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Lamotrigine Extended Release 300 mg Tablet, 30-count — NDC 49884-0605-11 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Lamotrigine Extended Release 300 mg Tablet, 30-count — NDC 49884-605-11 (Billing 49884-0605-11)

by Par Health USA, LLC · 30 TABLET in 1 BOTTLE

This is a package of 30 tablets of Lamotrigine Extended Release 300 mg Tablet from Par Health USA, LLC, no longer marketed (first marketed Jan 2013), no longer in the FDA NDC Directory, this package's marketing ended Sep 2026; retail pharmacies pay about $1.26 per tablet (NADAC). It is the main listing for this product, which comes in 3 package sizes.

NDC 49884-0605-11
🏷️ FDA NDC (as labeled) 49884-605-11 billing pads the product segment with a zero
This package
Contains30-count Cost per ea$1.26 NADAC Per package$37.79 / 30 tablets Pack sizes3 compare ↓
Also priced by: Medicaid pays $2.10/unit · Part D plans $1.29/unit — full pricing hub ↓
Main listing for product 49884-605 · Also comes in: 100 tablets 49884-605-01 500 tablets 49884-605-05
Rx only Generic Discontinued Non-controlled ⚠ On shortage ⚠ Discontinued by firm ⇄ 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

NDC database record

One package, one record: these facts belong to NDC 49884-605-11 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
49884 labeler · 605 product · 11 package
Package marketed since
Jan 18, 2013
Package marketing ended
Sep 30, 2026
Sample package
No — commercial package
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 4988460511 7
Medicaid fills, this package
1,429 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026
⚠️
Active FDA shortage. Lamotrigine Tablet, Extended Release is currently reported in shortage by the FDA. Shortage details →
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Sep 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 49884-605-11
Product NDC 49884-605
11-digit billing NDC 49884060511
NCPDP billing unit EA — each (per item)
RxCUI 850087, 850091, 900156, 900164, 1098608, 1146690
UNII U3H27498KS
Application # ANDA201791
SPL Set ID fb59c76a-9b6f-40ea-ac3a-58c3195c4377
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 Discontinued
FDA listing status Discontinued by firm (certified through Sep 2026)
Marketing start 2013-01-18
Marketing end 2026-09-30
Route ORAL
Dosage form TABLET
Substance LAMOTRIGINE

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

GPI-14 72600040007550
GPI class lamoTRIgine ER
GCN Seq No 067221
GCN 29725
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 ER 300 MG TABLET
FDB brand name Lamotrigine Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 067221
  • GCN: 29725
  • GPI-14 (Medi-Span): 72600040007550
  • HICL (First Databank): 007378
  • AHFS class code: 28:12.92.00
  • RxCUI (RxNorm): 850087
Why two NDCs? The FDA registers this code as 49884-605-11 — 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 → 49884-0605-11. 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 ER 300 MG TABLET Ingredient Lamotrigine
📖 What it is MedlinePlus · NLM

Lamotrigine extended-release (long-acting) tablets are used with other medications to treat certain types of seizures in patients who have epilepsy. All types of lamotrigine tablets (tablets, orally disintegrating tablets, and chewable tablets) other than the extended-release tablets are used alone or with other medications to treat seizures in people who have epilepsy or Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). All types of lamotrigine tablets other than the extended-release tablets are also used to increase the time between episodes of...

Read the full MedlinePlus article ↗
📗 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 →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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 $1.260 $37.79 / 30 tablets
Medicaid paysCMS SDUD · 12 mo $2.10 $63.00 / 30 tablets
Medicare drug plans payPart D · Q2 2026 $1.29 $38.56 / 30 tablets
NADAC price history (per ea) — tap or hover for the price & month
Jan 2022 Aug 2022 Jan 2026 Sep 2026 $4.968 $1.192
▼ Down 71% 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
49884-0605-01 49884-605-01 100 TABLET in 1 BOTTLE — — 2013-01-18 — Discontinued by firm
49884-0605-05 49884-605-05 500 TABLET in 1 BOTTLE — — 2013-01-18 — Discontinued by firm
49884-0605-11 You're viewing this Main listing 30 TABLET in 1 BOTTLE $1.26 / ea $37.79 2013-01-18 Sep 30, 2026 Discontinued by firm

You're viewing the smallest of 3 pack sizes for this product.

