Zonisamide (Zonegran)

When is zonisamide used?

Zonisamide is used to treat partial seizures—that is, seizures that begin in a limited area of the brain, and may sometimes spread throughout the brain or “generalize”. It is approved to be used as adjunctive therapy—that is, to be added to other seizure medicine.

However it is often used “off-label” as a single seizure medication. Finally, zonisamide is often used off label, either alone or with another drug, to treat other seizure types and epilepsy syndromes, including generalized epilepsies, Lennox-Gastaut syndrome, infantile spasms and others.

Besides its use in epilepsy, when else is zonisamide used?

Although zonisamide is only approved for use in epilepsy, doctors have found that it may be helpful in patients suffering from pain syndromes and depression.

What are the most common side effects of zonisamide?

Most people who take zonisamide tolerate it without unwanted side effects. Those who experience undesirable effects most often complain of:

  • sleepiness or fatigue
  • dizziness
  • loss of appetite/weight
  • upset stomach
  • headache
  • agitation or irritability

Some less-common side effects include:

  • poor coordination or tremor
  • speech problems
  • poor concentration
  • itching
  • vision problems

If these problems do not go away within several days, or are really bothersome, call the doctor, but never stop or reduce the medicine on your own. Sometimes the doctor can help with these side effects by changing the prescription:

  • reducing the overall amount of zonisamide
  • changing the amount taken at certain times, such as taking a greater proportion of the drug at bedtime to reduce daytime sleepiness
  • prescribing smaller doses at more frequent intervals

Allergic reactions

Approximately 1 in 20 people who take zonisamide have a red rash within the first few weeks of taking it. If this happens, tell the doctor or nurse right away, to be sure that it is not the beginning of a serious problem. Although it is quite rare for the rash to be serious, no rash should be ignored as it might require a switch to a different seizure medicine.

What are the most serious side effects of zonisamide?

Serious reactions to zonisamide are very rare. However, anyone who takes this medicine should be aware of the following warning signs that might indicate the start of a serious problem:

  • Rash
  • Fever, sore throat, sores in the mouth, or easy bruising (could mean a blood problem)
  • Sudden back pain, pain in the stomach area, pain when urinating, or bloody or dark urine (could mean a kidney stone)
  • Decreased sweating or rise in body temperature, especially in a child
  • Depression
  • Unusual thoughts

If you notice mood changes with zonisamide, speak to your doctor or nurse. A slight reduction in the dosage may improve moodiness or depression. If you had a history of depression before starting zonisamide, your doctor may consider other treatments such as antidepressants or referral to a counselor or psychiatrist.


The rash may take various forms, from small red spots or blotches on the surface of the skin to large blisters. It may be preceded or accompanied by itchiness. When you first start taking zonisamide (specifically during the first 2 to 4 weeks), watch closely for any signs of a rash. Alert your doctor if you detect changes in your skin. If a rash progresses, you may develop a fever or a feeling of sickness. Occasionally, fever comes before the rash. Again, no rash should be ignored, but should be reported to the doctor or nurse immediately to make sure it is not serious and to determine the need for a change in medication.

Blood disorders

A few people have developed serious blood disorders, aplastic anemia and agranulocytosis, while taking zonisamide. The numbers are so small that not much can be said about a possible relationship, but you should tell the doctor if you develop symptoms such as fever, sores in your mouth, or easy bruising as these can be early warning signs of a more serious problem.

Kidney stones

Kidney stones occurred in about 1 in 80 people, usually after taking zonisamide for 6 to 12 months. Most people who get kidney stones have had kidney stones before. Contact your doctor immediately if you develop symptoms that could indicate a kidney stone, such as sudden back pain, abdominal pain, or blood in the urine. People who take zonisamide are encouraged to drink plenty of water as this might reduce the risk of stone formation.

Decreased sweating

Decreased sweating is a rare but serious side effect that has been reported in children. This is most common in the summer heat, and can lead to high body temperature, and even heatstroke. Parents are cautioned to watch their children, make sure they drink plenty of fluids, and avoid excessive heat.

Depression or psychosis

Tell your doctor if you feel depressed or have unusual thoughts while taking zonisamide.

A complete list of all reactions to zonisamide can be found in the package insert, but it is important to remember that only a tiny number of people have any of these serious problems.

Who should not take zonisamide?

The only people who definitely should not take zonisamide are those who are allergic to it or to other medicines in the same family, called sulfonamides. If you have ever been told that you are allergic to sulfa drugs (such as Bactrim or Septra), you should not take zonisamide, or take it only after carefully discussing it with your doctor.

Because zonisamide is metabolized in the liver and eliminated in the urine, people with liver and kidney disease use zonisamide with caution. The dosage may have to be increased more slowly.

People with a history of kidney stones should probably avoid zonisamide.

Can zonisamide be taken with other medicines?

Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.

Your body gets rid of zonisamide more quickly if you are also taking certain other seizure medicines, such as:

  • carbamazepine (Tegretol, Tegretol XR, Carbatrol)
  • phenobarbital
  • primidone (Mysoline)
  • phenytoin (Dilantin, Phenytek)

If this applies to you, your doctor may plan to give you more zonisamide than you would otherwise take.

If a woman takes zonisamide during pregnancy,
will it hurt the baby?

In the United States, the Food and Drug Administration (FDA) assigns each medication to a Pregnancy Category according to whether it has been proven to be harmful in pregnancy. Zonisamide is listed in Pregnancy Category C. This indicates that caution is advised, but the benefits of the medicine may outweigh the potential risks. Studies in animals have shown some harm to the baby, but there have been no good studies in women.

Talk to your doctor or another health professional if you are pregnant or plan to become pregnant. There is not yet enough information available to estimate the risk of birth defects if zonisamide is taken during pregnancy. Nor is enough known to compare the risk with zonisamide to the risk with other seizure medicines. In general, the risk of defects is higher for women who take more than one seizure medicine and for women with a family history of birth defects.

All women who are capable of becoming pregnant should take at least 0.4 mg (400 mcg) of the vitamin called folic acid every day because it helps to prevent specific birth defects called Neural Tube Defects. (The most well-known of these is spina bifida, in which the spinal cord is not completely enclosed.) Women with epilepsy should take between 1 and 4 mg of folic acid daily during their reproductive years. If the doctor thinks a woman is at especially high risk, the larger dose of folic acid—4 mg (4000 mcg) per day—may be recommended, beginning before the woman becomes pregnant.

Some babies born to mothers taking antiepileptic medications have had inadequate blood clotting within the first 24 hours after birth. It is often recommended that the mother be given 10 to 20 mg of vitamin K per day during the last month of pregnancy to prevent this problem.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their seizure medicine is handled by the body. Even though this may not apply to zonisamide, the doctor may recommend checking the level of medication in the blood regularly during pregnancy so that the dosage can be adjusted as needed.

About 50% of zonisamide in the mother’s bloodstream passes into breast milk, however how much of this actually enters the baby’s bloodstream is not known. Further, how zonisamide affects the baby is unknown. That said, it is strongly felt by neurologists and epileptologists that the benefits of breastfeeding largely outweigh the risks of exposing the baby to antiepileptic medications, including zonisamide. As a matter of fact, the American Academy of Neurology and the American Epilepsy Society both recommend breastfeeding in women with epilepsy.