{ "query": "lamotrigine", "ingredient": "lamotrigine", "slug": "lamotrigine", "rxcui": "28439", "brands": [ "Lamictal", "Subvenite" ], "names": [ "lamotrigine" ], "classes": [], "alternatives": [], "label": { "route_mode": "ORAL", "route_counts": { "ORAL": 104 }, "boxed_warning": "WARNING: SERIOUS SKIN RASHES LAMICTAL XR can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8% (8 per 1,000) in pediatric patients (aged 2 to 16 years) receiving immediate-release lamotrigine as adjunctive therapy for epilepsy and 0.3% (3 per 1,000) in adults on adjunctive therapy for epilepsy. In a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking adjunctive immediate release lamotrigine, there was 1 rash-related death. LAMICTAL XR is not approved for patients younger than 13 years. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate. The risk of serious rash caused by treatment with LAMICTAL XR is not expected to differ from that with immediate-release lamotrigine. However, the relatively limited treatment experience with LAMICTAL XR makes it difficult to characterize the frequency and risk of serious rashes caused by treatment w...", "indications_and_usage": "is indicated for: \u2022 adjunctive therapy for primary generalized tonic-clonic seizures (PGTC) and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. ( 1.1 ) \u2022 conversion to monotherapy in patients aged 13 years and older with partial-onset seizures who are receiving treatment with a single antiepileptic drug (AED). ( 1.2 ) Limitation of use: Safety and effectiveness in patients younger than 13 years have not been established. ( 1.3 ) 1.1 Adjunctive Therapy LAMICTAL XR is indicated as adjunctive therapy for primary generalized tonic-clonic (PGTC) seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. 1.2 Monotherapy LAMICTAL XR is indicated for conversion to monotherapy in patients aged 13 years and older with partial-onset seizures who are receiving treatment with a single antiepileptic drug (AED). Safety and effectiveness of LAMICTAL XR have not been established (1) as initial monotherapy or (2) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. 1.3 Limitation of Use Safety and effectiveness of LAMICTAL XR for use in patients younger than 13 years hav...", "contraindications": "is contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see Boxed Warning , Warnings and Precautions ( 5.1 , 5.3 )] . Hypersensitivity to the drug or its ingredients. ( Boxed Warning , 4 )", "warnings_and_cautions": "\u2022 Life-threatening serious rash and/or rash-related death: Discontinue at the first sign of rash, unless the rash is clearly not drug related. ( Boxed Warning , 5.1 ) \u2022 Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluate patients immediately if they develop signs or symptoms of systemic inflammation. Discontinue LAMICTAL XR if an alternative etiology is not established. ( 5.2 ) \u2022 Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms (DRESS), may be fatal or life threatening. Early signs may include rash, fever, and lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic failure, blood dyscrasias, or acute multiorgan failure. LAMICTAL XR should be discontinued if alternate etiology for this reaction is not found. ( 5.3 ) \u2022 Cardiac rhythm and conduction abnormalities: Based on in vitro findings, LAMICTAL XR could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Any expected or observed benefit of LAMICTAL XR in an individual patient with clinically ...", "warnings": "", "adverse_reactions": "The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: \u2022 Serious Skin Rashes [see Warnings and Precautions ( 5.1 )] \u2022 Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions ( 5.2 )] \u2022 Multiorgan Hypersensitivity Reactions and Organ Failure [see Warnings and Precautions ( 5.3 )] \u2022 Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions ( 5.4 )] \u2022 Blood Dyscrasias [see Warnings and Precautions ( 5.5 )] \u2022 Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.6 )] \u2022 Aseptic Meningitis [see Warnings and Precautions ( 5.7 )] \u2022 Withdrawal Seizures [see Warnings and Precautions ( 5.10 )] \u2022 Status Epilepticus [see Warnings and Precautions ( 5.11 )] \u2022 Most common adverse reactions with use as adjunctive therapy (treatment difference between LAMICTAL XR and placebo \u22654%) were dizziness, tremor/intention tremor, vomiting, and diplopia. ( 6.1 ) \u2022 Most common adverse reactions with use as monotherapy were similar to those seen with previous trials conducted with immediate-release lamotrigine and LAMICTAL XR. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-8...", "drug_abuse_and_dependence": "", "controlled_substance": "", "recent_major_changes": "Boxed Warning Dosage and Administration ( 2.1 , 2.2 ) Warnings and Precautions, Serious Skin Rashes ( 5.1 ) Concomitant Use with Estrogen-Containing Products, Including Oral Contraceptives ( 5.9 ) Sudden Unexplained Death in Epilepsy ( 5.12 ) \u2013 removal 10/2025 4/2025 10/2025 4/2025 4/2025", "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Medication Guide). Rash Prior to initiation of treatment with LAMICTAL XR, inform patients that a rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and instruct them to report any such occurrence to their healthcare providers immediately. Hemophagocytic Lymphohistiocytosis Prior to initiation of treatment with LAMICTAL XR, inform patients that excessive immune activation may occur with LAMICTAL XR and that they should report signs or symptoms such as fever, rash, or lymphadenopathy to a healthcare provider immediately. Multiorgan Hypersensitivity Reactions, Blood Dyscrasias, and Organ Failure Inform patients that multiorgan hypersensitivity reactions and acute multiorgan failure may occur with LAMICTAL XR. Isolated organ failure or isolated blood dyscrasias without evidence of multiorgan hypersensitivity may also occur. Instruct patients to contact their healthcare providers immediately if they experience any signs or symptoms of these conditions [see Warnings and Precautions ( 5.3 , 5.5 )]. Cardiac Rhythm and Conduction Abnormalities Inform patients tha...", "spl_medguide": "MEDICATION GUIDE LAMICTAL (la-MIK-tal) XR (lamotrigine) extended-release tablets What is the most important information I should know about LAMICTAL XR? 1. LAMICTAL XR may cause a serious skin rash that may cause you to be hospitalized or even cause death. There is no way to tell if a mild rash will become more serious. A serious skin rash can happen at any time during your treatment with LAMICTAL XR, but is more likely to happen within the first 2 to 8 weeks of treatment. Children aged between 2 and 16 years have a higher chance of getting this serious skin rash while taking LAMICTAL XR. LAMICTAL XR is not approved for use in children younger than 13 years. The risk of getting a serious skin rash is higher if you: 1. take LAMICTAL XR while taking valproate [DEPAKENE (valproic acid) or DEPAKOTE (divalproex sodium)]. 2. take a higher starting dose of LAMICTAL XR than your healthcare provider prescribed. 3. increase your dose of LAMICTAL XR faster than prescribed. The risk of serious skin reactions may be associated with a variant in genes called HLA\u2011B*1502 in people from Asian origin (mainly of Han Chinese and Thai origin). See \u201c Before taking LAMICTAL XR, tell your healthcare provi...", "clinical_studies": "14.1 Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures The effectiveness of LAMICTAL XR as adjunctive therapy in subjects with PGTC seizures was established in a 19-week, international, multicenter, double-blind, randomized, placebo-controlled trial in 143 patients aged 13 years and older (n = 70 on LAMICTAL XR, n = 73 on placebo). Patients with at least 3 PGTC seizures during an 8-week baseline phase were randomized to 19 weeks of treatment with LAMICTAL XR or placebo added to their current AED regimen of up to 2 drugs. Patients were dosed on a fixed-dose regimen, with target doses ranging from 200 to 500 mg/day of LAMICTAL XR based on concomitant AEDs (target dose = 200 mg for valproate, 300 mg for AEDs not altering plasma lamotrigine levels, and 500 mg for enzyme-inducing AEDs). The primary efficacy endpoint was percent change from baseline in PGTC seizure frequency during the double-blind treatment phase. For the intent-to-treat population, the median percent reduction in PGTC seizure frequency was 75% in patients treated with LAMICTAL XR and 32% in patients treated with placebo, a difference that was statistically significant, defined as a 2-sided P value < 0.05...", "brand_name": "LAMICTAL XR", "manufacturer": "GlaxoSmithKline LLC", "application_number": "NDA022115", "pharm_class_epc": [ "Anti-epileptic Agent [EPC]", "Mood Stabilizer [EPC]" ], "route": [ "ORAL" ], "effective_time": "20251010", "set_id": "3e2c9a35-6a39-41d7-ad84-3c0bb8894b09", "has_boxed_warning": true, "controlled": false, "mentions_rems": false }, "faers": { "total": 94757, "serious": 70756, "death": 9008, "hospitalization": 30967, "primary_suspect": 94072, "top_reactions": [ [ "Drug Ineffective", 8662 ], [ "Seizure", 7215 ], [ "Off Label Use", 5937 ], [ "Fatigue", 4991 ], [ "Nausea", 4826 ], [ "Dizziness", 4584 ], [ "Rash", 4444 ], [ "Headache", 4310 ], [ "Toxicity To Various Agents", 3976 ], [ "Depression", 3904 ], [ "Vomiting", 3685 ], [ "Somnolence", 3485 ], [ "Anxiety", 3434 ], [ "Foetal Exposure During Pregnancy", 3268 ], [ "Drug Interaction", 3238 ] ], "by_year": { "2019": 9351, "2020": 8383, "2021": 7708, "2022": 6686, "2023": 7040, "2024": 7704, "2025": 7913, "2026": 3600 }, "by_year_primary": { "2019": 9339, "2020": 8374, "2021": 7659, "2022": 6573, "2023": 6891, "2024": 7546, "2025": 7813, "2026": 3515 } }, "faers_base": { "total": 20692304, "serious_share": 0.5742697381596559, "death_share": 0.09102355155810585 }, "recalls": [ { "class": "Class III", "date": "20220720", "reason": "Labeling: Label Error on Declared Strength", "firm": "AVKARE Inc.", "status": "Terminated" }, { "class": "Class III", "date": "20200528", "reason": "Presence of Foreign Substance consistent with granules from desiccant packs used during storage", "firm": "AVKARE Inc.", "status": "Terminated" }, { "class": "Class I", "date": "20191220", "reason": "Cross Contamination; Lamotrigine Tablets 100 mg USP was contaminated with enalapril maleate.", "firm": "Taro Pharmaceuticals U.S.A., Inc.", "status": "Terminated" }, { "class": "Class II", "date": "20180911", "reason": "Failed Dissolution Specifications: Out of Specification for Dissolution test (Buffer Stage) at the 5-hour time point during stability testing.", "firm": "Torrent Pharma Inc.", "status": "Terminated" }, { "class": "Class III", "date": "20160819", "reason": "Tablets/Capsules Imprinted With Wrong ID: incorrect imprint debossed on the tablets.", "firm": "Unichem Pharmaceuticals Usa Inc", "status": "Terminated" } ], "recall_total": 5, "drugsfda": { "applications": 61, "nda": 6, "anda": 53, "first_approval": "19941227", "rems": false, "rems_last": "20120307", "labeling_supplements": 111, "labeling_recent": 22, "sponsors": [ "ACTAVIS ELIZABETH", "ACTAVIS TOTOWA", "AIPING PHARM INC", "AJANTA PHARMA LTD", "ALEMBIC", "ALEMBIC PHARMS LTD", "ALKEM LABS LTD", "AMNEAL PHARMS" ], "unapproved": false, "first_approval_fmt": "12/27/1994" }, "trials": { "total": 229, "completed": 172, "terminated": 23, "with_results": 72, "industry": 114, "phase3": 49, "results_share": 0.4186046511627907, "terminated_share": 0.10043668122270742 }, "pubmed": { "rct": 253, "meta": 72, "recent_rct": 15, "cochrane": [ { "pmid": "38078494", "title": "Lamotrigine add-on therapy for drug-resistant focal epilepsy", "year": "2023" }, { "pmid": "34523118", "title": "Lamotrigine in the maintenance treatment of bipolar disorder", "year": "2021" }, { "pmid": "33475151", "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents", "year": "2021" }, { "pmid": "32609387", "title": "Lamotrigine add-on therapy for drug-resistant generalised tonic-clonic seizures", "year": "2020" }, { "pmid": "32196639", "title": "Lamotrigine add-on therapy for drug-resistant focal epilepsy", "year": "2020" }, { "pmid": "30734919", "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents", "year": "2019" }, { "pmid": "29952431", "title": "Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review", "year": "2018" }, { "pmid": "28195639", "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents", "year": "2017" }, { "pmid": "27841445", "title": "Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review", "year": "2016" }, { "pmid": "27329345", "title": "Lamotrigine add-on for drug-resistant partial epilepsy", "year": "2016" }, { "pmid": "24297457", "title": "Lamotrigine for chronic neuropathic pain and fibromyalgia in adults", "year": "2013" }, { "pmid": "21328280", "title": "Lamotrigine for acute and chronic pain", "year": "2011" } ] }, "payments": { "year": "2024", "usd": 7780.6, "records": 412, "by_name": [ [ "Subvenite", 7780.6 ] ], "names_checked": [ "lamotrigine", "Lamictal", "Subvenite" ], "source": "bulk-index" }, "partd": { "year": "2024", "claims": 4397432, "beneficiaries": 679546, "spend": 221328775.36000004, "by_brand": [ { "brand": "Lamotrigine", "claims": 4154338, "per_claim": 14.252862889, "is_generic": true }, { "brand": "Lamotrigine ER", "claims": 157313, "per_claim": 262.50211216, "is_generic": false }, { "brand": "Lamictal", "claims": 43491, "per_claim": 1381.7262951, "is_generic": false }, { "brand": "Lamotrigine ODT", "claims": 23561, "per_claim": 380.47410169, "is_generic": false }, { "brand": "Lamictal XR", "claims": 15467, "per_claim": 3123.9674908, "is_generic": false }, { "brand": "Lamictal ODT", "claims": 1808, "per_claim": 1675.1766759, "is_generic": false }, { "brand": "Subvenite", "claims": 821, "per_claim": 15.038246041, "is_generic": false }, { "brand": "Lamotrigine (Orange)", "claims": 347, "per_claim": 652.48948127, "is_generic": false }, { "brand": "Lamotrigine ODT (Orange)", "claims": 86, "per_claim": 332.80151163, "is_generic": false }, { "brand": "Subvenite (Orange)", "claims": 70, "per_claim": 705.05385714, "is_generic": false }, { "brand": "Lamotrigine (Blue)", "claims": 52, "per_claim": 505.56384615, "is_generic": false }, { "brand": "Lamotrigine (Green)", "claims": 34, "per_claim": 1262.8838235, "is_generic": false }, { "brand": "Lamictal (Orange)", "claims": 15, "per_claim": 415.15, "is_generic": false }, { "brand": "Subvenite (Blue)", "claims": 15, "per_claim": 464.80333333, "is_generic": false }, { "brand": "Subvenite (Green)", "claims": 14, "per_claim": 1376.8457143, "is_generic": false } ], "per_claim": 50.33136961754043 }, "mdl": [], "dsc": [ { "date": "20180425", "title": "FDA warns of serious immune system reaction with seizure and mental health medicine lamotrigine (Lamictal)", "url": "https://www.fda.gov/Drugs/DrugSafety/ucm605470.htm", "kind": "drug", "matched": "lamotrigine" } ], "settlements": [ { "year": 2012, "company": "GlaxoSmithKline", "amount_usd": 3000000000.0, "amount_text": "$3 billion ($1B criminal, $2B civil)", "violations": "Criminal: Off-label promotion, failure to disclose safety data. Civil: paying kickbacks to physicians, making false and misleading statements concerning the safety of Avandia, reporting false best prices and underpaying rebates owed under the Medicaid Drug Rebate Program", "products": "Avandia (not providing safety data), Wellbutrin, Paxil (promotion of paediatric use), Advair, Lamictal, Zofran, Imitrex, Lotronex, Flovent, Valtrex", "laws": "False Claims Act, FDCA", "urls": [ "https://www.justice.gov/opa/pr/2012/July/12-civ-842.html", "https://web.archive.org/web/20240714112314/https://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failure-report" ], "matched": "lamictal" } ], "prescrire": null, "eml": { "listed": true, "status": "AddedToEml", "name": "lamotrigine", "matched": "lamotrigine", "stewardship": [] }, "exposure": { "years": [ "2024", "2025", "2026" ], "reports_recent": 18874, "fills": 4397432, "per_million": 4292.050451263373, "ratio": 1.5500644045230312, "median": 2768.949753790441 }, "scores": { "safety": { "score": 43, "letter": "F", "why": [ "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)", "FDA issued 1 Drug Safety Communication(s) naming this drug since 2010, most recently 2018 (-8)", "4,292 FDA reports naming it as the suspect drug per million Medicare fills, 1.6x the median drug on this site (-4)", "Death share in reports is near or below the FAERS average (1.0x)", "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)", "1 Class I recall(s): reasonable probability of serious harm (-10)" ], "weight": 0.35 }, "evidence": { "score": 66, "letter": "C", "why": [ "253 randomized trials and 72 systematic reviews/meta-analyses indexed in PubMed", "On the WHO Model List of Essential Medicines (shown for context; no score effect)", "12 independent Cochrane review(s) exist", "Only 42% of completed registered trials posted results (-8)", "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)" ], "weight": 0.25 }, "regulatory": { "score": 66, "letter": "C", "why": [ "Recalls since 2016: 1 Class I, 1 Class II, 3 Class III across 53 generic makers (-21)", "22 label changes approved since 2021: the safety story is still moving (-8)", "Label lists recent major changes to warnings or indications (-5)" ], "weight": 0.15 }, "conflict": { "score": 65, "letter": "C", "why": [ "Maker paid $3 billion ($1B criminal, $2B civil) in 2012 to settle federal allegations naming this drug (Criminal: Off-label promotion, failure to disclose safety data. Civil: paying kickbacks to) (-35)", "Pharma paid doctors $7,781 tied to this drug last year: negligible", "Not named in any pending federal MDL" ], "weight": 0.15 }, "options": { "score": 70, "letter": "C", "why": [ "Generic versions approved (53 applications)", "No same-class alternatives found: little leverage to switch (-30)" ], "weight": 0.1 } }, "total": 58, "grade": "D", "questions": [ "In 2018 the FDA issued a safety communication about this drug (FDA warns of serious immune system reaction with seizure and mental health medicine lamotrigine (Lamictal)). Does that risk apply to me?", "The maker paid $3 billion in 2012 to settle federal allegations about how this drug was marketed. Is my use one of the uses that was promoted improperly?", "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?", "The most-reported problems in FDA's adverse event data are seizure, fatigue. How would we recognize and handle those?", "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?", "What result are we expecting, by when, and what is the plan if it does not happen?", "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)" ] }