the maximum recommended human dose (MRHD) of 400 mg/day. In dogs, cardiovascular malformations were found in approximately 50% of all fetuses exposed to the high dose, which was associated with maternal plasma levels (44 mcg/mL) approximately equal to the highest levels measured in humans receiving the MRHD. Incidences of skeletal malformations were also increased at the high dose, and fetal growth retardation and increased frequencies of skeletal variations were seen at all doses in this study.
The low dose produced maternal plasma levels (12 mcg/mL) about 0.25 times the highest human levels. In cynomolgus monkeys, administration of zonisamide (10 mg/kg/day or 20 mg/kg/day) to pregnant animals during organogenesis resulted in embryo-fetal deaths at both doses. The possibility that these deaths were due to malformations cannot be ruled out.
The lowest embryolethal dose in monkeys was associated with peak maternal plasma zonisamide levels (5 mcg/mL) approximately 0.1 times the highest levels measured in patients at the MRHD. In a mouse embryo-fetal development study, treatment of pregnant animals with zonisamide (125 mg/kg/day, 250 mg/kg/day or 500 mg/kg/day) during the period of organogenesis resulted in increased incidences of fetal malformations (skeletal and/or craniofacial defects) at all doses tested. The low dose in this study is approximately 1.5 times the MRHD on a mg/m 2 basis.
In rats, increased frequencies of malformations (cardiovascular defects) and variations (persistent cords of thymic tissue, decreased skeletal ossification) were observed among the offspring of dams treated with zonisamide (20 mg/kg/day, 60 mg/kg/day, or 200 mg/kg/day) throughout organogenesis at all doses. The low effect dose is approximately 0.5 times the MRHD on a mg/m 2 basis. Perinatal death was increased among the offspring of rats treated with zonisamide (10 mg/…
🧒 Pediatric Use ▾
Pediatric Use The safety and effectiveness of zonisamide in children under age 16 have not been established. Acute myopia and secondary angle closure glaucoma have been reported in pediatric patients (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Cases of oligohidrosis and hyperpyrexia have been reported (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection ).
Zonisamide commonly causes metabolic acidosis in pediatric patients (see WARNINGS, Metabolic Acidosis subsection). Hyperammonemia with encephalopathy has been reported in pediatric patients (see WARNINGS, Hyperammonemia and Encephalopathy subsection). Chronic untreated metabolic acidosis in pediatric patients may cause nephrolithiasis and/or nephrocalcinosis, osteoporosis and/or osteomalacia (potentially resulting in rickets), and may reduce growth rates.
A reduction in growth rate may eventually decrease the maximal height achieved. The effect of zonisamide on growth and bone-related sequelae has not been systematically investigated.
🧓 Geriatric Use ▾
Geriatric Use Single dose pharmacokinetic parameters are similar in elderly and young healthy volunteers (see CLINICAL PHARMACOLOGY, Specific Populations subsection ). Clinical studies of zonisamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
OVERDOSAGE Human Experience Experience with zonisamide daily doses over 800 mg/day is limited. During zonisamide clinical development, three patients ingested unknown amounts of zonisamide as suicide attempts, and all three were hospitalized with CNS symptoms. One patient became comatose and developed bradycardia, hypotension, and respiratory depression; the zonisamide plasma level was 100.1 mcg/mL measured 31 hours post-ingestion.
Zonisamide plasma levels fell with a half-life of 57 hours, and the patient became alert five days later. Management No specific antidotes for zonisamide overdosage are available. Following a suspected recent overdose, emesis should be induced or gastric lavage performed with the usual precautions to protect the airway.
General supportive care is indicated, including frequent monitoring of vital signs and close observation. Zonisamide has a long half-life (see CLINICAL PHARMACOLOGY section ). Due to the low protein binding of zonisamide (40%), renal dialysis may be effective.
The effectiveness of renal dialysis as a treatment of overdose has not been formally studied. A poison control center should be contacted for information on the management of zonisamide overdosage.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Mechanism of Action The precise mechanism(s) by which zonisamide exerts its antiseizure effect is unknown. Zonisamide demonstrated anticonvulsant activity in several experimental models. In animals, zonisamide was effective against tonic extension seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol.
Zonisamide raised the threshold for generalized seizures in the kindled rat model and reduced the duration of cortical focal seizures induced by electrical stimulation of the visual cortex in cats. Furthermore, zonisamide suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human epilepsy is unknown.
Zonisamide may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that zonisamide blocks sodium channels and reduces voltage-dependent, transient inward currents (T-type Ca 2+ currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that zonisamide binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux.
Other in vitro studies have demonstrated that zonisamide (10 mcg/mL to 30 mcg/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [ 3 H]-GABA (rat hippocampal slices). Thus, zonisamide does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that zonisamide facilitates both dopaminergic and serotonergic neurotransmission.
Zonisamide is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of zonisamide is unknown. However, as a carbonic anhydrase inhibitor, zonisamide may cause metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection).
