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Lamotrigine 100 mg Tablet, 500-count — NDC 13668-0047-05 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Lamotrigine 100 mg Tablet, 500-count — NDC 13668-047-05 (Billing 13668-0047-05)

by Torrent Pharmaceuticals Limited · 500 TABLET in 1 BOTTLE

This is a package of 500 tablets of Lamotrigine 100 mg Tablet from Torrent Pharmaceuticals Limited, marketed since Jan 2009 and currently FDA-listed; retail pharmacies pay about $0.0487 per tablet (NADAC).

NDC 13668-0047-05
🏷️ FDA NDC (as labeled) 13668-047-05 billing pads the product segment with a zero
This package
Contains500-count Cost per ea$0.0487 NADAC Per package$24.35 / 500 tablets Pack sizes6 compare ↓
Also priced by: Medicaid pays $0.1130/unit · Part D plans $0.1041/unit — full pricing hub ↓
Product page 13668-0047-01 Also comes in: 30 tablets 13668-047-30 60 tablets 13668-047-60 100 tablets 13668-047-01 100 tablets 13668-047-74 2500 tablets 13668-047-31
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 13668-047-05
Product NDC 13668-047
11-digit billing NDC 13668004705
NCPDP billing unit EA — each (per item)
RxCUI 198427, 198428, 198429, 282401, 751139, 751563, 753451
UNII U3H27498KS
UPC 0313668048605, 0313668045017
Application # ANDA078947
SPL Set ID 3448839b-4933-4ef9-a80a-9e504d2c5696
Established class (EPC) Anti-epileptic Agent; Mood Stabilizer
Mechanism of action Organic Cation Transporter 2 Inhibitors; Dihydrofolate Reductase Inhibitors
Physiologic effect Decreased Central Nervous System Disorganized Electrical Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2009-01-27
Route ORAL
Dosage form TABLET
Substance LAMOTRIGINE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 017871
GCN 64316
HICL code 007378
Ingredient (HICL) Lamotrigine
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H4
Therapeutic class — intermediate (HIC2) Anticonvulsants
HIC3 code H4B
Therapeutic class — specific (HIC3) Anticonvulsants
AHFS code 28:12.92.00
AHFS class Anticonvulsants, Miscellaneous
FDB label name LAMOTRIGINE 100 MG TABLET
FDB brand name Lamotrigine
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 017871
  • GCN: 64316
  • HICL (First Databank): 007378
  • AHFS class code: 28:12.92.00
  • RxCUI (RxNorm): 198427
Why two NDCs? The FDA registers this code as 13668-047-05 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 13668-0047-05. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Mood Stabilizer class.

Pharmacologic class Mood Stabilizer, Anti-epileptic Agent
Drug family (ATC) Other antiepileptics
How it works Dihydrofolate Reductase Inhibitors, Organic Cation Transporter 2 Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name LAMOTRIGINE 100 MG TABLET Ingredient Lamotrigine
📗 Our plain-language guide HelloPharmacist
  • It treats epilepsy, helping control certain seizure types. Some forms, like tablets, chewables and orally disintegrating tablets, are also used to delay mood episodes in bipolar I...
  • Lamotrigine can cause serious, even life-threatening skin reactions, mostly in the first 2 to 8 weeks. We can't tell which rashes are dangerous, so call your doctor right away abou...
  • Take it by mouth exactly as prescribed, increasing slowly as planned. Skipping ahead raises rash risk. Extended-release tablets are once daily and must be swallowed whole. Food doe...
  • Please don't stop on your own. Stopping suddenly can trigger withdrawal seizures. Your doctor will taper you off over at least 2 weeks.
📖 Read our full Lamotrigine guide →
1
Nutrient depletion considerations

Lamotrigine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Lamotrigine nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.049 $24.35 / 500 tablets
Medicaid paysCMS SDUD · 12 mo $0.1130 $56.50 / 500 tablets
Medicare drug plans payPart D · Q2 2026 $0.1041 $52.05 / 500 tablets
NADAC price history (per ea) — tap or hover for the price & month
Jan 2022 Aug 2022 Jan 2026 Sep 2026 $0.064 $0.044
▼ Down 20% over the last 24 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
13668-0047-01 13668-047-01 Main listing 100 TABLET in 1 BOTTLE $0.0487 / ea $4.87 2009-01-27 — Active
13668-0047-05 You're viewing this 500 TABLET in 1 BOTTLE $0.0487 / ea $24.37 2009-01-27 — Active
13668-0047-30 13668-047-30 30 TABLET in 1 BOTTLE — — 2009-01-27 — Active
13668-0047-31 13668-047-31 2500 TABLET in 1 BOTTLE — — 2009-01-27 — Active
13668-0047-60 13668-047-60 60 TABLET in 1 BOTTLE — — 2009-01-27 — Active
13668-0047-74 13668-047-74 100 TABLET in 1 DOSE PACK — — 2009-01-27 — Active

This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($0.0487 NADAC).

