Zonisamide is among the newer broad spectrum anti-epileptic drugs, effective against focal and generalized epilepsies. It can be taken once daily and is well tolerated. The current article focuses on clinical efficacy and safety of zonisamide in epilepsy (as add on or as monotherapy). There is long term data as well as comparative studies against carbamazepine.
antipsychotics history, managment of psychosis,side effect of antipsychotics, mechanism of antipsychotics, atypical antipsychotics,2nd generation antipsychotics.
antipsychotics history, managment of psychosis,side effect of antipsychotics, mechanism of antipsychotics, atypical antipsychotics,2nd generation antipsychotics.
Treatment Options for Drug-Resistant Epilepsy
In some people with drug resistant epilepsy, there are effective treatment options, with a high chance of seizure freedom. These include:
Resective Epilepsy Surgery
Resective epilepsy surgery consists of removing the area of the brain that is causing the seizures. However, for a patient to be a good candidate for surgery, the following conditions have to be met:
The area of the brain where seizures originate is clearly identified.
That area of the brain can be safely removed with surgery. In other words if the risk is greater than “minimal risk,” the patient is not a candidate.
The probability to achieve seizure freedom with epilepsy surgery varies depending on the structures of the brain involved. For example, patients whose seizures originate in the temporal lobe have a 50% to 70% chance of achieving seizure-freedom.
Today, newer, less-invasive techniques are being used in the place of resective surgery in appropriate cases. These include the use of laser, in which a laser probe burns the area of the brain causing the seizures. However, these new techniques may not work for all candidates for resective surgery.
Specific Metabolic Treatment
While metabolic causes of epilepsy are uncommon, identifying some of these conditions can lead to specific treatments to allow the body to compensate for the metabolic change.
Examples are treatment with a ketogenic diet for GLUT1 deficiency, treatment with pyridoxine or pyridoxal-5-phosphate for vitamin dependent epilepsies, and creatine supplementation for creatine deficiency syndromes.
Specific Genetic Causes
Identifying a specific genetic cause can help your doctor choose the best treatment for seizures.
For example, with SCN1A pathogenic variants, medications such as Oxcarbazepine (Trileptal), Carbamazepine (Tegretol) or Phenytoin (Dilantin) should be avoided. Whereas with other types of pathogenic variants, such as SCN2A and SCN8A variants, these medications can be very helpful.
Some specific treatments which target the underlying problem caused by the genetic variant are in clinical trials, and may improve learning and development as well as help with seizures.
Immunotherapy
In the last decade, the role of inflammatory processes in certain types of epilepsy has been recognized. In these cases, medications that counteract these processes have been used with success. However, they have to be used with caution as they are associated with a variety of adverse events.
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Stroke is common. This presentation discusses the broad outlines of acute stroke management, especially in the first 24 hours after onset of symptoms. It would be useful for physicians as well as neurologists.
Stroke is common in pregnancy. All physicians and obstetricians caring for pregnant women should be familiar with symptoms of stroke, as well as its diagnosis and treatment. This presentation gives an overview about the latest management of stroke in pregnant women.
Stroke is a leading cause of death and disability. All doctors should have a basic knowledge about stroke management. This presentation gives a summary of treatment options in acute brain stroke.
Multiple sclerosis is a demyelinating disease affecting brain, optic nerves and spinal cord. It is characterised by frequent relapses. Now, there are a number of effective treatment options for MS. Earlier, only clinical parameters were considered to evaluate the efficacy of MS treatments. However, now, we need to look at disability as well as MRI parameters. All these points are included in NEDA (no evidence of disease activity). This presentation looks at the definition and classification of NEDA. It also looks at NEDA rates with various treatment options.
NEUROLOGICAL DISORDERS DUE TO METABOLIC DERANGEMENTSSudhir Kumar
Metabolic and endocrine disorders can present with neurological signs and symptoms. It is important to recognise them so that can be promptly treated. Majority of symptoms fully reverse if treatment is started on time. This presentation looks at some common metabolic/endocrine disorders with neurological manifestations. The description is in the form of case series.
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This presentation discusses the revised McDonald's criteria (2017) for the diagnosis of multiple sclerosis. Major changes from the last diagnostic criteria proposed in 2010 have been discussed. Clinical and MRI criteria for dissemination in space and time have been discussed.
Today, everyone needs to market self. Some market their products, and others market their skills. Is marketing difficult? It is difficult, however, it can become easy, if we follow certain protocol. This talk gives you some insights into effective ways of marketing.
Addressing hypertension to reduce the burden of stroke 19 feb2018 (1)Sudhir Kumar
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
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ZONISAMIDE IN TREATMENT OF EPILEPSY
1. DR SUDHIR KUMAR MD DM
Consultant Neurologist
Apollo Hospitals, Hyderabad
Evolving role of
Zonisamide as a potential
Monotherapy in Focal
Seizures
2. Zonisamide: Introduction
• Unique chemical structure – unrelated to other AEDs
• First approved in Japan in 1989, South Korea in 1992, USA in
2000, Europe in 2005 & in India 2008
• Over 2 million patient years of experience with Zonisamide in
epilepsy1
Baulac M. et al. Epilepsy Res 2007;75:75-83
O
N
CH2SO2NH2
3. Zonisamide: Indication
• Indicated as monotherapy and adjunctive therapy in adults >18
years with following seizure types
- Partial seizures with or without secondarily generalized
seizures
- Generalized seizures
- Mixed seizures
4.
5. Efficacy Parameters
• The proportion of patients remaining seizure free for
≥24 months was similar for both groups
Zonisamide Carbamazepine
Patients remaining
seizure free for
≥24 months
32.3% 35.2%
6. 58.4
27.7
5.8
61.4
27.8
2.5
0
10
20
30
40
50
60
70
12 Months 18 Months 24 Months
Zonisamide
Carbamazepine
Zonisamide showed
comparable Retention
Rates at 12 and 18 months
and higher Retention Rates
compared to
Carbamazepine at 24
months
Retention Rates
Epilepsia, 55(10):1534–1543, 2014
7. Efficacy Parameters – Retention Rate
• Retention rates were generally similar between treatment
groups at all time points throughout the extension study.
The primary efficacy assessment was retention rate,
which is a measurement of both efficacy and
tolerability, providing an indication of an agent’s
overall effectiveness.
8. • Overall retention rate
was 66.1% at 1-year
and 55.1% at 6-year
follow-up.
• In Patients with
monotherapy
retention rate was
73.4% at 1 year and
70.8% at 6 year
follow-up vs. 62.9%
at 1 year follow-up
and 44.1% at 6 year
follow-up in patients
with adjuvant
therapy.
9. Summary
• This long-term assessment of zonisamide monotherapy in adults with
newly diagnosed epilepsy is notable because no other currently
available AED has been studied in a double-blind monotherapy
setting over such a long treatment duration.
• Study is unique in providing ≥24-month seizure freedom data for
currently available AEDs under double-blind conditions.
Once-daily zonisamide Monotherapy demonstrated
favorable long-term safety and maintenance of efficacy in
treating partial seizures in adults with newly diagnosed
epilepsy.
10. Initial
Monotherapy
Polytherapy (ies)
Alternative Monotherapies
First Add-on
Strategy and Outcomes with Antiepileptic Drugs
50%
10%
5%
5%
Seizure-free
at least for one year
Newly Diagnosed /treated
70%
drug
sensitive
Kwan et al. N Engl J Med 2000;342(5):314-9
30% drug
resistant
Monotherapy # 47%
Polytherapy # 53%
ZNS
11. Zonisamide monotherapy: Open label prospective
studies
Neuropsychiatric Disease and Treatment 2014:10 493–498
Author (year) Type of epilepsy Patients type (n)
Zonisamide
dosage
% seizure-free
Fujii et al (1989) localization related Treatment naïve
(25)
8 mg/kg/day 68%
Kumagai et al
(1989)
localization related
and generalized
Children (44) 12 mg/kg/day 72%
Hayakawa et al
(1994)
localization related
and generalized
Children, newly
diagnosed (32)
2-10 mg/kg/day 66%
Miura (2004) localization related Chidren, treatment
naïve (72)
8 mg/kg/day 79.2%
Seki et al (2004) localization related
and generalized
Children (68) Upto 12
mg/kg/day
82%
20. Total 12 studies documenting the clinical evaluation of Zonisamide in
epilepsy were selected that met the following criteria
1) Open-label studies performed in epileptic patients to whom ZNS was
administered as monotherapy or add-on therapy at standard dosages
2) The duration of the study was at least 6 months
3) At least one of the outcome measures had to be reported,
4) Populations of adults and/or children were included
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 249–259
21. Long-term safety and effectiveness of zonisamide in the
treatment of epilepsy: a review of the literature
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 2
22. Long-term safety and effectiveness of zonisamide in the
treatment of epilepsy: a review of the literature
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 2
23. Percentage of patients continuing treatment with
zonisamide
Percentages of patients who continued to use this drug after 1 year ranged
between 50% and 60%,
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 2
24. Percentage of responders: patients achieving a 50%
seizure reduction
37% and 50% of patients responded to Zonisamide when added to other AEDs &
60% and 65% of patients Responded to Zonisamide when it was used as
monotherapy
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 2
25. Percentage of patients withdrawing from zonisamide
for adverse effects
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 2
26. Important adverse effects in some clinical studies
Zaccara and Specchio et al. Neuropsychiatric Disease and Treatment 2009:5 24
27. Partial-onset
seizures
Class I
studies
Class II
studies
Class III
studies
Efficacy /
effectiveness level
ADULTS 2 1 30
Level A: CBZ, PHT
Level B: VPA
Level C: OXC, LTG,
GBP, TPM
Glauser T, et al. Epilepsia 2006;47:1094–120
ILAE guidelines: evidence-based analysis of AED
efficacy and effectiveness as initial monotherapy
Structured literature review of all relevant
articles (1940 – July 2005)
Total of 50 RCTs and seven meta-analyses
28. Comparison of the efficacy and tolerability of
zonisamide and controlled-release carbamazepine in
newly diagnosed partial epilepsy
Michael Baulac¹, Martin J Brodie², Luigi Giorgi³, Joanna Segieth³
¹Universite Paris V1, Hôpital Pitié-Salpêtrière, Paris, France
²Western Infirmary, Glasgow, Scotland, ³ Eisai Ltd, Hatfield UK
Lancet Neurology June 2012
29. • To evaluate the efficacy of once-daily zonisamide (ZNS) vs. twice-daily
controlled-release carbamazepine (CBZ) when administered as monotherapy to
adult patients with newly diagnosed partial epilepsy
• Phase 3, international, multicentre, randomised, double-blind, non-
inferiority trial
– 583 randomised patients from 120 centres in 22 countries in Asia, Australia
and Europe
• 52 week study
• Designed in accordance with European Medicines Agency (EMA)
regulatory recommendations and International League Against Epilepsy
(ILAE) guidelines1
• Employed flexible dosing to reproduce (as closely as possible) conditions
of clinical practice
Study Design
30. Zonisamide vs carbamazepine-CR: rates of seizure freedom*
100
0
20
40
60
80
%Patients
ZNS
(n=223)
79.4
CBZ
(n=233)
83.7
*Seizure free (at last evaluated dose) for 6 months. Patients with new onset partial seizures.
