Topiramate: Difference between revisions

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			{{Short description\|Medication used to treat epilepsy and migraine}}
	{{drugbox
			{{Use dmy dates\|date=January 2024}}
	\| verifiedrevid = 408963882
			{{cs1 config \|name-list-style=vanc \|display-authors=6}}
	\| IUPAC_name = 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
			{{Infobox drug
	\| image = Topiramate.svg
			\| Verifiedfields = changed
	\| image2 = Topiramate 3D.png
			\| Watchedfields = changed
	\| width = 191
			\| verifiedrevid = 408971931
	\| CASNo_Ref = {{cascite\|correct\|CAS}}
			\| image = Topiramate structure.svg
	\| UNII_Ref = {{fdacite\|correct\|FDA}}
			\| width = 175
	\| UNII = 0H73WJJ391
			\| alt =
	\| InChI = 1/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1
			\| image2 = Topiramate 3D.png
	\| InChIKey = KJADKKWYZYXHBB-XBWDGYHZBQ
			\| alt2 =
	\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}
			\| caption =
	\| ChEMBL = 220492
	\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChI = 1S/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1
	\| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChIKey = KJADKKWYZYXHBB-XBWDGYHZSA-N
	\| CAS_number = 97240-79-4
	\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
	\| ChemSpiderID = 4447672
	\| ATC_prefix = N03
	\| ATC_suffix = AX11
	\| ATC_supplemental =
	\| PubChem = 5284627
	\| DrugBank = APRD00237
	\| KEGG_Ref = {{keggcite\|correct\|kegg}}
	\| KEGG = D00537
	\| C = 12 \| H = 21 \| N = 1 \| O = 8 \| S = 1
	\| molecular_weight = 339.363 g/mol
	\| smiles = O=S(=O)(OC21OC(O13OC(O3CO2)(C)C)(C)C)N
	\| bioavailability = 80%
	\| protein_bound =
	\| metabolism = 30% hepatic, 70% is excreted unchanged
	\| elimination_half-life = 19 to 23 hours
	\| pregnancy_AU = B3
	\| pregnancy_US = C
	\| legal_UK = POM
	\| legal_US = Rx-only
	\| routes_of_administration = Oral
	\| excretion = 70% renal (in urine) in unchanged form
	}}

			<!-- Clinical data -->
	'''Topiramate''' (brand name '''Topamax''') is an ] (antiepilepsy) drug. It was originally produced by ] and ], Inc., both divisions of ]. It was discovered in 1979 by ] and Joseph F. Gardocki during their research work at McNeil Pharmaceutical.<ref>{{cite journal \|last1=Maryanoff \|first1=BE \|last2=Nortey \|first2=SO \|last3=Gardocki \|first3=JF \|last4=Shank \|first4=RP \|last5=Dodgson \|first5=SP \|title=Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds \|journal=Journal of medicinal chemistry \|volume=30 \|issue=5 \|pages=880–7 \|year=1987 \|pmid=3572976}}</ref><ref>{{cite journal \|last1=Maryanoff \|first1=BE \|last2=Costanzo \|first2=MJ \|last3=Nortey \|first3=SO \|last4=Greco \|first4=MN \|last5=Shank \|first5=RP \|last6=Schupsky \|first6=JJ \|last7=Ortegon \|first7=MP \|last8=Vaught \|first8=JL \|title=Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives \|journal=Journal of medicinal chemistry \|volume=41 \|issue=8 \|pages=1315–43 \|year=1998 \|pmid=9548821 \|doi=10.1021/jm970790w}}</ref><ref>B. E. Maryanoff and J. F. Gardocki, "Anticonvulsant sulfamate derivatives", U.S. Patent 4,513,006 (1985)</ref> Generic versions are available in Canada and were FDA approved in September 2006. ] was recently granted final approval for generic topiramate 25, 100, and 200 mg tablets and sprinkle capsules by the FDA for sale in the US. 50 mg tablets were granted tentative approval.<ref>http://www.medscape.com/viewarticle/544994</ref> The last patent for topiramate in the U.S. was for pediatric use; this patent expired on February 28, 2009.<ref>http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx</ref>
			\| pronounce =
			\| tradename = Topamax, Trokendi XR, Qudexy XR, others
			\| Drugs.com = {{drugs.com\|monograph\|topiramate}}
			\| MedlinePlus = a697012
			\| DailyMedID = Topiramate
			\| pregnancy_AU = D
			\| pregnancy_AU_comment =
			\| pregnancy_category=
			\| routes_of_administration = ]
			\| class =
			\| ATC_prefix = N03
			\| ATC_suffix = AX11
			\| ATC_supplemental =

			<!-- Legal status -->
	==Indications==
			\| legal_AU = S4
	Topiramate treats ] in children and adults and was originally marketed as an anticonvulsant. In children it is indicated for the treatment of ], a disorder that causes seizures and developmental delay. It is also ] (FDA) approved for, and most frequently prescribed for, the prevention of ]s. Psychiatrists have used topiramate to treat ],<ref>{{cite journal \|last1=Arnone \|first1=D \|title=Review of the use of Topiramate for treatment of psychiatric disorders \|journal=Annals of general psychiatry \|volume=4 \|issue=1 \|pages=5 \|year=2005 \|pmid=15845141 \|pmc=1088011 \|doi=10.1186/1744-859X-4-5}}</ref> and often use topiramate to augment psychotrophics or counteract weight gain associated with numerous antidepressants. However, a 2006 ] concluded that there is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness.<ref>{{cite journal \|last1=Vasudev \|first1=Kamini \|last2=MacRitchie \|first2=Karine \|last3=Geddes \|first3=John \|last4=Watson \|first4=Stuart \|last5=Young \|first5=Allan H \|last6=Young \|first6=Allan H \|title=Topiramate for acute affective episodes in bipolar disorder \|year=2006 \|doi=10.1002/14651858.CD003384.pub2}}</ref> On May 21, 2010, Ortho-McNeil plead guilty and was fined {{currency\|6.14 million\|US}} by the FDA for promoting Topamax to treat psychiatric disorders, without applying for any approval and there was no data from any well-controlled clinical trial to demonstrate that Topamax was safe and effective to treat any psychiatric conditions.<ref>{{cite web\|date=2010-05-21\|accessdate=2010-05-25\|title=Ortho-McNeil Pharmaceutical, LLC Pleads Guilty to Illegal Promotion of Topamax\|work=FDA website\|url=http://www.fda.gov/ICECI/CriminalInvestigations/ucm213163}}</ref>
			\| legal_AU_comment =
			\| legal_BR = C1
			\| legal_BR_comment = <ref>{{Cite web \|author=Anvisa \|author-link=Brazilian Health Regulatory Agency \|date=31 March 2023 \|title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial \|trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control\|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 \|url-status=live \|archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 \|archive-date=3 August 2023 \|access-date=16 August 2023 \|publisher=] \|language=pt-BR \|publication-date=4 April 2023}}</ref>
			\| legal_CA = Rx-only
			\| legal_CA_comment =
			\| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			\| legal_DE_comment =
			\| legal_NZ = <!-- Class A, B, C -->
			\| legal_NZ_comment =
			\| legal_UK = POM
			\| legal_UK_comment =
			\| legal_US = Rx-only
			\| legal_US_comment = <ref name="Trokendi FDA label">{{cite web \| title=Trokendi XR- topiramate capsule, extended release \| website=DailyMed \| url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2dc7957e-a3e5-46bb-aa66-f3250f872f5e \| access-date=8 November 2021 \| archive-date=8 November 2021 \| archive-url=https://web.archive.org/web/20211108230847/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2dc7957e-a3e5-46bb-aa66-f3250f872f5e \| url-status=live }}</ref><ref name="Topamax FDA label">{{cite web \| title=Topamax- topiramate tablet, coated Topamax- topiramate capsule, coated pellets \| website=DailyMed \| url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21628112-0c47-11df-95b3-498d55d89593 \| access-date=8 November 2021 \| archive-date=8 November 2021 \| archive-url=https://web.archive.org/web/20211108230855/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21628112-0c47-11df-95b3-498d55d89593 \| url-status=live }}</ref><ref name="Qsymia FDA label">{{cite web \| title=Qsymia- phentermine and topiramate capsule, extended release \| website=DailyMed \| url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b-15789aba40f9 \| access-date=8 November 2021 \| archive-date=26 October 2021 \| archive-url=https://web.archive.org/web/20211026061736/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b-15789aba40f9 \| url-status=live }}</ref><ref name="Qudexy FDA label">{{cite web \| title=Qudexy XR- topiramate capsule, extended release \| website=DailyMed \| url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f54677-3a22-4c38-9b92-923020164e15 \| access-date=8 November 2021 \| archive-date=8 November 2021 \| archive-url=https://web.archive.org/web/20211108230852/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f54677-3a22-4c38-9b92-923020164e15 \| url-status=live }}</ref><ref name="Eprontia FDA label">{{cite web \| title=Eprontia - topiramate solution \| website=DailyMed \| url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2a4df59-fead-4a01-9021-9eda02c48010 \| access-date=19 December 2021 \| archive-date=19 December 2021 \| archive-url=https://web.archive.org/web/20211219213622/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2a4df59-fead-4a01-9021-9eda02c48010 \| url-status=live }}</ref>
			\| legal_EU = Rx-only
			\| legal_EU_comment = <ref>{{Cite web \|url=https://www.ema.europa.eu/documents/psusa/topiramate-list-nationally-authorised-medicinal-products-psusa/00002996/202201_en.pdf \|title=Active substance(s): topiramate \| work = List of nationally authorised medicinal products \| publisher = European Medicines Agency \| date = September 2022 \|access-date=6 September 2022 \|archive-date=6 September 2022 \|archive-url=https://web.archive.org/web/20220906054013/https://www.ema.europa.eu/en/documents/psusa/topiramate-list-nationally-authorised-medicinal-products-psusa/00002996/202201_en.pdf \|url-status=live }}</ref>
			\| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			\| legal_UN_comment =
			\| legal_status = <!-- For countries not listed above -->

