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Lamotrigine

Description Generic formulation Indications Dose titration Plasma levels monitoring Cautions Interactions Special populations Behavioural and cognitive effects in patients with epilepsy Psychiatric use
Lamotrigine
Lamotrigine structure
CAS No.
84057-84-1
Chemical Name:
Lamotrigine
Synonyms
LTG;BW-430;BW-430C;LAMICTAL;LAMOTRIGIN;GI 267119X;Lemotrigine;LAMOTRIGINE;Lamictal XR;LAMOTRINGINE
CBNumber:
CB4166704
Molecular Formula:
C9H7Cl2N5
Formula Weight:
256.09
MOL File:
84057-84-1.mol

Lamotrigine Properties

Melting point:
177-181°C
Boiling point:
503.1±60.0 °C(Predicted)
Density 
1.572±0.06 g/cm3(Predicted)
Flash point:
9℃
storage temp. 
2-8°C
solubility 
DMSO: 20 mg/mL at 60 °C, soluble
pka
5.7(at 25℃)
form 
powder
color 
white
Merck 
14,5353
InChIKey
PYZRQGJRPPTADH-UHFFFAOYSA-N
CAS DataBase Reference
84057-84-1(CAS DataBase Reference)
EWG's Food Scores
1
FDA UNII
U3H27498KS
NCI Dictionary of Cancer Terms
lamotrigine
NCI Drug Dictionary
Lamictal
ATC code
N03AX09
SAFETY
  • Risk and Safety Statements
Symbol(GHS) 
GHS02,GHS08,GHS06
Signal word  Danger
Hazard statements  H225-H301+H311+H331-H370-H301
Precautionary statements  P210-P260-P280-P301+P310-P311
Hazard Codes  T,Xi,F
Risk Statements  25-36/37/38-39/23/24/25-23/24/25-11
Safety Statements  45-36-26-36/37-16
RIDADR  UN 2811 6.1/PG 3
WGK Germany  3
RTECS  XY5850700
HazardClass  6.1(b)
PackingGroup  III
HS Code  29336990
Toxicity LD50 in mice, rats (mg/kg): 250, >640 orally (Sawyer)

Lamotrigine price More Price(57)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich L-019 Lamotrigine solution 1.0mg/mL in methanol, ampule of 1mL, certified reference material 84057-84-1 019-1ml $99.6 2021-12-16 Buy
Sigma-Aldrich L-019 Lamotrigine solution 1.0?mg/mL in methanol, ampule of 1?mL, certified reference material, Cerilliant? 84057-84-1 1 mL $103 2021-12-16 Buy
Sigma-Aldrich Y0001030 Lamotrigine European Pharmacopoeia (EP) Reference Standard 84057-84-1 $190 2021-12-16 Buy
Sigma-Aldrich 1356756 Lamotrigine United States Pharmacopeia (USP) Reference Standard 84057-84-1 150mg $1080 2021-12-16 Buy
TCI Chemical L0241 Lamotrigine >98.0%(HPLC)(T) 84057-84-1 1g $68 2021-12-16 Buy

Lamotrigine Chemical Properties,Uses,Production

Description

Lamotrigine is a second- generation antiepileptic drug (AED) known by the proprietary brand name of Lamictal® (GlaxoSmithKline, Brentford) in the UK and USA.

Generic formulation

MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

Indications

Epilepsy: monotherapy and adjunctive therapy of focal and generalized seizures.

Recommendations summarized from NICE (2012)

Dose titration

Epilepsy— monotherapy
25 mg od for 14 days, 50 mg od for 14 days, then increased to a maximum of 100 mg every 7– 14 days; usual maintenance 100– 200 mg daily, divided into 1– 2 doses (max. 500 mg daily).

Epilepsy— adjunctive therapy (with valproate)
25 mg on alternate days for 14 days, 25 mg od for 14 days, then increased by a maximum of 50 mg every 7– 14 days; usual maintenance 100– 200 mg daily, divided into 1– 2 doses (max. 500 mg daily).

Epilepsy— adjunctive therapy (with enzyme- inducing AED and without valproate)
50 mg od for 14 days, 50 mg bd for 14 days, then increased by a maximum of 100 mg every 7– 14 days; usual maintenance 200– 400 mg daily, divided into two doses (max. 700 mg daily).

Epilepsy— adjunctive therapy (without enzyme- inducing AED and without valproate)
25 mg od for 14 days, 50 mg od for 14 days, then increased by a maximum of 100 mg every 7– 14 days; usual maintenance 100– 200 mg daily, divided into 1 or 2 doses.
Bipolar disorder— monotherapy or adjunctive therapy (without enzyme- inducing AED and without valproate)
25 mg od for 14 days, 50 mg daily, divided into 1 or 2 doses for 14 days, 100 mg daily, divided into 1 or 2 doses for 7 days; usual maintenance 200 mg daily, divided into 1 or 2 doses (max. 400 mg daily).

Bipolar disorder— adjunctive therapy (with valproate)
25 mg on alternate days for 14 days, 25 mg od for 14 days, 50 mg daily, divided into 1 or 2 doses; usual maintenance 100 mg daily, divided into 1 or 2 doses (max. 200 mg daily).

Bipolar disorder— adjunctive therapy (with enzyme- inducing AED and without valproate)
50 mg od for 14 days, 50 mg bd for 14 days, 100 mg bd for 7 days; 150 mg bd for 7 days; usual maintenance 200 mg bd.

If stopping lamotrigine, patients with epilepsy need to reduce the dose gradually over about 2 weeks to minimize the risk of relapse. This does not apply to patients who take lamotrigine for bipolar disorder, although NICE (2015) recommend that it be reduced gradually over at least 4 weeks to minimize the risk of relapse.

Plasma levels monitoring

Although plasma levels can be measured, and a therapeutic range has been postulated (2.5– 15 mg/ L), there is only a loose relationship between serum concentration and clinical effectiveness/ adverse effects. The routine measurement of plasma levels in clinical practice is therefore unnecessary, although it can sometimes be useful in guiding dosage adjustments in situations associated with changes in lamotrigine pharmacokinetics, such as pregnancy, puerperium, and polymedication.

Cautions

Interactions

With AEDs With other drugs With alcohol/food
There are no known specific interactions between alcohol and lamotrigine, and there are no specific foods that must be excluded from diet when taking lamotrigine.

Special populations

Hepatic impairment
Renal impairment
Reduce maintenance dose in significant impairment.

Pregnancy

Behavioural and cognitive effects in patients with epilepsy

Lamotrigine is characterized by an overall positive psychotropic profile, especially in terms of antidepressant properties. There are mixed findings about its possible effects on anxiety symptoms. The main adverse behavioural effects include irritability, agitation, and aggression (especially in patients with learning disability). However, these are not very common. There is no evidence of a significantly increased risk of thought disorders or cognitive deficits (at least at commonly used therapeutic doses). Positive effects on cognitive functions seem to be associated with EEG changes, rather than enhanced cognition.

Psychiatric use

The use of lamotrigine for the treatment of behavioural symptoms emerged from the observation of mood improvement in patients taking this medication for partial epilepsy. The main use of lamotrigine in psychiatry settings is for the maintenance therapy of bipolar disorder (prevention of depressive episodes), for which there is an approved indication from both FDA and EMA. There is evidence of a modest benefit in acute bipolar depression and unipolar depression (especially in more severely depressed patients). Reassuring data show no increased risk for switch- over placebo, indicating that lamotrigine is a reasonable choice for the treatment of acute bipolar depression in patients already on mood stabilizers, including those who have demonstrated adverse effects, such as switching on commonly used antidepressants. Other off- label uses have been investigated with preliminary positive results in borderline personality disorder (anger, affective lability, impulsivity), whereas supportive evidence is limited for use in obsessive- compulsive disorder (augmentation therapy), post- traumatic stress disorder, schizophrenia, schizoaffective disorder, alcohol and opiate withdrawal, cocaine dependence, behavioural, and psychological symptoms of dementia.

