Advanced search
Publication Cover
Expert Opinion on Drug Metabolism & Toxicology Volume 4, 2008 - Issue 4
Submit an article Journal homepage
346
Views
43
CrossRef citations to date
0
Altmetric
Drug Evaluation

Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety

Sanjeev V Kothare Associate Director, Sleep Center for Children Fellowship Director, Pediatric Sleep Medicine Training Program, Division of Epilepsy & Clinical Neurophysiology, Department of Neurology, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Fegan 9 Boston, MA 02115, USA +1 617 355 6663; +1 617 730 0463; [email protected]
, MD FAAP &
Joseph Kaleyias Consultant Children's Hospital of Patras, Paediatric Neurology Department, 40 Erythrou Stavrou, 26500 Patra, Greece
, MD PhD
Pages 493-506 | Published online: 23 Apr 2008

Bibliography

  • Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314-9
  • Brodie MJ. Zonisamide as adjunctive therapy for refractory partial seizures. Epilepsy Res 2006;68(Suppl 2):S11-6
  • Baulac M. Introduction to zonisamide. Epilepsy Res 2006;68(Suppl 2):S3-9
  • Masuda Y, Utsui Y, Shiraishi Y, et al. Relationships between plasma concentrations of diphenylhydantoin, phenobarbital, carbamazepine, and 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), a new anticonvulsant agent, and their anticonvulsant or neurotoxic effects in experimental animals. Epilepsia 1979;20:623-33
  • Leppik IE. Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure 2004;13(Suppl):S5-9
  • Eisai Ltd. Zonegran® 25 mg, 50 mg, 100 mg hard capsules. Available from: www.emea.europa.eu/humandocs/PDFs/EPAR/zonegran/H-577-PI-en.pdf [Last accessed 20 January 2008]
  • Mimaki T. Clinical pharmacology and therapeutic drug monitoring of zonisamide. Ther Drug Monit 1998;20:593-7
  • Shah J, Shellenberger K, Canafax DM. Zonisamide: chemistry, biotranformation, and pharmacokinetics. In: Levy RH, Mattson RH, Meldrum BS, Perucca E, editors, Antiepileptic drugs. 5th edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002. p. 873-9
  • Perucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokinet 1996;31:29-46
  • Sills GJ, Brodie MJ. Pharmacokinetics and drug interactions with zonisamide. Epilepsia 2007;48:435-41
  • Biton V. Zonisamide: newer antiepileptic agent with multiple mechanisms of action. Expert Rev Neurother 2004;4:935-43
  • Walker MC, Patsalos PN. Clinical pharmacokinetics of new antiepileptic drugs. Pharmacol Ther 1995;67:351-84
  • Kochak G, Page J, Buchanan R, et al. Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment of refractory complex partial seizures. J Clin Pharmacol 1998;38:166-71
  • Leppik IE. Zonisamide. Epilepsia 1999;40(Suppl 5):S23-9
  • Stiff DD, Robicheau JT, Zemaitis M. Reductive metabolism of the anticonvulsant agent, zonisamide, a 1,2-benzisoxazole derivative. Xenobiotica 1992;22:1-11
  • Nakasa H, Ohmori S, Kitada M. Formation of 2-sulphamoylacetylphenol from zonisamide under aerobic conditions in rat liver microsomes. Xenobiotica 1996;26:495-501
  • MacDonald RL. Zonisamide: mechanism of action. In: Levy R, Mattson R, Meldrum B, Perucca E. Antiepileptic drugs. (fifth ed). Philadelpia, PA: Lippincott, Williams & Witkins Healthcare; 2002. p. 867-72
  • Hori M, Ito M, Yoshida K, Shimuzu M. Effect of anticonvulsants on spiking activity induced by cortical freezing in cats. Epilepsia 1979;20:25-36
  • Ito T, Hori M, Yoshida K, Shimuzu M. Effect of anticonvulsants on experimental cortical epilepsy induced by tungstic acid gels in rats. Arch Int Pharmacodyn Ther 1979;241:287-99
  • Suzuki S, Kawakami K, Nishimura S, et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 1992;12:21-7
  • Kito M, Maechara M, Watanbe K. Mechanisms of T-type calcium channel blockage by zonisamide. Seizure 1996;5:115-9
  • Rock DM, MacDonald RL, Taylor CP. Blockade of sustsained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res 1989;3:138-43
  • Biton V. Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol 2007;30:230-40
  • Ueda Y, Doi T, Tokumaru J, Wwillmore LJ. Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res 2003;116:1-6
  • Kaneko S, Okada M, Hirano T, et al. Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo, and carbamazepine does not antagonize adenosine effect in vitro: mechanisms of blockade of seizure spread. Jpn J Psychiatry Neurol 1993;47:371-3
  • Okada M, Kawata Y, Mizuno K, et al. Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode. Br J Pharmacol 1998;124:1277-85
  • Masuda Y, Karasawa T. Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung 1993;43:416-8
  • Mori A, Noda Y, Packer L. The anticonvulsant zonisamide scavenges free radicals. Epilepsy Res 1998;30:153-8
  • Noda Y, Mori A, Parker L. Zonisamide inhibits nitric oxide synthase activity induced by N-methyl-D-aspartate and buthionine sulfoximine in the rat hippocampus. Res Commun Mol Pathol Pharmacol 1999;105:23-33
  • Oowen A, Ijaz S, Miyashita H, et al. Zonisamide as neuroprotective agent in an adult gerbil model of global forebrain ischaemia: a histological, in vivo microdialysis and behavioral study. Brain Res 1997;770:115-22
  • Komatsu M, Hiramatsu M, Willmore LJ. Zonisamide reduces the increase in 8-hydroxyl-2-deoxyguanosine levels formed during iron-induced epileptogenesis in the brain of rats. Epilepsia 2000;41:1091-4
  • Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy:interactions between antiepileptic drugs and other drugs. Lancet Neurol 2003;2:473-81
  • Levy RH, Rageneau-Majelessi I, Garnett WR, et al. Lack of a clinically significant effect of zonisamide on phenytoin steady-state pharmacokinetics in patients with epilepsy. J Clin Pharmacol 2004;44:1230-4
  • Levy RH, Rageneau-Majelessi I, Brodie MJ, et al. Lack of clinically significant pharmacokinetic interactions between zonisamide and lamotrigine at steady state in patients with epilepsy. Ther Drug Monit 2005;27:193-8
  • Rageneau-Majlessi I, Levy RH, Bergen D, et al. Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients. Epilepsy Res 2004;62:1-11
  • Rageneau-Majlessi I, Levy RH, et al. Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Clin Pharmacokinet 2005;44:517-23
  • Minami T, Ieiri I, Ohtsubo K, et al. Influence of additional therapy with zonisamide (Excegran) on protein binding and metabolism of carbamazepine. Epilepsia 1994;35:1023-5
  • Dodgson SJ, Shank RP, Maryanoff BE. Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia 2000;41(Suppl 1):S35-9
  • Kossoff EH, Pyzik PL, Furth SL, et al. Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet. Epilepsia 2002;39:1168-71
  • Bialer M. The pharmacokinetics and interactions of new antiepileptic drugs: an overview. Ther Drug Monit 2005;27:722-6
  • Shinoda M, Akita M, Hasegawa M, Hasegawa T, Nabesima T. The necessity of adjusting the dosage of zonisamide when co administrated with other anti-epileptic drugs. Biol Pharmacol Bull 1996;19:1090-92
  • Griffith SG, Dai Y. Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clin Ther 2004;26:2056-65
  • Sackellares JC, Ramsay RE, Wilder BJ, et al. Randomized, controlled, clinical trial of zonisamide as adjunctive treatment for refractory partial seizures. Epilepsia 2004;45:610-7
  • Faught E, Ayala R, Montouris GG, et al. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology 2001;57:1774-9
  • Schmidt D, Jacob R, Loiseau P, et al. Zonisamide for an add-on treatment of refractory epilepsy: a European double blind trial. Epilepsy Res 1993;15:67-73
  • Brodie MJ, Duncan R, Vespignani H, et al. Dose-dependent safety and efficacy of zonisamide: a randomized, double blind, placebo-controlled study in patients with refractory partial seizures. Epilepsia 2005;46:31-41