This pack accounts for about 19% of this product's recent Medicaid fills; most go to the 100 tablets pack. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 500-count package — 500 tablet in 1 bottle.
How does this package differ from NDC 13668-0047-30?
Both are Lamotrigine 100 mg Tablet — the drug itself is identical. This page's package is the 500-count one, while NDC 13668-0047-30 is the 30 tablets package.
What NDC number is used to bill for this package of Lamotrigine 100 mg Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Lamotrigine 100 mg 00904-7008-61 Major 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mgthis 13668-0047-05 Torrent 500 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 16714-0195-01 Northstar 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 29300-0112-01 Unichem 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 59746-0246-01 Jubilant 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 65862-0228-01 Aurobindo 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 68084-0319-01 American 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 68382-0008-01 Zydus 100 tablets $0.049 AB Availability likely —
Subvenite 100 mg 69102-0319-01 OWP 100 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 72888-0026-00 Advagen 1000 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 82009-0132-10 Quallent 1000 tablets $0.049 AB Availability likely —
Lamotrigine 100 mg 69918-0370-30 Nordic 30 tablets $1.625 AB Availability likely +3235%
Lamotrigine 100 mg 51672-4254-06 Sun 30 tablets $1.625 AB Availability likely +3235%
Lamictal 100 mg 00173-0642-55 GlaxoSmithKline 100 tablets $10.918 AB Availability likely +22305%
Lamotrigine 100 mg 00615-7975-39 NCS 30 tablets — AB FDA listed —
Lamotrigine 100 mg 42291-0367-01 AvKARE 100 tablets — AB FDA listed —
Lamotrigine 100 mg 43063-0203-30 PD-Rx 30 tablets — AB FDA listed —
Lamotrigine 100 mg 46708-0275-30 Alembic 30 tablets — AB FDA listed —
Lamotrigine 100 mg 50090-2130-00 A-S 30 tablets — AB FDA listed —
Lamotrigine 100 mg 51672-4131-00 Sun 100 tablets — AB FDA listed —
Lamotrigine 100 mg 55111-0221-01 Dr.Reddy's 100 tablets — AB FDA listed —
Lamotrigine 100 mg 55154-2065-00 Cardinal 10 tablets — AB FDA listed —
Lamotrigine 100 mg 55154-2330-00 Cardinal 10 tablets — AB FDA listed —
Lamotrigine 100 mg 62332-0038-30 Alembic 30 tablets — AB FDA listed —
Lamotrigine 100 mg 65841-0684-01 Zydus 100 tablets — AB FDA listed —
Lamotrigine 100 mg 67046-0359-03 Coupler 30 tablets — AB FDA listed —
Lamotrigine 100 mg 67877-0165-01 Ascend 100 tablets — AB FDA listed —
Lamotrigine 100 mg 68071-3514-06 NuCare 60 tablets — AB FDA listed —
Lamotrigine 100 mg 68071-3607-06 NuCare 60 tablets — AB FDA listed —
Lamotrigine 100 mg 68071-3944-06 NuCare 60 tablets — AB FDA listed —
Lamotrigine 100 mg 68788-7223-03 Preferred 30 tablets — AB FDA listed —
Lamotrigine 100 mg 68788-7871-03 Preferred 30 tablets — AB FDA listed —
Lamotrigine 100 mg 70518-2343-01 REMEDYREPACK 30 tablets — AB FDA listed —
Lamotrigine 100 mg 70518-2563-00 REMEDYREPACK 30 tablets — AB FDA listed —
Lamotrigine 100 mg 71205-0245-30 Proficient 30 tablets — AB FDA listed —
Lamotrigine 100 mg 71335-0706-01 Bryant 30 tablets — AB FDA listed —
Lamotrigine 100 mg 71335-2328-01 Bryant 30 tablets — AB FDA listed —
Lamotrigine 100 mg 72789-0206-60 PD-Rx 60 tablets — AB FDA listed —
Lamotrigine 100 mg 82868-0005-30 Northwind 30 tablets — AB FDA listed —
Lamotrigine 100 mg 70518-2889-00 REMEDYREPACK 30 tablets — AB FDA listed —
Lamotrigine 100 mg 84677-0033-30 Golden 30 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2009
On the market since
Jan 2009
📍
2026
Currently FDA-listed
17 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color white
ShapeRound
Imprint45
Size6 mm
ScoringScored — splits in 2
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive ingredients.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerTorrent Pharmaceuticals Limited
Application holderTORRENT PHARMACEUTICALS LTD
FDA applicationANDA078947 (ANDA)
Labeler code13668
First marketedJan 2009
Product typeHuman Prescription Drug
Portfolio182 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~2 min read ▾

WARNING: SERIOUS SKIN RASHES See full prescribing information for complete boxed warning. Cases of life-threatening serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and/or rash-related death have been caused by lamotrigine. The rate of serious rash is greater in pediatric patients than in adults.

Additional factors that may increase the risk of rash include: coadministration with valproate. exceeding recommended initial dose of lamotrigine tablets. exceeding recommended dose escalation for lamotrigine tablets. presence of the HLA-B*1502 allele. (5.1) Benign rashes are also caused by lamotrigine; however, it is not possible to predict which rashes will prove to be serious or life threatening. Lamotrigine tablets should be discontinued at the first sign of rash, unless the rash is clearly not drug related.

( 5.1 ) WARNING: SERIOUS SKIN RASHES Lamotrigine tablets can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.3% to 0.8% in pediatric patients (aged 2 to 17 years) and 0.08% to 0.3% in adults receiving lamotrigine tablets. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking lamotrigine tablets as adjunctive therapy.

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. In addition to age, factors that may increase the risk of occurrence or the severity of rash caused by lamotrigine tablets include (1) coadministration of lamotrigine tablets with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of lamotrigine tablets, (3) exceeding the recommended dose escalation for lamotrigine tablets, or (4) the presence of the HLA-B*1502 allele However, cases have occurred in the absence of these factors.

Nearly all cases of life-threatening rashes caused by lamotrigine tablets have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.

Although benign rashes are also caused by lamotrigine tablets, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, lamotrigine tablets should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring [see Warnings and Precautions ( 5.1 )] .

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Lamotrigine tablet is indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older: partial-onset seizures. primary generalized tonic-clonic (PGTC) seizures. generalized seizures of Lennox-Gastaut syndrome. ( 1.1 ) Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. ( 1.1 ) Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy.

( 1.2 ) Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness of lamotrigine tablets in the acute treatment of mood episodes has not been established.

1.1Epilepsy Adjunctive Therapy Lamotrigine tablets are indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: partial-onset seizures. primary generalized tonic-clonic (PGTC) seizures. generalized seizures of Lennox-Gastaut syndrome. Monotherapy Lamotrigine tablets are indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).

Safety and effectiveness of lamotrigine tablets have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.

1.2Bipolar Disorder Lamotrigine tablets are indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see Clinical Studies ( 14.2 )] . Limitations of Use Treatment of acute manic or mixed episodes is not recommended. Effectiveness of lamotrigine tablets in the acute treatment of mood episodes has not been established.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Dosing is based on concomitant medications, indication, and patient age. ( 2.1 , 2.2 , 2.3 , 2.4 ) To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. Lamotrigine Tablets Starter Kits are available for the first 5 weeks of treatment.

( 2.1 , 16 ) Do not restart lamotrigine tablets in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. ( 2.1 , 5.1 ) Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing products, including oral contraceptives. ( 2.1 , 5.9 ) Discontinuation: Taper over a period of at least 2 weeks (approximately 50% dose reduction per week).

( 2.1 , 5.10 ) Epilepsy: Adjunctive therapy—See Table 1 for patients older than 12 years and Tables 2 and 3 for patients aged 2 to 12 years. ( 2.2 ) Conversion to monotherapy—See Table 4. ( 2.3 ) Bipolar disorder: See Tables 5 and 6.

( 2.4 )

2.1General Dosing Considerations Rash There are suggestions that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of lamotrigine tablets with valproate, (2) exceeding the recommended initial dose of lamotrigine tablets, or (3) exceeding the recommended dose escalation for lamotrigine tablets. However, cases have occurred in the absence of these factors [see Boxed Warning ]. Therefore, it is important that the dosing recommendations be followed closely.

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation for lamotrigine tablets is exceeded and in patients with a history of allergy or rash to other AEDs. Lamotrigine Tablets Starter Kits provide lamotrigine tablets at doses consistent with the recommended titration schedule for the first 5 weeks of treatment, based upon concomitant medications, for patients with epilepsy (older than 12 years) and bipolar I disorder (adults) and are intended to help reduce the potential for rash.

The use of Lamotrigine Tablets Starter Kits is recommended for appropriate patients who are starting or restarting lamotrigine tablets [see How Supplied/Storage and Handling ( 16 )] . It is recommended that lamotrigine tablets not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine tablets, the need to restart with the initial dosing recommendations should be assessed.

The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications [see Clinical Pharmacology ( 12.3 )].

Lamotrigine Tablets Added to Drugs Known to Induce or Inhibit Glucuronidation Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine. Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing products, including oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Valproate inhibits glucuronidation.