CBZ-CR, controlled-release carbamazepine; ZNS, zonisamide.1
Initiation (ZNS 100mg/day, CBZ 200 mg/day) and up-titration (to 300 and 600 mg/day, respectively), followed by 26- to 78-week flexible dosing period
(200–500 and 400–1200 mg/day, respectively)
1. Baulac M, et al. Lancet Neurology 2012;11:579–88;
2. Glauser T, et al. Epilepsia 2006; 47:1094–120
Phase 3, international, multicentre,
randomised, double-blind, non-inferiority
trial
583 randomised patients from 120 centres
in 22 countries in Asia, Australia and Europe
52 week study
Designed in accordance with European
Medicines Agency (EMA) regulatory
recommendations and International
League Against Epilepsy (ILAE)
guidelines1
Comparable Seizure freedom rate
31. Zonisamide dose (mg) Carbamazepine dose (mg)
1.5%
8.7%
88.7%
1.0%2.8%
8.5%
87.0%
1.7%
0
10
20
30
40
50
60
70
80
90
100
200 300 400 500 400 600 800 1200
Patients(%)
Relatively low doses of the monotherapy AEDs
were sufficient to obtain 6-month seizure-freedom
*Percentages shown are based on population of patients who achieved 26-week seizure freedom
32. Zonisamide
(N=281)
Carbamazepine
(N=300)
TEAEs, n (%) 170 (60.5) 185 (61.7)
Treatment-related TEAEs, n (%) 102 (36.3) 115 (38.3)
Severe TEAEs, n (%) 17 (6.0) 17 (5.7)
Serious TEAEs, n (%) 15 (5.3) 17 (5.7)
TEAEs leading to withdrawal, n (%) 31 (11.0) 35 (11.7)
TEAEs leading to dose reduction, n (%) 4 (1.4) 3 (1.0)
Overall incidence of
treatment-emergent adverse events
• Overall incidence of TEAEs was similar between groups
• Incidence of TEAEs leading to discontinuation was also similar
between groups
33. Zonisamide
(N=281)
Carbamazepine
(N=300)
Headache, n (%) 29 (10.3) 37 (12.3)
Appetite decreased, n (%) 22 (7.8) 5 (1.7)
Somnolence, n (%) 17 (6.0) 23 (7.7)
Dizziness, n (%) 11 (3.9) 23 (7.7)
Weight decreased, n (%) 19 (6.8) 0 (0.0)
Incidence of treatment-emergent
adverse events (≥5%)
• Decreased appetite and weight loss were more frequently
reported with ZNS than CBZ
• Dizziness was more frequently reported with CBZ than ZNS
34. • Focal-onset seizures in adults:
– Level A : only CBZ, PHT, LEV and ZNS have established level A evidence
of efficacy/effectiveness as initial monotherapy
– Level B: VPA (probably effective)
– Level C: GBP, LTG, OXC, TPM (possibly effective), PB
Epilepsia. 2013 Mar;54(3):551-63.
36. Adapted from: Johannessen Landmark C & Johannessen SI. Drugs 2008;68:1925–39;
1. Biton V. Clin Neuropharmacol. 2007;30(4):230–40
mGluR=metabotropic glutamate receptor; VGCC=voltage-gated
calcium channel; VGPC=voltage-gated potassium channel;
VGSC=voltage-gated sodium channel
VGSC
VGPC Intracellular signalling pathways regulating
excitability in the postsynaptic neuron
Na+
K+
Na+
Cl–
Ca2+
Ca2+
VGCC
SV2A
VGCC
Ca2+
Na+
VGSC
Glutamate
Excitatory synapse
GABA
Inhibitory synapse
GABAB α2δ
Broad Spectrum
MEMBRANE STABILIZATION :
• Zonisamide displays multiple
mechanisms
of action including:1
– inhibition of Na+ channels
– reduction of T-type Ca2+ currents
NEUROMODULATION :
• Shown to facilitate the dopaminergic &
serotonergic transmission
• Demonstrated to cause blockade of
potassium evoked glutamate-mediated
excitatory synaptic transmission
NEUROPROTECTION :
• Scavenging free radicals
• CARBONIC ANHYDRASE INHIBITOR
37. Zonisamide has a long elimination half-life
1. See individual product SPC; 2. Wilfong AA et al. Neuropsych Dis Treat 2006;2:269-280.
*Monohydroxy derivative = oxcarbazepine active metabolite GBP = Gabapentin; TGB = Tiagabine; LEV = Levetiracetam;
PGB = Pregablin; ZNS = Zonegran Half-lives shown are longest stated within each PI and rounded to the nearest hour1
ZNS can be given once-daily after titration phase;1
enabling a once-daily dose regimen and assuring
steady therapeutic drug levels after titration phase2
Time (hours)
GBO
MHD* 11h
Topiramate 21h
Lamotrigine 33h
Zonisamide 60h
Carbamazepine 36h
Eslicarbazepine acetate 24h
Valproate 20h
Lacosamide 13h
TGB 9h
LEV 8h
PGB 6h
GBP 7h
38. Zonisamide : Drug interactions
Does not induce or inhibit
P450
Does not induce its own
metabolism
No effect on plasma levels of
other AEDs
Plasma levels affected by
drugs which induce or
inhibit CYP3A4
No interaction with oral
contraceptives
ZNS alone 60–70 h
PHT 27 h
PB - CBZ 38 h
VPA 46 h
ZNS T½ with other AEDs
Half-life stays > 24 hours with other
AEDs
39. Drug - Drug Interaction profile
1. Zonegran Summary of Product Characteristics;
2. 2. Keppra® Summary of Product Characteristics; 3. Sills G & Brodie M. Epilepsia 2007;48:435‒41.