Description

Lamotrigine is a new mazine, glutamate inhibitor anticonvulsant that significantly reduces the incidence of refractory partial seizures. The drug is reported to produce fewer CNS side effects than diazepam or sodium phenytoin. It is also indicated as add-on therapy for the treatment of generalized seizures not satisfactorily controlled by other anti-epileptics.

Chemical Properties

White to Cream Coloured Powder

Originator

Burroughs Wellcome (United Kingdom)

Uses

An anticonvulsant. Inhibits glutamate release, possible through inhibition of Sodium, Potassium and Calcium currents. Used in treatment of bipolar depression.

Uses

antibacterial

Uses

For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression.

Definition

ChEBI: A member of the class of 1,2,4-triazines in which the triazene skeleton is substituted by amino groups at positions 3 and 5, and by a 2,3-dichlorophenyl group at position 6.

Manufacturing Process

A mixture of 2,3-dichlorophenylglyoxylamide (54.5 g, 0.25 mol), aminoguanidine hydrochloride (33.15 g, 0.30 mol), ethanol (1 liter) and concentrated hydrochloric acid (4 ml) were heated under reflux for 6 hours at pH 1.5. The resulting solution was evaporated to dryness, the solid was dissolved in water (2 L; resulting pH 2.5) and the solution was basified to pH 13 by the addition of 50% aqueous sodium hydroxide (45 ml) at <15°C. The mixture was filtered, the solid washed with 0.88 N ammonia solution and dried to give (E)-2-(2',3'-dichlorophenyl)-2-(guanidinylimino)acetamide (59.5 g, 87%) m.p. 231-233°C. Recrystallisation of this product (2.2 g) from npropanol (60 ml) afforded pure material (1.83 g, 83%), m.p. 238-239°C (decomp.).
(E)-2-(2',3'-dichlorophenyl)-2-(guanidinylimino)acetamide (0.3 g) was dissolved in ethanol (10 ml) and was irradiated by exposure to sunlight. After 5 days 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine (Lamotrigine) was detected by TLC in the liquor material. Melting point of lamotrigine 218°C.

brand name

Lamictal (Glax oSmithKline).

Therapeutic Function

Anticonvulsant

World Health Organization (WHO)

Lamotrigine is a relatively new antiepilepsy agent acting through stabilization of neuronal membranes and preventing liberation of neurotransmitters.

Biological Functions

Lamotrigine has a broad spectrum of action and is effective in generalized and partial epilepsies. Its primary mechanism of action appears to be blockage of voltagedependent sodium channels, although its effectiveness against absence seizures indicates that additional mechanisms may be active. Lamotrigine is almost completely absorbed from the gastrointestinal tract, and peak plasma levels are achieved in about 2 to 5 hours. The plasma half-life after a single dose is about 24 hours. Unlike most drugs, lamotrigine is metabolized primarily by glucuronidation. Therefore, it appears likely that lamotrigine will not induce or inhibit cytochrome P450 isozymes, in contrast to most AEDs.
Severe skin rashes appear to be the major concern with lamotrigine use.The incidence of rash is greater in children than in adults.Other adverse effects are similar to those of drugs with the same mechanism of action, such as cerebellovestibular changes leading to dizziness, diplopia, ataxia, and blurred vision. Disseminated intravascular coagulation has been reported.

General Description

Lamotrigine, an AED of the phenyltriazine class, has beenfound effective against refractory partial seizures. Likephenytoin and CBZ, its main mechanism of action appears tobe blockade of sodium channels that is both voltage- and usedependent.It also inhibits the high-threshold calcium channel,possibly through inhibition of presynaptic N-type calciumchannels and also blocks glutamate release.Lamotrigine is metabolized predominantly by glucuronidation.The major inactive urinary metabolites isolated are 2-Nglucuronide(76%) and 5-N-glucuronide (10%) because thearomatic ring is somewhat deactivated by the presence ofchlorine atoms toward arene oxide formation.Coadministration of lamotrigine with valproate, however,greatly increases the incidence of its idiosyncratic reactions.It is conceivable that in the presence of VPA, an inhibitor ofUDP-glucuronyl transferase, the concentration of the reactivearene oxide intermediate may be increased because of the reducedcapacity of UDP-glucuronyl transferase to metabolizelamotrigine via normal glucuronidation pathways.

