Lamotrigine

Structural formula
General
Non-proprietary name	Lamotrigine
other names	3,5-diamino-6- (2,3-dichlorophenyl) -1,2,4-triazine ( IUPAC ) Lamotriginum ( lat. )
Molecular formula	C 9 H 7 Cl 2 N 5
External identifiers / databases
CAS number 84057-84-1 EC number 281-901-8 ECHA InfoCard 100,074,432 PubChem 3878 DrugBank DB00555 Wikidata Q410346
Drug information
ATC code	N03 AX09
Drug class	Anticonvulsant
Mechanism of action	Sodium and calcium channel blockers
properties
Molar mass	256.09 g · mol -1
Physical state	firmly
Melting point	216-218 ° C
pK s value	5.7
solubility	0.17 mg / ml (25 ° C); 0.57 mg / ml (37 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 301 P: 301 + 310
Toxicological data	205 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lamotrigine is a drug from the group of anti-epileptic drugs that has been approved for patients aged 12 and over since 1993 . In addition to the therapy of epilepsy , it is also used for mood disorders . Lamotrigine was developed and first marketed by GlaxoSmithKline . It has been available as a generic since June 2005 .

pharmacology

Pharmacodynamics (mechanism of action)

Lamotrigine blocks sodium and voltage-dependent calcium channels in nerve cells and prevents the release of the excitatory neurotransmitters aspartate and glutamate . This means that stimuli can only spread to a reduced extent from one nerve cell to another. The inhibition of neuronal α4β2 nACh receptors brought about by lamotrigine - probably via lumen blockade - could contribute to the antiepileptic effect. In the depression model, values ​​of BDNF and VEGF are positively influenced by lamotrigine.

Areas of application

In the treatment of epilepsy , it leads to freedom from seizures in 40–60% of patients. However, experience shows that the effectiveness in myoclonus can be reduced.

In addition to the treatment of epilepsy, it is mainly used for the prophylaxis of recurrent depression and of depressive states in the case of bipolar disorder . In the treatment of manias , on the other hand, it shows rather minor effects. Lamotrigine has a mood stabilizer and thus joins the phase prophylactic drugs . Due to the membrane-stabilizing property of lamotrigine, it is used in addition to other anti-epileptic drugs (phenytoin, valproic acid, carbamazepine) in neuromyotonia (e.g. the rare Isaac syndrome).

In addition, in a study of stroke patients, a reduction in pain was observed in 30% of those involved. Good effectiveness in HIV-associated polyneuropathy is also described. Even if the effectiveness of lamotrigine for neuropathic pain is questionable, the Federal Joint Committee has recommended the off-label use of lamotrigine for neuropathic pain since 2013 .

More recently, the remedy has also been used by neurologists against migraines - but not against headaches , but in cases in which the migraine aura (neurological deficits, paralysis, visual field defects due to the migraine) is in the foreground.

The combination with serotonin reuptake inhibitors for better treatment of depersonalization and derealization symptoms is also being investigated, although lamotrigine alone has no effect against these symptoms.

Lamotrigine is also used successfully in the treatment of the rare hallucinogen-induced persistent cognitive disorder. Lamotrigine, like other preparations, can bring relief to the also rare visual snow syndrome .

Tolerability, known side effects

Lamotrigine is usually well tolerated. However, if the dose is increased too quickly, dangerous skin and mucous membrane reactions ( rash , exfoliative dermatitis, Stevens-Johnson syndrome ) can occur.

In rare cases, double vision , dizziness, headache, nausea, movement disorders ( ataxia ), muscle tremors ( tremor ), Lyell syndrome ( syndrome of scalded skin ), agranulocytosis , sleep disorders or even behavioral disorders are described as side effects .

The US Food and Drug Administration (FDA) announced on April 25, 2018 about the rare but serious risk of hemophagocytic lymphohistiocytosis (HLH) associated with lamotrigine, which can become life-threatening if the immune system is overactivated. HLH can occur within days to weeks of starting treatment.

In 3% of the cases a paradoxical accumulation of seizures can occur (rebound seizures). Liver damage at the start of treatment cannot be ruled out. For this reason, liver function should be monitored at the beginning of drug therapy.

If none of the side effects have occurred after eight weeks of treatment, it can be assumed that the drug is tolerated. Exceptions are switching from another medication, simultaneous use of other medication and milder symptoms shortly after an increased dose.

Interactions

The pain reliever paracetamol can increase the breakdown of lamotrigine in the body. As an alternative, there are pain relievers with the active ingredient ibuprofen .

A malaria therapy or prophylaxis may lead to a reduction of the efficacy of lamotrigine or the anti-malarial drug.

Interactions with rifampicin can also occur, which reduce availability by up to 40%.

Therapy with lamotrigine and other anti-epileptic drugs can lead to increased side effects. With carbamazepine therapy , lamotrigine is broken down more quickly because carbamazepine is an enzyme inducer . More substance must therefore be taken. The same applies to drugs with the active ingredients phenytoin , phenobarbital and primidone . With valproic acid therapy ( inhibitor ), lamotrigine is broken down more slowly. In order to avoid side effects, lamotrigine in combination with valproic acid must be added much more slowly.

The lamotrigin concentration in the plasma is disturbed by the use of the contraceptive pill. Taking the pill reduces lamotrigine levels by up to 50%. There may be more seizures. Stopping the pill causes the level to rise, so the rate of side effects increases. Conversely, lamotrigine may also interfere with the effectiveness of hormonal contraceptives , as the progestin levonorgestrel is broken down more quickly. Therefore, patients should be advised to be aware of changes in their menstrual pattern, i.e. H. Breakthrough bleeding to report immediately. No data are available for other gestagens.

Trade names

Monopreparations

Elmendos (D), Gerolamic (A), Lamictal (D, A, CH), Lamotribene (A), Lamotrigine Desitin Quadro (D), numerous generics (D, A, CH)

literature

• S. Brunnhuber, S. Frauenknecht, K. Lieb: Intensive course in psychiatry and psychotherapy. Urban & Fischer, Munich 2005, ISBN 3-437-42131-X .

Individual evidence

1. ↑ ^{a b c} Entry on lamotrigine. In: Römpp Online . Georg Thieme Verlag, accessed on July 12, 2019.
2. ↑ ^{a b} Datasheet Lamotrigine ≥ 98%, powder from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
3. ↑ Entry on lamotrigine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
4. ↑ C. Zheng et al .: The anticonvulsive drug lamotrigine blocks neuronal α4β2 nicotinic acetylcholine receptors . In: J Pharmacol Exp Ther . tape 335 , no. 2 , 2010, p. 401-408 , doi : 10.1124 / jpet.110.171108 , PMID 20688974 .
5. ↑ HM Abelaira et al.: Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats . In: Pharmacol. Biochem. Behav. tape 101 , no. 3 , 2012, p. 348-353 , doi : 10.1016 / j.pbb.2012.01.019 , PMID 22306746 .
6. ↑ HM Abelaira et al .: Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats . In: Neurochem. Int. tape 59 , no. 8 , 2011, p. 1163–1174 , doi : 10.1016 / j.neuint.2011.10.007 , PMID 22044672 .
7. ^ R. Sun, N. Li, T. Li: VEGF regulates antidepressant effects of lamotrigine . In: Eur Neuropsychopharmacol . tape 22 , no. 6 , 2012, p. 424-430 , doi : 10.1016 / j.euroneuro.2011.09.010 , PMID 22033393 .
8. ↑ INSERM US14-- ALL RIGHTS RESERVED: Orphanet: Isaacs Syndrome. Retrieved May 25, 2019 . 
9. ↑ Drugs Directive / Annex VI: Initiation of an opinion procedure - Off-label use of lamotrigine for central neuropathic pain after a stroke. In: g-ba.de. Federal Joint Committee , November 5, 2013, accessed on February 25, 2017 . 
10. ↑ M. Sierra, ML Phillips, MV Lambert et al: Lamotrigine in the treatment of depersonalization disorder. In: Journal of Clinical Psychiatry. Volume 62, 2001, pp. 826-827.
11. ↑ N. Medford, M. Sierra, D. Baker, AS David: Understanding and treating depersonalization disorder. In: Advances in Psychiatric Treatment. Volume 11, No. 2, 2005, pp. 92-100. doi: 10.1192 / apt.11.2.92 .
12. ↑ M. Sierra, ML Phillips, G. Ivin et al: A placebo-controlled crossover trial of lamotrigine in depersonalization disorder. In: Journal of Psychopharmacology . Volume 17, 2003, pp. 103-105. doi: 10.1177 / 0269881103017001712 .
13. ↑ L. Hermle, M. Simon, M. Ruchsow, M. Geppert: Hallucinogen-persisting perception disorder. In: Therapeutic advances in psychopharmacology. Volume 2, number 5, October 2012, pp. 199-205, doi: 10.1177 / 2045125312451270 . PMID 23983976 , PMC 3736944 (free full text).
14. ↑ Visual Snow: a Potential Cortical Hyperexcitability Syndrome. Retrieved May 21, 2018 . 
15. ↑ Information from the FDA on lamotrigine: excessive reaction of the immune system. (akdae.de)
16. ↑ DailyMed - LAMICTAL - lamotrigine tablet LAMICTAL- lamotrigine tablet, chewable LAMICTAL ODT- lamotrigine tablet, orally disintegrating LAMICTAL- lamotrigine LAMICTAL ODT- lamotrigine. Accessed May 1, 2019 . 
17. ↑ Information for professionals of the Swiss Medicines Compendium: Lamotrigin Sandoz®; July 2006.
18. ↑ ABDATA Pharma-Daten-Service: LAMOTRIGIN Desitin Quadro 100 mg tablets package insert . In: Apotheken-Umschau . December 19, 2018 ( apotheken-umschau.de ).

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 !