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Lamotrigine Extended Release 250 mg Tablet, 500-count

by Par Health USA, LLC · 500 TABLET in 1 BOTTLE (49884-604-05)

NDC 49884-0604-05

🏷️ FDA NDC (as labeled) 49884-604-05 billing pads the product segment with a zero

This package

Contains500-count Pack sizes3 compare ↓

Also comes in: 30 tablets 49884-0604-11 100 tablets 49884-0604-01

Rx only Generic Discontinued Non-controlled ⚠ Discontinued by firm

🗂️ Data synced 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 Dr. Brian Staiger, PharmD

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

⚠️

Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. 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

FDA NDC (as labeled) 49884-604-05

Product NDC 49884-604

11-digit billing NDC 49884060405

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

Marketing start 2013-01-18

Marketing end 2026-09-30

Route ORAL

Dosage form TABLET

Substance LAMOTRIGINE

GPI-14 72600040007545

GPI class lamoTRIgine ER

Why two NDCs? The FDA registers this code as 49884-604-05 — 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 → 49884-0604-05. 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.

🏭 Manufacturer & labeler

LabelerPar Health USA, LLC

Application holderPH HEALTH LTD

FDA applicationANDA201791 (ANDA)

Labeler code49884

First marketedJan 2013

Product typeHuman Prescription Drug

Portfolio212 products on file

🔎 All NDCs from Par Health USA, LLC

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.

🩺 Clinical

📖 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

I completely understand the impatience — but the slow ramp-up is one of the most important safety steps with lamotrigine. Going too fast significantly raises your risk of a serious...
Why does my doctor keep telling me to increase my dose so slowly? Can't we just get to the right dose faster?
That's a fair question, and the honest answer is: with lamotrigine, we can't reliably tell in advance which rashes are harmless and which are dangerous. So the rule is — call your...
What kind of rash should I worry about? I get skin reactions from all sorts of things.

📖 Read our full Lamotrigine guide →

Patient education

📘 MedlinePlus patient leaflet ↗

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.

💊 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
UNII 1CS02G8656
Methacrylic acid is a synthetic polymer used as a coating material and binder in tablets and capsules. It helps control how and where the medication releases in the digestive system.
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.

3 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?

Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

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.

💲 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 system	Per each	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly	No Part D plan price is available for this NDC in our data.

ℹ️

No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.

Try another pack size: 30 tablets 100 tablets

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.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Lamotrigine 250 mg 00228-1638-03	Actavis	30 tablets	$1.253	AB	Availability likely	—
Lamotrigine 250 mg 16714-0893-01	NorthStar	30 tablets	$1.253	AB	Availability likely	—
lamotrigine 250 mg 31722-0244-30	Camber	30 tablets	$1.253	AB	Availability likely	—
Lamotrigine 250 mg 65162-0988-03	Amneal	30 tablets	$1.253	AB	Availability likely	—
Lamictal Xr 250 mg 00173-0781-00	GlaxoSmithKline	30 tablets	$44.163	AB	Availability likely	—
Lamotrigine Extended-Release 250 mg 10370-0334-11	Par	30 tablets	—	AB	FDA listed	—
Lamotrigine 250 mg 42291-0447-30	AvKARE	30 tablets	—	AB	FDA listed	—
Lamotrigine 250 mg 46708-0418-30	Alembic	30 tablets	—	AB	FDA listed	—
Lamotrigine Extended Release 250 mgthis 49884-0604-05	Par	500 tablets	—	—	Discontinued	—
Lamotrigine 250 mg 55111-0419-05	Dr.Reddy's	500 tablets	—	AB	FDA listed	—
Lamotrigine 250 mg 62332-0418-30	Alembic	30 tablets	—	AB	FDA listed	—
Lamotrigine 250 mg 68382-0983-05	Zydus	500 tablets	—	AB	FDA listed	—
lamotrigine 250 mg 69117-0048-01	Yiling	30 tablets	—	AB	FDA listed	—
Lamotrigine 250 mg 70771-1518-03	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.

💊 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 tablets49884-0604-11 2,923 Rx · $456,620

100 tablets49884-0604-01 No Medicaid data

500 tablets this page49884-0604-05 No Medicaid data

Drug total (last 4 qtrs): 2,923 Rx · 158,639 units · $456,620 gross reimbursed

Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Lamotrigine extended release — the ingredient across all brands.

