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Zonisamide structure.svg
Ball-and-stick model of the zonisamide molecule
Trade namesZonegran, others
  • benzo[d]isoxazol-3-ylmethanesulfonamide
Clinical data
Drug classSulfonamide[1]
Main usesEpilepsy (partial seizures)[1]
Side effectsAbdominal pain, nausea, constipation, dry mouth, dizziness[1]
  • AU: D
Routes of
By mouth
External links
License data
Legal status
Protein binding40%[2]
MetabolismLiver through CYP3A4[2]
Elimination half-life63 hours in plasma[2]
ExcretionKidney (62%); Faeces (3%)[2]
Chemical and physical data
Molar mass212.22 g·mol−1
3D model (JSmol)
Melting point162 °C (324 °F)
  • O=S(=O)(N)Cc2noc1ccccc12
  • 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) checkY

Zonisamide, sold under the brand name Zonegran, is a medication used in addition to other medications to treat epilepsy, specifically partial seizures.[1] There is also some evidence for its use in Parkinson's.[3] It is taken by mouth.[1]

Common side effects include abdominal pain, nausea, constipation, dry mouth, and dizziness.[1] Other side effects may include hair loss, nystagmus, and bone marrow disorders.[4] Use during pregnancy may harm the baby and use during breastfeeding is not recommended.[5] It is in the sulfonamide family of chemicals and is not recommended in people allergic to these.[1][4]

Zonisamide was approved for medical use in the United States in 2000.[1] It is available as a generic medication.[6] In the United States it costs less than 20 USD per month as of 2021.[6] It is also relatively inexpensive in the United Kingdom.[4]

Medical uses


Zonisamide is used for adjunctive and monotherapy treatment of partial seizures.[7][8][9]

In Japan it is also used for generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.[10]


It has been approved for the treatment of the motor symptoms of Parkinson's disease (PD), as an adjunct to levodopa, in a few countries such as Japan.[3][11] In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009.[12] In addition, there is clinical evidence that zonisamide in combination with levodopa control of motor symptoms of PD but evidence for the treatment of the non motor symptoms of PD lacking.[13][14]


Zonisamide has been used for migraine preventation, when topiramate is either ineffective or cannot be continued due to side effects.[11]


It is typically started at 100 mg per day and may be increased up to 400 mg per day.[1] The typical long term dose is 300 mg per day.[4]

Side effects

Side effects by frequency:[2][15][16]

Very common (>10% incidence)

  • Anorexia
  • Somnolence
  • Dizziness
  • Agitation
  • Irritability
  • Confusional state
  • Depression
  • Diplopia
  • Memory impairment
  • Decreased bicarbonate

Common (1-10% incidence)


Zonisamide and other carbonic anhydrase inhibitors such as topiramate, furosemide, and hydrochlorothiazide have been known to interfere with amobarbital, which has led to inadequate anesthetization during the Wada test.[17] Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.[2]

Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.[18]

Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.[19]

Mechanism of action

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 T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity).[9] It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). It is also known to modulate GABAergic and glutamatergic neurotransmission.[9][20][21][22][23]



Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption.[24][19]


Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5,[25] to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.[26]


Zonisamide was discovered by Uno and colleagues in 1972[27] and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan.[28] It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004.[29] Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)[30] and Europe (starting in Germany and the United Kingdom).[31]

Society and culture


The cost of this medication in the U.S. is $30 (USD) for 100 capsules (100 mg) [32]



