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Medical Areas: Neurology | Family Medicine | Genetic Disease
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Zonegran (zonisamide) Capsules
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Dainippon Pharmaceutical
Approval Status: Approved March 2000
Treatment Area: Adjunctive therapy for treatment of partial seizures in adults with epilepsy
Zonegran is indicated for use as an adjunctive therapy for
treatment of partial seizures (or focal seizures) in
adults with epilepsy.
Zonegran, which has been available in Japan since 1989 under the
trade name of Excegran, will be available on the U.S. market in
Epilepsy is a neurological dysfunction in which sudden and
excessive bursts of electrical energy are emitted in the brain.
Among the several different general categories of seizures are
partial seizures, seizures resulting from electricity in local
neuron populations; and generalized seizures, which occur in more
general areas of the brain and often cause more serious symptoms.
There are an estimated 2 million epilepsy sufferers in the U.S.
alone. Approximately one third of these patients do not have
sufficient control of their seizures with the anti-epileptic drugs
currently available to them.
Three multicenter, placebo-controlled, double-blind studies
examined the effects of the investigational drug as an adjunctive
therapy in 499 patients with partial onset seizures for whom one or
two antiepileptic drugs were ineffective. The primary measure of
effectiveness was median percent reduction in seizure
In the first study, two dose escalation regimens were studied.
Treatment with Zonegran was statistically significant for doses of
100, 200, or 400 mg/day, but not for 300 mg/day, when compared to
In the second study, varied doses of Zonegran or placebo were
administered twice daily, while in the third study, they were
administered once daily. In both studies, results indicated that
Zonegran 400-600 mg/day was significantly more effective than
placebo in weeks 5-12 of the study. No significant differences were
found between once and twice daily dosing. Results also suggested
that 100 and 400 mg/day were significantly effective in the first 4
weeks of the study during which only secondary comparisons were
Approximately 27% of patients treated with Zonegran experienced
75% or more reduction in seizure frequency, while only 12% of
placebo-treated patients experienced such reduction.
Common side effects of Zonegran include but are not limited
- Renal calculi
- Loss of appetite
- Gastrointestinal symptoms
Possible rare but serious side effects of Zonegran include but
are not limited to:
- Severe rash (i.e. Stevens Johnson Syndrome [SJS] and toxic
epidermal necrolysis [TEN])
- Serious hematologic events, such as aplastic anemia or
- Oligohydrosis and hyperthermia in pediatric
Mechanism of Action
The precise mechanism(s) by which zonisamide exerts its
antiseizure effect is unknown. Zonisamide 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. Zonisamide 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.
Zonisamide may produce these effects through action at sodium
and calcium channels. In vitro pharmacological studies
suggest that zonisamide blocks sodium channels and reduces
voltage-dependent, 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 ug/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.
Zonisamide also has weak carbonic anhydrase inhibiting activity,
but this pharmacologic effect is not thought to be a major
contributing factor in the antiseizure activity of
(From FDA Label)
Visit the Dainippon Pharmaceutical Co. Ltd. web site,
to learn more about Zonegran and about other products, research,
and services provided by the company that developed this drug.
For more information about epilepsy, visit the official web site
of the Epilepsy Foundation, a non-profit volunteer agency devoted
to research, education, advocacy, and services in the community for
people with epilepsy and their families:
This is what the Epilepsy Foundation says to do
and not to do if you encounter a person having an
What To Do:
- Look for medical identification.
- Protect from nearby hazards.
- Loosen ties or shirt collars.
- Protect head from injury.
- Turn on side to keep airway clear unless injury exists.
- Reassure as consciousness returns.
- If a single seizure lasted less than 5 minutes, ask if hospital
- If there are multiple seizures, or if one seizure lasts longer
than 5 minutes, call an ambulance.
- If person is pregnant, injured, or diabetic, call for aid at
What Not To Do:
- Don't put any hard implement in the mouth.
- Don't try to hold tongue. It can't be swallowed.
- Don't try to give liquids during or just after
- Don't use artificial respiration unless breathing is absent
after muscle jerks subside, or unless water has been inhaled.
- Don't restrain.