Biological Activity

Anticonvulsant. Inhibits glutamate release, possibly through inhibition of Na + , K + and Ca 2+ currents.

Biochem/physiol Actions

Anticonvulsant.

Mechanism of action

The most probable explanation for lamotrigine's efficacy is its ability to produce a blockade of sodium channel repetitive firing. In addition, lamotrigine appears to reduce glutaminergic excitatory transmission, although the mechanism for this action remains unclear.

Pharmacokinetics

Following oral administration, lamotrigine is absorbed rapidly and completely, exhibiting linear pharmacokinetics and modest protein binding (55%). Lamotrigine is metabolized predominantly by N-glucuronidation and subsequent urinary elimination of its major metabolite, the quaternary 2-N-glucuronide (80–90%), the minor 5-amino-N-glucuronide (8–10%), and unchanged drug (8–10%). Lamotrigine's usual elimination half-life of 24–35 hours is reduced to 13–15 hours in patients taking enzymeinducing AEDs. The presence of valproate increases the lamotrigine half-life substantially by inhibiting N-glucuronidation, necessitating a reduction in dose to avoid toxicity. Hepatic disease patients may demonstrate a reduced capacity to for lamotrigine glucuronidation, thus reducing its rate of clearance.

Clinical Use

Lamotrigine is a 5-phenyl-1,2,4-triazine derivative indicated as monotherapy or as an adjunct for partial seizures in adults, as adjunct in patients with Lennox-Gastaut syndrome, and as adjunct for partial seizures in children 2 years of age and older. Lamotrigine may have additional benefit in combating myoclonic and typical absence seizures. It is approved for use in the maintenance treatment of bipolar disorder.

Side effects

The usefulness of lamotrigine is limited by the increased incidence of serious rashes, particularly in children or patients taking valproate. This increase, however, may be attenuated by very slow dose escalation, because most rashes appear within the first 8 weeks of treatment. The drug should be discontinued if a rash appears at any time. Additionally, lamotrigine may be associated with development of myoclonus after 2 to 3 years of drug treatment. Additional common side effects associated with lamotrigine therapy include dizziness, diplopia, headache, ataxia, blurred vision, somnolence, and nausea.

Lamotrigine Preparation Products And Raw materials

Raw materials

Preparation Products


Lamotrigine Suppliers

Global( 351)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Hebei Zhanyao Biotechnology Co. Ltd
15369953316 15369953316
admin@zhanyaobio.com CHINA 2131 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
Guangzhou PI PI Biotech Inc
+8618371201331
020-81716319 sales@pipitech.com;87478684@qq.com China 3284 55
Shanghai Zheyan Biotech Co., Ltd.
18017610038
zheyansh@163.com CHINA 3623 58
career henan chemical co
+86-0371-55982848
sales@coreychem.com China 29953 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28229 58
Casorganics US Corp
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Xiamen AmoyChem Co., Ltd
+86 592-605 1114
sales@amoychem.com CHINA 6369 58
BOC Sciences
1-631-485-4226
1-631-614-7828 inquiry@bocsci.com United States 19752 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58

View Lastest Price from Lamotrigine manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2022-01-25 Lamotrigine
84057-84-1
US $1.00 / g 10g 99.5% 1000kg Guangzhou Biocar Biotechnology Co.,Ltd.
2022-01-25 Lamotrigine
84057-84-1
US $9.90-9.90 / g/Bag 10g/Bag 99.99%HPLC.USP42——Powder、Oil、Pills、Capsules、Tablets,Customized packaging 100KG/Month Wuhan Biocar Pharmacy Co., Ltd.
2022-01-25 Lamotrigine
84057-84-1
US $0.00 / KG 100g 98%+ 100kg WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD

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