Top reported reactions

Seizure4,309

Toxicity To Various Agents3,928

Drug Interaction3,259

Completed Suicide3,074

Fatigue3,000

Dizziness2,988

Nausea2,977

Age at onset

Neonate940

Infant278

Child526

Adolescent460

Adult6,203

Elderly1,270

Reporter sex

Serious outcomes

Hospitalization23,552

Life-threatening4,925

Reports over time (by year) — tap or hover for the count & year

Most recent year is provisional (FAERS lags ~3 months).

Where does this data come from?

Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDC	Description	Per unit	Per pack	Marketing start	Status
49884-0604-01	100 TABLET in 1 BOTTLE (49884-604-01)	—	—	2013-01-18	Discontinued by firm
49884-0604-05 You're viewing this	500 TABLET in 1 BOTTLE (49884-604-05)	—	—	2013-01-18	Discontinued by firm
49884-0604-11	30 TABLET in 1 BOTTLE (49884-604-11)	$1.25 / ea	$37.60	2013-01-18	Active

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

This pack shows little to no recent Medicaid volume — the 30 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 49884-0604-05?

NDC 49884-0604-05 is a 500-count package — 500 tablet in 1 bottle.

What is the difference between NDC 49884-0604-05 and NDC 49884-0604-11?

Both are Lamotrigine Extended Release 250 mg Tablet — the drug itself is identical. NDC 49884-0604-05 is the 500-count package, while NDC 49884-0604-11 is the 30 tablets package.

What NDC number is used to bill for this package of Lamotrigine Extended Release 250 mg Tablet?

Bill NDC 49884-0604-05 — the 11-digit billing format is 49884060405. 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.

🧭 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)	✓ Available
NADAC pharmacy acquisition price (CMS)	— Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
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)	— Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.

“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

Why is there no price listed?

The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.

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 FDA registers it as 49884-604-05, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 49884-0604-05, written without dashes as 49884060405. The Identity section at the top of this page lists every form of this code.

What do the three segments of this NDC mean?

In 49884-0604-05, the first segment (49884) is the labeler code FDA assigned to Par Health USA, LLC; the middle segment (0604) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (05) identifies this exact package size and type. Together they name one specific package of one specific product.

Does this product come in other package sizes?

Yes — the FDA directory lists 2 other package presentations of this same product, including 30 tablets (49884-0604-11), 100 tablets (49884-0604-01). 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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

🚨 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…

💊 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…

🤒 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…

🔄 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 ~2 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…

🤰 Pregnancy ~2 min read ▾

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…

🧒 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…

🧬 Mechanism of Action 212 words ▾

📦 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…

💬 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…

Glossary — plain-language definitions of medical terms used in this label:

contraindicated: Should not be used in that situation, because the risk is considered too high.

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

adjunctive therapy: A medicine added alongside a main treatment to help it work better.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

angioedema: Rapid swelling deep under the skin, often around the eyes, lips, tongue, or throat.

anorexia: Loss of appetite, or not feeling hungry (on a drug label this means reduced appetite, not the eating disorder).

anxiety: A feeling of worry, nervousness, or unease, sometimes along with a racing heart or restlessness.

apnea: A pause or temporary stop in breathing.

aseptic meningitis: Swelling of the membranes around the brain and spinal cord that is not caused by common bacteria.

asthenia: Unusual weakness or lack of physical strength and energy.

ataxia: Loss of muscle coordination that makes walking, balance, and controlled movements clumsy or unsteady.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

clearance: How quickly the body removes a medicine from the blood, usually through the liver and kidneys.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

congenital anomaly: A physical difference or defect that a baby is born with, present from before birth.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

cytochrome P450: A large family of enzymes, mostly in the liver, that break down many medicines so the body can remove them.

depression: A lasting low mood with loss of interest that affects everyday life.

diarrhea: Loose, watery bowel movements that happen more often than normal.

diplopia: Double vision, or seeing two images of a single object.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

dose reduction: Lowering the amount of a medicine, often to ease side effects or fit a person's needs.

double-blind: A study in which neither the patients nor their doctors know who is getting the real medicine and who is getting the dummy.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

emesis: The medical word for vomiting, or bringing up the contents of the stomach through the mouth.

