Zonisamide

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Contraindications

Hypersensitivity to zonisamide or sulfonamides

Cautions

Maintain fluid intake due to risk of kidney stone formation

Discontinue treatment if significant sustained increase in creatinine occurs

Risk of serious skin reactions; consider discontinuation in patients who develop unexplained rash

Sedation may occur

Slowing and fatigue may occur within first month of treatment

Risk of rare, but potentially fatal, anaphylactic reactions (including blood dyscrasias and skin reactions)

Risk of metabolic acidosis

Use appropriate precautions for handling and disposal

Increase in suicidal ideation may occur with use; see FDA Warning on potential suicidal behavior

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity reported; early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash not evident; if such signs or symptoms present, evaluate immediately; discontinue therapy if an alternative etiology for signs or symptoms cannot be established

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Cordarone or Pacerone (amiodarone)
• Antifungals, such as Sporanox (itraconazole) or Nizoral (ketoconazole)
• Carbonic anhydrase inhibitors, such as Diamox (acetazolamide) or Neptazane (methazolamide)
• Biaxin (clarithromycin) or Prevpac (lansoprazole, amoxicillin, and clarithromycin)
• Cardizem, Dilacor, or Tiazac (diltiazem)
• E.E.S., E-Mycin, or Erythrocin (erythromycin)
• Luvox (fluvoxamine)
• HIV protease inhibitors, such as Crixivan (indinavir), Viracept (nelfinavir), Norvir (ritonavir), or Kaletra (lopinavir and ritonavir)
• Medications for irritable bowel disease, motion sickness, Parkinson's disease, ulcers, or urinary problems
• Other medications for seizures, such as Carbatrol, Epitol, or Tegretol (carbamazepine), Luminal or Solfoton (phenobarbital), Dilantin or Phenytek (phenytoin), or Depakene or Depakote (valproic acid)
• Serzone (nefazodone)
• Hormonal contraceptives (birth control pills, patches, rings, and injections)
• Actos (pioglitazone), Actoplus MET (pioglitazone and metformin), or Duetact (pioglitazone and glimepiride)
• Mycobutin (rifabutin)
• Rifadin or Rimactane (rifampin)
• St. John's wort
• Calan, Covera, Isoptin, or Verelan (verapamil)
• TAO (troleandomycin — not available in the United States)

Zonisamide and Other Interactions

Zonisamide may cause drowsiness, dizziness, or vision problems. Don't drive or perform any activity that requires alertness until you know how this medicine affects you.

Zonisamide and Alcohol

Alcohol may worsen certain side effects of zonisamide. Talk to your doctor before drinking alcohol while taking this medicine.

Zonisamide and Grapefruit

Grapefruit and grapefruit juice may interact with the way zonisamide is absorbed in the body.

Talk to your doctor about this potential interaction.

• Seizure (Epilepsy)

Zonisamide may cause serious side effects, including:

1. Serious skin rash that can cause death.
2. Less sweating and increase in your body temperature (fever).
3. Suicidal thoughts or actions in some people.
4. Increased level of acid in your blood (metabolic acidosis).
5. Problems with your concentration, attention, memory, thinking, speech, or language.
6. Blood cell changes such as reduced red and white blood cell counts.

These serious side effects are described below.

1. Zonisamide may cause a serious skin rash that can cause death. 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.
2. Zonisamide may cause you to sweat less and to increase your body temperature (fever). 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.
   Call your health care provider right away if you have:
   • a skin rash
   • high fever, recurring fever, or long lasting fever
   • less sweat than normal
3. Like other antiepileptic drugs, Zonisamide may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
   Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
   • thoughts about suicide or dying
   • attempt to commit suicide
   • new or worse depression
   • new or worse anxiety
   • feeling agitated or restless
   • panic attacks
   • trouble sleeping (insomnia)
   • new or worse irritability
   • acting aggressive, being angry, or violent
   • acting on dangerous impulses
   • an extreme increase in activity and talking (mania)
   • other unusual changes in behavior or mood
   • Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
   How to watch for early symptoms of suicidal thoughts and actions:
   • Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
   • Keep all follow-up visits with your healthcare provider as scheduled.
   Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
   Do not stop zonisamide without first talking to a healthcare provider.
   Stopping zonisamide suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
4. 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
   • 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.
5. Zonisamide may cause problems with your concentration, attention, memory, thinking, speech, or language.
6. Zonisamide can cause blood cell changes 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.

Zonisamide can have other serious side effects. For more information ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effect that bothers you.

• Do not take zonisamide if you are allergic to medicines that contain sulfa.
• Do not drink alcohol or take other drugs that make you sleepy or dizzy while taking zonisamide until you talk to your health care provider. Zonisamide taken with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how zonisamide affects you. Zonisamide can slow your thinking and motor skills.

Grapefruit and grapefruit juice may interact with zonisamide and lead to potentially dangerous effects. Discuss the use of grapefruit products with your healthcare provider.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your kidney function

The recommended dose range of zonisamide for the treatment of partial seizures in adults is 100mg-400mg/day.

You should not use this medicine if you are allergic to zonisamide.

You may not be able to take zonisamide if you have ever had a severe allergic to a sulfa drug.

To make sure zonisamide is safe for you, tell your doctor if you have:

• liver disease;

• kidney disease;

• stomach flu or illness causing diarrhea;

• a growth disorder;

• a bone disorder that causes soft or weak bones or low bone mineral density;

• a history of depression, or suicidal thoughts or actions;

• if you have ever had metabolic acidosis (too much acid in your blood); or

• if you have been on a ketogenic diet (high-fat, high-protein, low-carb).

You may have thoughts about suicide while taking this medicine. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

In animal studies, zonisamide caused birth defects and infant death. It is not known whether these effects would occur in people taking doses recommended for humans. Ask your doctor about your personal risk. Use effective birth control to prevent pregnancy while you are taking zonisamide.

If you are already pregnant, do not start or stop taking zonisamide during pregnancy without your doctor's advice. Zonisamide can cause metabolic acidosis, which could harm an unborn baby. However, having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking zonisamide.

Zonisamide can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Zonisamide is not approved for use by anyone younger than 18 years old.

Seizure Disorders

Management (in combination with other anticonvulsants) of partial seizures in adults with epilepsy.1 2 3 8

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For zonisamide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to zonisamide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of zonisamide in children younger than 16 years. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of zonisamide have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of zonisamide in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving zonisamide.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking zonisamide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using zonisamide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Methenamine

Using zonisamide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Calcifediol
• Orlistat

Using zonisamide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminolevulinic Acid
• Ginkgo

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of zonisamide. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood or bone marrow problems (eg, agranulocytosis, aplastic anemia) or
• Depression, history of or
• Mental illness (eg, psychosis) or
• Metabolic acidosis (high acid in the blood)—Use with caution. May make these conditions worse.

• Breathing or lung problems, severe or
• Diarrhea or
• Ketogenic diet, history of—Use with caution. May cause side effects to become worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Zonegran

• Anticonvulsant, Miscellaneous

Renal clearance decreases with decreased renal function. Marked renal impairment (CrCl less than 20 mL/minute) was associated with an increase in AUC of 35%.

Less than 16 years of age: Not recommended
16 years of age and older: See adult dosing

Because this drug and its metabolites are excreted by the kidneys, patients with renal disease should be treated with caution, and might require slower titration and more frequent monitoring. Therapy should be discontinued in patients who develop acute renal failure or where a clinically significant sustained increase in serum creatinine is observed.