Topiramate

Structural formula
General
Non-proprietary name	Topiramate
other names	2,3: 4,5-Bis- O- (1-methylethylidene) -β- D -fructopyranose sulfamate
Molecular formula	C 12 H 21 NO 8 S
External identifiers / databases
CAS number 97240-79-4 EC number 619-263-3 ECHA InfoCard 100.129.713 PubChem 5284627 ChemSpider 4447672 DrugBank DB00273 Wikidata Q221174
Drug information
ATC code	N03 AX11
Drug class	Anti-epileptic
properties
Molar mass	339.4 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 315-319-335 P: 261-305 + 351 + 338
Toxicological data	> 1500 mg kg −1 ( LD 50 ,  rat ,  ip )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Topiramate (trade name: Topamax ) is a drug used for epilepsy and migraines . Individual reports describe a positive effect of topiramate in cluster headache prophylaxis. In Germany it was only sold by Janssen-Cilag until the patent expired in 2009 .

Mechanism of action

Topiramate works through various mechanisms that prevent nerve cells from being overly excited. Topiramate blocks the (strengthening) glycine binding site on the excitatory glutamatergic AMPA receptor and increases its inhibitory effect by binding to GABA receptors . Topiramate also inactivates the voltage-dependent sodium channel , which prevents the cell from generating action potentials in rapid succession . Furthermore, it has a modulating effect on certain voltage-dependent calcium channels and causes a weak inhibition of certain isoenzymes of carbonic anhydrase .

Pharmacokinetics

Topiramate is well absorbed by the body and is given as a tablet. The half-life is between 20 and 30 hours. Topiramate is largely excreted unchanged via the kidneys. Therefore, if the kidney function is impaired, the dose of the drug must be reduced. The anti- epileptic drugs carbamazepine and phenytoin lower the level of topiramate in the blood. In combination with these, the topiramate dose must be adjusted.

application

Topiramate is used in doses of 25 to 200 mg as an anti-epileptic. It is used in adults and adolescents as an additional drug for focal and generalized seizures and for Lennox-Gastaut syndrome . Topiramate is also approved for the prophylaxis of migraine attacks. According to the recommendations of the German Migraine and Headache Society , topiramate can also be used for the preventive treatment of cluster headaches . Recently, topiramate has also been tested in relation to the treatment of chronic PTSD (post- traumatic stress disorder ). The first encouraging results are reported here. Topiramate requires a prescription .

Topiramate for alcohol and cocaine addiction

The release of dopamine in the corticomesolimbic system is reduced by topiramate; the drug could probably be used in the therapy of alcohol addicts. This treatment option was investigated in more detail in a double-blind , randomized, and placebo-controlled study . For 14 weeks, 371 test subjects received either topiramate in increasing doses (up to 300 mg / day from the fifth week) or placebo . In addition to drug therapy, short one-on-one discussions were held weekly. If the days with heavy alcohol consumption are considered, this proportion decreased in the topiramate group from 81.5% to 43.8% and in the placebo group from 82% to 51.8%. In the topiramate group, side effects such as paresthesia , taste disorders or concentration disorders were more common . The authors of the study see topiramate as a promising therapeutic option for alcohol addiction. Various parameters such as dosage and duration of action still need to be clarified.

According to a double-blind, placebo-controlled study from the University of Pennsylvania, topiramate significantly increases the likelihood of remaining abstinent from cocaine and the likelihood of achieving a three-week abstinence period compared to placebo. Another study concluded that topiramate can significantly reduce cocaine cravings in 25% of participants.

Use during pregnancy and breastfeeding

Topiramate has shown teratogenic effects in mice, rats and rabbits . Data from pregnancy registries (North American Antiepileptic Pregnancy Registry, NAAED, and the UK Epilepsy and Pregnancy Registry) showed cases of serious malformations in the child when the mother took topiramate in the first trimester of pregnancy . Preclinical data also indicate a teratogenic potential of the drug. A phased plan procedure has been initiated in Germany . Topiramate should not be used during pregnancy for the treatment of migraines. Topiramate is excreted in the milk of lactating rats. Limited human observations indicate significant excretion in breast milk.

