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Zonisamide is an anti-convulsant used to control seizures in the treatment of epilepsy , a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain.


Zonisamide decreases abnormal activity and excitement within the brain that may trigger seizures. While zonisamide controls the partial seizures (focal seizures) associated with epilepsy, there is no known cure for the disease.

Some physicians have also used zonisamide in the treatment of mood disorders. As of 2004, zonisamide is additionally under study for the treatment of migraine headaches and neuropathic (nerve) pain .


In the United States, zonisamide is sold under the brand name Zonegran. Zonisamide is classified as a sulfonamide anticonvulsant. The precise mechanisms by which it works are unknown.

Recommended dosage

Zonisamide is taken by mouth in tablet form. It is prescribed by physicians in varying dosages, usually from 100 mg to 400 mg daily.

Beginning a course of treatment which includes zonisamide requires a gradual dose-increasing regimen. Adults and teenagers 16 years or older typical take 100 mg per day for the first two weeks. Daily dosages of zonisamide may then be increased 100 mg once every two weeks until reaching the full daily dose (usually not more than 400 mg.) It may take several weeks to realize the full benefits of zonisamide.

Persons should not take a double dose of anticonvulsant medications. If a daily dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped.

When discontinuing treatment with zonisamide, physicians typically direct patients to gradually reduce their daily dosages. Stopping the medicine suddenly may cause seizures to occur or become more frequent.


Persons taking zonisamide should avoid alcohol and central nervous system depressants (medications including antihistimines, sleep medications, and some pain medications). Combining these substances with zonisamide can exacerbate (heighten) the side effects of alcohol and other medications.

A physician should be consulted before taking zonisamide with certain non-perscription medications, such as medicines for asthma, appetite control, coughs, colds, sinus problems, allergies, and hay fever.

Zonisamide may inhibit perspiration, causing body temperature to increase during physical activity. Persons taking zonisamide are at a greater risk for heat stroke . Caution should be used during strenuous exercise , prolongued exposure during hot weather, and while using saunas or hot tubs.

Zonisamide may not be suitable for persons with a history of liver or kidney disease, mental illness, high blood presure, angina (chest pain), irregular heartbeats, or other heart problems.

Before beginning treatment with zonisamide, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant, or plan to become pregnant. Most physicians recommend using effective birth control while taking zonisamide, as it may cause defects to a developing fetus. Patients who become pregnant while taking zonisamide should contact their physician.

Side effects

Research indicates that zonisamide is generally well tolerated. However, it may case a variety of usually mild side effects. Headache, nausea and fatigue , and weakness are the most frequently reported side effects of zonisamide. Other possible side effects include:

  • difficulty sleeping
  • nervousness
  • anxiety
  • abdominal pain
  • difficulty with memory
  • double vision
  • loss of appetite
  • restlessness
  • drowsiness
  • diarrhea or constipation
  • indigestion
  • aching joints and muscles
  • unpleasant taste in mouth or dry mouth
  • tingling or prickly feeling on the skin

Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication. However, if any symptoms persist or become too uncomfortable, the prescribing physician should be consulted.

Other, uncommon side effects of zonisamide can be serious. A patient taking zonisamide who experiences any of the following symptoms should contact their physician:

  • rash or bluish patches on the skin
  • discouragement, feeling sad or empty
  • mood or mental changes
  • shakiness or unsteady walking
  • lack of appetite
  • kidney stones
  • difficulty breathing
  • chest pain
  • slow or irregular heartbeat
  • faintness
  • confusion or loss of consciousness
  • persistent, severe headaches
  • persistent fever or pain


Zonisamide may have negative interactions with some antifungal medications, antihistimines, antidepressants, antibiotics, and monoamine oxidase inhibitors (MAOIs). Other medications such as diazepam (Valium), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), HIV protease inhibitors (indinavir), ritonavir (Norvir), ipratropium (Atrovent), isoniazid, phenobarbital (Luminal, Solfoton), nefazodone, metronidazole, acetazolamide (Diamox), phenytoin (Dilantin), primidone , propranolol (Inderal); and rifampin (Rifadin, Rimactane) may also adversely react with zonisamide.

Zonisamide is sometimes prescribed as part of a combination of drugs to prevent seizures. The physician will carefully monitor the combination drug therapy, as sometimes zonisamide will potentite (enhance) the effects of other anticonvulsant medications.

Zonisamide may decrease the effectiveness of some forms of oral contraceptives (birth control pills).

Zonisamide should not be taken by those allergic to sulfa drugs.



Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Richmond Hill, Ontario: Firefly Books, 2001.


"Zonisamide." Medline Plus. National Library of Medicine. (March 20, 2004). <>.


Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. <>.

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. (860)586-7505. <>.

Adrienne Wilmoth Lerner

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