Chemical: Drug
zonisamide

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


Annotated Labels

  1. FDA Label for zonisamide
  2. EMA Label for zonisamide and CYP3A4


last updated 09/16/2014

2. EMA Label for zonisamide and CYP3A4

Informative PGx

Genes and/or phenotypes found in this label

  • CYP3A4
    • dosage, metabolism/PK, Dosage & administration section, Drug interactions section, Pharmacokinetics section
    • source: European Medicines Agency

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for zonisamide

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA HLA-A *02:07:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *07:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *15:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *46:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *08:03:02 N/A N/A N/A
No VIP available CA VA
rs2306719 NC_000015.10:g.63341039T>C, NC_000015.9:g.63633238T>C, NG_028022.1:g.45838A>G, NM_001218.4:c.526-256A>G, NM_001293642.1:c.346-256A>G, NM_206925.2:c.526-256A>G, XM_005254655.1:c.346-256A>G, XR_932358.1:n.768-775T>C, rs17763221, rs59688855
T > C
SNP
No VIP available CA VA
rs4984241 NC_000015.10:g.63331264A>G, NC_000015.9:g.63623463A>G, NG_028022.1:g.55613T>C, NM_001218.4:c.875-3134T>C, NM_001293642.1:c.695-4031T>C, NM_206925.2:c.875-4031T>C, XM_005254655.1:c.695-4031T>C, XR_932358.1:n.768-10550A>G, rs57855406
A > G
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Zonisamida [Spanish]
  • Zonisamidum [Latin]
  • zonisamide
Trade Names
  • Exceglan
  • Excegram
  • Excegran
  • Zonegran
Brand Mixture Names

PharmGKB Accession Id

PA451978

Type(s):

Drug

Description

Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may be a carbonic anhydrase inhibitor although this is not one of the primary mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels leading to a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.

Source: Drug Bank

Indication

For use as adjunctive treatment of partial seizures in adults with epilepsy.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Zonisamide binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity.

Source: Drug Bank

Pharmacology

Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and calcium channels, which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). 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).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Primarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2-sulfamoylacetyl phenol, respectively.

Source: Drug Bank

Protein Binding

40% (at concentrations of 1.0-7.0 microg/mL)

Source: Drug Bank

Absorption

Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.

Source: Drug Bank

Half-Life

63 hours

Source: Drug Bank

Toxicity

Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.

Source: Drug Bank

Route of Elimination

Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.

Source: Drug Bank

Volume of Distribution

  • 1.45 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C8H8N2O3S

Source: Drug Bank

Isomeric SMILES

c1ccc2c(c1)c(no2)CS(=O)(=O)N

Source: OpenEye

Canonical SMILES

NS(=O)(=O)CC1=NOC2=CC=CC=C12

Source: Drug Bank

Average Molecular Weight

212.226

Source: Drug Bank

Monoisotopic Molecular Weight

212.025562822

Source: Drug Bank

SMILES

NS(=O)(=O)CC1=NOC2=CC=CC=C12

Source: Drug Bank

InChI String

InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
CA1 (source: Drug Bank )
CA10 (source: Drug Bank )
CA11 (source: Drug Bank )
CA12 (source: Drug Bank )
CA13 (source: Drug Bank )
CA14 (source: Drug Bank )
CA2 (source: Drug Bank )
CA3 (source: Drug Bank )
CA4 (source: Drug Bank )
CA5A (source: Drug Bank )
CA5B (source: Drug Bank )
CA6 (source: Drug Bank )
CA7 (source: Drug Bank )
CA8 (source: Drug Bank )
CA9 (source: Drug Bank )
CACNA1G (source: Drug Bank )
CACNA1H (source: Drug Bank )
CACNA1I (source: Drug Bank )
MAOA (source: Drug Bank )
MAOB (source: Drug Bank )
SCN11A (source: Drug Bank )
SCN1A (source: Drug Bank )
SCN1B (source: Drug Bank )
SCN2B (source: Drug Bank )
SCN3A (source: Drug Bank )
SCN3B (source: Drug Bank )
SCN4A (source: Drug Bank )
SCN4B (source: Drug Bank )
SCN5A (source: Drug Bank )
SCN9A (source: Drug Bank )

Drug Interactions

Interaction Description
telithromycin - zonisamide Telithromycin may reduce clearance of Zonisamide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Zonisamide if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
triprolidine - zonisamide The CNS depressants, Triprolidine and Zonisamide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
triprolidine - zonisamide The CNS depressants, Triprolidine and Zonisamide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
voriconazole - zonisamide Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of zonosamide if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if amprenavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if atazanavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - clarithromycin Clarithromcyin, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if clarithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if conivaptan is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if darunavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if delavirdine is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if fosamprenavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if imatinib is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if indinavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if isoniazid is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - itraconazole Itraconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if itraconazole is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - ketoconazole Ketonconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if ketoconazole is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - lopinavir Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if lopinavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - mefloquine Mefloquine may decrease the serum concentration and therapeutic effect of zonisamide. Concomitant therapy is contraindicated in patients with history of convulsions. (source: Drug Bank )
zonisamide - methotrimeprazine Additive CNS depressant effects. Reduce zonisamide dose by half upon initiation of methotrimeprazine. Zonisamide dose may be adjusted once methotrimeprazine dose has been established. Monitor for increased CNS depression. (source: Drug Bank )
zonisamide - nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nefazodone is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nelfinavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nicardipine is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - quinidine Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if quinidine is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - ritonavir Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if ritonavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if saquinavir is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - telithromycin Telithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
zonisamide - voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to zonisamide: 7

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics. 2013. Kaniwa Nahoko, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors. Pharmacogenetics and genomics. 2011. Mirza Nasir S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Key factors in the discovery and development of new antiepileptic drugs. Nature reviews. Drug discovery. 2010. Bialer Meir, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics. 2008. Kaniwa Nahoko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics. 2006. Seo Takayuki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Defining the clinical role of pharmacogenetics in antiepileptic drug therapy. The pharmacogenomics journal. 2006. Dlugos D J, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-6725-01
DrugBank:
DB00909
ChEBI:
10127
KEGG Compound:
C07504
KEGG Drug:
D00538
PubChem Compound:
5734
PubChem Substance:
188654
46505278
BindingDB:
10888
ChemSpider:
5532
Therapeutic Targets Database:
DAP000500
FDA Drug Label at DailyMed:
6d2f9c84-a597-4055-8815-8fbcdf4c4876

Clinical Trials

These are trials that mention zonisamide and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.