Zonisamide dosage, forms, and strengths

Zonisamide, a generic anticonvulsant, is a safe and effective maintenance treatment for partial seizures. It’s commonly used in combination with other drug treatments. Doses are taken by mouth once or twice a day as a capsule or liquid, providing a reliable option for seizure control. 

2.8 million people (1 in 100) in the U.S. have some form of seizure disorder. The incidence is about 150,000 new cases per year. Of those people diagnosed with epilepsy, 46% are diagnosed with partial seizures. 

Zonisamide forms and strengths

Most people will take zonisamide in capsule form, which is available as a generic or under the brand name Zonegran. Those with difficulty swallowing capsules can take a liquid formulation, also available under the brand name Zonisamide.

• Capsules: 25 mg, 50 mg, 100 mg

• Oral suspension (liquid): 100 mg/5 mL

Zonisamide dosage for adults

The Food and Drug Administration (FDA) has approved zonisamide as an adjunctive treatment for partial seizures in adults and teens 16 years of age and older. Due to medical safety concerns, healthcare providers do not prescribe zonisamide to individuals with a history of allergies to zonisamide or sulfonamide drugs.

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Zonisamide dosage for partial seizures

Partial seizures (focal seizures) affect a specific area or one hemisphere of the brain. Unlike generalized seizures, which involve both sides of the brain and often lead to loss of consciousness, partial seizures typically do not cause a complete loss of awareness. However, they may result in impairment during the episode. 

Prevalence of Partial Seizures

2.8 million people (1 in 100) in the U.S. have some form of seizure disorder. The incidence is about 150,000 new cases per year. Of those people diagnosed with epilepsy, 46% are diagnosed with partial seizures. 

Types of Patial Seizeures

Partial seizures can be simple or complex. Most people with partial seizures have complex partial seizures, which start in one part of the brain and spread to another. People usually experience some impairment of consciousness. After the seizure, people need a few minutes or longer before they feel normal again. 

A minority of people with partial seizures have simple partial seizures. These are seizures that start and stay in one part of the brain. They don’t involve changes in consciousness or require a recovery period after the seizure.

Treatment Approach for Partial Seizures

First-line treatment: The standard first-line treatments for partial seizures are the anticonvulsants carbamazepine and lamotrigine. Many people achieve seizure control with a single medication. 

Refractory Seizures: If, however, seizures continue to occur (“refractory” seizures), healthcare providers will add a second drug called an adjunctive (“add-on”) or adjuvant (“helper”) treatment. 

Zonisamide is one possible choice in that group of second-line adjuvant therapies. 

Zonisamide's unique mechanism of action, which involves blocking the sodium and calcium channels that make nerves electrically conductive, sets it apart from other antiepileptic drugs. This unique action slows the nervous system and effectively controls seizures, with minimal side effects compared to other drugs. 

As an adjunctive therapy for partial seizures, zonisamide is taken once or twice daily. Doses start at a lower dose of 100 mg daily and are gradually increased until seizures are controlled. Although the maximum recommended dosage is 600 mg daily, there is no evidence that daily doses above 400 mg are beneficial.

• Standard dosage for the adjunctive treatment of partial seizures: 100–600 mg taken in a single dose or two divided doses daily

• Maximum dosage for the adjunctive treatment of partial seizures: 600 mg daily

Zonisamide dosage for children

The FDA has not approved zonisamide tablets for pediatric use. However, zonisamide oral suspension is FDA-approved for use in adolescents 16 years and older. The dosages are identical to those for adults.

• Standard zonisamide dosage for the adjunctive treatment of partial seizures in children 16 years of age and older: 100–600 mg taken in a single dose or two divided doses daily

• Maximum zonisamide dosage for the adjunctive treatment of partial seizures in children 16 years of age and older: 600 mg daily

Zonisamide dosage restrictions

Kidney or Liver Disease

Healthcare providers do not need to adjust doses for people with kidney, liver, or other medical conditions. However, there is a risk of side effects in people with kidney or liver impairment. In those cases, prescribers may start with a lower dose and slowly increase it (titration). Because of the increased risk of side effects, they will monitor people with renal or hepatic impairment more closely.

Zonisamide dosage for pets

Veterinarians use zonisamide as a maintenance treatment for epilepsy in dogs and cats. They may prescribe it as a stand-alone therapy or add-on treatment to other seizure medications.

Cats are usually given daily doses of 5–10 mg per kilogram of body weight. Dogs are usually prescribed 5 mg/kg daily, but veterinarians double the dose if the dog is also being given phenobarbital for seizure control. 

Zonisamide is a safe drug for pets. Its side effects are minimal; however, some pets may experience drowsiness, low energy, and loss of appetite.

How to take zonisamide

It's important to remember that stopping zonisamide doses without consulting a healthcare provider can be harmful. By following this advice, patients and caregivers can feel informed and responsible in managing their treatment. 

• General guidelines:

  • Take this medicine as directed. 

  • Please read the Medication Guide included with the medicine.

  • Do not stop taking zonisamide doses until talking to the prescriber.

  • Zonisamide tablets or oral suspension can be taken with or without food.

• How to take zonisamide capsules:

  • Swallow the zonisamide capsule whole. Do not break, chew, or open it.

  • Store zonisamide capsules at room temperature, protected from light and moisture.

• How to take zonisamide oral suspension:

  • Always shake the zonisamide oral suspension to mix the medicine before measuring a dose.

  • Use a calibrated oral syringe or other calibrated medicine measure device. Do not use kitchen tools or tableware.

  • Store zonisamide at room temperature and protect it from light. 

  • Throw away the zonisamide bottle and any remaining medicine 30 days after the bottle is opened.

Zonisamide dosage FAQs

How long does it take zonisamide to work?

