Zonisamide (Oral)

Zonisamide is a sulphonamide and it works as an anti-convulsant used in adjunctive therapy in people with Parkinson's disease or partial onset seizures.

Overview

As an anti-epilepsy medication, the precise mechanism by which Zonisamide manages to prevent seizures is currently unknown. It is unrelated to other anti-seizure agents, and it is believed to block sodium and/or T-type calcium channels. This results in the suppression of seizure-form activity known as neuronal hypersynchronization. The compound is also known to be a carbonic anhydrase inhibitor similar to acetazolamide, which also modules glutamergic and GABAergic neurotransmission.

In addition to preventing seizures, Zonisamide is also effective in treating the motor symptoms associated with Parkinson's disease and has been studied in patients with obesity for its benefits in helping to promote weight loss. Zonisamide has also been used as a migraine prevention medicine, most notably when the drug topiramate cannot be used due to side effects or is otherwise ineffective. In patients with bipolar depression, psychiatrists have used Zonisamide off-label as a mood stabilizer to treat the condition.

The medicine was first discovered by a team of Japanese pharmacists in 1972. It was initially marketed as Excegran, and since 2000 it has been marketed under the name Zonegran in the United States, Asia and Europe.

Conditions treated

Type of medicine

  • Anticonvulsant

Side effects

Alongside its desired effects, Zonisamide may also cause one or more unwanted effects. Although not all of the listed side effects may occur, some of the ones that do could require medical attention. The most common side effects reported by patients include discouragement, irritability, loss of interest or pleasure, changes in mood, a feeling of sadness or emptiness, difficulty concentrating, tiredness, difficulty sleeping, shakiness, unsteady walking and a dry mouth. For dry mouth, healthcare experts recommend sucking on hard candy or ice cubes, chewing sugarless gum or simply drinking a cold glass of water.

As the patient continues to take a course of the medication as prescribed, the effects mentioned should lessen as the body adjusts to the medication. Many of the side effects associated with Zonisamide are not bothersome enough to cause the patient any major problems, but if side effects continue to persist over a long period of time or get worse as treatment continues, the patient is advised to seek advice from their doctor immediately - and to let their doctor know what other medications, supplements, vitamins or herbs they are also taking.

Other side effects caused by Zonisamide which are experienced much less frequently than the ones mentioned above (but often enough to merit mentioning) include agitation, delusions, hallucinations, bruising and skin rash. If any of these symptoms occur and do not dissipate after regular use of the medication, the patient is advised to seek medical attention.

Approximately 10% of patients who are prescribed Zonisamide experience gastrointestinal issues such as acid reflux. In these instances, the patient should contact a pharmacist or healthcare professional who may prescribe proton-pump inhibitors to reduce the level of acid in the stomach, which will alleviate these symptoms. Some patients may experience a lack of appetite and could experience weight loss as a result of taking the medication for a prolonged period.

Dosage

As with all anti-seizure medications, it is imperative that Zonisamide is only taken as directed by a physician. This means that patients should not take a higher dose than the one prescribed, and should stick to the planned dose frequency. Additionally, patients who are advised to cease treatment with Zonisamide should do so as and when instructed by a doctor, even if they have a supply of the drug remaining.

Zonisamide can be taken with or without food. The tablets should be swallowed whole and not crushed or chewed. Because dosages will vary depending on the reason for prescription, patient physiology and individual needs, it is important to pay attention to both the instructions of the doctor and the instructions printed on the packaging of the medicine. The strength of the drug, the number of doses each day and the length of time between doses all play a part in determining the most suitable dose size.

Although the manufacturers of Zonisamide provide general dosage instructions with the medicine, it should be reiterated that the recommended dose may be altered at the discretion of the doctor overseeing the patient. Factors discussed between doctor and patient are usually the number one concern when it comes to establishing both the frequency and dose size administered.

For treatment of seizures, the typical starting dose is 100mg per day, taken orally. After the doctor has had some time to observe the effects of the medicine at this dose (usually up to two weeks), they may increase dosage to 200mg per day in a single or divided dose, for up to two weeks again. From here, the dose can then be increased again to 300mg per day, then 400mg per day either as a singular daily dose or as two separate doses in one day. Because of the long half-life of Zonisamide, each iteration of dosage should be kept stable for at least two weeks in order to achieve a steady state at every level. A maintenance dose of 400mg per day is common, with the maximum dose per day not exceeding 600mg.

Dosage of Zonisamide to prevent seizures in children is not recommended by the manufacturer; however, a doctor may prescribe a smaller dose to a patient aged under 16 if they feel that the patient may benefit from use of the drug.

For treatment of Parkinson's disease, the therapeutic doses of this medication are considerably lower than those seen in the treatment of epilepsy. PD patients can expect to be prescribed in the region of 50-100mg of Zonisamide per day.

Patients with bipolar depression are typically prescribed between 100mg and 200mg of Zonisamide per day, dependent on physiology and mood. Because Zonisamide is used 'off-label' for the treatment of bipolar disorders, its use is typically at the discretion of a doctor and reliable data on its efficacy does not exist, although some studies do suggest that patients respond well to it at doses not exceeding 260mg per day.

Patients are warned against taking double doses of the drug. If the patient misses a dose, they are advised to continue taking the drug as normal at the next planned dose, omitting the missed dose and simply taking the next course as standard.

Activities which require mental alertness, such as driving or operating heavy machinery, should be avoided until the patient has an understanding of how the medication affects them, or until the patient has acclimatized to the medication.

In the event of overdose, symptoms which develop include extremely slow or extremely fast heartbeat, difficulty breathing, seizures, loss of coordination, flushed skin and unconsciousness. Patients who overdose on Zonisamide require immediate medical attention. Patients or their caregivers should call either the emergency services (911) or the Poison Control Center (1-800-222-1222) as soon as possible.

Interactions

Medications often interact with other drugs or chemicals present in the human body, and this process can change the effects or efficacy of the medicine. It can result in one medication becoming ineffective in treating a condition, or can even create a dangerous reaction in the patient. Because of this, it is imperative that patients keep a detailed list of all medications they are currently taking - either prescribed or self-administered. Your doctor should know everything you are taking, and this extends to over the counter, non-prescription medicines and supplements.

Below is a partial list of major drugs which are known to have interacted negatively with Zonisamide. Patients who are currently taking any of these medicines should notify their doctor prior to taking the first dose of Zonisamide:

  • Psuedoephedrine
  • Abilify
  • Aspirin
  • Phenobarbital
  • Codeine
  • Bydramine
  • Cardec
  • Dramamine
  • Fluoxetine
  • Olanzapine
  • Scopolamine
  • Subutex

Patients are urged to make their doctor aware if they are taking any other substances which might increase drowsiness, mood swings, nausea and other side effects, including (but not limited to) alcohol, marijuana, cough suppressants, sleeping tablets, muscle relaxants and painkillers. Patients are also advised to consult the ingredient listings on medicines they are currently taking in order to ensure no unexpected interactions take place. Some over the counter cold and flu remedies contain ingredients intended to cause drowsiness, and great care should be taken when using them on a course of Zonisamide, in order to avoid unpleasant and potentially harmful side effects.

Warnings

In addition to any existing allergies or prescription drugs administered, the patient is encouraged to discuss their medical history, current health problems, and allergies.

There have been potentially fatal reactions to sulphonamides like Zonisamide, albeit rarely. Severe reactions to sulphonamides can result in the following:

These reactions can occur regardless of dose or route of administration. If hypersensitivity or other potentially serious reactions occur, the patient should cease use of Zonisamide immediately, or at the very least be frequently observed by a healthcare professional for signs of serious issues, such as a severe rash associated with Stevens-Johnson syndrome. At a rate of 46 per million-patient exposure, such instances are rare but great care should be taken when first using the drug.

