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Lamotrigine
drug data and news
Lamotrigine drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Lamotrigine | ||||||||||||||||||||||||||||||||||||||||||
| Brand Names/Synonyms | BW 430C; CHEMBANK1734; Lamictal; Lamictal Cd; Lamotrigina [Spanish]; Lamotrigine; Lamotrigine [Usan:Ban:Inn]; Lamotriginum [Latin] | ||||||||||||||||||||||||||||||||||||||||||
| Indication | For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome; For the maintenance treatment of Bipolar I Disorder | ||||||||||||||||||||||||||||||||||||||||||
| Sponsored links | Description | Not Available | |||||||||||||||||||||||||||||||||||||||||
| Pharmacology | Lamotrigine, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamotrigine is also used in the treatment of depression and bipolar disorder. Lamotrigine is thought to exert its anticonvulsant effect by stabilizing presynaptic neuronal membranes. Lamotrigine inhibits sodium currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excilatory amino acid, glutamate. | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism Of Action | One proposed mechanism of action of Lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. in vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). | ||||||||||||||||||||||||||||||||||||||||||
| Lamotrigine News (When available) |
Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise ... Feb 9, 2006 Sudden Akathisia After a Ziprasidone Dose Reduction Mar 2, 2006 Next "Step" in Treating Bipolar Depression Feb 14, 2006 New Studies Help Patients With Treatment-Resistant Bipolar ... Feb 1, 2006 New clues on bipolar causes, treatments Feb 3, 2006 Myocarditis During Clozapine Treatment Feb 14, 2006 Health Tip: Drugs to Avoid While Breast-Feeding Feb 16, 2006 Predictors of Recurrence in Bipolar Disorder: Primary Outcomes ... Feb 8, 2006 2005 - the year of recovery for GSK Feb 9, 2006 2005 - the year of recovery for GSK 09 Feb 2006 Tourette’s Symptoms Provoked by Lamotrigine in a Bipolar Patient Jan 24, 2006 New Studies Help Patients With Treatment-Resistant Bipolar ... Feb 1, 2006 New clues on bipolar causes, treatments Feb 3, 2006 People Can Suffer from Bipolar Disorder for Years until It is ... Jan 30, 2006 Brief Reports: Patterns of Psychotropic Medication Use by Race ... Jan 25, 2006 Excerpts From Night Falls Fast Jan 23, 2006 Continuity of Antidepressant Treatment for Adults With Depression ... Jan 24, 2006 Adjunctive Lamotrigine Decreases Primary Generalized Tonic-Clonic ... Dec 9, 2005 Weight and Cholesterol Gains Greater with Valproate than with ... Dec 8, 2005 59th Annual AES Meeting Dec 2, 2005 Lithium Placental Passage and Obstetrical Outcome: Implications ... Nov 13, 2005 Secondary Mania in Older Adults Nov 13, 2005 Consilient Health Ltd. Concludes Licensing/Supply Agreement With ... Nov 22, 2005 Interim Results Show Long-Acting Injectable Risperidone Comparable ... Nov 14, 2005 Cognitive Side Effects of Antiepileptic Drugs in Children Oct 3, 2005 Mood Swings Oct 7, 2005 Antidepressants Should Be First Line Approach for Nerve Tissue ... Sep 29, 2005 Frovatriptan-Induced Hypomania Sep 24, 2005 Many meds don't mix with the sun Sep 21, 2005 The Treatment of Bipolar Disorder – Medications for Mania Sep 13, 2005 FDA-Approved Office Lithium Test Expected To Enhance Clinical Care Aug 30, 2005 Dr. Gijsman and Colleagues Reply Jul 29, 2005 Lamictal cuts effectiveness of the pill Jul 11, 2005 Teva reports mixed results Jul 31, 2005 Antidepressants for Bipolar Depression Jul 29, 2005 Teva Reports Second Quarter 2005 Results Aug 1, 2005 New Hope for Bipolar Disorder Jul 28, 2005 Lamictal reduces efficacy of the Pill Jul 14, 2005 Antidepressants for Bipolar Depression Jul 29, 2005 Isidingo: What's up with Paul? Jul 27, 2005 Consilient Health Enters the UK and Dutch Generics Market With a ... Jul 26, 2005 Antidepressants should be first-line approach for nerve tissue ... Jul 23, 2005 Wockhardt bottomline grows 72% Jul 19, 2005 Neuropathic Pain Market to Reach $3.5 Billion by 2014, Despite ... Jul 11, 2005 | ||||||||||||||||||||||||||||||||||||||||||
| Dosage Forms | Tablet; Chewable | ||||||||||||||||||||||||||||||||||||||||||
| Drug_Category | Antimanic Agents; Antidepressants; Anticonvulsants; Analgesics; Anticonvulsants; Calcium Channel Blockers; Excitatory Amino Acid Antagonists; ATC:N03AX09 | ||||||||||||||||||||||||||||||||||||||||||
| Absorption | 98% | ||||||||||||||||||||||||||||||||||||||||||
| Interactions |
-->Interactions for Lamotrigine: Effects of Lamotrigine on the Pharmacokinetics of Other Drugs:. LAMICTAL Added to Carbamazepine: LAMICTAL has no appreciable effect on steady-state carbamazepine plasma concentration. Limited clinical data suggest there is a higher incidence of dizziness, diplopia, ataxia, and blurred vision in patients receiving carbamazepine with LAMICTAL than in patients receiving other EIAEDs with LAMICTAL. The mechanism of this interaction is unclear. The effect of lamotrigine on plasma concentrations of carbamazepine-epoxide is unclear. In a small subset of patients (n = 7) studied in a placebo-controlled trial, lamotrigine had no effect on carbamazepine-epoxide plasma concentrations, but in a small, uncontrolled study (n = 9), carbamazepine-epoxide levels were seen to increase. LAMICTAL Added to Valproate: When LAMICTAL was administered to 18 healthy volunteers receiving valproate in a pharmacokinetic study, the trough steady-state valproate concentrations in plasma decreased by an average of 25% over a 3-week period, and then stabilized. However, adding LAMICTAL to the existing therapy did not cause a change in plasma valproate concentrations in either adult or pediatric patients in controlled clinical trials. LAMICTAL Added to Lithium: The pharmacokinetics of lithium were not altered in healthy subjects (n = 20) by co-administration of 100 mg/day lamotrigine for 6 days. LAMICTAL Added to Phenytoin: LAMICTAL has no appreciable effect on steady-state phenytoin plasma concentrations in patients with epilepsy. Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6. Effects of Other Drugs on the Pharmacokinetics of Lamotrigine: . Valproate Added to LAMICTAL: The addition of valproate increases lamotrigine steady-state concentrations in normal volunteers by slightly more than 2-fold. Enzyme-Inducing Antiepileptic Drugs (e.g., carbamazepine, phenytoin, phenobarbital, primidone) Added to LAMICTAL: The addition of EIAEDs decreases lamotrigine steady-state concentrations by approximately 40%. Bupropion Added to LAMICTAL: The pharmacokinetics of a 100-mg single dose of lamotrigine in 12 healthy volunteers were not changed by co-administration of bupropion at 300 mg/day starting 11 days before the lamotrigine dose. Other Psychotropic Drugs Added to LAMICTAL: Results of in vitro experiments suggest that clearance of lamotrigine is unlikely to be reduced by concomitant administration of amitriptyline, clonazepam, clozapine, fluoxetine, haloperidol, lorazepam, phenelzine, risperidone, sertraline, or trazodone. Interactions With Folate Inhibitors: Lamotrigine is an inhibitor of dihydrofolate reductase. Prescribers should be aware of this action when prescribing other medications that inhibit folate metabolism. Interactions With Oral Contraceptives: In women taking lamotrigine, there have been reports of decreased lamotrigine concentrations following introduction of oral contraceptives and reports of increased lamotrigine concentrations following withdrawal of oral contraceptives. Dosage adjustments may be necessary to maintain clinical response when starting or stopping oral contraceptives during lamotrigine therapy. The net effects of drug interactions with LAMICTAL are summarized in Table 3.
Drug/Laboratory Test Interactions: None known. Carcinogenesis, Mutagenesis, Impairment of Fertility: No evidence of carcinogenicity was seen in 1 mouse study or 2 rat studies following oral administration of lamotrigine for up to 2 years at maximum tolerated doses (30 mg/kg per day for mice and 10 to 15 mg/kg per day for rats, doses that are equivalent to 90 mg/m2 and 60 to 90 mg/m2, respectively). Steady-state plasma concentrations ranged from 1 to 4 mcg/mL in the mouse study and 1 to 10 mcg/mL in the rat study. Plasma concentrations associated with the recommended human doses of 300 to 500 mg/day are generally in the range of 2 to 5 mcg/mL, but concentrations as high as 19 mcg/mL have been recorded. Lamotrigine was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian mouse lymphoma assay). In 2 cytogenetic assays (the in vitro human lymphocyte assay and the in vivo rat bone marrow assay), lamotrigine did not increase the incidence of structural or numerical chromosomal abnormalities. No evidence of impairment of fertility was detected in rats given oral doses of lamotrigine up to 2.4 times the highest usual human maintenance dose of 8.33 mg/kg per day or 0.4 times the human dose on a mg/m2 basis. The effect of lamotrigine on human fertility is unknown. Pregnancy: Teratogenic Effects: Pregnancy Category C. No evidence of teratogenicity was found in mice, rats, or rabbits when lamotrigine was orally administered to pregnant animals during the period of organogenesis at doses up to 1.2, 0.5, and 1.1 times, respectively, on a mg/m2 basis, the highest usual human maintenance dose (i.e., 500 mg/day). However, maternal toxicity and secondary fetal toxicity producing reduced fetal weight and/or delayed ossification were seen in mice and rats, but not in rabbits at these doses. Teratology studies were also conducted using bolus intravenous administration of the isethionate salt of lamotrigine in rats and rabbits. In rat dams administered an intravenous dose at 0.6 times the highest usual human maintenance dose, the incidence of intrauterine death without signs of teratogenicity was increased. A behavioral teratology study was conducted in rats dosed during the period of organogenesis. At day 21 postpartum, offspring of dams receiving 5 mg/kg per day or higher displayed a significantly longer latent period for open field exploration and a lower frequency of rearing. In a swimming maze test performed on days 39 to 44 postpartum, time to completion was increased in offspring of dams receiving 25 mg/kg per day. These doses represent 0.1 and 0.5 times the clinical dose on a mg/m2 basis, respectively. Lamotrigine did not affect fertility, teratogenesis, or postnatal development when rats were dosed prior to and during mating, and throughout gestation and lactation at doses equivalent to 0.4 times the highest usual human maintenance dose on a mg/m2 basis. When pregnant rats were orally dosed at 0.1, 0.14, or 0.3 times the highest human maintenance dose (on a mg/m2 basis) during the latter part of gestation (days 15 to 20), maternal toxicity and fetal death were seen. In dams, food consumption and weight gain were reduced, and the gestation period was slightly prolonged (22.6 vs. 22.0 days in the control group). Stillborn pups were found in all 3 drug-treated groups with the highest number in the high-dose group. Postnatal death was also seen, but only in the 2 highest doses, and occurred between day 1 and 20. Some of these deaths appear to be drug-related and not secondary to the maternal toxicity. A no-observed-effect level (NOEL) could not be determined for this study. Although LAMICTAL was not found to be teratogenic in the above studies, lamotrigine decreases fetal folate concentrations in rats, an effect known to be associated with teratogenesis in animals and humans. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Non-Teratogenic Effects: As with other antiepileptic drugs, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. There have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-partum concentrations after delivery. Dosage adjustments may be necessary to maintain clinical response. Pregnancy Exposure Registry: To facilitate monitoring fetal outcomes of pregnant women exposed to lamotrigine, physicians are encouraged to register patients, before fetal outcome (e.g., ultrasound, results of amniocentesis, birth, etc.) is known, and can obtain information by calling the Lamotrigine Pregnancy Registry at (800) 336-2176 (toll-free). Patients can enroll themselves in the North American Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll-free). Labor and Delivery: The effect of LAMICTAL on labor and delivery in humans is unknown. Use in Nursing Mothers: Preliminary data indicate that lamotrigine passes into human milk. Because the effects on the infant exposed to LAMICTAL by this route are unknown, breast-feeding while taking LAMICTAL is not recommended. Pediatric Use: LAMICTAL is indicated as adjunctive therapy for partial seizures in patients above 2 years of age and for the generalized seizures of Lennox-Gastaut syndrome. Safety and effectiveness for other uses in patients with epilepsy below the age of 16 years have not been established . Safety and effectiveness in patients below the age of 18 years with Bipolar Disorder has not been established. Geriatric Use: Clinical studies of LAMICTAL for epilepsy and in Bipolar Disorder did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | LD50=250 (mg/kg) (in rat, mice); LD50>640 orally (mg/kg) (in rat, mice) (Sawyer); Decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, rolling eyeballs | ||||||||||||||||||||||||||||||||||||||||||
| Organisms Affected | Humans and other mammals | ||||||||||||||||||||||||||||||||||||||||||
| Chemical IUPAC Name | 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine | ||||||||||||||||||||||||||||||||||||||||||
| Chemical Formula | C9H7Cl2N5 | ||||||||||||||||||||||||||||||||||||||||||
| Molecular Weight | 256.091 g/mol | ||||||||||||||||||||||||||||||||||||||||||
| Smiles String | C1=CC(=C(C(=C1)Cl)Cl)C2=C(N=C(N=N2)N)N | ||||||||||||||||||||||||||||||||||||||||||
| Melting Point | 216-218 oC (uncorr) | ||||||||||||||||||||||||||||||||||||||||||
| Water Solubility | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| State | Solid | ||||||||||||||||||||||||||||||||||||||||||
| LogP/Hphobicity | 1.497 | ||||||||||||||||||||||||||||||||||||||||||
| Isoelectric Point | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Biotransformation | Hepatic | ||||||||||||||||||||||||||||||||||||||||||
| Half Life | 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure) | ||||||||||||||||||||||||||||||||||||||||||
| Protein Binding [%] | 55% | ||||||||||||||||||||||||||||||||||||||||||
| RxList Link | RXlist | ||||||||||||||||||||||||||||||||||||||||||
| Sponsored links | |||||||||||||||||||||||||||||||||||||||||||
| Drug Reference |
http://www.drugs.com/cons/Lamotrigine.html http://www.rxlist.com/cgi/generic/lamotrigine.htm | ||||||||||||||||||||||||||||||||||||||||||
| Drug Type | Approved Drug | ||||||||||||||||||||||||||||||||||||||||||
| Accession No | APRD00570 | ||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 84057-84-1 | ||||||||||||||||||||||||||||||||||||||||||
| KEGG Compound ID | C07066 | ||||||||||||||||||||||||||||||||||||||||||
| PubChem ID | SID:7847420 | ||||||||||||||||||||||||||||||||||||||||||
| PharmGKB ID | PA450164 | ||||||||||||||||||||||||||||||||||||||||||
| SwissProt ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| GenBank ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Drug ID Number [DIN] | 2248232 | ||||||||||||||||||||||||||||||||||||||||||
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