			<!-- Pharmacokinetic data -->
	This drug has been investigated for use in treating alcoholism<ref>{{cite journal \|last1=Johnson \|first1=BA \|last2=Ait-Daoud \|first2=N \|last3=Bowden \|first3=CL \|last4=Diclemente \|first4=CC \|last5=Roache \|first5=JD \|last6=Lawson \|first6=K \|last7=Javors \|first7=MA \|last8=Ma \|first8=JZ \|title=Oral topiramate for treatment of alcohol dependence: a randomised controlled trial \|journal=Lancet \|volume=361 \|issue=9370 \|pages=1677–85 \|year=2003 \|pmid=12767733 \|doi=10.1016/S0140-6736(03)13370-3}}</ref><ref name="Alc">{{cite journal \|last1=Johnson \|first1=BA \|last2=Rosenthal \|first2=N \|last3=Capece \|first3=JA \|last4=Wiegand \|first4=F \|last5=Mao \|first5=L \|last6=Beyers \|first6=K \|last7=McKay \|first7=A \|last8=Ait-Daoud \|first8=N \|last9=Anton \|first9=RF \|title=Topiramate for treating alcohol dependence: a randomized controlled trial \|journal=JAMA : the journal of the American Medical Association \|volume=298 \|issue=14 \|pages=1641–51 \|year=2007 \|pmid=17925516 \|doi=10.1001/jama.298.14.1641}}</ref> and obesity,<ref>{{cite journal \|last1=Van Ameringen \|first1=M \|last2=Mancini \|first2=C \|last3=Pipe \|first3=B \|last4=Campbell \|first4=M \|last5=Oakman \|first5=J \|title=Topiramate treatment for SSRI-induced weight gain in anxiety disorders \|journal=The Journal of clinical psychiatry \|volume=63 \|issue=11 \|pages=981–4 \|year=2002 \|pmid=12444810}}</ref><ref>{{cite journal \|last1=Wilding \|first1=J \|last2=Van Gaal \|first2=L \|last3=Rissanen \|first3=A \|last4=Vercruysse \|first4=F \|last5=Fitchet \|first5=M \|last6=Obes-002 Study \|first6=Group \|title=A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects \|journal=International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity \|volume=28 \|issue=11 \|pages=1399–410 \|year=2004 \|pmid=15486569 \|doi=10.1038/sj.ijo.0802783}}</ref> especially to reduce ].<ref>{{cite journal \|last1=Shapira \|first1=NA \|last2=Goldsmith \|first2=TD \|last3=McElroy \|first3=SL \|title=Treatment of binge-eating disorder with topiramate: a clinical case series \|journal=The Journal of clinical psychiatry \|volume=61 \|issue=5 \|pages=368–72 \|year=2000 \|pmid=10847312}}</ref><ref>{{cite journal \|last1=McElroy \|first1=SL \|last2=Arnold \|first2=LM \|last3=Shapira \|first3=NA \|last4=Keck Jr \|first4=PE \|last5=Rosenthal \|first5=NR \|last6=Karim \|first6=MR \|last7=Kamin \|first7=M \|last8=Hudson \|first8=JI \|title=Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial \|journal=The American journal of psychiatry \|volume=160 \|issue=2 \|pages=255–61 \|year=2003 \|pmid=12562571}}</ref>
			\| bioavailability = 80%
			\| protein_bound = 13–17%; 15–41%
			\| metabolism = ] (20–30%)
			\| metabolites =
			\| onset =
			\| elimination_half-life = 21 hours
			\| duration_of_action =
			\| excretion = Urine (70–80%)

			<!-- Identifiers -->
	The drug is also used in clinical trials to treat ].<ref>{{cite journal \|last1=Berlant \|first1=J \|last2=Van Kammen \|first2=DP \|title=Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report \|journal=The Journal of clinical psychiatry \|volume=63 \|issue=1 \|pages=15–20 \|year=2002 \|pmid=11838620}}</ref> A pilot study suggested that topiramate is effective against infantile spasms.<ref>{{cite journal \|last1=Glauser \|first1=TA \|last2=Clark \|first2=PO \|last3=Strawsburg \|first3=R \|title=A pilot study of topiramate in the treatment of infantile spasms \|journal=Epilepsia \|volume=39 \|issue=12 \|pages=1324–8 \|year=1998 \|pmid=9860068}}</ref> Another study recommends topiramate as an effective treatment in the prevention of ] in preterm infants after an ]-] injury.<ref>{{cite journal \|last1=Follett \|first1=PL \|last2=Deng \|first2=W \|last3=Dai \|first3=W \|last4=Talos \|first4=DM \|last5=Massillon \|first5=LJ \|last6=Rosenberg \|first6=PA \|last7=Volpe \|first7=JJ \|last8=Jensen \|first8=FE \|title=Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate \|journal=The Journal of neuroscience : the official journal of the Society for Neuroscience \|volume=24 \|issue=18 \|pages=4412–20 \|year=2004 \|pmid=15128855 \|doi=10.1523/JNEUROSCI.0477-04.2004}}</ref>
			\| CAS_number_Ref = {{cascite\|correct\|??}}
			\| CAS_number = 97240-79-4
			\| CAS_supplemental =
			\| PubChem = 5284627
			\| IUPHAR_ligand = 6849
			\| DrugBank_Ref = {{drugbankcite\|changed\|drugbank}}
			\| DrugBank = DB00273
			\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
			\| ChemSpiderID = 4447672
			\| UNII_Ref = {{fdacite\|correct\|FDA}}
			\| UNII = 0H73WJJ391
			\| KEGG_Ref = {{keggcite\|correct\|kegg}}
			\| KEGG = D00537
			\| ChEBI_Ref =
			\| ChEBI =
			\| ChEMBL_Ref = {{ebicite\|correct\|EBI}}
			\| ChEMBL = 220492
			\| NIAID_ChemDB =
			\| PDB_ligand = TOR
			\| synonyms = Topiramic acid