Zonisamide is a long-term therapy used to control seizures. Its full therapeutic effect is usually evaluated and determined after several months of treatment. 

After a single oral dose, zonisamide reaches its peak concentrations in the body within two to six hours. This process takes slightly longer if the dose is taken with food. It takes about 14 days of daily dosing before zonisamide concentrations in the body reach a steady state (where the drug maintains consistent therapeutic effects). At that point, the drug provides consistent seizure control 24 hours a day.

How long does zonisamide stay in your system?

Zonisamide is a long-acting drug. Clinical studies indicate that its half-life in the body’s plasma is 63 hours, and in the red blood cells, it is over 100 hours. Thus, it may take over two weeks to completely clear from the body. 

What happens if I miss a dose of zonisamide?

Ask your healthcare provider what to do if you miss a dose of zonisamide. The prescribing information and the medication guide do not provide any recommendations or instructions regarding t missed doses. 

How long can you take zonisamide?

People usually take zonisamide for months or even years, but it has no if it works and doesn’t cause any side effects. 

How do I stop taking zonisamide?

Do not stop taking zonisamide unless instructed by your healthcare provider. Suddenly, stopping zonisamide can cause severe seizures, including seizures that don’t stop (status epilepticus).

When it’s time to stop taking zonisamide, your healthcare provider will gradually reduce the dose before discontinuation. After discontinuing zonisamide, the prescriber will likely substitute another antiseizure medication. The list of possible substitutes is very long and includes drugs like gabapentin, topiramate, valproate, and pregabalin.

What is the maximum dosage for zonisamide?

The maximum recommended dosage for zonisamide is 600 mg daily, though most clinicians do not exceed 400 mg daily, as higher doses have not shown additional benefits.  You are likely to have side effects when doses exceed 300 mg daily.

Can you overdose on zonisamide?

Yes. Do not take more zonisamide than prescribed. As it will not help control seizures and may cause serious side effects. If an overdose happens, call a poison control helpline or seek medical treatment. Possible symptoms of an overdose include nausea, vomiting, sleepiness, lethargy, and frequent urination. 

What interacts with zonisamide?

To avoid possible drug interactions, make sure to inform your healthcare provider about all the drugs, over-the-counter (OTC) products, and natural supplements you’re taking before you start taking zonisamide, particularly:

• Anything that makes you sleepy, including sleeping pills, narcotic pain relievers, benzodiazepines, allergy medications, cannabinoid products, or alcohol 

• Drugs called carbonic anhydrase inhibitors, such as acetazolamide or brinzolamide

• Antiepileptic drugs carbamazepine, phenobarbital, phenytoin, or primidone

• The antibiotic erythromycin

• The antifungal drug ketoconazole

• The migraine drug dihydroergotamine

• The immune suppressant cyclosporine

What happens when you mix zonisamide and alcohol?

Do not drink alcohol when taking zonisamide. The combination can increase drowsiness and impairment, affecting your coordination and judgment. 

What should I avoid when taking zonisamide?

Avoid drinking grapefruit juice when taking zonisamide, as it may affect how the drug is metabolized (broken down in the body). 

Allergy medications may make you more drowsy than usual if you’re taking anticonvulsants like zonisamide.

Do not drive or engage in risky activity until you know how zonisamide affects your alertness and judgment.

If you are on a ketogenic diet, ask the healthcare provider for medical advice about continuing or modifying the diet.

Is it safe to take zonisamide during pregnancy?

Zonisamide is a risky drug to take during pregnancy. Women of childbearing age who are not pregnant should use effective birth control when taking zonisamide. The drug can cause acidosis (high acid levels), which can affect the growth and health of a fetus. Your healthcare provider performs blood tests to monitor acid levels regularly to ensure safety. Newborns may also need blood tests at birth to check for acidosis. 

Is it safe to take zonisamide while breastfeeding?

Zonisamide passes into breast milk, but its effect on a nursing infant is unknown. Mothers should monitor their children carefully for unusual sleepiness, lethargy, or feeding issues.

What are the side effects of zonisamide?

Zonisamide's most common side effects are drowsiness, dizziness, decreased appetite, concentration problems, memory problems, coordination problems (ataxia), trouble walking, irritability, agitation, and weight loss.

What are the serious side effects of zonisamide?

Serious adverse effects include kidney stones, metabolic acidosis (high acid levels), high ammonia levels, eye problems, aplastic anemia, depression, psychosis, suicidal thoughts, and severe allergic reactions or drug reactions. There is also an increased risk of heat stroke. 

Talk to a doctor if you experience signs of a serious adverse reaction like:

• Thinking about suicide or hurting yourself

• New or worsening depression

• New or worsening anxiety

• Panic attacks

• Severe mood swings or changes

• Reckless or unusual behaviors

• Excessive tiredness (fatigue)

• Irregular heartbeats

• Loss of appetite

• Vision changes

• Yellowing of the skin or eyes (jaundice)

Sources

• Active epilepsy prevalence among U.S. adults is 1.1% and differs by educational level—National Health Interview Survey, United States, 2021, Epilepsy Behavior

• Handling delayed or missed dose of antiseizure medications, Neurology

• Partial epilepsy, StatPearls

• Zonegran drug summary, Prescriber’s Digital Reference (PDR)

• Zonegran zonisamide capsule prescribing information, DailyMed (NIH National Library of Medicine)

• Zonisamide suspension prescribing information, DailyMed (NIH National Library of Medicine)

• Zonisamide, StatPearls

• Zonisamide capsule prescribing information, DailyMed (NIH National Library of Medicine)

• A retrospective study of the efficacy of zonisamide in controlling seizures in 57 cats. Journal of Veterinary Internal Medicine.