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 tablet in 1 bottle.
How does this package differ from NDC 49884-0605-01?
Both are Lamotrigine Extended Release 300 mg Tablet — the drug itself is identical. This page's package is the 30-count one, while NDC 49884-0605-01 is the 100 tablets package.
What NDC number is used to bill for this package of Lamotrigine Extended Release 300 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 300 mg 00228-1580-03 Actavis 30 tablets $1.260 AB Availability likely —
Lamotrigine 300 mg 16714-0627-01 NorthStar 30 tablets $1.260 AB Availability likely —
lamotrigine 300 mg 31722-0245-30 Camber 30 tablets $1.260 AB Availability likely —
Lamotrigine Extended Release 300 mgthis 49884-0605-11 Par 30 tablets $1.260 — Discontinued —
Lamotrigine 300 mg 65162-0990-03 Amneal 30 tablets $1.260 AB Availability likely —
Lamictal Xr 300 mg 00173-0761-00 GlaxoSmithKline 30 tablets $48.647 AB Availability likely +3762%
Lamotrigine Extended-Release 300 mg 10370-0256-11 Par 30 tablets — AB FDA listed —
Lamotrigine 300 mg 42291-0448-30 AvKARE 30 tablets — AB FDA listed —
Lamotrigine 300 mg 46708-0419-30 Alembic 30 tablets — AB FDA listed —
Lamotrigine 300 mg 55111-0428-05 Dr.Reddy's 500 tablets — AB FDA listed —
Lamotrigine 300 mg 62332-0419-30 Alembic 30 tablets — AB FDA listed —
Lamotrigine 300 mg 68382-0984-05 Zydus 500 tablets — AB FDA listed —
lamotrigine 300 mg 69117-0049-01 Yiling 30 tablets — AB FDA listed —
Lamotrigine 300 mg 70771-1519-03 Zydus 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

🏛️
2013
On the market since
Jan 2013
📍
2026
Currently FDA-listed
13 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 brown / white / yellow / gray
ShapeRound
ImprintPar;605
Size1 mm
ScoringNot scored
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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
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

LabelerPar Health USA, LLC
Application holderPH HEALTH LTD
FDA applicationANDA201791 (ANDA)
Labeler code49884
First marketedJan 2013
Product typeHuman Prescription Drug
Portfolio216 products on file

More NDCs from Par Health USA, LLC labeler code 49884

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 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~2 min read ▾

WARNING: SERIOUS SKIN RASHES Lamotrigine extended-release 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.

Lamotrigine extended-release 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 lamotrigine extended-release is not expected to differ from that with immediate-release lamotrigine.

However, the relatively limited treatment experience with lamotrigine extended-release makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with lamotrigine extended-release. In addition to age, factors that may increase the risk of occurrence or the severity of rash caused by lamotrigine extended-release include (1) coadministration of lamotrigine extended-release with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of lamotrigine extended-release, (3) exceeding the recommended dose escalation for lamotrigine extended-release, 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 immediate-release lamotrigine 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 extended-release, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, lamotrigine extended-release 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 ) ] . 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 extended-release. exceeding recommended dose escalation for lamotrigine extended-release. ( 5.1 ) 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 extended-release should be discontinued at the first sign of rash, unless the rash is clearly not drug related. ( 5.1 )

🎯 Indications and Usage 190 words ▾

1 INDICATIONS AND USAGE Lamotrigine extended-release is indicated for: 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 ) 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 )

1.1Adjunctive Therapy Lamotrigine extended-release 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.

1.2Monotherapy Lamotrigine extended-release 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 lamotrigine extended-release have not been established (1) as initial monotherapy or (2) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.

1.3Limitation of Use Safety and effectiveness of lamotrigine extended-release for use in patients younger than 13 years have not been established.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Lamotrigine Extended-Release Tablets are taken once daily, with or without food. Tablets must be swallowed whole and must not be chewed, crushed, or divided. Do not exceed the recommended initial dosage and subsequent dose escalation.

( 2.1 ) Initiation of adjunctive therapy and conversion to monotherapy requires slow titration dependent on concomitant AEDs; the prescriber must refer to the appropriate algorithm in Dosage and Administration. ( 2.2 , 2.3 ) Adjunctive therapy: Target therapeutic dosage range is 200 to 600 mg daily and is dependent on concomitant AEDs. ( 2.2 ) Conversion to monotherapy: Target therapeutic dosage range is 250 to 300 mg daily.

( 2.3 ) Conversion from immediate-release lamotrigine to lamotrigine extended-release: The initial dose of lamotrigine extended-release should match the total daily dose of the immediate-release lamotrigine. Patients should be closely monitored for seizure control after conversion. ( 2.4 ) Do not restart lamotrigine extended-release 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 )

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 extended-release with valproate, (2) exceeding the recommended initial dose of lamotrigine extended-release, or (3) exceeding the recommended dose escalation for lamotrigine extended-release. 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 extended-release is exceeded and in patients with a history of allergy or rash to other AEDs. It is recommended that lamotrigine extended-release 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 extended-release, 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 Extended-Release 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 extended-release in patients on estrogen-containing products including contraceptives and atazanavir/ritonavir, see below and Table 5 . For dosing considerations for lamotrigine extended-release in patients on other drugs known to induce or inhibit glucuronidation, see Table 1 and Table 5. Target Plasma Levels: A therapeutic plasma concentration range has not been established for lamotrigine.

Dosing… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 136 words ▾

3 DOSAGE FORMS AND STRENGTHS Extended-Release Tablets: 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, and 300 mg. ( 3.1 , 16 )

3.1Extended-Release Tablets 25 mg, round, beige, biconvex, film-coated tablet debossed with “561” on one side and “Par” on the other 50 mg, round, white, biconvex, film-coated tablet debossed with “562” on one side and “Par” on the other 100 mg, round, brown, biconvex, film-coated tablet debossed with “563” on one side and “Par” on the other 200 mg, round, yellow, biconvex, film-coated tablet debossed with “564” on one side and “Par” on the other 250 mg, round, white, biconvex, film-coated tablet debossed with “604” on one side and “Par” on the other 300 mg, round, grey, biconvex, film-coated tablet debossed with “605” on one side and “Par” on the other

⛔ Contraindications 54 words ▾

4 CONTRAINDICATIONS Lamotrigine extended-release 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 ~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 extended-release 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 (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.

Lamotrigine 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 extended-release could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Any expected or observed benefit of lamotrigine extended-release in an individual patient with clinically important structural or functional heart disease must be carefully weighed against the risk for serious arrythmias 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 ] The risk of serious rash caused by treatment with lamotrigine extended-release is not expected to differ from that with immediate-release lamotrigine [see BOXED WARNING ] . However, the relatively limited treatment experience with lamotrigine extended-release makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with lamotrigine extended-release. Pediatric Population The incidence of serious rash associated with hospitalization and discontinuation of immediate-release lamotrigine in a prospectively followed cohort of pediatric patients (aged 2 to 16 years) with epilepsy receiving adjunctive therapy with immediate-release lamotrigine was approximately 0.8% (16 of 1,983).

When 14 of these cases were reviewed by 3 expert dermatologists, there was considerable disagreement as to their proper classification. To illustrate, 1 dermatologist considered none of the cases to be Stevens-Johnson syndrome; another assigned 7 of the 14 to this diagnosis. There was 1 rash-related death in this 1,983-patient cohort.

Additionally, there have been rare cases of toxic epidermal necrolysis 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, 1.2% (6 of 482) experienced a serious rash compared with 0.6% (6 of 952) patients not taking valproate.

Lamotrigine extended-release is not approved in patients younger than 13 years. Adult Population Serious rash associated with hospitalization and discontinuation of immediate-release lamotrigine occurred in 0.3% (11 of 3,348) of adult patients who received immediate-release lamotrigine in premarketing clinical trials of epilepsy. In worldwide postmarketing experience, rare cases of rash-related death have been reported, but their numbers are too few to permit… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS 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 ) ] Most common adverse reactions with use as adjunctive therapy (treatment difference between lamotrigine extended-release and placebo ≥4%) were dizziness, tremor/intention tremor, vomiting, and diplopia.

( 6.1 ) Most common adverse reactions with use as monotherapy were similar to those seen with previous trials conducted with immediate-release lamotrigine and lamotrigine extended-release. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393 and/or www.parhealth.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience with Lamotrigine Extended-Release for Treatment of Primary Generalized Tonic-Clonic and Partial-Onset Seizures Most Common Adverse Reactions in Clinical Trials : Adjunctive Therapy in Patients with Epilepsy : 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. In these 2 trials, adverse reactions led to withdrawal of 4 (2%) patients in the group receiving placebo and 10 (5%) patients in the group receiving lamotrigine extended-release.