For dosing considerations for lamotrigine tablets in patients on estrogen-containing products, including contraceptives, and atazanavir/ritonavir, see below and Table 13. For dosing considerations for lamotrigine tablets in patients on other drugs known to induce or inhibit glucuronidation, see Tables 1, 2, 5 to 6, and 13. Target Plasma Levels for Patients with Epilepsy or Bipolar Disorder A therapeutic plasma conce… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 127 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 25 mg, 100 mg, 150 mg, and 200 mg; scored. ( 3.1 , 16 )

3.1Tablets 25 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "45" on one side and break line on other side. 100 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1047" on one side and break line on other side. 150 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1048" on one side and break line on other side.

200 mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1049" on one side and break line on other side.

⛔ Contraindications 50 words ▾

4 CONTRAINDICATIONS Hypersensitivity to the drug or its ingredients. (Boxed Warning, 4 ) Lamotrigine tablets are 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 )] .

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS 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 ) Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluate patients immediately if they develop signs or symptoms of systemic inflammation. Discontinue lamotrigine tablets if an alternative etiology is not established.

( 5.2 ) Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms, 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.

Lamotrigine tablets should be discontinued if alternate etiology for this reaction is not found. ( 5.3 ) Cardiac rhythm and conduction abnormalities: Based on in vitro findings, lamotrigine tablets could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Any expected or observed benefit of lamotrigine tablets in an individual patient with clinically important structural or functional heart disease must be carefully weighed against the risk for serious arrhythmias and/or death for that patient.

( 5.4 ) Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): May occur, either with or without an associated hypersensitivity syndrome. Monitor for signs of anemia, unexpected infection, or bleeding. ( 5.5 ) Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors.

( 5.6 ) Aseptic meningitis: Monitor for signs of meningitis. ( 5.7 ) Medication errors due to product name confusion: Strongly advise patients to visually inspect tablets to verify the received drug is correct. ( 5.8 , 16 , 17 )

5.1Serious Skin Rashes [see Boxed Warning] Pediatric Population The incidence of serious rash associated with hospitalization and discontinuation of lamotrigine tablets in a prospectively followed cohort of pediatric patients (aged 2 to 17 years) is approximately 0.3% to 0.8%. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking lamotrigine tablets as adjunctive therapy. Additionally, there have been rare cases of toxic epidermal necrolysis (TEN) with and without permanent sequelae and/or death in U.S. and foreign postmarketing experience.

There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in pediatric patients. In pediatric patients who used valproate concomitantly for epilepsy, 1.2% (6 of 482) experienced a serious rash compared with 0.6% (6 of 952) patients not taking valproate. Adult Population Serious rash associated with hospitalization and discontinuation of lamotrigine tablets occurred in 0.3% (11 of 3,348) of adult patients who received lamotrigine tablets in premarketing clinical trials of epilepsy.

In the bipolar and other mood disorders clinical trials, the rate of serious rash was 0.08% (1 of 1,233) of adult patients who received lamotrigine tablets as initial monotherapy and 0.13% (2 of 1,538) of adult patients who received lamotrigine tablets as adjunctive therapy. No fatalities occurred among these individuals. However, in worldwide postmarketing experience, rare cases of rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate.

Among the rashes leading to hospitalization were Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, and those associated with multiorgan hypersensitivity [see Warnings and Precautions ( 5.3 )] . Risk Factors Concomitant Use of Valproate There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Epilepsy: Most common adverse reactions (incidence ≥10%) in adults were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children included vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, and tremor. ( 6.1 ) Bipolar disorder: Most common adverse reactions (incidence >5%) in adults were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: Serious Skin Rashes [see Warnings and Precautions ( 5.1 )] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions ( 5.2 )] Multiorgan Hypersensitivity Reactions and Organ Failure [see Warnings and Precautions ( 5.3 )] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions ( 5.4 )] Blood Dyscrasias [see Warnings and Precautions ( 5.5 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.6 )] Aseptic Meningitis [see Warnings and Precautions ( 5.7 )] Withdrawal Seizures [see Warnings and Precautions ( 5.10 )] Status Epilepticus [see Warnings and Precautions ( 5.11 )]

6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Epilepsy Most Common Adverse Reactions in All Clinical Trials: Adjunctive Therapy in Adults with Epilepsy: The most commonly observed (≥5% for lamotrigine tablets and more common on drug than placebo) adverse reactions seen in association with lamotrigine tablets during adjunctive therapy in adults and not seen at an equivalent frequency among placebo-treated patients were: dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, vomiting, and rash.

Dizziness, diplopia, ataxia, blurred vision, nausea, and vomiting were dose related. Dizziness, diplopia, ataxia, and blurred vision occurred more commonly in patients receiving carbamazepine with lamotrigine tablets than in patients receiving other AEDs with lamotrigine tablets. Clinical data suggest a higher incidence of rash, including serious rash, in patients receiving concomitant valproate than in patients not receiving valproate [see Warnings and Precautions ( 5.1 )].

Approximately 11% of the 3,378 adult patients who received lamotrigine tablets as adjunctive therapy in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were rash (3.0%), dizziness (2.8%), and headache (2.5%). In a dose-response trial in adults, the rate of discontinuation of lamotrigine tablets for dizziness, ataxia, diplopia, blurred vision, nausea, and vomiting was dose related.

Monotherapy in Adults with Epilepsy: The most commonly observed (≥5% for lamotrigine tablets and more common on drug than placebo) adverse reactions seen in association with the use of lamotrigine tablets during the monotherapy phase of the controlled trial in adults not seen at an equivalent rate in the control group were vomiting, coordination abnormality, dyspepsia, nausea, dizziness, rhinitis, anxiety, insomnia, infection, pain, weight decrease, chest pain, and dysmenorrhea. The most commonly observed (≥5% for lamotrigine tablets and more common on drug than placebo) adverse reactions associated with the use of lamotrigine tablets during the conversion to monotherapy (add-on) period, not seen at an equivalent frequency among low-dose valproate-treated patients, were dizziness, headache, nausea, asthenia, coordination ab… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Valproate increases lamotrigine concentrations more than 2-fold. ( 7 , 12.3 ) Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. ( 7 , 12.3 ) Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%.

( 7 , 12.3 ) Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively. ( 7 , 12.3 ) Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended ( 7 , 12.3 ) Significant drug interactions with lamotrigine tablets are summarized in this section. Uridine 5´-diphospho-glucuronyl transferases (UGT) have been identified as the enzymes responsible for metabolism of lamotrigine.

Drugs that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGT, may also enhance the metabolism of lamotrigine. Those drugs that have been demonstrated to have a clinically significant impact on lamotrigine metabolism are outlined in Table 13.

Specific dosing guidance for these drugs is provided in the Dosage and Administration section, and, for women taking estrogen-containing products, including oral contraceptives, in the Warnings and Precautions section [see Dosage and Administration ( 2.1 ), Warnings and Precautions (5.9)]. Additional details of these drug interaction studies are provided in the Clinical Pharmacology section [see Clinical Pharmacology ( 12.3 )] . Table 13.

Established and Other Potentially Significant Drug Interactions ↓= Decreased (induces lamotrigine glucuronidation). ↑= Increased (inhibits lamotrigine glucuronidation). ?= Conflicting data. Concomitant Drug Effect on Concentration of Lamotrigine or Concomitant Drug Clinical Comment Estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel ↓ lamotrigine ↓ levonorgestrel Decreased lamotrigine concentrations approximately 50%. Decrease in levonorgestrel component by 19%.