Low potential for ZNS to affect the AEDs below, or other medications,
including oral contraceptives1–3
†ZNS should be used with caution in patients treated concomitantly with carbonic anhydrase inhibitors such as
topiramate, as there are insufficient data to rule out a possible pharmacodynamic interaction1
*No interaction studies have been conducted between ZNS and LEV. However, neither product PI state an expected
interaction between the two products1,2
ZNS†Lamotrigine Phenytoin
CBZ LEV*
No known
interactions
No known
interactions
Noclinically
relevant
interactions
ZNS = Zonegran;
LEV =
Levetiracetam
Sodium
valproate
40. Zonisamide – Dosage & Administration
For monotherapy & adjunctive therapy in the treatment of
seizures:
• Start with 100mg once a day
• Titrate at 1 – 2 weeks interval
• Average maintenance dosage is 200 – 400 mg/day
• Maximum recommended dose is 600 mg/day
41. Is 100mg the right dose to initiate therapy?
As adjunctive therapy in the treatment of partial seizures
• 100 mg is the recommended starting dose1,2
• 100 mg is Minimum therapeutic dose3
• Pivotal Global trials conducted by initiating at 100 mg3,4,5
• Standard textbooks recommend to start at 100 mg6,7
1. Zonegran International Prescribing Information available at www.zonegran.com
2. Exegran International Prescribing Information available athttp://www.e-search.ne.jp/~jpr/HTML/EJPR002.HTM
3. Faught E,& Ayala R, et.al. Neurology 2001; 57: 1774-79.
4.Schmidt D & Jacob R et al. Epilepsy Res 1993;15:67-73
5.Sackellares JC & Ramsay RE et al. Epilepsia 2004;45(6):610-617
6. Seino M & Fujitani B. ‘Zonisamide’ in Simon Shorvon’s ‘The Treatment of Epilepsy’ 2nd Edition 2005: 48: 548-59 Blackwell Publications
7.Seino M & Leppik I.E. ‘Zonisamide’ in Jerome Engel JR’s ‘Epilepsy A Comprehensive Text Book’ 2nd Edition; 162:1695-1701.Lippincott Williams & Wilkins
42. Relation between the
Dose and effective Blood Plasma Concentration
Ono T and Yagi K : “ Clinical Efficacy and safety of a new AntiEpileptic Drug, Zonisamide ”
A multi – Institutional Phase III study
The study was conducted on total 538 patients across 34 institutions
On an average 2.9 antiepileptic drugs were already used before adding
Zonisamide
• Carbamazepine , Phenytoin, Sodium Valporate and phenobarbital
Zonisamide was initiated with 100mg/day dosage and increased at 1-2
weekly intervals gradually by 100mg/day (mean dose of 6.08±2.89
mg/kg/day)
43. Relation between the
Dose and effective Blood Plasma Concentration
• Analysis of 308 patients was
done in whom blood serum
concentration of zonisamide was
measured
• A linear relation ship was
observed in the blood plasma
drug concentration and
therapeutic efficacy, with
significant difference in favor of
increasing drug concentration &
therapeutic efficacy observed
(p<0.05 in-between groups)
#p<0.05 versus moderate
improvement; *p<0.05 versus
unchanged
44. Zonisamide : Broad spectrum drug?
ZNS studies in Japan
– Compilation of data (Seino 2004; Yagi 2004)
– 1008 patients from controlled and uncontrolled studies,
over a 7-year period at 56 centers
Seizure type / syndromic context N Responders
Simple, complex partial 507 50-57%
Secondary generalized 168 60%
GTC 46 59%
Absence (typical, atypical) 13 62%
Atonic 10 50%
myoclonic 7 43%
Generalised ep. (IGE, West, Lennox, others) 282 22-66%
46. Poor Medicine Compliance
• Forgetting to take medication is a particularly serious matter for
patients suffering from seizures.