eosinophilia: A higher-than-normal level of eosinophils, a type of white blood cell often linked to allergies or drug reactions.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

extended-release: A pill or capsule made to release its medicine slowly over many hours, so it can be taken less often; often labeled ER or XR.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

glucuronidation: The process where enzymes attach a sugar-like molecule to a drug so it dissolves in water and leaves the body.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

heart failure: A condition in which the heart cannot pump blood as well as it should, causing tiredness, breathlessness, and swelling.

hemodialysis: A treatment that uses a machine to filter waste and extra fluid from the blood when the kidneys cannot.

hemorrhage: Bleeding, especially heavy or uncontrolled bleeding, either inside the body or from an outside wound.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

hepatitis: Inflammation of the liver, which can be caused by infections, alcohol, or certain medicines.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

immediate-release: A standard pill or capsule that releases all of its medicine soon after it is swallowed.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

insomnia: Trouble falling asleep, staying asleep, or getting restful sleep.

irritability: Getting annoyed, frustrated, or angry more easily than usual.

lymphadenopathy: Swollen or enlarged lymph nodes, often felt as lumps in the neck, armpits, or groin.

mania: A period of unusually high energy, racing thoughts, and an excited or irritable mood that is more extreme than normal.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

metabolite: A new substance formed when the body breaks a medicine down.

monotherapy: Treatment using a single medicine by itself.

myalgia: Muscle pain or aching.

narrow therapeutic index: Describes a medicine where the helpful dose and the harmful dose are very close, so small changes in the amount matter a lot.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

nystagmus: Rapid, involuntary back-and-forth movements of the eyes that a person cannot control.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

Overdosage: The label section describing what can happen if too much of a medicine is taken and how it may be treated.

pancytopenia: A low level of all three main blood cell types at once: red cells, white cells, and platelets.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

placebo: An inactive treatment with no real medicine in it, such as a sugar pill, used for comparison in a study.

placebo-controlled: Describes a study that compares people taking the real medicine against people taking a dummy pill with no active ingredient.

plasma concentration: The amount of medicine measured in the liquid part of the blood at a given time.

postpartum: The period of time right after a woman gives birth.

Pregnancy Exposure Registry: A study that collects health information from women who took a medicine while pregnant to learn how safe it is.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

pruritus: Itching of the skin.

randomized: Assigned to a treatment group purely by chance, like a coin flip, so the groups being compared start out fair and similar.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

seizure: A sudden burst of abnormal electrical activity in the brain that can cause shaking, staring, confusion, or loss of awareness.

somnolence: Feeling very sleepy or drowsy, with trouble staying awake during the day.

status epilepticus: A seizure that lasts a long time, or repeated seizures without recovery in between, which is a medical emergency.

Stevens-Johnson syndrome: A rare, serious reaction causing painful blistering and peeling of the skin and the moist linings of the mouth, eyes, and other areas.

suicidal behavior: Actions a person takes to try to end their own life, or steps taken in preparation for it.

syncope: The medical term for fainting, a brief loss of consciousness from a temporary drop in blood flow to the brain.

taper: Gradually lowering a dose in steps before stopping, rather than quitting all at once.

therapeutic index: A measure of how much room there is between a helpful dose of a medicine and a dose that could be harmful.

thrombocytopenia: A low level of platelets, the blood cells that help form clots, which can lead to easier bruising or bleeding.

titration: Slowly adjusting a medicine's dose up or down in small steps to find the amount that works best with the fewest side effects.

toxic epidermal necrolysis: A rare, life-threatening reaction in which large areas of the top layer of skin blister and peel away, like a severe burn.

transporter: A protein that moves drugs across cell membranes, carrying them either into or out of cells.

tremor: Shaking or trembling of part of the body, such as the hands, that a person cannot control.

trimester: One of the three roughly three-month stages that a pregnancy is divided into.

UGT: A family of enzymes that attach a sugar-like molecule to a drug, making it easier for the body to remove.

ulceration: The forming of an open sore on the skin or on a lining inside the body, such as the stomach.

urticaria: Raised, itchy welts on the skin, commonly called hives.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

vertigo: A spinning sensation that makes you feel like you or the room around you is moving.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

withdrawal: Uncomfortable physical or mental symptoms that appear when a medicine the body has gotten used to is reduced or stopped.

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

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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.

Lamotrigine Extended Release 250 mg Tablet, 500-count

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