Loading…
Zonisamide is a brand name for Zonisamide. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: INDICATIONS AND USAGE Zonisamide capsules are indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.
Verbatim from this product's FDA label. Tap a section to expand.
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 ).
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.
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. , 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.
, European, or Japanese development programs. S. 2%) zonisamide patients discontinued treatment because of rash compared to none on placebo. S. 4% of patients (12 events per 1,000 patient-years of exposure). 8 events per 1,000 patient years).
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.
CONTRAINDICATIONS
Zonisamide capsules are contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in United States of America? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
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, gastroenteritis, stomatitis, cholelithiasis, glossitis, melena, rectal hemorrhage, ulcerative stomatitis, gastro-duodenal ulcer, dysphagia, gum hemorrhage.
Rare:
Cholangitis, hematemesis, cholecystitis, cholestatic jaundice, colitis, duodenitis, esophagitis, fecal incontinence, mouth ulceration.
Hematologic and Lymphatic:
Infrequent: Leukopenia, anemia, immunodeficiency, lymphadenopathy.
Rare:
Thrombocytopenia, microcytic anemia, petechia.
Metabolic and Nutritional:
Infrequent: Peripheral edema, weight gain, edema, thirst, dehydration.
Rare:
Hypoglycemia, hyponatremia, lactic dehydrogenase increased, SGOT increased, SGPT increased.
Musculoskeletal:
Infrequent: Leg cramps, myalgia, myasthenia, arthralgia, arthritis.
Nervous System:
Frequent: Tremor, convulsion, abnormal gait, hyperesthesia, incoordination.
Infrequent:
Hypertonia, twitching, abnormal dreams, vertigo, libido decreased, neuropathy, hyperkinesia, movement disorder, dysarthria, cerebrovascular accident, hypotonia, peripheral neuritis, reflexes increased.
Rare:
Dyskinesia, dystonia, encephalopathy, facial paralysis, hypokinesia, hyperesthesia, myoclonus, oculogyric crisis.
Behavioral Abnormalities -Non-Psychosis-Related:
Infrequent: Euphoria.
Respiratory:
Frequent: Pharyngitis, cough increased.
Infrequent:
Dyspnea.
Rare:
Apnea, hemoptysis.
Skin and Appendages:
Frequent: Pruritus.
Infrequent:
Maculopapular rash, acne, alopecia, dry skin, sweating, eczema, urticaria, hirsutism, pustular rash, vesiculobullous rash.
Special Senses:
Frequent: Amblyopia, tinnitus.
Infrequent:
Conjunctivitis, parosmia, deafness, visual field defect, glaucoma.
Rare:
Photophobia, iritis.
Urogenital:
Infrequent: Urinary frequency, dysuria, urinary incontinence, hematuria, impotence, urinary retention, urinary urgency, amenorrhea, polyuria, nocturia.
Rare:
Albuminuria, enuresis, bladder pain, bladder calculus, gynecomastia, mastitis, menorrhagia. POST MARKETING EXPERIENCE The following serious adverse reactions have been reported since approval and use of zonisamide capsules worldwide.
These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, rhabdomyolysis, increased creatine phosphokinase, drug reaction with eosinophilia and systemic symptoms (DRESS), acute myopia and secondary angle closure glaucoma, and hyperammonemia and encephalopathy (see WARNINGS ).
To report SUSPECTED ADVERSE REACTIONS, contact Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088.
, 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. , 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 oligohidrosis was reported in 403 pediatric patients, an incidence of 1 case per 285 patient - years of exposure. S. or European development programs, fewer than 100 pediatric patients participated in these trials.
In the first 11 years of marketing in Japan, 38 cases were reported, an estimated reporting rate of about 1 case per 10,000 patient-years of exposure. , 2 cases were reported, an estimated reporting rate of about 12 cases per 10,000 patient-years of exposure.
These rates are underestimates of the true incidence because of under-reporting. S. Decreased sweating and an elevation in body temperature above normal characterized these cases. Many cases were reported after exposure to elevated environmental temperatures.