Additionally, healthcare professionals should be made aware of any previous addictions or substance misuse issues the patient has experienced in the past. This includes prescription medicines as well as alcohol, over-the-counter medication and street drugs. Because Zonisamide has a propensity to affect mobility skills during the initial stages of use, patients should avoid the use of alcohol completely until adjusted to a maintenance dose, and should only use alcohol sparingly from this point onwards.

Zonisamide has the potential to cause fetal abnormalities or embryofetal deaths. This medication should only be used during pregnancy if the benefits outweigh the risks, as potential harm to the fetus includes decreased fetal growth and decreased fetal oxygenation; the ability for the fetus to tolerate labor may also be affected. However, if a woman becomes pregnant while currently on a course of Zonisamide, therapy should not be immediately discontinued and should instead be tapered off. Instantly stopping the medication can lead to breakthrough seizures, which could have incredibly serious consequences for mother and child.

The drug is excreted into breast milk, at a concentration similar to the level of Zonisamide found in blood plasma. A decision to either discontinue breastfeeding or discontinue use of the medicine should therefore be taken by the mother. Due to the lengthy retention time of the drug within the body, mothers are advised not to resume breastfeeding until four weeks after Zonisamide therapy has been withdrawn.

Storage

Zonisamide should be stored at room temperature, and out of direct sunlight, in the container it came in. It should be kept away from excess heat and moisture (avoid storing in the bathroom).

If a doctor or qualified health professional determines that Zonisamide treatment is no longer necessary, they should advise the patient on the correct disposal of the remaining supply of the medication. Great care should be taken when disposing of the tablets so that pets or children are unable to inadvertently consume them. Unused Zonisamide tablets should not be flushed down the toilet. The best way to dispose of unwanted medication is to utilise a take-back program. In order to find out about tack-back programs in your area, you should contact your local recycling department who will be able to advise you further on pharmacies or community centers which participate in such schemes.

As with all medications, Zonisamide should be kept out of the reach and sight of children. Many medicine containers are not child-resistant, which can lead to infants and young children opening them and consuming the pills contained within. When storing potentially harmful medication, think "up and away"- store them in a high-up, difficult to reach area or designated medicine cupboard.

Summary

Zonisamide is incredibly beneficial in the treatment of epilepsy, and is also useful in combatting symptoms of Parkinson's disease and bipolar disorder (mania). However, taking too high a dose can place the patient at great risk, and patients who do not communicate fully and truthfully with healthcare professionals may also be putting themselves in harm's way.

As an anticonvulsant, it is particularly effective in preventing partial-onset seizures, seizures associated with Lennox-Gastaut syndrome, myoclonic seizures, tonic-clonic seizures and infantile spasm.

Certain studies have also proven the efficacy of Zonisamide in helping with weight loss; it is therefore sometimes used sparingly and temporarily as an anti-obesity treatment. Off-label uses such as this and the treatment of migraine are decided at the discretion of a qualified physician.

The medication is currently approved for use in the treatment of seizures in the United States, United Kingdom, Japan and Australia. It is approved as a treatment for tremors associated with Parkinson's disease, as an adjunct to Levodopa, in Japan.

When taken as directed, Zonisamide prevents the onset of symptoms which may have been untreatable by other medicines, allowing patients to undertake activities and enjoy life in a way that was previously untenable. In order to get the most out of the medication, patients should take the advice of their doctors, pharmacists and healthcare professionals, and ensure that they stick to the prescribed dose at the right frequency. Zonisamide works best when doctor and patient work together over a period of weeks or months in order to ascertain the most appropriate maintenance dose. This ultimately provides the patient with greater freedom to work and live a fuller, seizure-free life without having to worry about the onset of epilepsy symptoms - however, the drug can affect motor skills, so care is advised when undertaking strenuous tasks, even when acclimatized to a maintenance dose.

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Last Reviewed:
December 23, 2017
Last Updated:
April 27, 2018
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