Zonisamide (zoe NIS a mide) has been approved by the FDA to treat focal-onset seizures in adults with epilepsy.

Your epilepsy treatment should always be discussed with your healthcare provider before use. Based on their judgment and knowledge, a drug may be prescribed for other epilepsy types not included in the indications. For more information, please see the prescribing information.

How can you take zonisamide? (Available formulations)

Zonisamide is available as capsules, taken whole and with or without food.

Who should not take zonisamide?

If you are allergic to zonisamide, any of the inactive ingredients, or sulfonamides (a group of drugs that are named after a specific part of their molecule), then you should not take it.

Other considerations may influence whether you should take zonisamide. Tell your healthcare provider if you:

  • have or have had depression, mood problems, or suicidal thoughts or behavior.
  • have liver problems.
  • have kidney problems.
  • have a history of metabolic acidosis (too much acid in your blood).
  • have weak, brittle bones or soft bones (osteomalacia, osteopenia, or osteoporosis).
  • have a growth problem.
  • are on a diet high in fat called a ketogenic diet.
  • have diarrhea.
  • have high blood levels of ammonia are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed.

What is important to know about taking zonisamide?

Do not stop taking zonisamide suddenly unless directed to do so by your healthcare provider.

As with all antiseizure medications, zonisamide should be withdrawn gradually to minimize the risk of causing or worsening seizures or status epilepticus. You should not stop using zonisamide suddenly unless your healthcare provider tells you to stop the medicine because of a serious side effect.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking zonisamide with certain other medicines may cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider. Especially tell your healthcare provider if you take: drugs that cause sleepiness or dizziness, or alcohol.

Boxed warning
Risk of serious rash

Zonisamide may cause life-threatening rashes including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). While not all rashes are serious, there is no way to predict which ones will become life-threatening. These serious skin reactions are more likely to happen when you begin taking zonisamide within the first 4 months of treatment but may occur at later times. Tell your healthcare provider right away if you have a skin rash, blistering or peeling of your skin, hives, or painful sores in your mouth or around your eyes, so they can decide if you should continue taking zonisamide.

Women or those who are/plan to become pregnant
Use in pregnancy

At this time, there is not enough evidence regarding developmental risks associated with the use of zonisamide in pregnant people. In animal studies, there were instances of developmental issues at clinically relevant doses. However, having a seizure during pregnancy could harm both the pregnant individual and the baby. Tell your healthcare provider right away if you become pregnant. Do not start or stop taking seizure medication during pregnancy without your healthcare provider’s advice.

If you become pregnant while taking zonisamide, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiseizure medicine during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

Use during breastfeeding

Zonisamide is present in breast milk. It is unknown if there are effects on the breastfed infant, or if zonisamide impacts milk production. Talk to your healthcare provider about the risks. Your healthcare provider will consider the developmental and health benefits of breastfeeding along with your need for zonisamide and the potential effect on the infant from zonisamide or from your epilepsy.

Effect on birth control and fertility

Zonisamide may decrease the effectiveness of hormonal contraceptives, including birth control pills, injections, implants, skin patches, and vaginal rings. To prevent pregnancy while using zonisamide, use a barrier form of birth control: condom, diaphragm, cervical cap, or contraceptive sponge.

What are the side effects of zonisamide?

Zonisamide is approved by the FDA because it is safe and effective for the majority of people who take it. However, there are risks associated with all medicines. Some side effects caused by zonisamide can be very serious, and even life-threatening. It is important to be informed about these serious reactions and to be aware of their symptoms.

Common side effects

The most common side effects that were reported in studies of zonisamide are drowsiness (somnolence), anorexia (eating disorder associated with low body weight), dizziness, problems with movement and balance (ataxia), agitation/irritability, and difficulty with memory and/or concentration.

Rare, but serious side effects
Potentially fatal reactions to sulfonamides:

Zonisamide is part of a group of drugs called sulfonamides. Fatalities have occurred, although rarely, as a result of severe reactions to sulfonamides including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fulminant hepatic necrosis (liver cell death), agranulocytosis (a disease with severe white blood cell loss), aplastic anemia (no new blood cells), and other blood dyscrasias (abnormal blood). 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.

Other serious reactions, including serious blood or liver problems

Rare but life-threatening reactions involving the immune system or multi-organ hypersensitivity, which can cause serious blood or liver problems have been reported with zonisamide use. You may or may not have a rash with these types of reactions. Call your healthcare provider right away if you experience fever, frequent infections, severe muscle pain, swelling of your face, eyes, lips, or tongue, swollen lymph glands, unusual bruising or bleeding, weakness, fatigue, yellowing of your skin, or the white part of your eyes, trouble walking or seeing, seizures happening more often, or pain/tenderness in the area toward the top of your stomach (enlarged liver/spleen).

Suicidal thoughts or behaviors

Studies have found that people who take antiseizure medications including zonisamide may have suicidal thoughts or behaviors, which occur in approximately 1 in 500 patients. If you experience any thoughts or impulses to hurt yourself, you should contact your healthcare provider immediately.

Serious hematologic events

Zonisamide can cause blood cell changes (hematologic events) such as reduced red and white blood cell counts. Call your healthcare provider if you develop fever, sore throat, sores in your mouth, or unusual bruising.

Oligohidrosis and hyperthermia in pediatric patients

Zonisamide may cause you to sweat less (oligohidrosis) and increase your body temperature (hyperthermia). You may need to be hospitalized for this. You should watch for decreased sweating and fever, especially when it is hot and especially in children taking zonisamide.

Acute myopia and secondary angle closure glaucoma

Zonisamide may cause eye problems. Serious eye problems include a sudden decrease in vision (acute myopia) with or without eye pain and redness or a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma). These eye problems can lead to permanent loss of vision if not treated. Call your healthcare provider right away if you have any new eye symptoms, including any eye pain or redness or any new problems with your vision.

Metabolic acidosis

Zonisamide can increase the level of acid in your blood (metabolic acidosis). If left untreated, metabolic acidosis can cause brittle or soft bones (osteoporosis, osteomalacia, osteopenia), kidney stones and can slow the rate of growth in children. Metabolic acidosis can happen with or without symptoms. Sometimes people with metabolic acidosis will feel tired, not feel hungry (loss of appetite), feel changes in heartbeat, or have trouble thinking clearly. Your healthcare provider should do a blood test to measure the level of acid in your blood before and during your treatment with zonisamide

Cognitive/neuropsychiatric adverse events

The use of zonisamide was frequently associated with central nervous system-related adverse events. Zonisamide may cause problems with your concentration, attention, memory, thinking, speech, or language. Call your healthcare provider right away if you have any of these symptoms: problems with mood or thinking (new or worse depression; sudden changes in mood, behavior, or loss of contact with reality, sometimes associated with hearing voices or seeing things that are not really there; feeling sleepy or tired; trouble concentrating; or speech and language problems).

Hyperammonemia and encephalopathy

Hyperammonemia (high ammonia in the body) and encephalopathy (brain malfunctions) have been reported with the use of zonisamide. Zonisamide may cause metabolic acidosis that is associated with an increased risk for developing hyperammonemia. Hyperammonemia can happen with or without symptoms.