Heat stroke, requiring hospitalization, was diagnosed in some cases. There have been no reported deaths. Pediatric patients appear to be at an increased risk for zonisamide-associated oligohidrosis and hyperthermia. Patients, especially pediatric patients, treated with zonisamide should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather.
Caution should be used when zonisamide is prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, carbonic anhydrase inhibitors and drugs with anticholinergic activity.
The practitioner should be aware that the safety and effectiveness of zonisamide in pediatric patients have not been established, and that zonisamide is not approved for use in pediatric patients. Acute Myopia and Secondary Angle Closure Glaucoma Acute myopia and secondary angle closure glaucoma have been reported in patients receiving zonisamide.
Elevated intraocular pressure can lead to serious sequelae, including permanent vision loss, if left untreated. Symptoms in reported cases have included acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure.
Mydriasis may or may not be present. This syndrome may be associated with ciliochoroidal effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within one month after initiating zonisamide therapy.
In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with zonisamide has been reported both in pediatric patients and in adults. The primary treatment to reverse symptoms is discontinuation of zonisamide as rapidly as possible, according to the judgment of the treating physician.
Other therapeutic measures, in conjunction with discontinuation of zonisamide, may be helpful. Myopia and secondary angle closure glaucoma usually resolve or improve after discontinuation of zonisamide. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including zonisamide, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.
Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. 7) of suicidal thinking or behavior compared to patients randomized to placebo.
24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.
The risk did not vary substantially by age (5 years to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. 9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing zonisamide or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and 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, Cognitive/Neuropsychiatric Adverse Events subsection below). , decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) (see PRECAUTIONS , Laboratory Tests subsection).
This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase. Generally, zonisamide-induced metabolic acidosis occurs early in treatment, but it can develop at any time during treatment.
Metabolic acidosis generally appears to be dose-dependent and can occur at doses as low as 25 mg daily. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or specific drugs) may be additive to the bicarbonate lowering effects of zonisamide.
Some manifestations of acute or chronic metabolic acidosis include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated, metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis.
Nephrolithiasis has been observed in the clinical development program in 4 % of adults treated with zonisamide, has also been detected by renal ultrasound in 8 % of pediatric treated patients who had at least one ultrasound prospectively collected, and was reported as an adverse event in 3 % (4/133) of pediatric patients (see PRECAUTIONS , Kidney Stones subsection).
Metabolic acidosis can also increase the risk for hyperammonemia, particularly in the presence of drugs which can cause hyperammonemia. Chronic, untreated metabolic acidosis may result in osteomalacia (referred to as rickets in pediatric patients) and/or osteoporosis with an increased risk for fracture.
Of potential relevance, zonisamide treatment was associated with reductions in serum phosphorus and increases in serum alkaline phosphatase, changes that may be related to metabolic acidosis and osteomalacia (see PRECAUTIONS , Laboratory Tests subsection).
Chronic, untreated metabolic acidosis in pediatric patients 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.
Measurement of baseline and periodic serum bicarbonate during treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (using dose tapering).
If the decision is made to continue patients on zonisamide in the face of persistent acidosis, alkali treatment should be considered. Serum bicarbonate was not measured in the adjunctive controlled trials of adults with epilepsy. However, serum bicarbonate was studied in three clinical trials for indications which have not been approved: a placebo-controlled trial for migraine prophylaxis in adults, a controlled trial for monotherapy in epilepsy in adults, and an open label trial for adjunctive treatment of epilepsy in pediatric patients (3 years to 16 years).
In adults, mean serum bicarbonate reductions ranged from approximately 2 mEq/L at daily doses of 100 mg to nearly 4 mEq/L at daily doses of 300 mg. In pediatric patients, mean serum bicarbonate reductions ranged from approximately 2 mEq/L at daily doses from above 100 mg up to 300 mg, to nearly 4 mEq/L at daily doses from above 400 mg up to 600 mg.
In two controlled studies in adults, the incidence of a persistent treatment-emergent decrease in serum bicarbonate to less than 20 mEq/L (observed at 2 or more consecutive visits or the final visit) was dose-related at relatively low zonisamide doses.
