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Zonisamide Side Effects

For the Consumer

Applies to zonisamide: oral capsule, oral tablet

As well as its needed effects, zonisamide may cause unwanted side effects that require medical attention.

Severity: Major

If any of the following side effects occur while taking zonisamide, check with your doctor immediately:

More common:
  • Discouragement
  • feeling sad or empty
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • mood or mental changes
  • shakiness or unsteady walking
  • tiredness
  • trouble with concentrating
  • trouble with sleeping
Less common:
  • Agitation
  • bruising
  • delusions
  • hallucinations
  • large, flat blue or purplish patches on the skin
  • rash

If any of the following symptoms of overdose occur while taking zonisamide, get emergency help immediately:

Symptoms of overdose:
  • Difficult or labored breathing
  • faintness
  • loss of consciousness
  • slow or irregular heartbeat

Severity: Minor

Some zonisamide side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:
  • Abdominal or stomach pain
  • anxiety
  • difficulty with memory
  • dizziness
  • double vision
  • headache
  • loss of appetite
  • nausea
  • restlessness
  • sleepiness
  • sleeplessness
  • unusual drowsiness
  • unusual tiredness or weakness
Less common:
  • Aching muscles or joints
  • acid or sour stomach
  • bad, unusual, or unpleasant taste in the mouth
  • belching
  • change in taste
  • chills
  • constipation
  • diarrhea
  • difficulty with speaking
  • difficulty with thinking
  • dry mouth
  • fever
  • general ill feeling
  • headache
  • heartburn
  • indigestion
  • mental slowness
  • nervousness
  • runny or stuffy nose
  • sneezing
  • tingling, burning, or prickly feelings on the skin
  • uncontrolled, back and forth, or rolling eye movements
  • weight loss

For Healthcare Professionals

Applies to zonisamide: oral capsule


General side effects have included somnolence (17%), headache (10%), fatigue (8%), tiredness (7%), abdominal pain (6%), and flu syndrome (4%).[Ref]


Gastrointestinal side effects have included anorexia (13%), nausea (9%), diarrhea (5%), dyspepsia (3%), constipation (2%), and dry mouth (2%).[Ref]

Nervous system

Nervous system side effects have included dizziness (13%), ataxia (6%), nystagmus (4%), and paresthesia (4%). A case of restless legs syndrome has also been reported.[Ref]


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.

Reports have shown pediatric patients to be at an increased risk for zonisamide-associated oligohidrosis and hyperthermia.[Ref]

Other side effects have included speech abnormalities (5%), difficulties in verbal expression (2%), taste perversion (2%), and visual hallucinations.[Ref]


Two cases of zonisamide induced behavior disorders have been reported in children with plasma levels within or below the therapeutic range. A case of zonisamide induced mania has been reported.[Ref]

Psychiatric side effects have included agitation/irritability (9%), confusion (6%), difficulty concentrating (6%), difficulty with memory (6%), depression (6%), insomnia (6%), mental slowing (4%), anxiety (3%), nervousness (2%), and schizophrenic/schizophreniform behavior (2%). A case of zonisamide-induced mania has also been reported.[Ref]


Ocular side effects have included diplopia (6%).[Ref]


Dermatologic side effects have included rash (3%). A case of toxic epidermal necrolysis has also been reported.[Ref]


Zonisamide can cause metabolic acidosis, characterized by hyperchloremia and decreased serum bicarbonate. Metabolic acidosis is often asymptomatic.

Generally, zonisamide-induced metabolic acidosis occurs early in treatment, but may occur at any time during treatment.

The risk of development of zonisamide-induced metabolic acidosis appears to be greater at higher doses of zonisamide, but can occur with doses as low as 25 mg daily.

Conditions or therapies that may predispose patients to acidosis include renal disease, severe respiratory disorders, diarrhea, surgery, ketogenic diet, or other drugs (e.g. acetazolamide)

Signs and symptoms of persistent metabolic acidosis may include hyperventilation, fatigue and anorexia. More severe symptoms may include cardiac arrhythmias and stupor.

Chronic, untreated metabolic acidosis may increase the risk for kidney stones, nephrocalcinosis, and bone abnormalities (e.g., osteoporosis, osteomalacia, and rickets in pediatric patients) with an increased risk for fractures.

A pretreatment (baseline) and periodic measurements of serum bicarbonate are recommended during zonisamide treatment. In addition, if signs or symptoms of metabolic acidosis are observed, serum bicarbonate should be measured.[Ref]

Metabolic side effects have included weight loss (3%), metabolic acidosis and postmarketing reports of elevated creatine phosphokinase.[Ref]


Hematologic side effects have included ecchymosis (2%).[Ref]


Respiratory side effects have included rhinitis (2%).[Ref]


Endocrine side effects have included postmarketing reports of acute pancreatitis.


Musculoskeletal side effects have included postmarketing reports of rhabdomyolysis.


1. "Product Information. Zonegran (zonisamide)" Elan Pharmaceuticals, S. San Francisco, CA.

2. Chen JT, Garcia PA, Alldredge BK "Zonisamide-induced restless legs syndrome." Neurology 60 (2003): 147

3. Akman CI, Goodkin HP, Rogers DP, Riviello JJ Jr "Visual hallucinations associated with zonisamide." Pharmacotherapy 23 (2003): 93-6

4. Shimizu T, Yamashita Y, Satoi M, Togo A, Wada N, Matsuishi T, Ohnishi A, Kato H "Heat stroke-like episode in a child caused by zonisamide." Brain Dev 19 (1997): 366-8

5. Kimura S "Zonisamide-induced behavior disorder in two children." Epilepsia 35 (1994): 403-5

6. Sullivan KL, Ward CL, Zesiewicz TA "Zonisamide-induced Mania in an Essential Tremor Patient." J Clin Psychopharmacol 26 (2006): 439-40

7. Charles CL, Stoesz L, Tollefson G "Zonisamide-induced mania." Psychosomatics 31 (1990): 214-7

8. Majeres KD, Suppes T "A Cautionary Note When Using Zonisamide in Youths: A Case Report of Association With Toxic Epidermal Necrolysis." J Clin Psychiatry 65 (2004): 1720

It is possible that some side effects of zonisamide may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.