Description

Simple

A medication used to prevent or treat migraines and to control a disease called epilepsy, which leads to seizures.

Clinical

An anticonvulsant drug used in the control of epilepsy and in the prophylaxis and treatment of migraines.

Overview

Topiramate is a anti-epileptic drug used to manage seizures and prevent migraines.[4] It was initially approved by the FDA in 1996. In 2004, topiramate was approved for the prevention of migraine in adults.[6,19] Since 2012, the extended-release formulation has been approved in combination with [phentermine] for chronic weight management therapy in adults.[21]

Characteristics that distinguish topiramate from other antiepileptic drugs are a monosaccharide chemical structure containing a sulfamate, and 40% of its mass accounted for by oxygen.[4] Interestingly, topiramate was discovered by chance when... Read more

Pharmacology

Indication

Topiramate is indicated for the following conditions: 1)Monotherapy for partial onset or primary generalized tonic-clonic seizures for patients 2 years of age and above 2)Adjunctive therapy for partial onset seizures or primary generalized tonic-clonic seizures for both adult and pediatric patients... Read more

Pharmacodynamic

Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability.[ Read more

Mechanism of action

A seizure is an abnormal and unregulated electrical discharge occurring in the brain. This leads to transient interruption in brain function, manifested by reduced alertness, abnormal sensations, and focal involuntary movements or convulsions. Several types of seizures exist, with common types inclu... Read more

Absorption

After a 400mg dose in one clinical trial, topiramate reached maximal concentrations within 1.8-4.3 hours and ranged from 1.73-28.7 ug/mL. Food did not significantly affect the extent of absorption, despite delaying time to peak concentration. In patients with normal creatinine clearance, steady stat... Read more

Protein binding

Topiramate is not highly bound to plasma proteins, with an estimated plasma protein binding of 9-17% according to some studies.[3, Read more

Volume of distribution

The mean apparent volume of distribution of topiramate ranges from 0.6-0.8 L/kg when doses of 100mg to 1200mg are given.[3] Topiramate readily c... Read more

Clearance

The mean oral plasma clearance of topiramate ranges from 22-36 mL/min while the renal clearance is 17-18 mL/min, according to one pharmacokinetic study.[ Read more

Half life

The elimination half-life is reported to be in the range of 19-23 hours.[3] If topiramate is given with enzyme-inducers, the half-life can be re... Read more

Route of elimination

Topiramate is mainly eliminated through the kidneys.[15] About 70-80% of the eliminated dose is found unchanged in the ur... Read more

Toxicity

The LD50 of intraperitoneal topiramate in the rat is above 1500 mg/kg.[20]

Overdose information

In a study of 4 healthy adult women taking topiramate, the severity of clinical effects following an overdose ranged fr... Read more

Adverse Effects

Contraindications

  • Route:
    • Oral
  • Dose Form:
    • Capsule
    • Capsule, extended release
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Metabolic Acidosis
      • Drugbank Id: DBCOND0043658
  • With Drugs:
      • Name: Metformin
      • Drugbank Id: DB00331

Food Interactions

  • Avoid a ketogenic diet. This type of diet increases the risk of kidney stones.
  • Take with or without food. Food slightly alters absorption but not to any clinically significant extent.

Interactions

Type in a drug name to check for interaction with Topiramate
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Topiramate.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Topiramate.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Topiramate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
Topiramate may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Topiramate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Topiramate.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Topiramate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Topiramate is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine
Topiramate may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Deazaguanine
Topiramate may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Topiramate is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Topiramate is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
7,9-Dimethylguanine
Topiramate may increase the excretion rate of 7,9-Dimethylguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-azaguanine
Topiramate may increase the excretion rate of 8-azaguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-chlorotheophylline
Topiramate may increase the excretion rate of 8-chlorotheophylline which could result in a lower serum level and potentially a reduction in efficacy.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Topiramate.
9-Deazaguanine
Topiramate may increase the excretion rate of 9-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
9-Methylguanine
Topiramate may increase the excretion rate of 9-Methylguanine which could result in a lower serum level and potentially a reduction in efficacy.
Abacavir
Topiramate may decrease the excretion rate of Abacavir which could result in a higher serum level.
Acarbose
Topiramate may decrease the excretion rate of Acarbose which could result in a higher serum level.
21 References
  1. 1 . Ford L, Goldberg JL, Selan F, Greenberg HE, Shi Y: Comprehensive review of visual defects reported with topiramate. Clin Ophthalmol. 2017 May 23;11:983-992. doi: 10.2147/OPTH.S125768. eCollection 2017.PubMed: 28579749
  2. 2 . Brigo F, Bragazzi NL, Igwe SC, Nardone R, Trinka E: Topiramate in the Treatment of Generalized Convulsive Status Epilepticus in Adults: A Systematic Review with Individual Patient Data Analysis. Drugs. 2017 Jan;77(1):67-74. doi: 10.1007/s40265-016-0672-2.PubMed: 28004305
  3. 3 . Garnett WR: Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41 Suppl 1:S61-5.PubMed: 10768303
  4. 4 . Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE: An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41 Suppl 1:S3-9.PubMed: 10768292
  5. 5 . Wisniewski M, Lukasik-Glebocka M, Anand JS: Acute topiramate overdose--clinical manifestations. Clin Toxicol (Phila). 2009 Apr;47(4):317-20. doi: 10.1080/15563650601117954.PubMed: 19514879
  6. 6 . Wenzel RG, Schwarz K, Padiyara RS: Topiramate for migraine prevention. Pharmacotherapy. 2006 Mar;26(3):375-87. doi: 10.1592/phco.26.3.375.PubMed: 16503717
  7. 7 . Arnone D: Review of the use of Topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry. 2005 Feb 16;4(1):5. doi: 10.1186/1744-859X-4-5.PubMed: 15845141
  8. 8 . Maryanoff BE: Sugar sulfamates for seizure control: discovery and development of topiramate, a structurally unique antiepileptic drug. Curr Top Med Chem. 2009;9(11):1049-62. doi: 10.2174/156802609789630938.PubMed: 19860705
  9. 9 . Chung JY, Kim MW, Kim M: Efficacy of zonisamide in migraineurs with nonresponse to topiramate. Biomed Res Int. 2014;2014:891348. doi: 10.1155/2014/891348. Epub 2014 Jul 2.PubMed: 25101297
  10. 10 . Naegel S, Obermann M: Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference. Neuropsychiatr Dis Treat. 2010 Feb 3;6:17-28. doi: 10.2147/ndt.s6459.PubMed: 20169042
  11. 11 . Maryanoff BE, McComsey DF, Costanzo MJ, Hochman C, Smith-Swintosky V, Shank RP: Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform. J Med Chem. 2005 Mar 24;48(6):1941-7.PubMed: 15771438
  12. 12 . Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. doi: 10.1111/j.1528-1157.2000.tb06047.x.PubMed: 10768298
  13. 13 . Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25.PubMed: 17826101
  14. 14 . Caldwell GW, Wu WN, Masucci JA, McKown LA, Gauthier D, Jones WJ, Leo GC, Maryanoff BE: Metabolism and excretion of the antiepileptic/antimigraine drug, Topiramate in animals and humans. Eur J Drug Metab Pharmacokinet. 2005 Jul-Sep;30(3):151-64. doi: 10.1007/BF03190614.PubMed: 16250251
  15. 15 . Walker MC, Sander JW: Topiramate: a new antiepileptic drug for refractory epilepsy. Seizure. 1996 Sep;5(3):199-203.PubMed: 8902921
  16. 16 . Mary J. Allen; Sandeep Sharma (2019). GABA receptor. StatPearls.
  17. 17 . Merck Link
  18. 18 . Topamax, manufacturer's website Link
  19. 19 . FDA label, topiramate Link
  20. 20 . MSDS, Topiramate Link
  21. 21 . Qsymia approval information Link