			<!-- Chemical and physical data -->
	==Off the label usage==
			\| IUPAC_name = 2,3:4,5-Bis-''O''-(1-methylethylidene)-β-<small>D</small>-fructopyranose sulfamate
			\| C = 12
			\| H = 21
			\| N = 1
			\| O = 8
			\| S = 1
			\| SMILES = O=S(=O)(OC21OC(O13OC(O3CO2)(C)C)(C)C)N
			\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
			\| StdInChI = 1S/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1
			\| StdInChI_comment =
			\| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}}
			\| StdInChIKey = KJADKKWYZYXHBB-XBWDGYHZSA-N
			\| density =
			\| density_notes =
			\| melting_point =
			\| melting_high =
			\| melting_notes =
			\| boiling_point =
			\| boiling_notes =
			\| solubility =
			\| sol_units =
			\| specific_rotation =
			}}

			<!-- Definition and medical uses -->
	Recent clinical reports indicate that it may have mood stabilizing properties.<ref>{{cite journal \|last1=Letmaier \|first1=M \|last2=Schreinzer \|first2=D \|last3=Wolf \|first3=R \|last4=Kasper \|first4=S \|title=Topiramate as a mood stabilizer \|journal=International clinical psychopharmacology \|volume=16 \|issue=5 \|pages=295–8 \|year=2001 \|pmid=11552774}}</ref>
			'''Topiramate''', sold under the brand name '''Topamax''' among others, is a medication used to treat ] and prevent ].<ref name=AHFS2019/> It has also been used in ] and ].<ref name=AHFS2019>{{cite web \|title=Topiramate Monograph for Professionals \|url=https://www.drugs.com/monograph/topiramate.html \|website=Drugs.com \|publisher=American Society of Health-System Pharmacists \|access-date=5 March 2019 \|archive-date=6 March 2019 \|archive-url=https://web.archive.org/web/20190306044425/https://www.drugs.com/monograph/topiramate.html \|url-status=live }}</ref> For epilepsy this includes treatment for ] or ].<ref name=BNF76/> It is taken ] (by mouth).<ref name=AHFS2019/>
	Other off-label and investigational uses of topiramate include the treatment of ], ],<ref>{{cite journal \|last1=Hoopes \|first1=SP \|last2=Reimherr \|first2=FW \|last3=Hedges \|first3=DW \|last4=Rosenthal \|first4=NR \|last5=Kamin \|first5=M \|last6=Karim \|first6=R \|last7=Capece \|first7=JA \|last8=Karvois \|first8=D \|title=Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures \|journal=The Journal of clinical psychiatry \|volume=64 \|issue=11 \|pages=1335–41 \|year=2003 \|pmid=14658948}}</ref> ], ],<ref name="Alc"/> ],<ref>{{cite journal \|last1=Khazaal \|first1=Y \|last2=Cornuz \|first2=J \|last3=Bilancioni \|first3=R \|last4=Zullino \|first4=DF \|title=Topiramate for smoking cessation \|journal=Psychiatry and clinical neurosciences \|volume=60 \|issue=3 \|pages=384–8 \|year=2006 \|pmid=16732758 \|doi=10.1111/j.1440-1819.2006.01518.x}}</ref> ],<ref>{{cite journal \|last1=Celebisoy \|first1=N \|last2=Gökçay \|first2=F \|last3=Sirin \|first3=H \|last4=Akyürekli \|first4=O \|title=Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study \|journal=Acta neurologica Scandinavica \|volume=116 \|issue=5 \|pages=322–7 \|year=2007 \|pmid=17922725 \|doi=10.1111/j.1600-0404.2007.00905.x}}</ref> ],<ref>{{cite journal \|last1=Chong \|first1=MS \|last2=Libretto \|first2=SE \|title=The rationale and use of topiramate for treating neuropathic pain \|journal=The Clinical journal of pain \|volume=19 \|issue=1 \|pages=59–68 \|year=2003 \|pmid=12514458}}</ref> cluster headache,<ref>{{cite journal \|last1=Láinez \|first1=MJ \|last2=Pascual \|first2=J \|last3=Pascual \|first3=AM \|last4=Santonja \|first4=JM \|last5=Ponz \|first5=A \|last6=Salvador \|first6=A \|title=Topiramate in the prophylactic treatment of cluster headache \|journal=Headache \|volume=43 \|issue=7 \|pages=784–9 \|year=2003 \|pmid=12890134}}</ref> and ] dependence.<ref>{{ClinicalTrialsGov\|NCT00685178\|Clinical Trial of Topiramate for Cocaine Addiction}}</ref> Topiramate is also being studied with a mixture of ] to form a drug called ] for the treatment of obesity.

			<!-- Side effects and mechanisms -->
	==Pharmacology==
			Common side effects include ], feeling tired, ], abdominal pain, weight loss,<ref>{{Cite web\|title=Topiramate Side Effects: Common, Severe, Long Term\|url=https://www.drugs.com/sfx/topiramate-side-effects.html\|access-date=3 August 2021\|website=Drugs.com\|archive-date=10 April 2021\|archive-url=https://web.archive.org/web/20210410135224/https://www.drugs.com/sfx/topiramate-side-effects.html\|url-status=live}}</ref> and decreased cognitive function such as trouble concentrating.<ref name=AHFS2019/><ref name=BNF76>{{cite book\|title=British national formulary : BNF 76\|date=2018\|publisher=Pharmaceutical Press\|isbn=9780857113382\|pages=328\|edition=76}}</ref> Serious side effects may include ], increased ] levels resulting in ], and ].<ref name=AHFS2019/> Topiramate can cause birth defects including cleft lip and palate.<ref>{{Cite web \|date=18 June 2019 \|title=FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate) \|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-risk-oral-clefts-children-born-mothers-taking-topamax-topiramate \|website=FDA }}</ref> Risk/benefit should be carefully discussed with the full treatment team. Topiramate is considered "probably compatible" with lactation and is not contraindicated in breastfeeding, though monitoring of the infant for diarrhea or poor weight gain may be considered.<ref>{{Cite web \|last=Health \|first=MGH Center for Women's Mental \|date=10 August 2022 \|title=Essential Reads: Breastfeeding and Anti-Epileptic Drugs - MGH Center for Women's Mental Health \|url=https://womensmentalhealth.org/posts/essential-reads-breastfeeding-and-anti-epileptic-drugs/,%20https://womensmentalhealth.org/posts/essential-reads-breastfeeding-and-anti-epileptic-drugs/ \|access-date=27 December 2023 }}</ref><ref>{{Citation \|title=Topiramate \|date=2006 \|url=http://www.ncbi.nlm.nih.gov/books/NBK501259/ \|work=Drugs and Lactation Database (LactMed®) \|access-date=27 December 2023 \|place=Bethesda (MD) \|publisher=National Institute of Child Health and Human Development \|pmid=30000318}}</ref> The ] is unclear.<ref name=AHFS2019/>
	Chemically, topiramate is a ]-substituted ], related to ], a rather unusual chemical structure for an anticonvulsant.

			<!-- History and culture -->
	Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by ], ], and ]. Six ]s have been identified in humans, none of which constitutes more than 5% of an administered dose.
			Topiramate was approved for medical use in the United States in 1996.<ref name=AHFS2019/> It is available as a ].<ref name=BNF76/><ref>{{cite web \| title=Competitive Generic Therapy Approvals \| website=U.S. ] (FDA) \| date=29 June 2023 \| url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals \| access-date=29 June 2023 \| archive-date=29 June 2023 \| archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals \| url-status=live }}</ref><ref>{{cite web \| title=First Generic Drug Approvals 2023 \| website=U.S. ] (FDA) \| date=30 May 2023 \| url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals \| archive-url=https://web.archive.org/web/20230630003621/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals \| archive-date=30 June 2023 \| url-status=live \| access-date=30 June 2023}}</ref> In 2022, it was the 84th most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.<ref>{{cite web \| title=The Top 300 of 2022 \| url=https://clincalc.com/DrugStats/Top300Drugs.aspx \| website=ClinCalc \| access-date=30 August 2024 \| archive-date=30 August 2024 \| archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx \| url-status=live }}</ref><ref>{{cite web \| title = Topiramate Drug Usage Statistics, United States, 2013 - 2022 \| website = ClinCalc \| url = https://clincalc.com/DrugStats/Drugs/Topiramate \| access-date = 30 August 2024 }}</ref>

			==Medical uses==
	The exact mechanism of action is unknown,<ref>http://www.rxlist.com/topamax-drug.htm</ref> but four properties that may contribute to topiramate's antiepileptic and antimigraine efficacy include a blockage of voltage-dependent sodium channels, an augmentation of gamma-aminobutyrate acid activity at some subtypes of the GABA- A receptors, antagonism of AMPA/kainate subtype of the glutamate receptor, and inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV .
			]
			Topiramate is used to treat ] in children and adults, and it was originally used as an ].<ref name="Topamax Rx info" /> In children, it is indicated for the treatment of ], a disorder that causes seizures and ]. It is most frequently prescribed for the prevention of ]s<ref name="Topamax Rx info">{{cite web\|title=Topamax Prescribing Information\|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020505s055,020844s046lbl.pdf\|website=United States Food and Drug Administration\|access-date=11 April 2016\|archive-date=24 April 2016\|archive-url=https://web.archive.org/web/20160424132704/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020505s055,020844s046lbl.pdf\|url-status=live}}</ref> as it decreases the frequency of attacks.<ref>{{cite journal \| vauthors = Linde M, Mulleners WM, Chronicle EP, McCrory DC \| title = Topiramate for the prophylaxis of episodic migraine in adults \| journal = The Cochrane Database of Systematic Reviews \| volume = 6 \| issue = 6 \| pages = CD010610 \| date = June 2013 \| pmid = 23797676 \| pmc = 7388931 \| doi = 10.1002/14651858.CD010610 }}</ref><ref>{{cite journal \| vauthors = Ferrari A, Tiraferri I, Neri L, Sternieri E \| title = Clinical pharmacology of topiramate in migraine prevention \| journal = Expert Opinion on Drug Metabolism & Toxicology \| volume = 7 \| issue = 9 \| pages = 1169–1181 \| date = September 2011 \| pmid = 21756204 \| doi = 10.1517/17425255.2011.602067 \| s2cid = 207491096 }}</ref> Topiramate is used to treat ] and is recommended by the ] as one of the few medications showing effectiveness for this indication.<ref name="European Neurology">{{cite journal \| vauthors = Evers S, Jensen R \| title = Treatment of medication overuse headache--guideline of the EFNS headache panel \| journal = European Journal of Neurology \| volume = 18 \| issue = 9 \| pages = 1115–1121 \| date = September 2011 \| pmid = 21834901 \| doi = 10.1111/j.1468-1331.2011.03497.x \| s2cid = 2698885 \| doi-access = free }}</ref>

			===Pain===
	Its possible effect as a ] seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and ]-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on ] pores has been proposed as a mechanism.<ref name="pmid15571505">{{cite journal \|last1=Kudin \|first1=AP \|last2=Debska-Vielhaber \|first2=G \|last3=Vielhaber \|first3=S \|last4=Elger \|first4=CE \|last5=Kunz \|first5=WS \|title=The mechanism of neuroprotection by topiramate in an animal model of epilepsy \|journal=Epilepsia \|volume=45 \|issue=12 \|pages=1478–87 \|year=2004 \|pmid=15571505 \|doi=10.1111/j.0013-9580.2004.13504.x}}</ref>
			A 2018 review found topiramate of no use in chronic ].<ref>{{cite journal \| vauthors = Enke O, New HA, New CH, Mathieson S, McLachlan AJ, Latimer J, Maher CG, Lin CC \| display-authors = 6 \| title = Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis \| journal = CMAJ \| volume = 190 \| issue = 26 \| pages = E786–E793 \| date = July 2018 \| pmid = 29970367 \| pmc = 6028270 \| doi = 10.1503/cmaj.171333 }}</ref> Topiramate has not been shown to work as a pain medicine in ], the only neuropathic condition in which it has been adequately tested.<ref>{{cite journal \| vauthors = Wiffen PJ, Derry S, Lunn MP, Moore RA \| title = Topiramate for neuropathic pain and fibromyalgia in adults \| journal = The Cochrane Database of Systematic Reviews \| issue = 8 \| pages = CD008314 \| date = August 2013 \| volume = 2013 \| pmid = 23996081 \| pmc = 8406931 \| doi = 10.1002/14651858.CD008314.pub3 \| url = http://summaries.cochrane.org/CD008314/topiramate-for-treating-neuropathic-pain-or-fibromyalgia#sthash.QswJ7Tr9.dpuf \| access-date = 6 September 2013 \| url-status = live \| veditors = Derry S \| archive-url = https://web.archive.org/web/20140331085009/http://summaries.cochrane.org/CD008314/topiramate-for-treating-neuropathic-pain-or-fibromyalgia#sthash.QswJ7Tr9.dpuf \| archive-date = 31 March 2014 }}</ref>

			===Other===
	While many ] have been associated with apoptosis in young animals, animal experiments have found that topiramate is the only anticonvulsant that does not induce ] in young animals at doses needed to produce an anticonvulsant effect.<ref name="Czuczwar-2004">{{cite journal \|last1=Czuczwar \|first1=K \|last2=Czuczwar \|first2=M \|last3=Cieszczyk \|first3=J \|last4=Gawlik \|first4=P \|last5=Luszczki \|first5=JJ \|last6=Borowicz \|first6=KK \|last7=Czuczwar \|first7=SJ \|title=Neuroprotective activity of antiepileptic drugs \|journal=Przeglad lekarski \|volume=61 \|issue=11 \|pages=1268–71 \|year=2004 \|pmid=15727029}}</ref>
			One common ] for topiramate is in the treatment of ].<ref>{{cite journal \| vauthors = Arnone D \| title = Review of the use of Topiramate for treatment of psychiatric disorders \| journal = Annals of General Psychiatry \| volume = 4 \| issue = 1 \| pages = 5 \| date = February 2005 \| pmid = 15845141 \| pmc = 1088011 \| doi = 10.1186/1744-859X-4-5 \| doi-access = free }}</ref><ref>{{cite journal \| vauthors = Vasudev K, Macritchie K, Geddes J, Watson S, Young A \| title = Topiramate for acute affective episodes in bipolar disorder \| journal = The Cochrane Database of Systematic Reviews \| issue = 1 \| pages = CD003384 \| date = January 2006 \| pmid = 16437453 \| doi = 10.1002/14651858.CD003384.pub2 \| veditors = Young AH }}</ref><ref>{{cite journal \| vauthors = Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR \| display-authors = 6 \| title = Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis \| journal = Lancet \| volume = 378 \| issue = 9799 \| pages = 1306–1315 \| date = October 2011 \| pmid = 21851976 \| doi = 10.1016/s0140-6736(11)60873-8 \| s2cid = 25512763 }}</ref> A review published in 2010 suggested a benefit of topiramate in the treatment of symptoms of ], however the authors noted that this was based only on one randomized controlled trial and requires replication.<ref>{{cite journal \| vauthors = Lieb K, Völlm B, Rücker G, Timmer A, Stoffers JM \| title = Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials \| journal = The British Journal of Psychiatry \| volume = 196 \| issue = 1 \| pages = 4–12 \| date = January 2010 \| pmid = 20044651 \| doi = 10.1192/bjp.bp.108.062984 \| doi-access = free }}</ref>