It has been studied for obesity.[33] It was to be sold, when combined with bupropion, as bupropion/zonisamide, until its development was discontinued.[34]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Zonisamide Monograph for Professionals". Drugs.com. Archived from the original on 27 February 2021. Retrieved 4 August 2021.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Zonegran Product Information" (PDF). TGA eBusiness Services. SciGen (Australia) Pty Ltd. 4 April 2013. Archived from the original on 15 October 2018. Retrieved 18 November 2013.
  3. 3.0 3.1 Grover ND, Limaye RP, Gokhale DV, Patil TR (November–December 2013). "Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson's disease". Indian Journal of Pharmacology. 45 (6): 547–55. doi:10.4103/0253-7613.121266. PMC 3847242. PMID 24347760.
  4. 4.0 4.1 4.2 4.3 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 350. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  5. "Zonisamide (Zonegran) Use During Pregnancy". Drugs.com. Archived from the original on 2 February 2021. Retrieved 5 August 2021.
  6. 6.0 6.1 "Zonisamide Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 5 August 2021.
  7. Élan Pharmaceuticals Inc (22 August 2003). "NDA 20-789/S-001; Zonegran (zonisamide) Capsules 25, 50, 100 mg FDA Approvable Labeling Text" (PDF). Zonisamide Approval History. Food and Drug Administration. Archived (PDF) from the original on 16 October 2012. Retrieved 24 August 2009.
  8. Eisai Ltd. (2005). "Zonegran Summary of Product Characteristics". electronic Medicines Compendium. Medicines.org.uk. Archived from the original on 8 November 2005. Retrieved 13 November 2005.
  9. 9.0 9.1 9.2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  10. Dainippon Pharmaceutical Co., Ltd. (2004). "EXCEGRAN Tablets 100 mg & EXCEGRAN Powder 20%" (PDF). Archived from the original (PDF) on 2007-09-28. Retrieved 13 March 2006.
  11. 11.0 11.1 Brayfield, A, ed. (8 March 2016). "Zonisamide: Martindale: The Complete Drug Reference". MedicinesComplete. London, UK: Pharmaceutical Press. Archived from the original on 27 August 2021. Retrieved 19 August 2017.
  12. Murata M, Hasegawa K, Kanazawa I (January 2007). "Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study". Neurology. 68 (1): 45–50. doi:10.1212/01.wnl.0000250236.75053.16. PMID 17200492. S2CID 894677.
  13. Grover ND, Limaye RP, Gokhale DV, Patil TR (2013). "Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson's disease". Indian Journal of Pharmacology. 45 (6): 547–55. doi:10.4103/0253-7613.121266. PMC 3847242. PMID 24347760.
  14. Matsunaga S, Kishi T, Iwata N (2017). "Combination Therapy with Zonisamide and Antiparkinson Drugs for Parkinson's Disease: A Meta-Analysis". Journal of Alzheimer's Disease. 56 (4): 1229–1239. doi:10.3233/JAD-161068. PMID 28157097.
  15. "Zonegran 25, 50, 100 mg Hard Capsules". electronic Medicines Compendium. Eisai Ltd. 8 October 2013. Archived from the original on 12 January 2015. Retrieved 18 November 2013.
  16. "zonisamide (Rx) - Zonegran". Medscape Reference. WebMD. Archived from the original on 4 December 2013. Retrieved 18 November 2013.
  17. Bookheimer S, Schrader LM, Rausch R, Sankar R, Engel J (February 2005). "Reduced anesthetization during the intracarotid amobarbital (Wada) test in patients taking carbonic anhydrase-inhibiting medications". Epilepsia. 46 (2): 236–43. doi:10.1111/j.0013-9580.2005.23904.x. PMID 15679504. S2CID 20730895.
  18. Nakasa H, Nakamura H, Ono S, Tsutsui M, Kiuchi M, Ohmori S, Kitada M (April 1998). "Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data". European Journal of Clinical Pharmacology. 54 (2): 177–83. doi:10.1007/s002280050442. PMID 9626925. S2CID 6508614.
  19. 19.0 19.1 "Zonegran 25, 50, 100 mg Hard Capsules". Electronic Medicines Compendium (eMC). Archived from the original on 14 February 2019. Retrieved 12 April 2017.
  20. Leppik IE (December 2004). "Zonisamide: chemistry, mechanism of action, and pharmacokinetics". Seizure. 13 Suppl 1 (Suppl 1): S5–9, discussion S10. doi:10.1016/j.seizure.2004.04.016. PMID 15511691. S2CID 13458791.
  21. Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (March 1990). "Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain". Medical Journal of Osaka University. 39 (1–4): 13–7. PMID 1369646.
  22. Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (March 1990). "[3H]zonisamide binding in rat brain". Medical Journal of Osaka University. 39 (1–4): 19–22. PMID 1369647.
  23. Ueda Y, Doi T, Tokumaru J, Willmore LJ (August 2003). "Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures". Brain Research. Molecular Brain Research. 116 (1–2): 1–6. doi:10.1016/S0169-328X(03)00183-9. PMID 12941455.
  24. "Zonisamide". www.drugbank.ca. Archived from the original on 2019-01-31. Retrieved 2019-01-31.
  25. Ohmori S, Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, Kitada M (May 1998). "Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells". Biochimica et Biophysica Acta (BBA) - General Subjects. 1380 (3): 297–304. doi:10.1016/s0304-4165(97)00156-6. PMID 9555064.
  26. Stiff DD, Robicheau JT, Zemaitis MA (January 1992). "Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative". Xenobiotica. 22 (1): 1–11. doi:10.3109/00498259209053097. PMID 1615700.
  27. Shah J, Kent S, Daniel MC (2002-06-15) [1972]. "Zonisamide". In René H, Levy RH, Brian SM, Perrucca E (eds.). Antiepileptic Drugs (Fifth ed.). Philadelphia: Lippincott Williams & Wilkins. p. 873. ISBN 0-7817-2321-3. Archived from the original on 2021-08-27. Retrieved 2007-11-07.
  28. Dainippon Sumitomo Pharma Co. Ltd. (2005). "Company History". Company Information. Dainippon Sumitomo Co., Ltd. Archived from the original on 13 February 2006. Retrieved 12 November 2005.
  29. Dainippon Pharmaceutical Co. Ltd. (2004). "Transfer of Rights Agreement for North America and Europe Reached on Zonegran". News Releases for Dainippon Pharmaceutical in 2004. Dainippon Sumitomo Pharma Co., Ltd. Archived from the original on 13 February 2006. Retrieved 12 November 2005.
  30. Dainippon Pharmaceutical Co. Ltd. (2005). "Dainippon Pharmaceutical and Eisai Conclude Agreement for the Development, Manufacture and Marketing of the Anti-Epileptic Agent Zonisamide in Asia". Dainippon Pharmaceutical News Releases for 2005. Dainippon Sumitomo Pharma Co., Ltd. Archived from the original on 22 February 2006. Retrieved 12 November 2005.
  31. Eisai Co. Ltd. (2005). "Eisai Announces Launch of Zonegran (zonisamide), Treatment For Epilepsy In the UK and Germany". Eisai 2005 News Releases. Eisai Co., Ltd. Archived from the original on 2005-10-28. Retrieved 12 November 2005.
  32. "Zonisamide Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 2 March 2021. Retrieved 10 April 2021.
  33. Gadde KM, Franciscy DM, Wagner HR, Krishnan KR (April 2003). "Zonisamide for weight loss in obese adults: a randomized controlled trial". JAMA. 289 (14): 1820–5. doi:10.1001/jama.289.14.1820. PMID 12684361.
  34. "Bupropion/zonisamide". AdisInsight. Springer. 20 May 2017. Archived from the original on 19 August 2017. Retrieved 19 August 2017.

External links

External sites: