Topiramate

Source: Wikipedia, the free encyclopedia.

Topiramate
Clinical data
Trade namesTopamax, Trokendi XR, Qudexy XR, others
Other namesTopiramic acid
AHFS/Drugs.comMonograph
MedlinePlusa697012
License data
Pregnancy
category
  • AU: D
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%
Protein binding13–17%; 15–41%
MetabolismLiver (20–30%)
Elimination half-life21 hours
ExcretionUrine (70–80%)
Identifiers
  • 2,3:4,5-Bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate
JSmol)
  • O=S(=O)(OC[C@@]21OC(O[C@H]1[C@@H]3OC(O[C@@H]3CO2)(C)C)(C)C)N
  • InChI=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 checkY
  • Key:KJADKKWYZYXHBB-XBWDGYHZSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Topiramate, sold under the brand name Topamax among others, is a medication used to treat

focal seizures.[10] It is taken orally (by mouth).[9]

Common side effects include

kidney stones.[9] Topiramate can cause birth defects including cleft lip and palate.[12] 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.[13][14] The mechanism of action is unclear.[9]

Topiramate was approved for medical use in the United States in 1996.

generic medication.[10][15][16] In 2021, it was the 66th most commonly prescribed medication in the United States, with more than 10 million prescriptions.[17][18]

Medical uses

A package of topiramate 25mg from Norway

Topiramate is used to treat

Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is most frequently prescribed for the prevention of migraines[19] as it decreases the frequency of attacks.[20][21] Topiramate is used to treat medication overuse headache and is recommended by the European Federation of Neurological Societies as one of the few medications showing effectiveness for this indication.[22]

Pain

A 2018 review found topiramate of no use in chronic low back pain.[23] Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition in which it has been adequately tested.[24]

Other

One common off-label use for topiramate is in the treatment of bipolar disorder.[25][26][27] A review published in 2010 suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder, however the authors noted that this was based only on one randomized controlled trial and requires replication.[28]

Topiramate has been used as a treatment for

alcohol use disorder.[30]

Other uses include treatment of obesity,[31][32] binge eating disorder,[33] and off-setting weight gain induced by taking antipsychotic medications.[34][35] In 2012, the combination of phentermine/topiramate was approved in the United States for weight loss.

Adverse effects

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,[36] 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 cause visual field defects.[37]
  • Topiramate may decrease effectiveness of oestrogen-containing oral contraceptives.
  • Taking topiramate in the first trimester of pregnancy may increase risk of cleft lip/cleft palate in infant.[38]
  • 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.[39]

Frequency

Adverse effects by incidence:[40][41][42][43]

Very common (>10% incidence) adverse effects include:

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.[44]

The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly.[45] 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.

cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D.[38]

Cognitive and word-finding difficulties, as they may occur in some patients, may respond to piracetam.[47][48]

Topiramate has been associated with a statistically significant increase in suicidality,[49] 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."[36][50]

Overdose

Symptoms of

polydrug exposure.[53] The most common signs of overdose are dilated pupils, somnolence, dizziness, psychomotor agitation, and abnormal, uncoordinated body movements.[51][52][53]

Interactions

Topiramate has many drug-drug interactions. Some of the most common are listed below:

Pharmacology

Chair-style representation of skeletal formula

The topiramate molecule is a sulfamate modified sugar, more specifically, fructose diacetonide, 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.[56] Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.

Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.

GABA-A receptors; (4) AMPA/kainate receptors; and (5) carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by a direct action.[58]
The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, the 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. The 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.

Topiramate inhibits maximal seizure activity in electroconvulsive therapy and in

mitochondrial permeability transition pores has been proposed as a mechanism.[59]

While many

anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants [see: levetiracetam, carbamazepine, lamotrigine] that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.[60]

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 to 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.[61][62][63]

History

Topiramate was discovered in 1979 by

McNeil Pharmaceuticals.[64][65]
Topiramate was first sold in 1996.
Mylan Pharmaceuticals 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.[67] The last patent for topiramate in the U.S. was for use in children and expired on 28 February 2009.[68]

Research

Topiramate is being studied as a potential treatment for

post traumatic stress disorder.[69]

There is some evidence for the use of topiramate in the management of cravings related to withdrawal from dextromethorphan.[70]

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.[71]

References

  1. FDA
    . Retrieved 22 October 2023.
  2. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  3. ^ "Trokendi XR- topiramate capsule, extended release". DailyMed. Archived from the original on 8 November 2021. Retrieved 8 November 2021.
  4. ^ "Topamax- topiramate tablet, coated Topamax- topiramate capsule, coated pellets". DailyMed. Archived from the original on 8 November 2021. Retrieved 8 November 2021.
  5. ^ "Qsymia- phentermine and topiramate capsule, extended release". DailyMed. Archived from the original on 26 October 2021. Retrieved 8 November 2021.
  6. ^ "Qudexy XR- topiramate capsule, extended release". DailyMed. Archived from the original on 8 November 2021. Retrieved 8 November 2021.
  7. ^ "Eprontia - topiramate solution". DailyMed. Archived from the original on 19 December 2021. Retrieved 19 December 2021.
  8. ^ "Active substance(s): topiramate" (PDF). List of nationally authorised medicinal products. European Medicines Agency. September 2022. Archived (PDF) from the original on 6 September 2022. Retrieved 6 September 2022.
  9. ^ a b c d e f g "Topiramate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 6 March 2019. Retrieved 5 March 2019.
  10. ^
    ISBN 9780857113382
    .
  11. ^ "Topiramate Side Effects: Common, Severe, Long Term". Drugs.com. Archived from the original on 10 April 2021. Retrieved 3 August 2021.
  12. ^ "FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate)". FDA. 18 June 2019.
  13. ^ Health, MGH Center for Women's Mental (10 August 2022). "Essential Reads: Breastfeeding and Anti-Epileptic Drugs - MGH Center for Women's Mental Health". Retrieved 27 December 2023.
  14. PMID 30000318
    , retrieved 27 December 2023
  15. ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
  16. ^ "First Generic Drug Approvals 2023". U.S. Food and Drug Administration (FDA). 30 May 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  17. ^ "The Top 300 of 2021". ClinCalc. Retrieved 14 January 2024.
  18. ^ "Topiramate - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  19. ^ a b "Topamax Prescribing Information" (PDF). United States Food and Drug Administration. Archived (PDF) from the original on 24 April 2016. Retrieved 11 April 2016.
  20. PMID 23797676
    .
  21. S2CID 207491096
    .
  22. S2CID 2698885
    .
  23. PMID 29970367
    .
  24. PMID 23996081. Archived
    from the original on 31 March 2014. Retrieved 6 September 2013.
  25. PMID 15845141
    .
  26. PMID 16437453
    .
  27. S2CID 25512763
    .
  28. PMID 20044651
    .
  29. PMID 20482511
    .
  30. ^ "VA/DoD Clinical Practice Guideline for the management of substance use disorders" (PDF). healthquality.va.gov. 31 December 2015. Archived (PDF) from the original on 31 August 2017. Retrieved 30 August 2017.
  31. S2CID 30103553
    .
  32. S2CID 24358798
    .
  33. ^ "Topiramate for Binge Eating Disorder". wa.kaiserpermanente.org. Archived from the original on 3 August 2021. Retrieved 3 August 2021.
  34. PMID 23302448
    .
  35. S2CID 26085987
    .
  36. ^ a b "Possible Side Effects - Topamax (topiramate)". Topamax.xom. Archived from the original on 28 January 2011. Retrieved 17 October 2014.
  37. ^ "Topamax (topiramate) tablets and sprinkle capsules". Fda.gov. Archived from the original on 12 January 2017. Retrieved 17 October 2014.
  38. ^ a b "Risk of oral clefts in children born to mothers taking Topamax (topiramate)". FDA Drug Safety Communication. Fda.gov. 6 January 2011. Archived from the original on 24 April 2019. Retrieved 11 July 2013.
  39. ^ "Seizures and Epilepsy in Children". www.hopkinsmedicine.org. 8 August 2021. Retrieved 19 July 2023.
  40. ^ "Topamax Tablets and Sprinkle Capsules PRODUCT INFORMATION" (PDF). TGA eBusiness Services. JANSSEN-CILAG Pty Ltd. 30 May 2013. Archived from the original on 29 March 2019. Retrieved 18 November 2013.
  41. ^ "topiramate (Rx) - Topamax, Trokendi XR". Medscape Reference. WebMD. Archived from the original on 19 May 2019. Retrieved 18 November 2013.
  42. ^ "Topiramate 100 mg film-coated Tablets". electronic Medicines Compendium. Sandoz Limited. 6 March 2013. Archived from the original on 21 May 2014. Retrieved 18 November 2013.
  43. ^ "TOPIRAMATE ( topiramate ) tablet TOPIRAMATE ( topiramate ) tablet [Torrent Pharmaceuticals Limited]". DailyMed. Torrent Pharmaceuticals Limited. August 2011. Archived from the original on 20 May 2014. Retrieved 18 November 2013.
  44. PMID 19916989
    .
  45. ^ Hulihan J (2001). "IMPORTANT DRUG WARNING" (PDF). FDA MedWatch. Ortho-McNeil Pharmaceutical. Archived from the original (PDF) on 13 January 2017. Retrieved 11 June 2018.
  46. S2CID 13562052
    .
  47. ^ Berthier, M.L. and Dávila, G., 2023. Pharmacotherapy for post-stroke aphasia: what are the options?. Expert Opinion on Pharmacotherapy, (just-accepted).
  48. ^ 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.
  49. ^ "Suicidality and Antiepileptic Drugs" (PDF). Food and Drug Administration. Archived from the original on 10 May 2017. Retrieved 11 July 2013.
  50. ^ "Topiramate". PubMed Health. National Center for Biotechnology Information, U.S. National Library of Medicine. Archived from the original on 5 August 2010.
  51. ^
    S2CID 205901501
    .
  52. ^
    PMID 24515527
    .
  53. ^
    S2CID 37784043
    .
  54. ^
    ISBN 978-0-85369-840-1
    .
  55. ^ "TOPAMAX (topiramate) Tablets Approved Labeling Text" (PDF). Ortho-McNeil Pharmaceutical. U.S. Food and Drug Administration. 29 June 2005. p. 14. Archived from the original (PDF) on 5 February 2007.
  56. ^ "FDA Data on Topamax" (PDF). Archived (PDF) from the original on 6 August 2021. Retrieved 6 August 2021.
  57. PMID 22939059. Archived from the original
    on 22 June 2017. Retrieved 22 May 2014.
  58. PMID 17199015
    .
  59. S2CID 7067509
    .
  60. PMID 15727029
    .
  61. PMID 19593736
    .
  62. S2CID 35752877
    .
  63. ^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1567–1569.
  64. PMID 3572976
    .
  65. PMID 9548821
    .
  66. ISBN 9780080457024. Archived
    from the original on 8 September 2017. Retrieved 17 September 2017.
  67. ^ Waknine Y (22 September 2006). "First-Time Generic Approvals: Seasonale, Imodium Advanced, and Topamax". Medscape.com. Archived from the original on 20 May 2013. Retrieved 11 July 2013.
  68. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". Accessdata.fda.gov. Archived from the original on 25 April 2016. Retrieved 17 October 2014.
  69. S2CID 12137726
    .
  70. ^ 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.
  71. doi:10.23970/ahrqepccer252
    .

External links

Media related to Topiramate at Wikimedia Commons