Pharmacokinetics Absorption Following a 200-400 mg oral zonisamide dose, peak plasma concentrations (range: 2 mcg/mL to 5 mcg/mL) in normal volunteers occur within 2-6 hours. In the presence of food, the time to maximum concentration is delayed; occurring at 4-6 hours, but food has no effect on the bioavailability of zonisamide. Zonisamide absorption is dose-proportional in the range of 200 mg to 400 mg.
C max and AUC, however, increase disproportionately at 800 mg, possibly due to saturable binding of zonisamide to red blood cells. Once a stable dose is reached, steady state is achieved within 14 days. Distribution The apparent volume of distribution (V/F) of zonisamide is about
1.45L/kg following a 400 mg oral dose. Zonisamide, at concentrations of 1 mcg/mL to 7 mcg/mL, is approximately 40% bound to human plasma proteins. Zonisamide extensively binds to erythrocytes, resulting in an eight-fold higher concentration of zonisamide in red blood cells than in plasma.
Protein binding of zonisamide is unaffected in the presence of therapeutic concentrations of phenytoin, phenobarbital or carbamazepine. Metabolism and Elimination Following oral administration of 14 C- zonisamide to healthy volunteers, only zonisamide was detected in plasma. Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.
Following multiple dosing, 62% of the radiolabeled dose was recovered in the urine, with 3% in the feces by day 10. Zonisamide undergoes acetylation by N-acetyl-transferases to form N-acetyl zonisamide and reduction to form the open ring metabolite, 2-sulfamoylacetyl phenol (SMAP). Of the excreted dose, 35% was recovered as zonisamide, 15% as N-acetyl zonisamide, and 50% as the glucuronide of SMAP.
Reduction of zonisamide to SMAP is mediated by cytochrome P450 isozyme 3A4 (CYP3A4). Zonis…
🧬 Mechanism of Action ▾
Mechanism of Action The precise mechanism(s) by which zonisamide exerts its antiseizure effect is unknown. Zonisamide demonstrated anticonvulsant activity in several experimental models. In animals, zonisamide was effective against tonic extension seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol.
Zonisamide raised the threshold for generalized seizures in the kindled rat model and reduced the duration of cortical focal seizures induced by electrical stimulation of the visual cortex in cats. Furthermore, zonisamide suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human epilepsy is unknown.
Zonisamide may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that zonisamide blocks sodium channels and reduces voltage-dependent, transient inward currents (T-type Ca 2+ currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that zonisamide binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux.
Other in vitro studies have demonstrated that zonisamide (10 mcg/mL to 30 mcg/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [ 3 H]-GABA (rat hippocampal slices). Thus, zonisamide does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that zonisamide facilitates both dopaminergic and serotonergic neurotransmission.
Zonisamide is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of zonisamide is unknown. However, as a carbonic anhydrase inhibitor, zonisamide may cause metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection).
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Zonisamide capsules USP, 25 mg are white to off white granular powder filled in size '4' hard gelatin capsules with pink colored cap printed with "ZA-31" in black ink and white colored body printed with "25 mg" in black ink, which are supplied as follows. NDC 72578-040-01 in bottles of 100's capsules with child-resistant closure NDC 72578-040-05 in bottles of 500's capsules Zonisamide capsules USP, 50 mg are white to off white granular powder filled in size '3' hard gelatin capsules with pink colored cap printed with "ZA-32" in black ink and white colored body printed with "50 mg" in black ink, which are supplied as follows.
NDC 72578-041-01 in bottles of 100's capsules with child-resistant closure NDC 72578-041-05 in bottles of 500's capsules Zonisamide capsules USP, 100 mg are white to off white granular powder filled in size '1' hard gelatin capsules with pink colored cap printed with "ZA-33" in black ink and white colored body printed with "100 mg" in black ink, which are supplied as follows. NDC 72578--042-01 in bottles of 100's capsules with child-resistant closure NDC 72578-042-05 in bottles of 500's capsules NDC 72578-042-10 in bottles of 1,000's capsules Storage Store at 20 o C to 25 o C (68 o F to 77 o F) [see USP Controlled Room Temperature].
Keep in dry place and protect from light. Medication Guide available at www.vionausa.com/medguides or call 1-888-304-5011. Manufactured by: Zydus Lifesciences Ltd.
Ahmedabad, India Distributed by: Viona Pharmaceuticals Inc. Cranford, NJ 07016 Rev.: 12/22
📋 Description ▾
DESCRIPTION Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The active ingredient is zonisamide, 1,2-benzisoxazole-3-methanesulfonamide. The molecular formula is C 8 H 8 N 2 O 3 S with a molecular weight of 212.23. Zonisamide, USP is a white to off white crystalline powder, pKa=10.2, and is moderately soluble in water (0.80 mg/mL) and
0.1N HCl (0.50 mg/mL). The chemical structure is: Zonisamide capsules, USP contain 25 mg or 50 mg or 100 mg zonisamide. Each capsule contains the inactive ingredients FD&C Blue #1, FD&C Red #4, gelatin, hydrogenated vegetable oil, microcrystalline cellulose, sodium lauryl sulfate, and titanium dioxide.
