Zonegran Side Effects

Generic Name: zonisamide

Note: This document contains side effect information about zonisamide. Some of the dosage forms listed on this page may not apply to the brand name Zonegran.

Some side effects of Zonegran may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to zonisamide: oral capsule, oral tablet

Along with its needed effects, zonisamide (the active ingredient contained in Zonegran) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking zonisamide:

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

Get emergency help immediately if any of the following symptoms of overdose occur while taking zonisamide:

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

Some side effects of zonisamide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions 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%).


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

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.


Patients (especially pediatric patients) treated with zonisamide (the active ingredient contained in Zonegran) 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.

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


Two cases of zonisamide (the active ingredient contained in Zonegran) 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.

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.


Ocular side effects have included diplopia (6%).


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


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 (the active ingredient contained in Zonegran) 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.

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


Hematologic side effects have included ecchymosis (2%).


Respiratory side effects have included rhinitis (2%).


Endocrine side effects have included postmarketing reports of acute pancreatitis.


Musculoskeletal side effects have included postmarketing reports of rhabdomyolysis.

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