Carbamazepine and carbamazepine epoxide ↓ lamotrigine ? carbamazepine epoxide Addition of carbamazepine decreases lamotrigine concentration approximately 40%. May increase carbamazepine epoxide levels. Lopinavir/ritonavir ↓ lamotrigine Decreased lamotrigine concentration approximately 50%.

Atazanavir/ritonavir ↓ lamotrigine Decreased lamotrigine AUC approximately 32%. Phenobarbital/primidone ↓ lamotrigine Decreased lamotrigine concentration approximately 40%. Phenytoin ↓ lamotrigine Decreased lamotrigine concentration approximately 40%.

Rifampin ↓ lamotrigine Decreased lamotrigine AUC approximately 40%. Valproate ↑ lamotrigine ? valproate Increased lamotrigine concentrations slightly more than 2-fold. There are conflicting study results regarding effect of lamotrigine on valproate concentrations: 1) a mean 25% decrease in valproate concentrations in healthy volunteers, 2) no change in valproate concentrations in controlled clinical trials in patients with epilepsy.

Effect of Lamotrigine Tablets on Organic Cationic Transporter 2 Substrates Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins [see Clinical Pharmacology ( 12.3 )] . This may result in increased plasma levels of certain drugs that are substantially excreted via this route. Coadministration of lamotrigine tablets with OCT2 substrates with a narrow therapeutic index (e.g., dofetilide) is not recommended.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data may cause fetal harm. ( 8.1 ) Hepatic impairment: Dosage adjustments required in patients with moderate and severe liver impairment. ( 2.1 , 8.6 ) Renal impairment: Reduced maintenance doses may be effective for patients with significant renal impairment. ( 2.1 , 8.7 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including lamotrigine tablets, during pregnancy. Encourage women who are taking lamotrigine tablets during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population (see Data).

The majority of lamotrigine tablets pregnancy exposure data are from women with epilepsy. In animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. Lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality.

The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including lamotrigine tablets, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions ( 5.10 )]. Dose Adjustments During Pregnancy and the Postpartum Period As with other AEDs, 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-pregnancy concentrations after delivery. Dose adjustments may be necessary to maintain clinical response. Data Human Data: Data from several international pregnancy registries have not shown an increased risk for malformations overall.

The International Lamotrigine Pregnancy Registry reported major congenital malformations in 2.2% (95% CI: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. The NAAED Pregnancy Registry reported major congenital malformations among 2.0% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. EURAP, a large international pregnancy registry focused outside of North America, reported major birth defects in 2.9% (95% CI: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester.

The frequency of major congenital malformations was similar to estimates from the general population. The NAAED Pregnancy Registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% CI: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. This finding has not been observed in ot… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including lamotrigine tablets, during pregnancy. Encourage women who are taking lamotrigine tablets during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population (see Data).

The majority of lamotrigine tablets pregnancy exposure data are from women with epilepsy. In animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. Lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality.

The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including lamotrigine tablets, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions ( 5.10 )]. Dose Adjustments During Pregnancy and the Postpartum Period As with other AEDs, 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-pregnancy concentrations after delivery. Dose adjustments may be necessary to maintain clinical response. Data Human Data: Data from several international pregnancy registries have not shown an increased risk for malformations overall.

The International Lamotrigine Pregnancy Registry reported major congenital malformations in 2.2% (95% CI: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. The NAAED Pregnancy Registry reported major congenital malformations among 2.0% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. EURAP, a large international pregnancy registry focused outside of North America, reported major birth defects in 2.9% (95% CI: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester.

The frequency of major congenital malformations was similar to estimates from the general population. The NAAED Pregnancy Registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% CI: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. This finding has not been observed in other large international pregnancy registries.

Furthermore, a case-control study based on 21 congenital anomaly registries covering over 10 million births in Europe reported an adjusted odds ratio for isolated oral clefts with lamotrigine exposure of 1.45 (95% CI: 0.8, 2.63). Several meta-analyses have not reported an increased ris… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use Epilepsy Lamotrigine tablets are indicated as adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of Lennox-Gastaut syndrome, and PGTC seizures. Safety and efficacy of lamotrigine tablets used as adjunctive treatment for partial-onset seizures were not demonstrated in a small, randomized, double-blind, placebo-controlled withdrawal trial in very young pediatric patients (aged 1 to 24 months). Lamotrigine tablets were associated with an increased risk for infectious adverse reactions (lamotrigine tablets 37%, placebo 5%), and respiratory adverse reactions (lamotrigine tablets 26%, placebo 5%).

Infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. Respiratory adverse reactions included nasal congestion, cough, and apnea. Bipolar Disorder Safety and efficacy of lamotrigine tablets for the maintenance treatment of bipolar disorder were not established in a double-blind, randomized withdrawal, placebo-controlled trial that evaluated 301 pediatric patients aged 10 to 17 years with a current manic/hypomanic, depressed, or mixed mood episode as defined by DSM-IV-TR.

In the randomized phase of the trial, adverse reactions that occurred in at least 5% of patients taking lamotrigine tablets (n = 87) and were twice as common compared with patients taking placebo (n = 86) were influenza (lamotrigine tablets 8%, placebo 2%), oropharyngeal pain (lamotrigine tablets 8%, placebo 2%), vomiting (lamotrigine tablets 6%, placebo 2%), contact dermatitis (lamotrigine tablets 5%, placebo 2%), upper abdominal pain (lamotrigine tablets 5%, placebo 1%), and suicidal ideation (lamotrigine tablets 5%, placebo 0%).

Juvenile Animal Data In a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as adults) were observed at the 2 highest doses. The no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m 2 basis.

🧓 Geriatric Use 85 words ▾

8.5Geriatric Use Clinical trials of lamotrigine tablets for epilepsy and bipolar disorder did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients. 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.

🆘 Overdosage 169 words ▾

10 OVERDOSAGE

10.1Human Overdose Experience Overdoses involving quantities up to 15 g have been reported for lamotrigine, some of which have been fatal. Overdose has resulted in ataxia, nystagmus, seizures (including tonic-clonic seizures), decreased level of consciousness, coma, and intraventricular conduction delay.

10.2Management of Overdose There are no specific antidotes for lamotrigine. Following a suspected overdose, hospitalization of the patient is advised. General supportive care is indicated, including frequent monitoring of vital signs and close observation of the patient.

If indicated, emesis should be induced; usual precautions should be taken to protect the airway. It should be kept in mind that immediate-release lamotrigine is rapidly absorbed [see Clinical Pharmacology ( 12.3 )]. It is uncertain whether hemodialysis is an effective means of removing lamotrigine from the blood.

In 6 renal failure patients, about 20% of the amount of lamotrigine in the body was removed by hemodialysis during a 4-hour session. A Poison Control Center should be contacted for information on the management of overdosage of lamotrigine tablets.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state.

The relevance of these models to human epilepsy, however, is not known. 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).

Effect of Lamotrigine on N-Methyl d-Aspartate-Receptor-Mediated Activity Lamotrigine did not inhibit N-methyl d-aspartate (NMDA)-induced depolarizations in rat cortical slices or NMDA-induced cyclic GMP formation in immature rat cerebellum, nor did lamotrigine displace compounds that are either competitive or noncompetitive ligands at this glutamate receptor complex (CNQX, CGS, TCHP). The IC 50 for lamotrigine effects on NMDA-induced currents (in the presence of 3 µM of glycine) in cultured hippocampal neurons exceeded 100 µM.

The mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established.

12.2Pharmacodynamics Folate Metabolism In vitro, lamotrigine inhibited dihydrofolate reductase, the enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate. Inhibition of this enzyme may interfere with the biosynthesis of nucleic acids and proteins. When oral daily doses of lamotrigine were given to pregnant rats during organogenesis, fetal, placental, and maternal folate concentrations were reduced.

Significantly reduced concentrations of folate are associated with teratogenesis [see Use in Specific Populations ( 8.1 )]. Folate concentrations were also reduced in male rats given repeated oral doses of lamotrigine. Reduced concentrations were partially returned to normal when supplemented with folinic acid.

Cardiac Electrophysiology Effect of Lamotrigine : In vitro studies show that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations. It inhibits human cardiac sodium channels with rapid onset and offset kinetics and strong voltage dependence, consistent with other Class IB antiarrhythmic agents. At therapeutic doses, lamotrigine did not slow ventricular conduction (widen QRS) in healthy individuals in a thorough QT study; however, in patients with clinically important structural or functional heart disease (i.e., patients with heart failure, valvular heart disease, congenital heart disease, conduction system disease, ventricular arrhythmias, cardiac channelopathies [e.g., Brugada syndrome], clinically important ischemic heart disease, or multiple risk factors for coronary artery disease), lamotrigine could slow ventricular conduction (widen QRS) and induce proarrhythmia, which can lead to sudden death.

Elevated heart rates could also increase the risk of ventricular conduction slowing with lamotrigine. Effect of Lamotrigine Metabolite : In dogs, lamotrigine is extensively metabolized to a 2-N- methyl metabolite. This metabolite causes dose-dependent prolongation of the PR interval, widening of the QRS complex, and, at higher doses, complete AV conduction block.

The in vitro electrophysiological effects of this metabolite have not been studied. Similar cardiovascular effects from this metabolite are not anticipated in humans because only trace amounts of the 2-N-methyl metabolite… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state.

The relevance of these models to human epilepsy, however, is not known. 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).

Effect of Lamotrigine on N-Methyl d-Aspartate-Receptor-Mediated Activity Lamotrigine did not inhibit N-methyl d-aspartate (NMDA)-induced depolarizations in rat cortical slices or NMDA-induced cyclic GMP formation in immature rat cerebellum, nor did lamotrigine displace compounds that are either competitive or noncompetitive ligands at this glutamate receptor complex (CNQX, CGS, TCHP). The IC 50 for lamotrigine effects on NMDA-induced currents (in the presence of 3 µM of glycine) in cultured hippocampal neurons exceeded 100 µM.

The mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established.

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Lamotrigine Tablets, USP 25-mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with "45" on one side and break line on other side. Bottle of 30 NDC-13668-045-30 Bottle of 60 NDC-13668-045-60 Bottle of 100 NDC-13668-045-01 Bottle of 500 NDC-13668-045-05 Bottle of 6600 NDC-13668-045-66 10 x 10 unit dose NDC-13668-045-74 Lamotrigine Tablets, USP 100-mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1047" on one side and break line on other side.

Bottle of 30 NDC-13668-047-30 Bottle of 60 NDC-13668-047-60 Bottle of 100 NDC-13668-047-01 Bottle of 500 NDC-13668-047-05 Bottle of 2500 NDC-13668-047-31 10 x 10 unit dose NDC-13668-047-74 Lamotrigine Tablets, USP 150-mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1048" on one side and break line on other side. Bottle of 30 NDC-13668-048-30 Bottle of 60 NDC-13668-048-60 Bottle of 100 NDC-13668-048-01 Bottle of 500 NDC-13668-048-05 Bottle of 1600 NDC-13668-048-16 9 x 10 unit dose NDC-13668-048-64 Lamotrigine Tablets, USP 200-mg White to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1049" on one side and break line on other side.

Bottle of 30 NDC-13668-049-30 Bottle of 60 NDC-13668-049-60 Bottle of 100 NDC-13668-049-01 Bottle of 500 NDC-13668-049-05 Bottle of 1300 NDC-13668-049-13 9 x 10 unit dose NDC-13668-049-64 Lamotrigine Tablets, USP Starter Kit for Patients Not Taking Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate (Orange Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "45" on one side and break line on other side. 100-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1047" on one side and break line on other side.

Blister pack of 42, 25-mg tablets and 7, 100-mg tablets NDC-13668-266-99 Lamotrigine Tablets, USP Starter Kit for Patients Taking Carbamazepine, Phenytoin, Phenobarbital, or Primidone and Not Taking Valproate (Green Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "45" on one side and break line on other side. 100-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "1047" on one side and break line on other side.

Blister pack of 84, 25-mg tablets and 14, 100-mg tablets NDC-13668-266-28 Lamotrigine Tablets, USP Starter Kit for Patients Taking Valproate (Blue Kit). 25-mg, white to off white, round shape, flat face beveled edge, uncoated tablets debossed with "45" on one side and break line on other side. Blister pack of 35 tablets NDC-13668-045-29 Storage Store at 20 o to 25 o C (68 o to 77 o F); excursions permitted to 15 o to 30 o C (59 o to 86 o F) [See USP Controlled Room Temperature].

📋 Description 147 words ▾

11 DESCRIPTION Lamotrigine, USP an AED of the phenyltriazine class, is chemically unrelated to existing AEDs. Lamotrigine's chemical name is 3,5-diamino-6-(2,3-dichlorophenyl)- as -triazine, its molecular formula is C 9 H 7 N 5 Cl 2 , and its molecular weight is 256.09. Lamotrigine, USP is a white to pale cream-colored powder and has a pK a of 5.7. Lamotrigine, USP is very slightly soluble in water (0.17 mg/mL at 25°C) and slightly soluble in

0.1M HCl (4.1 mg/mL at 25°C). The structural formula is: Lamotrigine tablets, USP are supplied for oral administration as 25-mg (white to off white), 100-mg (white to off white), 150-mg (white to off white), and 200-mg (white to off white) tablets. Each tablet contains the labeled amount of lamotrigine, USP and the following inactive ingredients: lactose monohydrate; magnesium stearate; microcrystalline cellulose; povidone; and sodium starch glycolate.

Meets USP Dissolution Test 3 Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Rash Prior to initiation of treatment with lamotrigine tablets, 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 lamotrigine tablets, inform patients that excessive immune activation may occur with lamotrigine tablets 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 lamotrigine tablets. 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 that, due to its mechanism of action, lamotrigine tablets could lead to irregular or slowed heart rhythm. This risk is increased in patients with underlying cardiac disease or heart conduction problems or who are taking other medications that affect heart conduction. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.

Patients who develop syncope should lie down with raised legs and contact their healthcare provider [see Warnings and Precautions ( 5.4 )] . Suicidal Thinking and Behavior Inform patients, their caregivers, and families that AEDs, including lamotrigine tablets, may increase the risk of suicidal thoughts and behavior. Instruct them to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior or thoughts about self-harm.

Instruct them to immediately report behaviors of concern to their healthcare providers. Worsening of Seizures Instruct patients to notify their healthcare providers if worsening of seizure control occurs. Central Nervous System Adverse Effects Inform patients that lamotrigine tablets may cause dizziness, somnolence, and other symptoms and signs of central nervous system depression.

Accordingly, instruct them neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on lamotrigine tablets to gauge whether or not it adversely affects their mental and/or motor performance. Pregnancy and Nursing Instruct patients to notify their healthcare providers if they become pregnant or intend to become pregnant during therapy and if they intend to breastfeed or are breastfeeding an infant. Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant.

This registry is collecting information about the safety of AEDs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 [see Use in Specific Populations ( 8.1 )] . Inform patients who intend to breastfeed that lamotrigine is present in breast milk and advise them to monitor their child for potential adverse effects of this drug.

Discuss the benefits and risks of continuing breastfeeding. Use of Estrogen-Containing Products, Including Oral Contraceptives Instruct women to notify their healthcare providers if they plan to start or stop use of oral contraceptives or other female hormonal preparations (including HRT). Starting estrogen-containing products, including oral contraceptives, may significantly decrease lamotrigine plasma levels, and stopping estrogen-containing oral contraceptives (including the pill-free week) may significantly increase lamotrigine plasma levels [… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Lamotrigine (la-MOE-tri-jeen) Tablets, USP What is the most important information I should know about lamotrigine tablets? 1. Lamotrigine tablets 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 lamotrigine tablets, but is more likely to happen within the first 2 to 8 weeks of treatment. Children and teenagers aged between 2 and 17 years have a higher chance of getting this serious skin rash while taking lamotrigine tablets.

The risk of getting a serious skin rash is higher if you: ● take lamotrigine tablets while taking valproate [DEPAKENE (valproic acid) or DEPAKOTE(divalproex sodium)]. ● take a higher starting dose of lamotrigine tablets than your healthcare provider prescribed. ● increase your dose of lamotrigine tablets faster than prescribed. The risk of serious skin reactions may be associated with a variant in genes called HLA-B*1502 in people from Asian origin (mainly of Han Chinese and Thai origin). See, “Before taking lamotrigine tablets, tell your healthcare provider about all of your health conditions”.

Call your healthcare provider right away if you have any of the following: ● a skin rash ● blistering or peeling of your skin ● hives ● painful sores in your mouth or around your eyes These symptoms may be the first signs of a serious skin reaction. A healthcare provider should examine you to decide if you should continue taking lamotrigine tablets. 2.

Other serious reactions, including serious blood problems or liver problems. Lamotrigine tablets can also cause other types of allergic reactions or serious problems that may affect organs and other parts of your body like your liver or blood cells. You may or may not have a rash with these types of reactions.

Call your healthcare provider right away if you have any of these symptoms: ● fever ● frequent infections ● severe muscle pain ● swelling of your face, eyes, lips, or tongue ● swollen lymph glands ● unusual bruising or bleeding, looking pale ● weakness, fatigue ● yellowing of your skin or the white part of your eyes • trouble walking or seeing • seizures for the first time or happening more often • pain and/or tenderness in the area towards the top of your stomach (enlarged liver and/or spleen) 3. In patients with known heart problems, the use of lamotrigine tablets may lead to a fast heart beat.

Call your healthcare provider right away if you: • have a fast, slow, or pounding heart beat. • feel your heart skip a beat. • have shortness of breath. • have chest pain. • feel lightheaded. 4. Like other antiepileptic drugs, lamotrigine tablets may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: ● thoughts about suicide or dying ● attempt to commit suicide ● new or worse depression ● new or worse anxiety ● feeling agitated or restless ● panic attacks ● trouble sleeping (insomnia) ● new or worse irritability ● acting aggressive, being angry, or violent ● acting on dangerous impulses ● an extreme increase in activity and talking (mania) ● other unusual changes in behavior or mood Do not stop lamotrigine tablets without first talking to a healthcare provider. ● Stopping lamotrigine tablets suddenly can cause serious problems. ● Suicidal thoughts or actions can be caused by things other than medicines.

If you have suicidal thoughts or actions, your healthcare provider may check for other causes. How can I watch for early symptoms of suicidal thoughts and actions in myself or a family member? ● Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. ● Keep all follow-up visits with your healthcare provider as scheduled. ● Call your healthcare provider between visits as needed, especia… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetics of lamotrigine have been studied in subjects with epilepsy, healthy young and elderly volunteers, and volunteers with chronic renal failure. Lamotrigine pharmacokinetic parameters for adult and pediatric subjects and healthy normal volunteers are summarized in Tables 14 and 16. Table 14.

Mean Pharmacokinetic Parameters a in Healthy Volunteers and Adult Subjects with Epilepsy a The majority of parameter means determined in each study had coefficients of variation between 20% and 40% for half-life and CL/F and between 30% and 70% for T max . The overall mean values were calculated from individual study means that were weighted based on the number of volunteers/subjects in each study. The numbers in parentheses below each parameter mean represent the range of individual volunteer/subject values across studies. b Carbamazepine, phenytoin, phenobarbital, and primidone have been shown to increase the apparent clearance of lamotrigine.

Estrogen-containing oral contraceptives and other drugs, such as rifampin and protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir, that induce lamotrigine glucuronidation have also been shown to increase the apparent clearance of lamotrigine [see Drug Interactions ( 7 )]. Adult Study Population Number of Subjects T max : Time of Maximum Plasma Concentration (h) t 1/2 : Elimination Half-life (h) CL/F: Apparent Plasma Clearance (mL/min/kg) Healthy volunteers taking no other medications: Single-dose lamotrigine Multiple-dose lamotrigine 179 36 2.2 (0.25 to 12.0) 1.7 (0.5 to 4.0) 32.8 (14.0 to 103.0) 25.4 (11.6 to 61.6) 0.44 (0.12 to 1.10) 0.58 (0.24 to 1.15) Healthy volunteers taking valproate: Single-dose lamotrigine Multiple-dose lamotrigine 6 18 1.8 (1.0 to 4.0) 1.9 (0.5 to 3.5) 48.3 (31.5 to 88.6) 70.3 (41.9 to 113.5) 0.30 (0.14 to 0.42) 0.18 (0.12 to 0.33) Subjects with epilepsy taking valproate only: Single-dose lamotrigine 4 4.8 (1.8 to 8.4) 58.8 (30.5 to 88.8) 0.28 (0.16 to 0.40) Subjects with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone b plus valproate: Single-dose lamotrigine 25 3.8 (1.0 to 10.0) 27.2 (11.2 to 51.6) 0.53 (0.27 to 1.04) Subjects with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone: b Single-dose lamotrigine Multiple-dose lamotrigine 24 17 2.3 (0.5 to 5.0) 2.0 (0.75 to 5.93) 14.4 (6.4 to 30.4) 12.6 (7.5 to 23.1) 1.10 (0.51 to 2.22) 1.21 (0.66 to 1.82) Absorption Lamotrigine is rapidly and completely absorbed after oral administration with negligible first-pass metabolism (absolute bioavailability is 98%).

The bioavailability is not affected by food. Peak plasma concentrations occur anywhere from 1.4 to 4.8 hours following drug administration. Dose Proportionality In healthy volunteers not receiving any other medications and given single doses, the plasma concentrations of lamotrigine increased in direct proportion to the dose administered over the range of 50 to 400 mg.

In 2 small studies (n=7 and 8) of patients with epilepsy who were maintained on other AEDs, there also was a linear relationship between dose and lamotrigine plasma concentrations at steady state following doses of 50 to 350 mg twice daily. Distribution Estimates of the mean apparent volume of distribution (Vd/F) of lamotrigine following oral administration ranged from 0.9 to

1.3L/kg. Vd/F is independent of dose and is similar following single and multiple doses in both patients with epilepsy and in healthy volunteers. Protein Binding Data from in vitro studies indicate that lamotrigine is approximately 55% bound to human plasma proteins at plasma lamotrigine concentrations from 1 to 10 mcg/mL (10 mcg/mL is 4 to 6 times the trough plasma concentration observed in the controlled efficacy trials).

Because lamotrigine is not highly bound to plasma proteins, clinically significant interactions with other drugs through competition for protein binding sites are unlikely. The binding of lamotrigine to plasma proteins d… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~2 min read ▾

12.2Pharmacodynamics Folate Metabolism In vitro, lamotrigine inhibited dihydrofolate reductase, the enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate. Inhibition of this enzyme may interfere with the biosynthesis of nucleic acids and proteins. When oral daily doses of lamotrigine were given to pregnant rats during organogenesis, fetal, placental, and maternal folate concentrations were reduced.

Significantly reduced concentrations of folate are associated with teratogenesis [see Use in Specific Populations ( 8.1 )]. Folate concentrations were also reduced in male rats given repeated oral doses of lamotrigine. Reduced concentrations were partially returned to normal when supplemented with folinic acid.

Cardiac Electrophysiology Effect of Lamotrigine : In vitro studies show that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations. It inhibits human cardiac sodium channels with rapid onset and offset kinetics and strong voltage dependence, consistent with other Class IB antiarrhythmic agents. At therapeutic doses, lamotrigine did not slow ventricular conduction (widen QRS) in healthy individuals in a thorough QT study; however, in patients with clinically important structural or functional heart disease (i.e., patients with heart failure, valvular heart disease, congenital heart disease, conduction system disease, ventricular arrhythmias, cardiac channelopathies [e.g., Brugada syndrome], clinically important ischemic heart disease, or multiple risk factors for coronary artery disease), lamotrigine could slow ventricular conduction (widen QRS) and induce proarrhythmia, which can lead to sudden death.

Elevated heart rates could also increase the risk of ventricular conduction slowing with lamotrigine. Effect of Lamotrigine Metabolite : In dogs, lamotrigine is extensively metabolized to a 2-N- methyl metabolite. This metabolite causes dose-dependent prolongation of the PR interval, widening of the QRS complex, and, at higher doses, complete AV conduction block.

The in vitro electrophysiological effects of this metabolite have not been studied. Similar cardiovascular effects from this metabolite are not anticipated in humans because only trace amounts of the 2-N-methyl metabolite (<0.6% of lamotrigine dose) have been found in human urine [see Clinical Pharmacology ( 12.3 )] . However, it is conceivable that plasma concentrations of this metabolite could be increased in patients with a reduced capacity to glucuronidate lamotrigine (e.g., in patients with liver disease, patients taking concomitant medications that inhibit glucuronidation).

Accumulation in Kidneys Lamotrigine accumulated in the kidney of the male rat, causing chronic progressive nephrosis, necrosis, and mineralization. These findings are attributed to α-2 microglobulin, a species- and sex-specific protein that has not been detected in humans or other animal species. Melanin Binding Lamotrigine binds to melanin-containing tissues, e.g., in the eye and pigmented skin.

It has been found in the uveal tract up to 52 weeks after a single dose in rodents.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Epilepsy Monotherapy with Lamotrigine in Adults with Partial-Onset Seizures Already Receiving Treatment with Carbamazepine, Phenytoin, Phenobarbital, or Primidone as the Single Antiepileptic Drug The effectiveness of monotherapy with lamotrigine was established in a multicenter, double-blind clinical trial enrolling 156 adult outpatients with partial-onset seizures. The patients experienced at least 4 simple partial-onset, complex partial-onset, and/or secondarily generalized seizures during each of 2 consecutive 4-week periods while receiving carbamazepine or phenytoin monotherapy during baseline.

Lamotrigine (target dose of 500 mg/day) or valproate (1,000 mg/day) was added to either carbamazepine or phenytoin monotherapy over a 4-week period. Patients were then converted to monotherapy with lamotrigine or valproate during the next 4 weeks, then continued on monotherapy for an additional 12-week period. Trial endpoints were completion of all weeks of trial treatment or meeting an escape criterion.

Criteria for escape relative to baseline were: (1) doubling of average monthly seizure count, (2) doubling of highest consecutive 2-day seizure frequency, (3) emergence of a new seizure type (defined as a seizure that did not occur during the 8-week baseline) that is more severe than seizure types that occur during study treatment, or (4) clinically significant prolongation of generalized tonic-clonic seizures. The primary efficacy variable was the proportion of patients in each treatment group who met escape criteria.

The percentages of patients who met escape criteria were 42% (32/76) in the group receiving lamotrigine and 69% (55/80) in the valproate group. The difference in the percentage of patients meeting escape criteria was statistically significant ( P= 0.0012) in favor of lamotrigine. No differences in efficacy based on age, sex, or race were detected.

Patients in the control group were intentionally treated with a relatively low dose of valproate; as such, the sole objective of this trial was to demonstrate the effectiveness and safety of monotherapy with lamotrigine, and cannot be interpreted to imply the superiority of lamotrigine to an adequate dose of valproate. Adjunctive Therapy with Lamotrigine in Adults with Partial-Onset Seizures The effectiveness of lamotrigine as adjunctive therapy (added to other AEDs) was initially established in 3 pivotal, multicenter, placebo-controlled, double-blind clinical trials in 355 adults with refractory partial-onset seizures.

The patients had a history of at least 4 partial-onset seizures per month in spite of receiving 1 or more AEDs at therapeutic concentrations and in 2 of the trials were observed on their established AED regimen during baselines that varied between 8 to 12 weeks. In the third trial, patients were not observed in a prospective baseline. In patients continuing to have at least 4 seizures per month during the baseline, lamotrigine or placebo was then added to the existing therapy.

In all 3 trials, change from baseline in seizure frequency was the primary measure of effectiveness. The results given below are for all partial-onset seizures in the intent-to-treat population (all patients who received at least 1 dose of treatment) in each trial, unless otherwise indicated. The median seizure frequency at baseline was 3 per week while the mean at baseline was 6.6 per week for all patients enrolled in efficacy trials.

One trial (n=216) was a double-blind, placebo-controlled, parallel trial consisting of a 24-week treatment period. Patients could not be on more than 2 other anticonvulsants and valproate was not allowed. Patients were randomized to receive placebo, a target dose of 300 mg/day of lamotrigine, or a target dose of 500 mg/day of lamotrigine.

The median reductions in the frequency of all partial-onset seizures relative to baseline were 8% in patients receiving placebo, 20% in patients receiving 300 mg/day of lamotrigine, and 36% in pa… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 128 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of carcinogenicity was seen in mice or rats following oral administration of lamotrigine for up to 2 years at doses up to 30 mg/kg/day and 10 to 15 mg/kg/day, respectively. The highest doses tested are less than the human dose of 400 mg/day on a body surface area (mg/m 2 ) basis. Lamotrigine was negative in in vitro gene mutation (Ames and mouse lymphoma tk ) assays and in clastogenicity (in vitro human lymphocyte and in vivo rat bone marrow) assays.

No evidence of impaired fertility was detected in rats given oral doses of lamotrigine up to 20 mg/kg/day. The highest dose tested is less than the human dose of 400 mg/day on a mg/m 2 basis.

📄 Recent Major Changes 45 words ▾

RECENT MAJOR CHANGES Boxed Warning 10/2025 Dosage and Administration ( 2.1 , 2.2 , 2.4 ) 4/2025 Warnings and Precautions, Serious Skin Rashes 10/2025 Concomitant Use with Estrogen-Containing Products, Including Oral Contraceptives (5.9) 4/2025 Sudden Unexplained Death in Epilepsy ( 5.12 ) – removal 4/2025

📄 Package Label / Principal Display Panel 128 words ▾

PRINCIPAL DISPLAY PANEL - 25 mg Lamotrigine Tablets - 25mg (Indrad) Lamotrigine Tablets - 25mg (Dahej) Lamotrigine Tablets - 25mg (VKT Pharma) 25mg-indrad 25mg-dahej 25mg-vkt

PRINCIPAL DISPLAY PANEL - 100 mg Lamotrigine Tablets - 100mg (Indrad) Lamotrigine Tablets - 100mg (Dahej) Lamotrigine Tablets - 100mg (VKT Pharma) 100mg-indrad 100mg-dahej 100mg-vkt

PRINCIPAL DISPLAY PANEL - 150 mg Lamotrigine Tablets - 100mg (Indrad) Lamotrigine Tablets - 100mg (Dahej) Lamotrigine Tablets - 100mg (VKT Pharma) 150mg-indrad 150mg-dahej 150mg-vkt

PRINCIPAL DISPLAY PANEL - 200 mg Lamotrigine Tablets- 200mg (Indrad) Lamotrigine Tablets- 200mg (Dahej) Lamotrigine Tablets- 200mg (VKT Pharma) 200mg-indrad 200mg-dahej 200mg-vkt

PRINCIPAL DISPLAY PANEL - 25 mg, 100 mg Starter Kit orange-kit

PRINCIPAL DISPLAY PANEL - 25 mg, 100 mg Starter Kit green-kit

PRINCIPAL DISPLAY PANEL - 25 mg Starter Kit blue-kit

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
18.9K
Units reimbursed last 4 qtrs
2M
Gross reimbursed last 4 qtrs
$226.7K
Avg / prescription
$11.97
Avg / unit
$0.1130
Latest quarter Q1 2026
4.8KRx
Medicaid pays / ea
$0.1130
gross reimbursed
vs
NADAC / ea
$0.0487
acquisition cost
=
Spread
+$0.0643
+132% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
76% FFS 24% MCO
Fee-for-service · 14,364 Rx Managed care · 4,572 Rx
State Medicaid map
Alaska: no data reported AK Maine: 1,462 units · 105 per 100k residents ME Washington: 78,717 units · 1,008 per 100k residents WA Idaho: 2,917 units · 149 per 100k residents ID Montana: 858 units · 75.8 per 100k residents MT North Dakota: 5,670 units · 724 per 100k residents ND Minnesota: 6,561 units · 114 per 100k residents MN Wisconsin: 7,863 units · 133 per 100k residents WI Michigan: 13,862 units · 138 per 100k residents MI New York: 35,478 units · 181 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 156,217 units · 3,690 per 100k residents OR Nevada: 4,828 units · 151 per 100k residents NV Wyoming: 690 units · 118 per 100k residents WY South Dakota: 1,831 units · 199 per 100k residents SD Iowa: 3,024 units · 94.3 per 100k residents IA Illinois: 3,169 units · 25.3 per 100k residents IL Indiana: 23,086 units · 336 per 100k residents IN Ohio: 16,703 units · 142 per 100k residents OH Pennsylvania: 16,523 units · 127 per 100k residents PA New Jersey: 5,130 units · 55.2 per 100k residents NJ Massachusetts: 1,573 units · 22.5 per 100k residents MA California: 1,397,609 units · 3,587 per 100k residents CA Utah: no data reported UT Colorado: 27,246 units · 464 per 100k residents CO Nebraska: no data reported NE Missouri: 11,973 units · 193 per 100k residents MO Kentucky: 17,095 units · 378 per 100k residents KY West Virginia: 6,425 units · 363 per 100k residents WV Virginia: 34,826 units · 400 per 100k residents VA Maryland: 35,189 units · 569 per 100k residents MD Connecticut: 1,140 units · 31.5 per 100k residents CT Rhode Island: no data reported RI Arizona: 5,865 units · 78.9 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: 8,275 units · 116 per 100k residents TN North Carolina: 3,801 units · 35.1 per 100k residents NC South Carolina: 1,350 units · 25.1 per 100k residents SC Delaware: no data reported DE Oklahoma: 2,199 units · 54.3 per 100k residents OK Louisiana: no data reported LA Mississippi: 1,104 units · 37.6 per 100k residents MS Alabama: no data reported AL Georgia: 6,570 units · 59.6 per 100k residents GA D.C.: 533 units · 78.5 per 100k residents DC Hawaii: 4,110 units · 286 per 100k residents HI Texas: 1,784 units · 5.8 per 100k residents TX Florida: 7,721 units · 34.1 per 100k residents FL
Units reimbursed · per 100k residents
5.83,690
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Oregon 3,690 /100k
2 California 3,587 /100k
3 Washington 1,008 /100k
4 North Dakota 724 /100k
5 Maryland 569 /100k
6 Colorado 464 /100k
7 Virginia 400 /100k
8 Kentucky 378 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
100 tablets13668-0047-01 83,381 Rx · $836,495
500 tablets this page13668-0047-05 18,936 Rx · $226,694
30 tablets13668-0047-30 No Medicaid data
2500 tablets13668-0047-31 No Medicaid data
60 tablets13668-0047-60 No Medicaid data
100 tablets13668-0047-74 No Medicaid data
Drug total (last 4 qtrs): 102,317 Rx · 7,666,979 units · $1,063,188 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Lamotrigine — the program that covers self-administered drugs. 15 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Lamotrigine. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$16.58M
Claims incl. refills
1.1M
Beneficiaries
533.3K
Spend / beneficiary
$31.09
Spend / claim
$15.37
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
← 13668-0045-01 · Torrent 13668-0048-01 · Torrent →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.