The capsule is imprinted with black pharmaceutical ink and contains following inactive ingredients: black iron oxide, potassium hydroxide, propylene glycol and shellac. Structured formula for Zonisamide
💬 Information for Patients ▾
Information for Patients Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking zonisamide capsules. Instruct patients to take zonisamide capsules only as prescribed. Advise patients as follows: (See Medication Guide) Zonisamide may produce drowsiness, especially at higher doses.
Patients should be advised not to drive a car or operate other complex machinery until they have gained experience on zonisamide sufficient to determine whether it affects their performance. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants. Patients should contact their physicians immediately if a skin rash develops (see WARNINGS, Serious Skin Reactions subsection).
Instruct patients to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Patients should contact their physician immediately if they develop signs or symptoms, such as sudden back pain, abdominal pain, and/or blood in the urine, that could indicate a kidney stone. Increasing fluid intake and urine output may reduce the risk of stone formation, particularly in those with predisposing risk factors for stones (see PRECAUTIONS, Kidney Stones subsection).
Patients should contact their physician immediately if a child has been taking zonisamide and is not sweating as usual with or without a fever (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection). Because zonisamide can cause hematological complications, patients should contact their physician immediately if they develop a fever, sore throat, oral ulcers, or easy bruising (see WARNINGS, Serious Hematologic Events subsection). Counsel patients and caregivers that AEDs, including zonisamide, may increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers (see WARNINGS, Suicidal Behavior and Ideation subsection). Warn patients about the possible development of hyperammonemia with or without encephalopathy. Although hyperammonemia may be asymptomatic, clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy and/or vomiting.
Instruct patients to contact their physician if they develop unexplained lethargy, vomiting, or changes in mental status (see WARNINGS, Hyperammonemia and Encephalopathy subsection) Patients should contact their physician immediately if they develop fast breathing, fatigue/tiredness, loss of appetite, or irregular heart beat or palpitations, which are possible manifestations of metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection). As with other AEDs, patients should contact their physician if they intend to become pregnant or are pregnant during zonisamide therapy.
Patients should notify their physician if they intend to breast-feed or are breast-feeding an infant (see PRECAUTIONS, Use in Nursing Mothers subsection). Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy.
To enroll, patients can call the toll-free number 1-888-233-2334 (see PRECAUTIONS , Pregnancy subsection) . Laboratory Tests In several clinical studies, zonisamide was associated with a mean increase in the concentration of serum creatinine and blood urea nitrogen (BUN) of approximately 8% over the baseline measur…
💬 Medication Guide ▾
MEDICATION GUIDE Zonisamide (zoe nis' a mide) Capsules, USP What is the most important information I should know about zonisamide? Zonisamide may cause serious side effects, including: Serious skin rash that can cause death. Serious allergic reactions that may affect different parts of the body.
Less sweating and increase in your body temperature (fever). Serious eye problems Suicidal thoughts or actions in some people. Increased level of acid in your blood (metabolic acidosis).
Problems with your concentration, attention, memory, thinking, speech, or language. Blood cell changes such as reduced red and white blood cell counts. These serious side effects are described below.
1. Zonisamide may cause a serious skin rash that can cause death. These serious skin reactions are more likely to happen when you begin taking zonisamide within the first 4 months of treatment but may occur at later times.
2. Zonisamide can cause other types of allergic reactions or serious problems that may affect different parts of the body such as your liver, kidneys, heart, or blood cells. You may or may not have a rash with these types of reactions.
These reactions can be very serious and can cause death. Call your health care provider right away if you have: • fever • severe muscle pain • rash • swollen lymph glands • swelling of your face • unusual bruising or bleeding • weakness, fatigue • yellowing of your skin or the white part of your eyes 3. Zonisamide may cause you to sweat less and to increase your body temperature (fever).
You may need to be hospitalized for this. You should watch for decreased sweating and fever, especially when it is hot and especially in children taking zonisamide. Call your health care provider right away if you have: • high fever, recurring fever, or long lasting fever • less sweat than normal 4.
Zonisamide may cause eye problems. Serious eye problems include: • sudden decrease in vision with or without eye pain and redness • a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma) These eye problems can lead to permanent loss of vision if not treated. Call your healthcare provider right away if you have any new eye symptoms, including any eye pain or redness or any new problems with your vision.
5. Like other antiepileptic drugs, zonisamide may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: • thoughts about suicide or dying • attempt to commit suicide • new or worse depression • new or worse anxiety • feeling agitated or restless • panic attacks • trouble sleeping (insomnia) • new or worse irritability • acting aggressive, being angry, or violent • acting on dangerous impulses • an extreme increase in activity and talking (mania) • other unusual changes in behavior or mood • Suicidal thoughts or actions can be caused by things other than medicines.If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
How can I watch for early symptoms of suicidal thoughts and actions? • Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. • Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms. Do not stop zonisamide without first talking to a healthcare provider.
Stopping zonisamide capsules suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus). 6.
Zonisamide capsules can increase the level of acid in your blood (metabolic acidosis). If left untreated, metabolic acidosis can cause brittle or soft bones (osteoporosis, osteomalacia, osteopenia), kidney stones and can slow the rate of growth in children. Metabolic acidosis can…