Dizziness was the most common reason for withdrawal in the group receiving lamotrigine extended-release (5 patients [3%]). The next most common adverse reactions leading to withdrawal in 2 patients each (1%) were rash, headache, nausea, and nystagmus. Table 4 displays the incidence of adverse reactions in these two 19-week, double-blind, placebo-controlled trials of patients with PGTC and partial onset seizures.

Table 4. Adverse Reactions in Pooled, Placebo-Controlled, Adjunctive Trials in Patients with Epilepsy a Body System/Adverse Reaction Percent of Patients Receiving Adjunctive Lamotrigine Extended-Release (n = 190) Percent of Patients Receiving Adjunctive Placebo (n = 195) Ear and labyrinth disorders Vertigo 3 <1 Eye disorders Diplopia Vision blurred 5 3 <1 2 Gastrointestinal disorders Nausea Vomiting Diarrhea Constipation Dry mouth 7 6 5 2 2 4 3 3 <1 1 General disorders and administration site conditions Asthenia and fatigue 6 4 Infections and infestations Sinusitis 2 1 Metabolic and nutritional disorders Anorexia 3 2 Musculoskeletal and connective tissue disorder Myalgia 2 0 Nervous system Dizziness Tremor and intention tremor Somnolence Cerebellar coordination and balance disorder Nystagmus 14 6 5 3 2 6 1 3 0 <1 Psychiatric disorders Depression Anxiety 3 3 <1 0 Respiratory, thoracic, and mediastinal disorders Pharyngolaryngeal pain 3 2 Vascular disorder Hot flush 2 0 a Adverse reactions that occurred in at least 2% of patients treated with lamotrigine extended-release and at a greater incidence than placebo.

Note: In these trials the incidence of nonserious rash was 2% for lamotrigine extended-release and 3% for placebo. In clinical trials evaluating immediate-release lamotrigine, the rate of serious rash was 0.3% in adults on adjunctive therapy for epilepsy [see BOXED WARNING ]. Adverse reactions were also analyzed to assess the incidence of the onset of an event in the titration period, and in the maintenance period, and if adverse reactions occurring… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Significant drug interactions with lamotrigine are summarized in this section. Additional details of these drug interaction studies, which were conducted using immediate-release lamotrigine, are provided in the Clinical Pharmacology section [see CLINICAL PHARMACOLOGY ( 12.3 ) ] . 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 ) ]. Table 5. 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 Extended-Release 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 extended-release with OCT2 substrates with a narrow therapeutic index (e.g., dofetilide) is not recommended. 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 (OCT2) substrates with narrow therapeutic index is not recommended. ( 7 , 12.3 )

👥 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 extended-release, during pregnancy. Encourage women who are taking lamotrigine extended-release 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).

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 extended-release, 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… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including lamotrigine extended-release, during pregnancy. Encourage women who are taking lamotrigine extended-release 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).

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 extended-release, 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 risk of major congenital malformations following lamotrigine exp… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Lamotrigine extended-release is indicated as adjunctive therapy for PGTC and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. Safety and effectiveness of lamotrigine extended-release for any use in patients younger than 13 years have not been established. Immediate-release lamotrigine is 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 immediate-release lamotrigine 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). Immediate-release lamotrigine was associated with an increased risk for infectious adverse reactions (lamotrigine 37%, placebo 5%), and respiratory adverse reactions (lamotrigine 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. 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 82 words ▾

8.5Geriatric Use Clinical trials of lamotrigine extended-release for epilepsy 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 152 words ▾

10 OVERDOSAGE

10.1Human Overdose Experience Overdoses involving quantities up to 15 g have been reported for immediate-release 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 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 extended-release.

🧬 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.

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 Electrophysiolgy 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 extended-release 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 or (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 extended-release 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 extended-release. 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 urin… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 212 words ▾

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.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Lamotrigine Extended-Release Tablets 25 mg, round, beige, biconvex, film-coated tablet debossed with “561” on one side and “Par” on the other 30 Tablets - (NDC 49884-561-11) 100 Tablets - (NDC 49884-561-01) 500 Tablets - (NDC 49884-561-05) 50 mg, round, white, biconvex, film-coated tablet debossed with “562” on one side and “Par” on the other 30 Tablets - (NDC 49884-562-11) 100 Tablets - (NDC 49884-562-01) 500 Tablets - (NDC 49884-562-05) 100 mg, round, brown, biconvex, film-coated tablet debossed with “563” on one side and “Par” on the other 30 Tablets - (NDC 49884-563-11) 100 Tablets - (NDC 49884-563-01) 500 Tablets - (NDC 49884-563-05) 200 mg, round, yellow, biconvex, film-coated tablet debossed with “564” on one side and “Par” on the other 30 Tablets - (NDC 49884-564-11) 100 Tablets - (NDC 49884-564-01) 500 Tablets - (NDC 49884-564-05) 250 mg, round, white, biconvex, film-coated tablet debossed with “604” on one side and “Par” on the other 30 Tablets – (NDC 49884-604-11) 100 Tablets – (NDC 49884-604-01) 500 Tablets – (NDC 49884-604-05) 300 mg, round, grey, biconvex, film-coated tablet debossed with “605” on one side and “Par” on the other 30 Tablets - (NDC 49884-605-11) 100 Tablets - (NDC 49884-605-01) 500 Tablets - (NDC 49884-605-05) Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature ] .

📋 Description ~1 min read ▾

11 DESCRIPTION Lamotrigine Extended-Release, 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 is a white to pale cream-colored powder and has a pK a of 5.7. Lamotrigine 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 Extended-Release Tablets are supplied for oral administration as 25 mg (round beige biconvex film-coated), 50 mg (round white biconvex film-coated), 100 mg (round brown biconvex film-coated), 200 mg (round yellow biconvex film-coated), 250 mg (round white biconvex film coated) and 300 mg (round grey biconvex film-coated) tablets. Each tablet contains the labeled amount of lamotrigine and the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, colloidal anhydrous silica (25 mg, 50 mg, 200 mg, 250 mg and 300 mg tablets only), methacrylic acid copolymer, talc, titanium dioxide, triethyl citrate, sodium bicarbonate, sodium laurel sulfate, iron oxide yellow (25 mg and 100 mg tablets only), iron oxide red (25 mg and 100 mg tablets only), D&C Yellow # 10 (200 mg tablet only), FD&C Yellow # 6 (200 mg tablet only) and black iron oxide (300 mg tablet only).

Lamotrigine extended-release tablets contain a modified-release eroding formulation as the core. The tablets are coated with an enteric coat and have pore forming ingredient in the coat to enable a controlled release of drug in the acidic environment of the stomach. The combination of the modified-release core and the enteric coat are designed to control the dissolution rate of lamotrigine over a period of approximately 12 to 15 hours, leading to a gradual increase in serum lamotrigine levels.

Chemical 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 extended-release, 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 extended-release, inform patients that excessive immune activation may occur with lamotrigine extended-release 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 extended-release. 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 extended-release 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 extended-release, 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 extended-release 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 extended-release 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 extended-release 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 contracept… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Lamotrigine (la-MO-tri-jen) Extended-Release Tablets What is the most important information I should know about Lamotrigine extended-release tablets? 1. Lamotrigine extended-release 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 extended-release tablets, 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 lamotrigine extended-release tablets.

Lamotrigine extended-release tablets is not approved for use in children younger than 13 years. The risk of getting a serious skin rash is higher if you: take lamotrigine extended-release tablets while taking valproate [DEPAKENE ® (valproic acid) or DEPAKOTE ® (divalproex sodium)]. take a higher starting dose of lamotrigine extended-release tablet than your healthcare provider prescribed. increase your dose of lamotrigine extended-release tablet 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 extended-release, 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 extended-release tablets.

2. Other serious reactions, including serious blood problems or liver problems. Lamotrigine extended-release 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 extended-release 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 (AEDs) , Lamotrigine extended-release 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 extended-release tablets without first talking to a healthcare provider.

Stopping lamotrigine extended-release 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… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics In comparison with immediate-release lamotrigine, the plasma lamotrigine levels following administration of lamotrigine extended-release are not associated with any significant changes in trough plasma concentrations, and are characterized by lower peaks, longer time to peaks, and lower peak-to-trough fluctuation, as described in detail below. Absorption Lamotrigine is absorbed after oral administration with negligible first-pass metabolism. The bioavailability of lamotrigine is not affected by food.

In an open-label, crossover study of 44 subjects with epilepsy receiving concomitant AEDs, the steady-state pharmacokinetics of lamotrigine were compared following administration of equivalent total doses of lamotrigine extended-release given once daily with those of lamotrigine immediate-release given twice daily. In this study, the median time to peak concentration (T max ) following administration of lamotrigine extended-release was 4 to 6 hours in subjects taking carbamazepine, phenytoin, phenobarbital, or primidone; 9 to 11 hours in subjects taking valproate; and 6 to 10 hours in subjects taking AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate.

In comparison, the median T max following administration of immediate-release lamotrigine was between 1 and 1.5 hours. The steady-state trough concentrations for extended-release lamotrigine were similar to or higher than those of immediate-release lamotrigine depending on concomitant AED (see Table 6 ). A mean reduction in the lamotrigine C max by 11% to 29% was observed for lamotrigine extended-release compared with immediate-release lamotrigine, resulting in a decrease in the peak-to-trough fluctuation in serum lamotrigine concentrations.

However, in some subjects receiving enzyme-inducing AEDs, a reduction in C max of 44% to 77% was observed. The degree of fluctuation was reduced by 17% in subjects taking enzyme-inducing AEDs; 34% in subjects taking valproate; and 37% in subjects taking AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate. Lamotrigine extended-release and immediate-release lamotrigine regimens were similar with respect to area under the curve (AUC, a measure of the extent of bioavailability) for subjects receiving AEDs other than those known to induce the metabolism of lamotrigine.

The relative bioavailability of extended-release lamotrigine was approximately 21% lower than immediate-release lamotrigine in subjects receiving enzyme-inducing AEDs. However, a reduction in exposure of up to 70% was observed in some subjects in this group when they switched to lamotrigine extended-release tablets. Therefore, doses may need to be adjusted in some patients based on therapeutic response.

Table 6. Steady-State Bioavailability of Lamotrigine Extended-Release Relative to Immediate-Release Lamotrigine at Equivalent Daily Doses (Ratio of Extended-Release to Immediate-Release 90% CI) a Enzyme-inducing AEDs include carbamazepine, phenytoin, phenobarbital, and primidone. Concomitant Antiepileptic Drug AUC (0-24ss) C max C min Enzyme-inducing antiepileptic drugs a 0.79 (0.69, 0.90) 0.71 (0.61, 0.82) 0.99 (0.89, 1.09) Valproate 0.94 (0.81, 1.08) 0.88 (0.75, 1.03) 0.99 (0.88, 1.10) Antiepileptic drugs other than enzyme-inducing antiepileptic drugs a or valproate 1.00 (0.88, 1.14) 0.89 (0.78, 1.03) 1.14 (1.03, 1.25) Dose Proportionality: In healthy volunteers not receiving any other medications and given lamotrigine extended-release once daily, the systemic exposure to lamotrigine increased in direct proportion to the dose administered over the range of 50 to 200 mg.

At doses between 25 and 50 mg, the increase was less than dose proportional, with a 2-fold increase in dose resulting in an approximately 1.6-fold increase in systemic exposure. 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 indepen… [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 Electrophysiolgy 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 extended-release 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 or (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 extended-release 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 extended-release. 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).

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures The effectiveness of Lamotrigine extended-release 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 lamotrigine extended-release and 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 lamotrigine extended-release 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 lamotrigine extended-release 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 lamotrigine extended-release and 32% in patients treated with placebo, a difference that was statistically significant, defined as a 2-sided P value ≤0.05.

Figure 1 presents the percentage of patients (X-axis) with a percent reduction in PGTC seizure frequency (responder rate) from baseline through the entire treatment period at least as great as that represented on the Y-axis. A positive value on the Y-axis indicates an improvement from baseline (i.e., a decrease in seizure frequency), while a negative value indicates a worsening from baseline (i.e., an increase in seizure frequency). Thus, in a display of this type, a curve for an effective treatment is shifted to the left of the curve for placebo.

The proportion of patients achieving any particular level of reduction in PGTC seizure frequency was consistently higher for the group treated with lamotrigine extended-release compared with the placebo group. For example, 70% of patients randomized to lamotrigine extended-release experienced a 50% or greater reduction in PGTC seizure frequency, compared with 32% of patients randomized to placebo. Patients with an increase in seizure frequency >100% are represented on the Y-axis as ≥-100%.