Use of topiramate and birth control

Patients who take oral combination contraceptives (“ birth control pills ”) in addition to topiramate must expect a possible reduction in the contraceptive effectiveness and increased breakthrough bleeding. The contraceptive safety of the birth control pill can also be influenced by topiramate without causing breakthrough bleeding.

Effects on ability to drive and use machines

Topiramate acts on the central nervous system. You may experience drowsiness, dizziness, or other similar symptoms. This can be especially dangerous if the patient has to drive or use machines.

Side effects

Topiramate can cause the following side effects :

• Loss and lack of sense of taste, up to and including inflammation in the mouth area.
• ringing noise in the ear, up to earache.
• decreased eyesight.
• the most common side effects are tingling sensations, especially in the arms and legs (so-called paresthesia ); however, these usually disappear after a while; a diet rich in potassium (bananas, dried fruit) can alleviate the paresthesia
• Ataxia (coordination disorder, e.g. greatly unsteady gait) - can also lead to very slow walking despite a walking aid (even if no aid was required before taking topiramate)
• Difficulty concentrating (in the middle of a sentence you don't know what to say. Search for words)
• a headache
• Disturbed memory (affects both short and long-term memory)
• the feeling of no longer being able to learn something
• increased irritability
• ( Depression )
• ( Sleep disorders ,) nightmares
• (Increase in appetite,) decrease in appetite (is therefore also used for eating disorders )
• (Trembling hands)
• chanting language or speech that is not perceived by the person concerned
• Occurrence of so-called dissociative seizures, fits of anger
• Hallucinations

Should there be any suspicion that z. If, for example, severe gait disorders are the effect of topiramate, this must be checked using psychological tests.

Web links

Commons : Topiramate  - collection of images, videos and audio files

Individual evidence

1. ↑ ^{a b c} Data sheet Topiramate from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
2. ^ S1 guideline for cluster headaches and trigemino-autonomic headaches of the German Society for Neurology (DGN). In: AWMF online (as of 2015)
3. ↑ H. Lüllmann, K. Mohr, L. Hein: Pharmakologie und Toxikologie. Thieme, 2006.
4. ↑ A. May, S. Evers, G. Brössner, T. Jürgens, AR Gantenbein, V. Malzacher, A. Straube: Guideline for the diagnosis, therapy and prophylaxis of cluster headaches, other trigeminal autonomic headaches, sleep-bound headaches and idiopathic sharp headache. Revised therapy recommendations of the German Migraine and Headache Society in cooperation with the DGN, ÖKSG, SKG. In: Neurology. ( Memento from August 20, 2016 in the Internet Archive ) 35 (3), 2016, pp. 137–151, (DMKG: PDF file) .
5. ↑ Jeffrey L. Berlant: Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder . In: BMC Psychiatry . tape 4 , no. 1 , August 2004, p. 24 , doi : 10.1186 / 1471-244X-4-24 ( biomedcentral.com ).
6. ^ Topiramate for Treating Alcohol Dependence. In: JAMA. 298, 2007, pp. 1641-1651.
7. ↑ Antiepileptic drugs alleviate alcohol dependence. ( Memento from February 27, 2017 in the Internet Archive ) on: aerzteblatt.de , October 10, 2007.
8. ↑ KM Kampman, H. Pettinati, KG Lynch, C. Dackis, T. Sparkman, C. Weigley, CP O'Brien: A pilot trial of topiramate for the treatment of cocaine dependence . In: Drug Alcohol Depend . tape 75 , no. 3 , 2004, p. 233-240 , PMID 15283944 .
9. ^ AD Reis, LA Castro, R. Faria, R. Laranjeira: Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial . In: Rev Bras Psiquiatr . tape 30 , no. 2 , 2008, p. 132-135 , PMID 18470406 .
10. ↑ Topiramate: indications of an increased risk of malformations when used in the first trimester. ( Memento from February 10, 2013 in the web archive archive.today ) BfArM, May 16, 2012.
11. ↑ ^{a b c} Technical information Topamax. January, Janssen-Cilag GmbH, status 2011.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !