lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)
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Introduction
Tradename: Lamictal.
Indications
- adjunctive treatment of partial seizures in patients > 16 years of age
- adjunctive therapy in primary generalized seizures, generalized tonic-clonic seizures[5][7]
- efficacy in myoclonic seizures & absence seizures[3]
- Lennox-Gastaut syndrome
- bipolar disorder, mania[12]
- poststroke epilepsy
- among anticonvulsants used as monotherapy in poststroke epilepsy, lamotrigine is associated with the lowest risk for mortality[18]
Contraindications
- concurrent administration of valproic acid*
- not effective for chronic neuropathic pain[13]
Caution:
- use cautiously in patients with significant renal or hepatic dysfunction
- do not discontinue use abruptly
Dosage
- start 50 mg PO QD for 14 days, then
- 50 mg BID for 14 days, then
- maintenance 150-250 mg BID.
- start low & go slow; watch for Stevens-Johnson syndrome[3]
* for use in connection with valproic acid[4]
Tabs: 25, 100, 150, 200 mg; Lamictal XR (extended-release) for partial seizures
Oral disintegrating tabs: Lamical ODT
Pharmacokinetics
- metabolized by glucuronidation with elimination of lamotrigine-glucuronides in the urine
elimination via liver
elimination via kidney
1/2life = 25 hours
1/2life = 12 hours with phenytoin, carbamazepine, phenobarbital, primidone
1/2life = 60-70 hours with valproic acid
protein binding = 55 %
Monitor
- HLA-B*1502 allele testing before starting lamotrigine in Asians (Hans Chinese & Thai) (see HLA-B*1502 allele)
- electrocardiogram as indicated
- monitor serum levels during pregnancy
Adverse effects
- common
- insomnia, acne
- weight loss common in elderly[5]
- otherwise, well-tolerated in older patients[3]
- not common (1-10%)
- headache, ataxia, dizziness, diplopia, sedation, lethargy, nystagmus
- nausea
- hematuria
- skin rash, acne, angioedema
- stop lamotrigine if skin rash; start gabapentin[3]
- EKG conduction delays, QRS complex widening
- serious
- increased chance of cleft lip or cleft palate in babies of pregnant women[8]
- among anticonvulsants, lamotrigine lowest in association with major congenital malformations (2.5% < 326 mg/day)[14]
- osteopenia & osteoporosis < carbamazepine, phenytoin, valproate[3]
- increased risk of arrhythmias in patients with heart disease, including heart failure, valvular heart disease, congenital heart disease, cardiac conduction system disease, ventricular arrhythmias, cardiac channelopathies such as Brugada syndrome, ischemic heart disease, or multiple risk factors for coronary artery disease[16]
- systematic review did not find sufficient evidence to support or refute lamotrigine association with sudden death or electrocardiogram changes[17]
- increased risk of Parkinson's disease (RR~1.8)[19]
Toxicity:
- associated with serum lamotrigine > 15 mg/L
- admit to telemetry, monitor for QRS widening
- activated charcoal for altert patients with intact airway
- infusion of sodium bicarbonate 150 meq in 1 L D5W may be of benefit for patients with QRS duration > 100 msec
- monitor serum K+
Drug interactions
- phenytoin, carbamazepine, primidone & barbiturates shorten the 1/2life
- estrogens induce glucuronidation, thus decrease lamotrigine levels[3]
- estrogen-containing oral contraceptives can decrease lamotrigine levels 40-60%[3]
- valproic acid prolongs the 1/2life & increases risk of life-threatening dermatitis (contraindicated)
- lamotrigine decreases valproic acid level
- lamotrigine increases carbamazepine level
- complex interactions with hormonal contraceptives[3]
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of gabapentinoid with psychotropic agent
More general terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 702
- ↑ Jump up to: 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021
- ↑ Jump up to: 4.0 4.1 Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Jump up to: 5.0 5.1 5.2 Journal Watch 25(15):118-19, 2005 Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML; VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(11):1868-73. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15955935
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Jump up to: 7.0 7.1 Biton V et al, Double-bind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures. Neurololgy 2005, 65:1737 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16344515
- ↑ Jump up to: 8.0 8.1 The Washington Manual of Medical Therapeutics, 33rd edition Foster C et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2010, pg 951
- ↑ FDA MedWatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Lamictal
Prescriber's Letter 13(11): 2006 Increased Risk of Oral Clefts with use of Lamotrigine (Lamictal) During Pregnancy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221111&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ Jump up to: 10.0 10.1 Lamictal (lamotrigine): Label Change - Risk of Aseptic Meningitis http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm222269.htm
- ↑ Greiner-Sosanko E et al Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam J Chromatogr Sci. 2007 October; 45(9): 616-622 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231334/
- ↑ Jump up to: 12.0 12.1 Inaba T, Sogawa R, Mizoguchi Y et al Lamotrigine Rechallenge in Treatment-Resistant Bipolar Disorder. Prim Care Companion CNS Disord. 2018 Mar 29;20(2):17m02231. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29659202 Free article.
Oya K, Sakuma K, Esumi S et al Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials with an enrichment design. Neuropsychopharmacol Rep. 2019 Sep;39(3):241-246 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31026388 Free article. - ↑ Jump up to: 13.0 13.1 Wiffen PJ, Derry S, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2013 Dec 3;12:CD006044. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24297457
- ↑ Jump up to: 14.0 14.1 Tomson T, Battino D, Bonizzoni E, et al Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurology. April 18, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29680205 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30107-8/fulltext
Pennell PB Prescribing antiepileptic drugs to women of reproductive age. Lancet Neurology. April 18, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29680207 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30154-6/fulltext - ↑ Jump up to: 15.0 15.1 FDA Safety Watch. April 25 2018 Lamictal (lamotrigine): Drug Safety Communication - Serious Immune System Reaction. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm605628.htm
- ↑ Jump up to: 16.0 16.1 FDA Safety Watch. March 31, 2021 Lamictal (lamotrigine): Drug Safety Communication - Studies Show Increased Risk of Heart Rhythm Problems in Patients with Heart Disease. https://www.fda.gov/safety/medical-product-safety-information/lamictal-lamotrigine-drug-safety-communication-studies-show-increased-risk-heart-rhythm-problems
Hurley D Epileptologists Push Back on FDA's New Cardiac Warning for Lamotrigin. NeurologyToday. April 1, 2021 https://journals.lww.com/neurotodayonline/Fulltext/2021/04010/Epileptologists_Push_Back_on_FDA_s_New_Cardiac.6.aspx - ↑ Jump up to: 17.0 17.1 Bunschoten JW, Husein N, Devinsky O et al Sudden Death and Cardiac Arrythmia With Lamotrigine: A Rapid Systematic Review. Neurology. 2022. March 8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35260442 https://n.neurology.org/content/early/2022/03/08/WNL.0000000000200164
- ↑ Jump up to: 18.0 18.1 Swift Yasgur B Lamotrigine Linked to Lowest Mortality Risk in Poststroke Epilepsy. Medscape. Jan 7, 2022 https://www.medscape.com/viewarticle/966285
- ↑ Jump up to: 19.0 19.1 Kneisel K Epilepsy Drugs May Up Risk of Parkinson's. Strongest association seen for sodium valproate. MedPage Today December 27, 2022 https://www.medpagetoday.com/neurology/seizures/102398
Belete D, Jacobs BM, Simonet C et al Association Between Antiepileptic Drugs and Incident Parkinson Disease in the UK Biobank. JAMA Neurol. Published online December 27, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36574240 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799620