Figure 1. Proportion of Patients by Responder Rate for Lamotrigine Extended-Release and Placebo Group (Primary Generalized Tonic-Clonic Seizures Study) This is Figure 1

14.2Adjunctive Therapy for Partial-Onset Seizures The effectiveness of immediate-release lamotrigine as adjunctive therapy was initially established in 3 pivotal, multicenter, placebo-controlled, double-blind clinical trials in 355 adults with refractory partial-onset seizures. The effectiveness of lamotrigine extended-release as adjunctive therapy in partial-onset seizures, with or without secondary generalization, was established in a 19-week, multicenter, double-blind, placebo-controlled trial in 236 patients aged 13 years and older (approximately 93% of patients were aged 16 to 65 years).

Approximately 36% were from the U.S. and approximately 64% were from other countries including Argentina, Brazil, Chile, Germany, India, Korea, Russian Federation, and Ukraine. Patients with at least 8 partial-onset seizures during an 8-week prospective baseline phase (or 4-week prospective baseline coupled with a 4-week historical baseline documented with seizure diary data) were randomized to treatment with lamotrigine extended-release (n = 116) or placebo (n = 120) added to their current regimen of 1 or 2 AEDs. Approximately half of the patients were taking 2 concomitant AEDs at baseline.

Target doses ranged from 200 to 500 mg/day of lamotrigine extended-release based on concomitant AED (target dose = 200 mg for valproate, 300 mg for AEDs not altering plasma lamotrigine, and 500 mg for enzyme-inducing AEDs). The median partial seizure frequency per week at base… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 129 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.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 126 words ▾

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.

📚 References 26 words ▾

15 REFERENCES 1. French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy. Epilepsia . 2010; 51 (10): 1936-1943.

📄 Recent Major Changes 42 words ▾

Boxed Warning 10/2025 Dosage and Administration ( 2.1 , 2.2 ) 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 90 words ▾

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 25 mg 30 tablets.

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 50 mg 30 tablets.

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 100 mg 30 tablets.

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 200 mg 30 tablets.

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 250 mg 30 tablets.

PRINCIPAL DISPLAY PANEL This is an image of Lamotrigine Extended-Release Tablets 300 mg 30 tablets.

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
1.4K
Units reimbursed last 4 qtrs
72.9K
Gross reimbursed last 4 qtrs
$153.1K
Avg / prescription
$107.12
Avg / unit
$2.1001
Latest quarter Q1 2026
27Rx
Medicaid pays / ea
$2.1001
gross reimbursed
vs
NADAC / ea
$1.2597
acquisition cost
=
Spread
+$0.8404
+67% 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 ⓘ
61% FFS 39% MCO
Fee-for-service · 873 Rx Managed care · 556 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 1,330 units · 13.3 per 100k residents MI New York: 12,910 units · 66.0 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 2,786 units · 65.8 per 100k residents OR Nevada: 510 units · 16.0 per 100k residents NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: 5,894 units · 85.9 per 100k residents IN Ohio: 2,657 units · 22.5 per 100k residents OH Pennsylvania: 3,120 units · 24.1 per 100k residents PA New Jersey: 2,220 units · 23.9 per 100k residents NJ Massachusetts: no data reported MA California: 26,291 units · 67.5 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: 720 units · 11.6 per 100k residents MO Kentucky: 547 units · 12.1 per 100k residents KY West Virginia: no data reported WV Virginia: 1,335 units · 15.3 per 100k residents VA Maryland: 2,850 units · 46.1 per 100k residents MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 2,040 units · 27.5 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 480 units · 4.4 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 750 units · 16.4 per 100k residents LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: 1,050 units · 73.2 per 100k residents HI Texas: 1,950 units · 6.4 per 100k residents TX Florida: 3,445 units · 15.2 per 100k residents FL
Units reimbursed · per 100k residents
4.485.9
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 Indiana 85.9 /100k
2 Hawaii 73.2 /100k
3 California 67.5 /100k
4 New York 66.0 /100k
5 Oregon 65.8 /100k
6 Maryland 46.1 /100k
7 Arizona 27.5 /100k
8 Pennsylvania 24.1 /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.
30 tablets this page49884-0605-11 1,429 Rx · $153,068
100 tablets49884-0605-01 No Medicaid data
500 tablets49884-0605-05 No Medicaid data
Drug total (last 4 qtrs): 1,429 Rx · 72,885 units · $153,068 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) ✓ Available
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 100 tablets (49884-0605-01), 500 tablets (49884-0605-05). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Par Health USA, LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 49884-0604-01 · Par 49884-0720-08 · Par →
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.