			Topiramate has been used as a treatment for ].<ref>{{cite journal \| vauthors = Johnson BA, Ait-Daoud N \| title = Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients \| journal = Current Pharmaceutical Design \| volume = 16 \| issue = 19 \| pages = 2103–2112 \| date = 2010 \| pmid = 20482511 \| pmc = 3063512 \| doi = 10.2174/138161210791516404 }}</ref> The U.S. Veterans Affairs and Department of Defense 2015 guidelines on substance use disorders list topiramate as a "strong for" in its recommendations for ].<ref>{{Cite web\|url=https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf\|title=VA/DoD Clinical Practice Guideline for the management of substance use disorders\|date=31 December 2015\|website=healthquality.va.gov\|access-date=30 August 2017\|archive-date=31 August 2017\|archive-url=https://web.archive.org/web/20170831041618/https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf\|url-status=live}}</ref>
	==Side effects==
	A ]-sponsored ] study suggested that cognitive side effects may be more common with topiramate than with ].<ref>{{cite journal \|last1=Blum \|first1=D \|last2=Meador \|first2=K \|last3=Biton \|first3=V \|last4=Fakhoury \|first4=T \|last5=Shneker \|first5=B \|last6=Chung \|first6=S \|last7=Mills \|first7=K \|last8=Hammer \|first8=A \|last9=Isoj�rvi \|first9=J \|title=Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy \|journal=Neurology \|volume=67 \|issue=3 \|pages=400–6 \|year=2006 \|pmid=16894098 \|doi=10.1212/01.wnl.0000232737.72555.06}}</ref> In studies of healthy volunteers, therapeutic doses of topiramate for bipolar disorder produced greater cognitive deficits than lamotrigine, including short term memory loss and word-finding difficulty.

			Other uses include treatment of obesity,<ref>{{cite journal \| vauthors = Verrotti A, Scaparrotta A, Agostinelli S, Di Pillo S, Chiarelli F, Grosso S \| title = Topiramate-induced weight loss: a review \| journal = Epilepsy Research \| volume = 95 \| issue = 3 \| pages = 189–199 \| date = August 2011 \| pmid = 21684121 \| doi = 10.1016/j.eplepsyres.2011.05.014 \| s2cid = 30103553 }}</ref><ref>{{cite journal \| vauthors = Kramer CK, Leitão CB, Pinto LC, Canani LH, Azevedo MJ, Gross JL \| title = Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials \| journal = Obesity Reviews \| volume = 12 \| issue = 5 \| pages = e338–e347 \| date = May 2011 \| pmid = 21438989 \| doi = 10.1111/j.1467-789X.2010.00846.x \| s2cid = 24358798 \| doi-access = free }}</ref> ],<ref>{{Cite web\|title=Topiramate for Binge Eating Disorder\|url=https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=ty7109\|access-date=3 August 2021\|website=wa.kaiserpermanente.org\|archive-date=3 August 2021\|archive-url=https://web.archive.org/web/20210803095925/https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=ty7109\|url-status=live}}</ref> and off-setting weight gain induced by taking ] medications.<ref>{{cite journal \| vauthors = Hahn MK, Cohn T, Teo C, Remington G \| title = Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters \| journal = Clinical Schizophrenia & Related Psychoses \| volume = 6 \| issue = 4 \| pages = 186–196 \| date = January 2013 \| pmid = 23302448 \| doi = 10.3371/CSRP.HACO.01062013 }}</ref><ref>{{cite journal \| vauthors = Mahmood S, Booker I, Huang J, Coleman CI \| title = Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents \| journal = Journal of Clinical Psychopharmacology \| volume = 33 \| issue = 1 \| pages = 90–94 \| date = February 2013 \| pmid = 23277264 \| doi = 10.1097/JCP.0b013e31827cb2b7 \| s2cid = 26085987 }}</ref> In 2012, the combination of ] was approved in the United States for weight loss.
	The side-effects reported by > 10% of subjects in at least 1 clinical study<ref>{{cite journal \|last1=Roy Chengappa \|first1=KN \|last2=Schwarzman \|first2=LK \|last3=Hulihan \|first3=JF \|last4=Xiang \|first4=J \|last5=Rosenthal \|first5=NR \|author6=Clinical Affairs Product Support Study-168 Investigators \|title=Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial \|journal=The Journal of clinical psychiatry \|volume=67 \|issue=11 \|pages=1698–706 \|year=2006 \|pmid=17196048}}</ref>
	Listed by prevalence:

			==Adverse effects==
	* ] (numbness & tingling) (23.7%)
			People taking topiramate should be aware of the following risks:
	* ] (17.5%)
			*Avoid activities requiring mental alertness and coordination until drug effects are realized.
	* ] (16.8%)
			*Topiramate may impair heat regulation,<ref name="side-effects" /> especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration.
	* ] (15.4%)
			*Topiramate may cause visual field defects.<ref>{{cite web\|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm195797.htm\|title=Topamax (topiramate) tablets and sprinkle capsules\|publisher=Fda.gov\|access-date=17 October 2014\|archive-date=12 January 2017\|archive-url=https://web.archive.org/web/20170112172852/http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm195797.htm\|url-status=live}}</ref>
	* ] (loss of appetite) (13.3%)
			*Topiramate may decrease the effectiveness of oestrogen-containing oral contraceptives.
	* ] (11.2%)
			*Taking topiramate in the first trimester of pregnancy may increase the risk of cleft lip/cleft palate in infants.<ref name="fda.gov"/>
			*As is the case for all antiepileptic drugs, it is advisable not to suddenly discontinue topiramate as there is a theoretical risk of rebound seizures.
			*Some studies have attributed loss of appetite and upper respiratory tract infection to topiramate, but studies have concluded their adverse events are not difficult to tolerate for most individuals.<ref>{{Cite web \|date=8 August 2021 \|title=Seizures and Epilepsy in Children \|url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/epilepsy/seizures-and-epilepsy-in-children \|access-date=19 July 2023 \|website=www.hopkinsmedicine.org }}</ref>

			===Frequency===
	The side-effects most frequently leading to discontinuation of therapy with topiramate were:
			Adverse effects by incidence:<ref name = TGA>{{cite web\|title=Topamax Tablets and Sprinkle Capsules PRODUCT INFORMATION\|work=TGA eBusiness Services\|publisher=JANSSEN-CILAG Pty Ltd\|date=30 May 2013\|access-date=18 November 2013\|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-02205-3\|format=PDF\|archive-date=29 March 2019\|archive-url=https://web.archive.org/web/20190329054936/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-02205-3\|url-status=live}}</ref><ref name = MSR>{{cite web\|title=topiramate (Rx) - Topamax, Trokendi XR\|work=Medscape Reference\|publisher=WebMD\|access-date=18 November 2013\|url=http://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023\|archive-date=19 May 2019\|archive-url=https://web.archive.org/web/20190519021543/https://reference.medscape.com/drug/topamax-trokendi-xr-topiramate-343023\|url-status=live}}</ref><ref name=EMC>{{cite web\|title=Topiramate 100 mg film-coated Tablets\|work=electronic Medicines Compendium\|publisher=Sandoz Limited\|date=6 March 2013\|access-date=18 November 2013\|url=http://www.medicines.org.uk/emc/medicine/22416/SPC/Topiramate+100+mg+film-coated+Tablets/\|archive-url= https://web.archive.org/web/20140521031853/http://www.medicines.org.uk/emc/medicine/22416/SPC/Topiramate+100+mg+film-coated+Tablets/ \|archive-date=21 May 2014 \|url-status=dead}}</ref><ref name = DM>{{cite web\|title=TOPIRAMATE ( topiramate ) tablet TOPIRAMATE ( topiramate ) tablet \|work=DailyMed\|publisher=Torrent Pharmaceuticals Limited\|date=August 2011\|access-date=18 November 2013\|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a4ff77b8-04bc-4edb-a085-8d6d8687f8d1\|archive-date=20 May 2014\|archive-url=https://web.archive.org/web/20140520220544/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a4ff77b8-04bc-4edb-a085-8d6d8687f8d1\|url-status=live}}</ref>
	* ] (4.1%)
	* memory problems (3.3%)
	* ] (3.3%)
	* ] (3.2%)
	* ] (3.2%)

			'''Very common (>10% incidence) adverse effects include:'''
	Rarely, the inhibition of ] may be strong enough to cause ] of clinical importance.<ref>{{cite journal \|last1=Mirza \|first1=Nasir \|last2=Marson \|first2=Anthony G. \|last3=Pirmohamed \|first3=Munir \|title=Effect of topiramate on acid-base balance: extent, mechanism and effects \|journal=British Journal of Clinical Pharmacology \|volume=68 \|pages=655–61 \|year=2009 \|doi=10.1111/j.1365-2125.2009.03521.x}}</ref>
			{{Columns-list\|
			* ]
			* ]
			* ] – e.g., pins and needles
			* ]
			* ]
			* ]
			* ]
			* ]
			* ]
			}}

			Rarely, the inhibition of ] may be strong enough to cause ] of clinical importance.<ref>{{cite journal \| vauthors = Mirza N, Marson AG, Pirmohamed M \| title = Effect of topiramate on acid-base balance: extent, mechanism and effects \| journal = British Journal of Clinical Pharmacology \| volume = 68 \| issue = 5 \| pages = 655–661 \| date = November 2009 \| pmid = 19916989 \| pmc = 2791971 \| doi = 10.1111/j.1365-2125.2009.03521.x }}</ref>
	The Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute ] and secondary angle closure ] in a small subset of people who take topiramate regularly.{{Citation needed\|date=June 2010}} The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage, and may reverse the visual impairment.

			The U.S. ] (FDA) has notified prescribers that topiramate can cause acute ] and secondary angle closure ] in a small subset of people who take topiramate regularly.<ref>{{cite web\|url=https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM173936.pdf\|title=IMPORTANT DRUG WARNING\| vauthors = Hulihan J \|date=2001\|website=FDA MedWatch\|publisher=Ortho-McNeil Pharmaceutical\|archive-url=https://wayback.archive-it.org/7993/20170113165159/https://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM173936.pdf\|archive-date=13 January 2017\|url-status=dead\|access-date=11 June 2018}}</ref> The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage and may reverse the visual impairment.
	Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.<ref name="pmid18645165">{{cite journal \|last1=Hunt \|first1=S \|last2=Russell \|first2=A \|last3=Smithson \|first3=WH \|last4=Parsons \|first4=L \|last5=Robertson \|first5=I \|last6=Waddell \|first6=R \|last7=Irwin \|first7=B \|last8=Morrison \|first8=PJ \|last9=Morrow \|first9=J \|title=Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register \|journal=Neurology \|volume=71 \|issue=4 \|pages=272–6 \|year=2008 \|pmid=18645165 \|doi=10.1212/01.wnl.0000318293.28278.33}}</ref> This might be particularly important for women who take topiramate to prevent migraine attacks.

			Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.<ref name="pmid18645165">{{cite journal \| vauthors = Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J \| display-authors = 6 \| title = Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register \| journal = Neurology \| volume = 71 \| issue = 4 \| pages = 272–276 \| date = July 2008 \| pmid = 18645165 \| doi = 10.1212/01.wnl.0000318293.28278.33 \| s2cid = 13562052 }}</ref> This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011, the FDA notified healthcare professionals and patients of an increased risk of development of ] and/or ] (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in ] D.<ref name="fda.gov">{{cite web \|url=https://www.fda.gov/Drugs/DrugSafety/ucm245085.htm \| work = FDA Drug Safety Communication \| title = Risk of oral clefts in children born to mothers taking Topamax (topiramate) \|publisher=Fda.gov \|date=6 January 2011 \|access-date=11 July 2013 \|archive-date=24 April 2019 \|archive-url=https://web.archive.org/web/20190424012653/https://www.fda.gov/Drugs/DrugSafety/ucm245085.htm \|url-status=live }}</ref>
	Most antiepileptic drugs, including topiramate, have been associated with a ] increase in ].<ref>http://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal%20slides.pdf</ref>

			Cognitive and word-finding difficulties, as they may occur in some patients, may respond to ].<ref>Berthier, M.L. and Dávila, G., 2023. Pharmacotherapy for post-stroke aphasia: what are the options?. Expert Opinion on Pharmacotherapy, (just-accepted).</ref><ref>Cumbo, E. and Ligori, L.D., 2010. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease. Epilepsy & Behavior, 17(4), pp.461-466.</ref>
	==Interactions==
	Topiramate has many drug-drug interactions, some of the most common are listed below:

			Carbonation dysgeusia (distortion of the sense of taste-sensation of carbonation) may respond to and/or be prevented with ].<ref>Charbonneau, M., Doyle-Campbell, C., Laskey, C. and Capoccia, K., 2020. Carbonation dysgeusia associated with topiramate. American Journal of Health-System Pharmacy, 77(14), pp.1113-1116.</ref>
	* As topiramate inhibits ], use with other inhibitors of carbonic anhydrase (e.g. ]) increases the risk of ].
	* ]s (e.g. ]) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.
	* Topiramate may increase the plasma-levels of phenytoin.
	* Topiramate itself is a weak inhibitor of ] and induces ]. Under topiramate a decrease of plasma-levels of estrogens (e.g. 'the pill') and ] have been noted.
	* Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
	* As listed in the 06/29/2005 label posted at the Drugs@FDA website page 14,'conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of Topiramate'.<ref></ref>
	* ] and hyperthermia were reported in post-marketing reports about topiramate; ] drugs (like trospium) can aggravate these disorders.

			Topiramate has been associated with a ] increase in ],<ref>{{cite web \|url=https://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal%20slides.pdf \|title=Suicidality and Antiepileptic Drugs \|website=] \|access-date=11 July 2013 \|archive-date=10 May 2017 \|archive-url=https://web.archive.org/web/20170510065536/https://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4344s1_09_01_Trileptal \|url-status=live }}</ref> and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."<ref name="side-effects">{{cite web\|url=http://www.topamax.com/how-topamax-may-help--what-to-expect.html\|archive-url=https://web.archive.org/web/20110128083201/http://www.topamax.com/how-topamax-may-help--what-to-expect.html\|url-status=dead\|archive-date=28 January 2011\|title=Possible Side Effects - Topamax (topiramate)\|publisher=Topamax.xom\|access-date=17 October 2014}}</ref><ref>{{cite web \| title = Topiramate \| url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000998/ \| archive-url = https://web.archive.org/web/20100805062310/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000998/ \| archive-date=5 August 2010 \| work = PubMed Health \| publisher = National Center for Biotechnology Information, U.S. National Library of Medicine }}</ref>
	==Dosage==
	The exact dosage of Topiramate depends on the diagnosis being treated. In order to avoid early side-effects (e.g. cognitive dysfunction) the initial dosage normally is low and increased in slow steps. The usual initial dosage is 25 to 50 mg daily in 2 single doses. Common dosages for maintenance treatment are 100 to 200 mg daily. The highest dosage recommended is 400 mg daily in divided doses, but higher doses have been used in patients using Topiramate as a primary seizure medication; doses up to 1600mg/day have been well tolerated.<ref>http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=7412</ref>

	==Overdose==		==Overdose==
			Symptoms of ] and ] exposure to topiramate range from ] to ], including in patients with no seizure history.<ref name=clintox>{{cite journal \| vauthors = Wiśniewski M, Łukasik-Głebocka M, Anand JS \| title = Acute topiramate overdose--clinical manifestations \| journal = Clinical Toxicology \| volume = 47 \| issue = 4 \| pages = 317–320 \| date = April 2009 \| pmid = 19514879 \| doi = 10.1080/15563650601117954 \| s2cid = 205901501 }}</ref><ref name=wills>{{cite journal \| vauthors = Wills B, Reynolds P, Chu E, Murphy C, Cumpston K, Stromberg P, Rose R \| title = Clinical outcomes in newer anticonvulsant overdose: a poison center observational study \| journal = Journal of Medical Toxicology \| volume = 10 \| issue = 3 \| pages = 254–260 \| date = September 2014 \| pmid = 24515527 \| pmc = 4141920 \| doi = 10.1007/s13181-014-0384-5 }}</ref> In children, overdose may also result in ].<ref name=wills/> Topiramate has been deemed the primary substance that led to fatal overdoses in cases that were complicated by ].<ref name=lofton>{{cite journal \| vauthors = Lofton AL, Klein-Schwartz W \| title = Evaluation of toxicity of topiramate exposures reported to poison centers \| journal = Human & Experimental Toxicology \| volume = 24 \| issue = 11 \| pages = 591–595 \| date = November 2005 \| pmid = 16323576 \| doi = 10.1191/0960327105ht561oa \| bibcode = 2005HETox..24..591L \| s2cid = 37784043 }}</ref> The most common signs of overdose are ], ], ], ], and ].<ref name=clintox/><ref name=wills/><ref name=lofton/>
	Overdose is rare. In most cases, acute exposure produced only minimal to moderate effects. Fatalities have occurred, but were the result of polydrug exposure.

			== Interactions ==
	Symptoms of overdose may include but are not limited to:<ref>http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=7412</ref>

			Topiramate has many drug-drug interactions. Some of the most common are listed below:
	* Agitation
			* As topiramate inhibits ], use with other inhibitors of carbonic anhydrase (e.g. ]) increases the risk of ].{{citation needed\|date=April 2016}}
	* Depression
			* ]s (e.g. ]) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.{{citation needed\|date=April 2016}}
	* Speech problems
			* Topiramate may increase the plasma levels of phenytoin.
	* Blurred vision, double vision
			* Topiramate itself is a weak inhibitor of ] and induces ]; a decrease in plasma levels of estrogens and ] has been noted during topiramate therapy. This can reduce the effectiveness of ] (birth control pills); use of alternative birth control methods is recommended.<ref name=Martindale_OC>{{cite book\| veditors = Sweetman SC \|chapter=Sex hormones and their modulators\|title=Martindale: The complete drug reference \|edition=36th \|year=2009 \|page=2068 \|publisher=Pharmaceutical Press \|location=London\|isbn=978-0-85369-840-1\|title-link=Martindale: The complete drug reference}}</ref> Neither ]s (IUDs) nor ] are affected by topiramate.<ref name=Martindale_OC/>
	* Troubled thinking
			* ] may cause increased sedation or drowsiness, and increase the risk of having a seizure.
	* Loss of coordination
			* As topiramate may result in acidosis other treatments that also do so may worsen this effect.<ref>{{cite web \| title = TOPAMAX (topiramate) Tablets Approved Labeling Text \| date = 29 June 2005 \| work = Ortho-McNeil Pharmaceutical \| publisher = U.S. Food and Drug Administration \| url = https://www.fda.gov/cder/foi/label/2005/020505s018lbl.pdf \| archive-url = https://web.archive.org/web/20070205092259/https://www.fda.gov/cder/foi/label/2005/020505s018lbl.pdf \| archive-date=5 February 2007 \|page=14}}</ref>
	* Inability to respond to things around you
			* ] and hyperthermia were reported in post-marketing reports about topiramate; ] drugs (like trospium) can aggravate these disorders.{{citation needed\|date=April 2016}}
	* Loss of consciousness
	* Confusion and coma
	* Fainting
	* Upset stomach and stomach pain
	* Loss of appetite and vomiting
	* Shortness of breath; fast, shallow breathing
	* Pounding or irregular heartbeat
	* Muscle weakness
	* Bone pain

			==Pharmacology==
	A specific antidote is not available. Treatment is entirely supportive.
			]
			The topiramate molecule is a ] modified sugar, more specifically, ] di], an unusual chemical structure for a pharmaceutical.

			Topiramate is quickly absorbed after oral use. It has a half-life of 21 hours and a steady state of the drug is reached in 4 days in patients with normal renal function.<ref>{{Cite web\|title=FDA Data on Topamax\|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020505s038s039,020844s032s034lbl.pdf\|url-status=live\|access-date=6 August 2021\|archive-date=6 August 2021\|archive-url=https://web.archive.org/web/20210806051822/https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020505s038s039,020844s032s034lbl.pdf}}</ref> Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by ], ], and ]. Six ]s have been identified in humans, none of which constitutes more than 5% of an administered dose.
	==Patient warnings==
	People taking topiramate should be aware of the following risks:
	*Avoid activities requiring mental alertness and coordination until drug effects are realized
	*Topiramate may impair heat regulation, especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration
	*Topiramate may decrease effectiveness of estrogen-containing oral contraceptives
	*Topiramate should not be suddenly discontinued, as this may cause increased seizure activity.<ref>http://www.rxlist.com/topamax-drug.htm</ref>

			Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.<ref>{{cite book \|vauthors= Porter RJ, Dhir A, Macdonald RL, Rogawski MA \|chapter= Mechanisms of action of antiseizure drugs \|title= Handb Clin Neurol \|year= 2012 \|volume= 108 \|pages= 663–681 \|doi= 10.1016/B978-0-444-52899-5.00021-6 \|pmid= 22939059 \|chapter-url= http://works.bepress.com/michael_rogawski/41/ \|series= Handbook of Clinical Neurology \|isbn= 9780444528995 \|access-date= 22 May 2014 \|archive-date= 22 June 2017 \|archive-url= https://web.archive.org/web/20170622140812/https://works.bepress.com/michael_rogawski/41/ \|url-status= dead }}</ref> These include (1) voltage-gated ]; (2) high-voltage-activated ]; (3) ]s; (4) AMPA/kainate receptors; and (5) ] isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by direct action.<ref>{{cite journal \| vauthors = Meldrum BS, Rogawski MA \| title = Molecular targets for antiepileptic drug development \| journal = Neurotherapeutics \| volume = 4 \| issue = 1 \| pages = 18–61 \| date = January 2007 \| pmid = 17199015 \| pmc = 1852436 \| doi = 10.1016/j.nurt.2006.11.010 }}</ref> The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, its relevance to clinical activity is uncertain. Effects on specific GABA-A receptor isoforms could also contribute to the antiseizure activity of the drug. Topiramate selectively inhibits cytosolic (type II) and membrane-associated (type IV) forms of carbonic anhydrase. Its action on carbonic anhydrase isoenzymes may contribute to the drug's side effects, including its propensity to cause metabolic acidosis and calcium phosphate kidney stones.
	==References==
	{{Reflist\|2}}

			Topiramate inhibits maximal seizure activity in electroconvulsive therapy and in ]-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on ] pores has been proposed as a mechanism.<ref name="pmid15571505">{{cite journal \| vauthors = Kudin AP, Debska-Vielhaber G, Vielhaber S, Elger CE, Kunz WS \| title = The mechanism of neuroprotection by topiramate in an animal model of epilepsy \| journal = Epilepsia \| volume = 45 \| issue = 12 \| pages = 1478–1487 \| date = December 2004 \| pmid = 15571505 \| doi = 10.1111/j.0013-9580.2004.13504.x \| s2cid = 7067509 \| doi-access = free }}</ref>
	==External links==

	{{Commons category}}
			While many ] have been associated with ] in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants ], carbamazepine, ]] that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.<ref name="Czuczwar-2004">{{cite journal \| vauthors = Czuczwar K, Czuczwar M, Cieszczyk J, Gawlik P, Luszczki JJ, Borowicz KK, Czuczwar SJ \| title = \| journal = Przeglad Lekarski \| volume = 61 \| issue = 11 \| pages = 1268–1271 \| year = 2004 \| pmid = 15727029 }}</ref>
	*

	*
			===Detection in body fluids===
	*
			Blood, serum, or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, or assist in a medicolegal death investigation. Plasma levels are usually less than 10 mg/L during therapeutic administration, but can range from 10 to 150 mg/L in overdose victims.<ref name="pmid19593736">{{cite journal \| vauthors = Goswami D, Kumar A, Khuroo AH, Monif T, Rab S \| title = Bioanalytical LC-MS/MS method validation for plasma determination of topiramate in healthy Indian volunteers \| journal = Biomedical Chromatography\| volume = 23 \| issue = 11 \| pages = 1227–41 \| date = November 2009 \| pmid = 19593736 \| doi = 10.1002/bmc.1273 }}</ref><ref>{{cite journal \| vauthors = Brandt C, Elsner H, Füratsch N, Hoppe M, Nieder E, Rambeck B, Ebner A, May TW \| display-authors = 6 \| title = Topiramate overdose: a case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticus \| journal = Epilepsia \| volume = 51 \| issue = 6 \| pages = 1090–1093 \| date = June 2010 \| pmid = 19889015 \| doi = 10.1111/j.1528-1167.2009.02395.x \| s2cid = 35752877 \| doi-access = }}</ref><ref>{{cite book \| vauthors = Baselt R \| title = Disposition of Toxic Drugs and Chemicals in Man \| edition = 8th \| publisher = Biomedical Publications \| location = Foster City, CA \| date = 2008 \| pages = 1567–1569 }}</ref>
	*

	*
			==History==
	*
			Topiramate was discovered in 1979 by ] and Joseph F. Gardocki during their research work at ].<ref>{{cite journal \| vauthors = Maryanoff BE, Nortey SO, Gardocki JF, Shank RP, Dodgson SP \| title = Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate and related compounds \| journal = Journal of Medicinal Chemistry \| volume = 30 \| issue = 5 \| pages = 880–887 \| date = May 1987 \| pmid = 3572976 \| doi = 10.1021/jm00388a023 }}</ref><ref>{{cite journal \| vauthors = Maryanoff BE, Costanzo MJ, Nortey SO, Greco MN, Shank RP, Schupsky JJ, Ortegon MP, Vaught JL \| display-authors = 6 \| title = Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives \| journal = Journal of Medicinal Chemistry \| volume = 41 \| issue = 8 \| pages = 1315–1343 \| date = April 1998 \| pmid = 9548821 \| doi = 10.1021/jm970790w }}</ref> Topiramate was first sold
	*
			in 1996.<ref>{{cite book\| vauthors = Pitkänen A, Schwartzkroin PA, Moshé SL \|title=Models of Seizures and Epilepsy \|date=2005 \|publisher=Elsevier \|location=Burlington \|isbn=9780080457024 \|page=539 \|url= https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539\|access-date=17 September 2017\|archive-date=8 September 2017\|archive-url=https://web.archive.org/web/20170908192246/https://books.google.com/books?id=Qw6KqLjwtZQC&pg=PA539\|url-status=live}}</ref> ] was granted final approval by the FDA for the sale of generic topiramate in the United States and the generic version was made available in September 2006.<ref>{{cite web \| vauthors = Waknine Y \| date = 22 September 2006 \|url=http://www.medscape.com/viewarticle/544994 \|title=First-Time Generic Approvals: Seasonale, Imodium Advanced, and Topamax \|publisher=Medscape.com \|access-date=11 July 2013 \|archive-date=20 May 2013 \|archive-url= https://web.archive.org/web/20130520134911/http://www.medscape.com/viewarticle/544994 \|url-status=live }}</ref> The last patent for topiramate in the U.S. was for use in children and expired on 28 February 2009.<ref>{{cite web\|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx\|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations\|publisher=Accessdata.fda.gov\|access-date=17 October 2014\|archive-date=25 April 2016\|archive-url= https://web.archive.org/web/20160425045412/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=020844&Product_No=002&table1=OB_Rx\|url-status=live}}</ref>
	*

	*
			== Research ==
	* , Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1
			Topiramate is being studied as a potential treatment for ] (PTSD).<ref>{{cite journal \| vauthors = Andrus MR, Gilbert E \| title = Treatment of civilian and combat-related posttraumatic stress disorder with topiramate \| journal = The Annals of Pharmacotherapy \| volume = 44 \| issue = 11 \| pages = 1810–1816 \| date = November 2010 \| pmid = 20923947 \| doi = 10.1345/aph.1P163 \| s2cid = 12137726 }}</ref>

			There is some evidence for the use of topiramate in the management of ].<ref>Roy AK 3rd, Hsieh C, Crapanzano K. Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With Alcohol? J Addict Med. 2015 Nov-Dec;9(6):499-501. doi: 10.1097/ADM.0000000000000152. PMID 26441400.</ref>

			A 2023 systematic review of seizure treatment for infants aged 1 to 36 months identified three studies that evaluated the use of topiramate. Though its adverse effects including upper respiratory tract infection and loss of appetite were rarely severe enough for the medication to be discontinued in this age group, its effectiveness in reducing seizures was inconclusive. The available research suffers from small sample sizes, inconsistent findings, and inadequate comparison groups.<ref>{{Cite report \| vauthors = Treadwell JR, Wu M, Tsou AY \|date=25 October 2022 \|title=Management of Infantile Epilepsies \|doi=10.23970/ahrqepccer252 \| doi-access= \| title-link=doi \| publisher=Agency for Healthcare Research and Quality }}</ref>

			== References ==
			{{Reflist}}

			== External links ==
			{{Commons category-inline}}

	{{Anticonvulsants}}		{{Anticonvulsants}}
	{{Mood stabilizers}}
	{{Bipolar disorder}}
	{{Antimigraine preparations}}		{{Antimigraine preparations}}
			{{Ion channel modulators}}
	{{Glutamatergics}}
			{{GABAA receptor positive modulators}}
			{{Ionotropic glutamate receptor modulators}}
			{{Portal bar \| Medicine}}
			{{Authority control}}

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