  • Leppik IE, Willmore LJ, Homan RW, et al. Efficacy and safety of zonisamide: results of a multicenter study. Epilepsy Res 1993;14:165-73
  • Yagi K, Seino M. Methodological requirements for clinical trials in refractory epilepsies-our experience with zonisamide. Prog Neuropsychopharmacol Biol Psychiatry 1992;16:79-85
  • Yamauchi T, Aikawa H. Efficacy of zonisamide; our experience. Seizure 2004;13(Suppl 1):S41-8
  • Iinuma K, Haginoya K. Clinical efficacy of zonisamide in childhood epilepsy after long-term treatment: a postmarketing, multi-institutional survey. Seizure 2004;13(Suppl 1):S34-9
  • Ohtahara S, Yamatogi Y. Safety of zonisamide therapy: prospective follow-up survey. Seizure 2004;13(Suppl 1):S50-5
  • Glauser TA, Pellock JM. Zonisamide in pediatric epilepsy: review of the Japanese experience. J Child Neurol 2002;17:87-96
  • Kothare SV, Kaleyias J, Mostofi N, et al. Efficacy and safety of zonisamide monotherapy in a cohort of children with epilepsy. Pediatr Neurol 2006;34:351-4
  • Kothare SV, Valencia I, Khurana DS, et al. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Dis 2004;6:267-70
  • Sakamoto K, Kurokawa S, Tomita S, et al. Therapeutic effects of zonisamide (AD-810) on infantile epilepsy. Med Consult New Remedies 1986;23:2571-81
  • Yamatogi Y, Ohtahara S. Current topics on treatment. In: Ohtahara S, Roger J, editors, New trends in pediatric epileptology. Okayama: Okayama University Medical School; 1991. p. 136-48
  • Lotze TE, Wilfong AA. Zonisamide treatment for symptomatic infantile spasms. Neurology 2004;62:296-8
  • Kishi T, Nejihashi Y, Kajiyama M, Ueda K. Successful zonisamide treatment for infants with hypsarrythmia. Pediatr Neurol 2000;23:274-7
  • Hikima A, Shimizu N, Takizawa N. Treatment of West syndrome with zonisamide: 13 case reports. No To Hattatsu 1993;25(Suppl):132
  • Yanagihara K, Imai K, Otani K, Futagi Y. The effect of zonisamide in West syndrome. No To Hattatsu 1995;27:500-2
  • Yanai S, Hanai T, Narazaki O. Treatment of infantile spasms with zonisamide. Brain Dev 1999;21:157-61
  • Kawawaki H, Tomiwa K, Shiraishi K, Murata R. Efficacy of zonisamide in West syndrome. No To Hattatsu 1999;31:263-7
  • Suzuki Y. Zonisamide in West syndrome. Brain Dev 2001;23:658-61
  • Ohno M, Shimotsuji Y, Abe J, et al. Zonisamide treatment of early infantile epileptic encephalopathy. Pediatr Neurol 2000;23:341-4
  • Yamatogi Y, Ohtahara S. Early-infantile epileptic encephalopathy with suppression-bursts, Ohtahara syndrome; its overview referring to our 16 cases. Brain Dev 2002;24:13-23
  • Henry TR, Leppik IE, Gumnit RJ, Jacobs M. Progressive myoclonus epilepsy treated with zonisamide. Neurology 1988;38:928-31
  • Kyllerman M, Ben-Menachem E. Zonisamide for progressive myoclonus epilepsy: long term observations in seven patients. Epilepsy Res 1998;29:109-14
  • Yoshimura I, Kaneko S, Yoshimura N, Murakami T. Long-term observations of two siblings with Lafora disease treated with zonisamide. Epilepsy Res 2001;46:283-7
  • Ohtahara S. Zonisamide in the management of epilepsy-Japanese experience. Epilepsy Res 2006;68(Suppl 2):S25-33
  • Tanabe M, Sakaue A, Takasu K, et al. Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse. Naunyn Schmiedebergs Arch Pharmacol 2005;372:107-14
  • Hasegawa H. Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments a retrospective, open label, uncontrolled study in VA hospital. Curr Res Opin 2004;20:577-80
  • Krusz JC. Treatment of chronic pain with zonisamide. Pain Pract 2003;3:317-20
  • Atli A, Dogra S. Zonisamide in the treatment of painful diabetic neuropathy: a randomized-double blind-placebo controlled pilot study. Pain Med 2005;6:225-34
  • Ashkenazi A, Benlifer A, Korenblit J, Silberstein SD. Zonisamide for migraine prophylaxis in refractory patients. Cephalalgia 2006;26:1199-202
  • Pakalnis A, Kring D. Zonisamide prophylaxis in refractory pediatric headache. Headache 2006;46:804-7
