Zonegran
Zonegran Uses, Dosage, Side Effects, Food Interaction and all others data.
The precise mechanism(s) by which zonisamide exerts its antiseizure effect is unknown. Zonegran demonstrated anticonvulsant activity in several experimental models. In animals, zonisamide was effective against tonic extension seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol. Zonegran raised the threshold for generalized seizures in the kindled rat model and reduced the duration of cortical focal seizures induced by electrical stimulation of the visual cortex in cats. Furthermore, zonisamide suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human epilepsy is unknown.Zonegran may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that zonisamide blocks sodium channels and reduces voltagedependent, transient inward currents (T-type Ca2+ currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that zonisamide binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux. Other in vitro studies have demonstrated that zonisamide (10–30 μg/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [3H]-GABA (rat hippocampal slices). Thus, zonisamide does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that zonisamide facilitates both dopaminergic and serotonergic neurotransmission.Zonegran is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of zonisamide is unknown. However, as a carbonic anhydrase inhibitor, zonisamide may cause metabolic acidosis
Zonegran is a sulfonamide and therefore unrelated to other seizure medications. The mechanism is not know but it may block sodium and calcium channels. Blocking of these channels may prevent neuronal hypersynchronization. Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid).
| Trade Name | Zonegran |
| Availability | Prescription only |
| Generic | Zonisamide |
| Zonisamide Other Names | Zonisamida, Zonisamide, Zonisamidum |
| Related Drugs | diazepam, topiramate, levetiracetam, Keppra, Topamax, Valium |
| Weight | 50mg, , 100mg, 25mg |
| Type | Tablet, Capsule, Oral Capsule |
| Formula | C8H8N2O3S |
| Weight | Average: 212.226 Monoisotopic: 212.025562822 |
| Protein binding | 40% (at concentrations of 1.0-7.0 µg/mL) |
| Groups | Approved, Investigational |
| Therapeutic Class | Adjunct anti-epileptic drugs |
| Manufacturer | Eisai Pharmaceuticals, Beacon Pharmaceuticals Ltd, Eisai Ltd, Eisai Indonesia Pt |
| Available Country | India, Bangladesh, United Kingdom, United States, Indonesia, Italy, Netherlands, Portugal, Spain, Switzerland, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zonegran is used for adjunctive therapy in the treatment of partial seizures in adults with epilepsy.
Zonegran is also used to associated treatment for these conditions: Partial-Onset Seizures
How Zonegran works
Zonegran binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonegran also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity.
Dosage
Zonegran dosage
Zonegranis recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Zonegran should be administered once or twice daily, using 25 mg or 100 mg capsules. Zonegran is given orally and can be taken with or without food. Capsules should be swallowed whole.Adults Over Age 16: The prescriber should be aware that, because of the long half-life of zonisamide, up to two weeks may be required to achieve steady state levels upon reaching a stable dose or following dosage adjustment. Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of zonisamide at steady state, noting that many of the side effects of zonisamide are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100-200 mg/day, the increase appears small and formal dose-response studies have not been conducted.The initial dose of Zonegran should be 100 mg daily. After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that Zonegran doses of 100-600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day. There is little experience with doses greater than 600 mg/day.
Side Effects
The most common adverse reactions with Zonegran (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration.In controlled clinical trials, 12% of patients receiving Zonegran as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received Zonegran in clinical studies discontinued treatment because of an adverse reaction. The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were doserelated
Toxicity
Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
Precaution
Somnolence is commonly reported, especially at higher doses of Zonegran. Zonegran is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering Zonegran to patients with hepatic and renal dysfunction
Food Interaction
- Avoid alcohol. Ingesting alcohol may increase drowsiness and dizziness.
- Take with or without food.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.
Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Zonegran Drug Interaction
Major: diphenhydramine, topiramateModerate: duloxetine, levetiracetam, lamotrigine, escitalopram, pregabalin, alprazolam, sertraline, cetirizineUnknown: omega-3 polyunsaturated fatty acids, polyethylene glycol 3350, albuterol, montelukast, levothyroxine, lacosamide, cyanocobalamin, ascorbic acid, cholecalciferol, ondansetron
Volume of Distribution
- 1.45 L/kg
Elimination Route
The absorption is rapid with a time to peak concentration of 2.8-3.9 hours. Food has not effect on bioavailability.
Half Life
63 hours
Clearance
- 0.30 - 0.35 mL/min/kg [patients not receiving enzyme-inducing antiepilepsy drugs (AEDs)]
- 0.35 - 0.5 mL/min/kg [Concomitant administration of phenytoin and carbamazepine]
Elimination Route
Zonegran is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.
Pregnancy & Breastfeeding use
Zonegran may cause serious adverse fetal effects, based on clinical and nonclinical data. Zonegran was teratogenic in multiple animal species.Zonegran treatment causes metabolic acidosis in humans. The effect of zonisamide-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) may be associated with decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus's ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state. Newborns of mothers treated with zonisamide should be monitored for metabolic acidosis because of transfer of zonisamide to the fetus and possible occurrence of transient metabolic acidosis following birth. Transient metabolic acidosis has been reported in neonates born to mothers treated during pregnancy with a different carbonic anhydrase inhibitor.
Contraindication
Zonegran is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
Special Warning
Patients With Renal Or Hepatic Disease: Because zonisamide is metabolized in the liver and excreted by the kidneys, patients with renal or hepatic disease should be treated with caution, and might require slower titration and more frequent monitoringPediatric Use: The safety and effectiveness of Zonegran in children under age 16 have not been established. Cases of oligohidrosis and hyperpyrexia have been reported. Zonegran commonly causes metabolic acidosis in pediatric patients. Chronic untreated metabolic acidosis in pediatric patients may cause nephrolithiasis and/or nephrocalcinosis, osteoporosis and/or osteomalacia (potentially resulting in rickets), and may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of zonisamide on growth and bonerelated sequelae has not been systematically investigated.Geriatric Use: Single dose pharmacokinetic parameters are similar in elderly and young healthy volunteers. Clinical studies of zonisamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Acute Overdose
Human Experience: Experience with Zonegran daily doses over 800 mg/day is limited. During Zonegran clinical development, three patients ingested unknown amounts of Zonegran as suicide attempts, and all three were hospitalized with CNS symptoms. One patient became comatose and developed bradycardia, hypotension, and respiratory depression; the zonisamide plasma level was 100.1 μg/mL measured 31 hours post-ingestion. Zonegran plasma levels fell with a half-life of 57 hours, and the patient became alert five days later.Management: No specific antidotes for Zonegran overdosage are available. Following a suspected recent overdose, emesis should be induced or gastriclavage performed with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation.Zonegran has a long half-life. Due to the low protein binding of zonisamide (40%), renal dialysis may be effective. The effectiveness of renal dialysis as a treatment of overdose has not been formally studied. A poison control center should be contacted for information on the management of Zonegran overdosage.
Innovators Monograph
You find simplified version here Zonegran
Zonegran contains Zonisamide see full prescribing information from innovator Zonegran Monograph, Zonegran MSDS, Zonegran FDA label
FAQ
What is the Zonegran used for?
Zonegran is used in combination with other medications to treat certain types of seizures.
What are side effects of Zonegran?
Zonegran may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- nausea,
- vomiting,
- weight loss,
- changes in taste,
- diarrhea,
- constipation,
- heartburn,
- dry mouth,
- headache,
- dizziness,
- confusion,
- irritability,
- difficulty falling asleep or staying asleep,
- difficulty with memory,
- pain, burning, numbness, or tingling in the hands or feet,
- uncontrollable eye movements,
- double vision,
Is Zonegran used for anxiety?
Zonegran may effectively augment response to anxiolytic medications in patients with treatment refractory anxiety.
Is Zonegran safe during pregnancy?
Zonegran may harm an unborn baby.Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant.
Is Zonegran safe during breastfeeding?
Zonegran is careful monitoring in exclusively breastfed infants.You should not breastfeed while using Zonegran.
Can I drink alcohol with Zonegran?
Alcohol can increase the nervous system side effects of Zonegran such as dizziness, drowsiness, and difficulty concentrating.You should avoid or limit the use of alcohol while being treated with Zonegran.
Can I take Zonegran for a long time?
Zonegran may cause metabolic acidosis .Metabolic acidosis that is left untreated for a long time may increase the risk that other medical problems, including kidney stones and bone problems that may lead to fractures, will develop.
Is Zonegran bad for liver?
Zonegran may cause serious allergic reactions called drug reaction with eosinophilia and systemic symptoms (DRESS) or multiorgan hypersensitivity, which may damage the liver, kidney, blood, heart, or muscles.
Is Zonegran a mood stabilizer?
Prevents seizures and stabilizes mood.Zonegran is used with other medicines to help control partial seizures.It can't be used by itself.
Can Zonegran be used to treat migraines?
Zonegran is effective and well tolerated for migraine prevention in patients refractory to topiramate. With the exception of the inhibition of T-type calcium channels by Zonegran, its mechanisms of action seem to be very similar to topiramate's.
Can Zonegran be abused?
The abuse and dependence potential of Zonegran has not been evaluated in human studies. In a series of animal studies,Zonegran did not demonstrate abuse liability and dependence potential.
When should I take Zonegran?
There is not a specific time of the day that you have to take Zonegran. However, it may be safer to take this medication in the evening time if you experience dizziness or sleepiness while on Zonegran.
How long does it take for Zonegran to work?
The Zonegran should begin working within 1-2 days.
What happens when I stop taking Zonegran?
Do not stop using Zonegran suddenly, even if you feel fine. Stopping suddenly may cause increased seizures.
Can Zonegran cause vision problems?
Taking Zonegran can cause permanent vision loss.
Will Zonegran make my weight gain?
No patients in the Zonegran group experienced significant weight gain.
Can Zonegran cause hyponatremia?
There were no cases of hyponatremia with Zonegran.
Can Zonegran be used alone?
Zonegran can be used alone or in combination with phenobarbital and/or potassium bromide.
Can I overdose on Zonegran?
Overdose symptoms may include slow heart rate, feeling light-headed, fainting, and slow or shallow breathing.