In the monotherapy trial of epilepsy, the incidence of a persistent treatment-emergent decrease in serum bicarbonate was 21% for daily zonisamide doses of 25 mg or 100 mg, and was 43% at a daily dose of 300 mg. In a placebo-controlled trial for prophylaxis of migraine, the incidence of a persistent treatment-emergent decrease in serum bicarbonate was 7% for placebo, 29% for 150 mg daily, and 34% for 300 mg daily.
The incidence of persistent markedly abnormally low serum bicarbonate (decrease to less than 17 mEq/L and more than 5 mEq/L from a pretreatment value of at least 20 mEq/L) in these controlled trials was 2% or less. In the pediatric study, the incidence of persistent, treatment-emergent decreases in serum bicarbonate to levels less than 20 mEq/L was 52% at doses up to 100 mg daily, was 90% for a wide range of doses up to 600 mg daily, and generally appeared to increase with higher doses.
The incidence of a persistent markedly abnormally low serum bicarbonate value was 4 % at doses up to 100 mg daily, was 18% for a wide range of doses up to 600 mg daily, and generally appeared to increase with higher doses. Some patients experienced moderately severe serum bicarbonate decrements down to a level as low as 10 mEq/L.
The relatively high frequencies of varying severities of metabolic acidosis observed in this study of pediatric patients (compared to the frequency and severity observed in various clinical trial development programs in adults) suggest that pediatric patients may be more likely to develop metabolic acidosis than adults.
Seizures on Withdrawal As with other AEDs, abrupt withdrawal of zonisamide in patients with epilepsy may precipitate increased seizure frequency or status epilepticus. Dose reduction or discontinuation of zonisamide should be done gradually.
Teratogenicity Women of child bearing potential who are given zonisamide should be advised to use effective contraception. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis.
A variety of fetal abnormalities, including cardiovascular defects, and embryo-fetal deaths occurred at maternal plasma levels similar to or lower than therapeutic levels in humans. These findings suggest that the use of zonisamide during pregnancy in humans may present a significant risk to the fetus (see PRECAUTIONS, Pregnancy subsection ).
Zonisamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Cognitive/ Neuropsychiatric Adverse Events Use of zonisamide was frequently associated with central nervous system-related adverse events.
The most significant of these can be classified into three general categories: 1) psychiatric symptoms, including depression and psychosis, 2) psychomotor slowing, difficulty with concentration, and speech or language problems, in particular, word-finding difficulties, and 3) somnolence or fatigue.
4% of placebo patients. 0% were hospitalized because of reported depression or suicide attempts. 2% of patients discontinued zonisamide or were hospitalized due to psychosis or psychosis-related symptoms compared to none of the placebo patients.
4% were hospitalized because of reported psychosis or related symptoms. Psychomotor slowing and difficulty with concentration occurred in the first month of treatment and were associated with doses above 300 mg/day. Speech and language problems tended to occur after 6 to 10 weeks of treatment and at doses above 300 mg/day.
Although in most cases these events were of mild to moderate severity, they at times led to withdrawal from treatment. Somnolence and fatigue were frequently reported CNS adverse events during clinical trials with zonisamide. 2% of the patients enrolled in controlled trials.
Somnolence and fatigue tended to occur within the first month of treatment. Somnolence and fatigue occurred most frequently at doses of 300 mg/day to 500 mg/day. Patients should be cautioned about this possibility and special care should be taken by patients if they drive, operate machinery, or perform any hazardous task.
Hyperammonemia and Encephalopathy Hyperammonemia and encephalopathy have been reported with the postmarketing use of zonisamide. Zonisamide treatment inhibits carbonic anhydrase activity, which may cause metabolic acidosis that is associated with an increased risk for developing hyperammonemia.
Hyperammonemia resulting from zonisamide can also be asymptomatic. The risks of hyperammonemia and various manifestations of encephalopathy may be increased in patients treated with zonisamide and concomitantly taking other medications that can cause hyperammonemia, including valproic acid or topiramate (see PRECAUTIONS ).
Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy and this risk may be increased by zonisamide use. , unexplained change in mental status, vomiting, or lethargy) of encephalopathy occur.
Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued. Hyperammonemia from zonisamide may resolve or decrease in severity with a decrease of the daily dose.