Medically Reviewed on 9/7/2022

Generic Name: zonisamide

Brand Names: Zonegran, Zonisade

Drug Class: Anticonvulsants, Other

What is zonisamide, and what is it used for?

Zonisamide is an anticonvulsant medication used as adjunctive therapy for partial onset seizures in people with epilepsy older than 16 years of age.

Seizures are caused by abnormal electrical activity in the brain and partial or focal seizure is a type of seizure in which the abnormal electrical activity is confined to a limited area of the brain. Zonisamide is also used off-label for binge-eating disorder, along with cognitive behavioral therapy, because it appears to suppress the appetite center in the brain.

Zonisamide reduces the duration of focal seizures, prevents seizure spread to other regions of the brain, and increases the threshold for generalized seizures. Zonisamide is more effective for the tonic (rigidity) phase than the clonic (convulsion) phase of seizures. Zonisamide stabilizes the membranes of nerve cells (neurons) and suppresses neuronal hypersynchronization by reducing the inflow of sodium and calcium currents and the action potential. Zonisamide has no effect on the neurotransmitters gamma-aminobutyric acid (GABA) or glutamate.


  • Do not use in patients with known hypersensitivity to sulfonamides, zonisamide, or any of its components. Although rare, fatal drug reactions have occurred. Reactions have included life-threatening skin reactions, multiorgan reactions, and blood disorders. Monitor the patient and discontinue zonisamide if hypersensitivity symptoms develop.
  • Zonisamide can reduce sweating and dangerously increase body temperature in pediatric patients. Zonisamide is not approved for use in children under 16 years.
  • Antiepileptic drugs including zonisamide can increase the risk of suicidal thoughts and behavior. Patients, their family and caregivers should be appropriately cautioned.
  • Abrupt discontinuation of zonisamide may increase seizure frequency or precipitate status epilepticus, a state of prolonged seizure lasting longer than 5 minutes.
  • Zonisamide causes fetal harm. Women of reproductive potential should be advised to use effective contraception.
  • May cause metabolic acidosis in certain patients. Risk factors include kidney disease, severe respiratory disease, diarrhea, status epilepticus, ketogenic diet, and some drugs.
  • Zonisamide can cause central nervous system (CNS) effects including psychiatric symptoms such as depression and psychosis, cognitive and speech problems, fatigue, and drowsiness. Patients should be cautioned to avoid performing tasks that require mental alertness.
  • Zonisamide can increase ammonia level, which is neurotoxic and may damage the brain. The risk is higher in patients with inborn metabolic errors.
  • Can cause kidney stones. Advise patients to increase water intake.
  • Can affect kidney function and increase creatinine levels and blood urea nitrogen (BUN).
  • Use zonisamide with caution in patients with impaired liver or kidney function.
  • There are reports of ophthalmic effects including acute myopia, angle closure glaucoma, ocular pain, and reduced visual acuity.

What are the side effects of zonisamide?

Common side effects of zonisamide include:

Less common side effects of zonisamide include:

Rare side effects of zonisamide include:

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

  • Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
  • Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
  • Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
  • Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.


If you have had a seizure, it means you have epilepsy. See Answer

What are the dosages of zonisamide?


  • 25 mg (Zonegran; generic)
  • 100 mg (Zonegran; generic)

Oral Suspension

  • 100 mg/5mL (Zonisade)


Partial Seizures

  • Indicated as adjunctive therapy for partial seizures
  • Initial: 100 mg orally every day
  • Increase to 200 mg/day after 2 weeks (may divide dose twice a day); may increase further by increments of 100 mg/day after a minimum of 2 weeks between adjustments; not to exceed 600 mg/day
  • Usual effective dose: 100-600 mg/day

Binge-eating Disorder (Off-label)

  • Initial: 100 mg orally every day
  • May increase by 100 mg increments every 2 weeks; not to exceed 600 mg/day (may divide every 12 hours after the first week)


Partial Seizures

  • Administer as in adults; initiate dosing at the lower end of the dosing range


Partial Seizures

Indicated as adjunctive therapy for partial seizures in adolescents aged 16 years and above

Children below 16 years

  • Safety and efficacy not established
  • Cases of oligohidrosis and hyperpyrexia have been reported

Children 16 years and above

  • Initial: 100 mg orally every day
  • Increase to 200 mg/day after 2 weeks (may divide dose twice a day); may increase further by increments of 100 mg/day after minimum of 2 weeks between adjustments; not to exceed 600 mg/day
  • Usual effective dose: 100-600 mg/day

Dosage Modifications (Adult and Pediatric)

Renal impairment

  • Titrate dose more slowly and frequently monitor
  • GFR less than 50 mL/min: Avoid use
  • Discontinue if acute renal failure develops or clinically significant sustained increase in creatinine/BUN

Hepatic impairment

  • Not studied


  • Zonisamide overdose can cause central nervous system (CNS) depression with low blood pressure (hypotension), slow heart rate (bradycardia), respiratory depression, and coma.
  • Overdose treatment includes maintenance of airway, induced vomiting, or gastric lavage to clear undigested stomach contents, and supportive care with frequent monitoring of vital signs.

What drugs interact with zonisamide?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Zonisamide has no known severe interactions with other drugs.
  • Serious interactions of zonisamide include:
    • abametapir
    • apalutamide
    • fexinidazole
    • idelalisib
    • ivosidenib
    • lonafarnib
    • metoclopramide intranasal
    • nefazodone
    • tucatinib
    • voxelotor
  • Zonisamide has moderate interactions with at least 48 different drugs.
  • Zonisamide has mild interactions with at least 73 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

  • Women of reproductive potential should use effective contraception during zonisamide therapy and for one month after discontinuation.
  • There are no adequate and well-controlled studies on use of zonisamide in pregnant women, however, animal reproductive studies show evidence of fetal malformations and loss of pregnancy.
  • Zonisamide should be used in pregnant women at the lowest effective doses, only if potential benefits to the mother outweigh potential risks to the fetus.
  • Zonisamide is known to cause metabolic acidosis. Newborn infants exposed to zonisamide should be monitored for metabolic acidosis after birth.
  • Zonisamide is present in breast milk and has potential for causing serious adverse reactions in the breastfed infant. Based on the importance of the drug to the mother, decision should be made to discontinue the drug or nursing.
  • A registry is available for women exposed to zonisamide during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or https://www.aedpregnancyregistry.org/).

What else should I know about zonisamide?

  • Take zonisamide exactly as prescribed.
  • Store zonisamide safely out of reach of children.
  • In case of overdose, seek medical help immediately or contact Poison Control.
  • Zonisamide can impair mental and physical abilities, avoid engaging in hazardous activities such as driving and operating heavy machinery until the drug effects can be determined.
  • Contact your physician immediately if you develop any of the following conditions:
  • Contact your physician if you notice your child sweating less than usual, with or without fever.
  • Zonisamide can cause kidney stones, increase your water intake during therapy. Contact your physician if you have symptoms of kidney stone, such as sudden back pain, abdominal pain or blood in urine.
  • Zonisamide may induce depression and suicidal thoughts. Seek support from family, friends and your healthcare provider if you feel depressed.
  • If you are a family member or caregiver of a patient on zonisamide therapy, be alert for signs and symptoms of depression and contact the healthcare provider if you notice unusual changes in the patient’s behavior.


Zonisamide is an anticonvulsant medication used as adjunctive therapy for partial onset seizures in people with epilepsy older than 16 years of age. Common side effects of zonisamide include drowsiness (somnolence), dizziness, headache, agitation, irritability, nausea, loss of appetite (anorexia), abdominal pain, diarrhea, indigestion (dyspepsia), constipation, vomiting, taste disorder (dysgeusia), dry mouth (xerostomia), weight loss, and others. Zonisamide causes fetal harm. Consult your doctor if pregnant, you may become pregnant, or are breastfeeding.

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Medically Reviewed on 9/7/2022