  • Drake ME Jr, Greathouse NI, Renner JB, Armentbright AD. Open-label zonisamide for refractory migraine. Clin Neuropharmacol 2004;27:274-80
  • Wang PW, Yang YS, Chandler RA, et al. Adjunctive zonisamide for weight loss in euthymic bipolar disorder patients: a pilot study. J Psychiatry Res 2008;42:451-7
  • Gadde KM, Franciscy DM, Wagner HR 2nd, Krishan KR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 2003;289:1820-5
  • Kim CS. Zonisamide effective for loss weight in women. J Fam Prac 2003;52:600-1
  • McElroy SL, Kotwal R, Guerdjikova AI, et al. Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry 2006;67:1897-906
  • Miwa H. Zonisamide for the treatment of Parkinson's disease. Expert Rev Neurother 2007;7:1077-83
  • Murata M, Hasegawa K, Kanaza I. The Japan Zonisamide on PD Study Group. Zonisamide improves motor function in Parkinson disease: a randomized double-blind study. Neurology 2007;68:45-50
  • Seki T, Kumagai N, Maezawa M. Effects of zonisamide monotherapy in children with epilepsy. Seizure 2004;13(Suppl 1):S26-32
  • Guni H, Hayashi K, Fukuyama Y, et al. Phase III clinical study of the new antiepileptic drug AD-810 (zonisamide) in patients with childhood epilepsy. Jpn J Pediatr 1988;41:439-50
  • Kothare SV, Kaleyias J. The adverse effects of antiepileptic drugs in children. Expert Opin Drug Saf 2007;6:251-65
  • Faught E. Review of United States and European clinical trials of zonisamide in the treatment of refractory partial-onset seizures. Seizure 2004;13(Suppl 1):S59-65
  • Leppik IE. Practical prescribing and long-term efficacy and safety of zonisamide. Epilepsy Res 2006;68(Suppl 2):S17-24
  • Kluger G, Zsoter A, Holthausen H. Long-term use of zonisamide in refractory childhood-onset epilepsy. Eur J Pediatr Neurol 2008;12:19-23
  • Loscher W, Schmidt D. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment of antiepileptic drugs. Epilepsia 2006;47:1253-84
  • Hamada K, Song HK, Ishida S, et al. Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats. Epilepsia 2001;42:1279-86
  • Wroe S. Zonisamide and renal calculi in patients with epilepsy: how big an issue? Curr Med Res Opin 2007;23:1765-73
  • Sampath A, Kossoff EH, Furth SL, et al. Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol 2007;22:375-8
  • Low PA, James S, Peschel T, et al. Zonisamide and associated oligohidrosis and hyperthermia. Epilepsy Res 2004;62:27-34
  • Knudsen JF, Thambi LR, Kapcala LP, Racoosin JA. Oligohydrosis and fever in pediatric patients treated with zonisamide. Pediatr Neurol 2003;28:184-9
  • Okumura A, Hayakawa F, Kuno K, Watanabe K. Oligohydrosis caused by zonisamide. No to Hattatsu 1996;28:44-7
  • Hosoda N, Niura H, Shirai H, et al. Clinical study on oligohydrosis in patients treated with zonisamide. Shonika Rinsyo 1996;49:2445-9
  • Reilly TP, Ju C. Mechanisms perspectives on sulphonamide-induced cutaneous drug reactions. Curr Opin Allergy Clin Immunol 2002;2:307-15
  • Chadwick DW, Marson AG. Zonisamide add-on for drug-resistant partial epilepsy. Cohrane Database Syst Rev 2002:CD001416
  • De Simone G, Supuran CT. Antiobesity carbonic anhydrase inhibitors. Curr Top Med Chem 2007;7:879-84
  • Sommerville ER. Seizure aggravation by antiepileptic drugs. Curr Treat Options Neurol 2006;8:289-96
  • Bialer M, Johannessen SI, Kupferbergh J, et al. Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI). Epilepsy Res 2002;51:31-71
  • Kondo T, Kaneko S, Amano Y, Egawa I. Preliminary report on teratogenic effects of zonisamide in the offspring of treated women with epilepsy. Epilepsia 1996;37:1242-4
  • Ohtahara S, Yamatogi Y. Erratum to ‘Safety of zonisamide therapy; prospective follow-up survey’. Seizure 2007;16:87-93
  • Uthman BM, Reichl A. Progressive myoclonic epilepsy. Curr Treat Options Neurol 2002;4:3-17

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.