• Missed AED doses can lead to breakthrough seizures and any
breakthrough seizure leaves the patients at risk of injury or at a
minimum negative lifestyle impact.
• While compliance is best with once daily dose, the risks of seizure
recurrence after missing a dose may also be greatest.
• Zonisamide’s particularly long 60 hour half-life offers additional
protection against therapy adherence issues if a dose is missed
47. Added clinical value of zonisamide as new
monotherapy option
• Effective as Monotherapy and early adjunctive in seizure control
• Efficacy / tolerability ratio similar to that of current best medical
practice (reference drug)
with
• Different mechanism of action
• Broad-spectrum activity
• Minimal drug-drug interactions
(no interaction with the combined oral contraceptive pill)
• Simple use: once daily dosing with easy titration
• Weight neutral
Zonisamide is a benzisoxazole derivative, first synthesized in 1972 and structurally distinct from other AEDs (Baulac, 2006).
Its anticonvulsant activity was discovered somewhat fortuitously and the drug has subsequently proved to have efficacy in a number of experimental seizure models (Baulac, 2006).
Zonisamide was first marketed for the treatment of partial seizures (with or without secondary generalization) in Japan in 1989 and has since gained regulatory
approval in the United States and Europe, in 2000 and 2005, respectively and for monotherapy & adjunctive therapy in adult with Partial seizures, Generalized seizures & Combined seizures in India 2008.
Over 2 million patient years of experience with Zonegran in epilepsy1
Algorythm
Monotherapy 60% of our patient population, and concerns nearly every patient
In addition some ptients are reconverted to a single drug treatment
Data on file
Data on file
Data on file
Current evidence suggests that ZNS has multiple modes of action.
It exerts its pharmacological effects by blockade of neuronal voltage-gated sodium channels and low-voltage activated (T-type) calcium channels.
A modest inhibitory effect on carbonic anhydrase has been reported, which is thought to be 100 to 200 times less potent than that of acetazolamide.
This mechanism is not believed to signifi cantly contribute to the antiepileptic actions of the drug.
ZNS causes reduction of glutamate-mediated synaptic excitation and alteration of monoamine (dopaminergic and serotonergic) neurotransmission.
Zonisamide also has several mechanisms that may increase its neuroprotection properties (ie, ability to protect neurons from damage due to certain biochemical reactions).
Decreasing lipid peroxidation in the cortex (lipid peroxidation is a chemical reaction in which free radicals can disrupt and destroy neuronal membranes), scavenging free radicals , reducing nitric oxide synthase (nitric oxide is a potentially damaging free radical), decreasing glutamate excitotoxicity (excitotoxicity contributes to lipid peroxidation and is linked to neuronal damage)
ZNS can be given once-daily after titration phase; enabling a once-daily dose regimen and assuring steady therapeutic drug levels after titration phase.
Current evidence, clinical experience, and pharmacokinetic principles would all suggest that the introduction of zonisamide as an adjunctive agent in the treatment of epilepsy will have little or no impact on the circulating concentrations of other AEDs and would not require any dosage adjustment in background therapy.
However, carbamazepine, phenytoin, and phenobarbital all induce the metabolism of zonisamide, thereby increasing clearance and reducing steady-state concentrations by induction.
Despite this interaction, the half-life of zonisamide is unlikely to be sufficiently reduced to necessitate any change in the dosing interval and, given that adjunctive agents are typically titrated to clinical effect, the clinical impact can be expected to be minimal.
Indeed, the interaction with enzyme-inducing AEDs may be advantageous by permitting a more rapid attainment of steady-state zonisamide concentrations.
Zonisamide does not metabolically interact with the hormonal components of the oral contraceptive pill and would not be expected to affect the metabolism of any other therapeutic agent.
In conclusion, the favorable pharmacokinetic and drug interaction profile of zonisamide, together with its broad spectrum of efficacy and good tolerability as determined across an excess of 2 million patient-years exposure, support its use as an adjunctive agent.
Overall, 80% of patients on ZNS monotherapy showed good control (≥ 50% seizure reduction). Sixty-nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of attaining the maintenance dose. One patient on polytherapy had a 75% reduction in seizure frequency for all three subtypes, whereas the other patient showed inadequate response.
