LAMICTAL XR- lamotrigine tablet, film coated, extended release LAMICTAL XR- lamotrigine kit

United States - English - NLM (National Library of Medicine)

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Active ingredient:
LAMOTRIGINE (UNII: U3H27498KS) (LAMOTRIGINE - UNII:U3H27498KS)
Available from:
GlaxoSmithKline LLC
INN (International Name):
LAMOTRIGINE
Composition:
LAMOTRIGINE 25 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
LAMICTAL XR is indicated as adjunctive therapy for primary generalized tonic-clonic (PGTC) seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. LAMICTAL XR is indicated for conversion to monotherapy in patients aged 13 years and older with partial-onset seizures who are receiving treatment with a single antiepileptic drug (AED). Safety and effectiveness of LAMICTAL XR have not been established (1) as initial monotherapy or (2) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. Safety and effectiveness of LAMICTAL XR for use in patients younger than 13 years have not been established. LAMICTAL XR 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)] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy ou
Product summary:
LAMICTAL XR (lamotrigine) extended-release tablets 25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 25”, unit-of-use bottles of 30 with orange caps (NDC 0173-0754-00). 50-mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 50”, unit-of-use bottles of 30 with orange caps (NDC 0173-0755-00). 100-mg, orange with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 100”, unit-of-use bottles of 30 with orange caps (NDC 0173-0756-00). 200-mg, blue with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 200”, unit-of-use bottles of 30 with orange caps (NDC 0173-0757-00). 250-mg, purple with a white center, caplet-shaped, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 250”, unit-of-use bottles of 30 with orange caps (NDC 0173-0781-00). 300-mg, gray with a white center, caplet-shaped, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 300”, unit-of-use bottles of 30 with orange caps (NDC 0173-0761-00). LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Taking Valproate (Blue XR Kit) 25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 25” and 50 mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 50”; blister pack of 21/25-mg tablets and 7/50-mg tablets (NDC 0173-0758-00). LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Taking Carbamazepine, Phenytoin, Phenobarbital, or Primidone, and Not Taking Valproate (Green XR Kit) 50-mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 50”; 100 mg, orange with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 100”; and 200 mg, blue with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 200”; blister pack of 14/50-mg tablets, 14/100-mg tablets, and 7/200-mg tablets (NDC 0173-0759-00). LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Not Taking Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate (Orange XR Kit) 25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 25”; 50 mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 50”; and 100 mg, orange with a white center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and “XR 100”; blister pack of 14/25-mg tablets, 14/50-mg tablets, and 7/100-mg tablets (NDC 0173-0760-00). Storage Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Authorization status:
New Drug Application
Authorization number:
0173-0754-00, 0173-0755-00, 0173-0756-00, 0173-0757-00, 0173-0758-00, 0173-0759-00, 0173-0760-00, 0173-0761-00, 0173-0781-00

LAMICTAL XR- lamotrigine

GlaxoSmithKline LLC

----------

MEDICATION GUIDE

LAMICTAL (la-MIK-tal) XR (lamotrigine) extended-release tablets

What is the most important information I should know about LAMICTAL XR?

LAMICTAL XR may cause a serious skin rash that may cause you to be hospitalized or even cause

death.

There is no way to tell if a mild rash will become more serious. A serious skin rash can happen at any

time during your treatment with LAMICTAL XR, but is more likely to happen within the first 2 to 8

weeks of treatment. Children aged between 2 and 16 years have a higher chance of getting this serious

skin rash while taking LAMICTAL XR. LAMICTAL XR is not approved for use in children younger

than 13 years.

The risk of getting a serious skin rash is higher if you:

take LAMICTAL XR while taking valproate [DEPAKENE (valproic acid) or DEPAKOTE

(divalproex sodium)].

take a higher starting dose of LAMICTAL XR than your healthcare provider prescribed.

increase your dose of LAMICTAL XR faster than prescribed.

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 LAMICTAL XR.

Other serious reactions, including serious blood problems or liver problems. LAMICTAL XR 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

weakness, fatigue

yellowing of your skin or the white part of your eyes

Like other antiepileptic drugs, LAMICTAL XR 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 LAMICTAL XR without first talking to a healthcare provider.

Stopping LAMICTAL XR suddenly can cause serious problems.

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal

thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions in myself or a family member?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about

symptoms.

LAMICTAL XR may cause aseptic meningitis, a serious inflammation of the protective membrane

that covers the brain and spinal cord.

Call your healthcare provider right away if you have any of the following symptoms:

headache

fever

nausea

vomiting

stiff neck

rash

unusual sensitivity to light

muscle pains

chills

confusion

drowsiness

Meningitis has many causes other than LAMICTAL XR, which your doctor would check for if you

developed meningitis while taking LAMICTAL XR.

LAMICTAL XR can cause other serious side effects. For more information ask your healthcare

provider or pharmacist. Tell your healthcare provider if you have any side effect that bothers you. Be

sure to read the section below entitled “What are the possible side effects of LAMICTAL XR?”

People prescribed LAMICTAL XR have sometimes been given the wrong medicine because many

medicines have names similar to LAMICTAL XR, so always check that you receive LAMICTAL XR.

Taking the wrong medication can cause serious health problems. When your healthcare provider gives

you a prescription for LAMICTAL XR:

Make sure you can read it clearly.

Talk to your pharmacist to check that you are given the correct medicine.

Each time you fill your prescription, check the tablets you receive against the pictures of the

tablets below.

These pictures show the distinct wording, colors, and shapes of the tablets that help to identify the

right strength of LAMICTAL XR. Immediately call your pharmacist if you receive a LAMICTAL XR

tablet that does not look like one of the tablets shown below, as you may have received the wrong

medication.

LAMICTAL XR (lamotrigine) extended-release tablets

25 mg, yellow

with white center

Imprinted with

LAMICTAL

XR 25

50 mg, green

with white center

Imprinted with

LAMICTAL

XR 50

100 mg, orange

with white center

Imprinted with

LAMICTAL

XR 100

200 mg, blue

with white center

Imprinted with

LAMICTAL

XR 200

250 mg, purple

with white center

Imprinted with

LAMICTAL

XR 250

300 mg, gray

with white center

Imprinted with

LAMICTAL

XR 300

What is LAMICTAL XR?

LAMICTAL XR is a prescription medicine used:

together with other medicines to treat primary generalized tonic-clonic seizures and partial-onset

seizures in people aged 13 years and older.

alone when changing from 1 other medicine used to treat partial-onset seizures in people aged 13

years and older.

It is not known if LAMICTAL XR is safe or effective in children younger than 13 years. Other forms

of LAMICTAL can be used in children aged 2 to 12 years.

It is not known if LAMICTAL XR is safe or effective when used alone as the first treatment of

seizures.

Do not take LAMICTAL XR:

if you have had an allergic reaction to lamotrigine or to any of the inactive ingredients in LAMICTAL

XR. See the end of this leaflet for a complete list of ingredients in LAMICTAL XR.

Before taking LAMICTAL XR, tell your healthcare provider about all of your health conditions, including if

you:

have had a rash or allergic reaction to another antiseizure medicine.

have or have had depression, mood problems, or suicidal thoughts or behavior.

have had aseptic meningitis after taking LAMICTAL (lamotrigine) or LAMICTAL XR.

are taking oral contraceptives (birth control pills) or other female hormonal medicines. Do not start or

stop taking birth control pills or other female hormonal medicine until you have talked with your

healthcare provider. Tell your healthcare provider if you have any changes in your menstrual pattern

such as breakthrough bleeding. Stopping these medicines while you are taking LAMICTAL XR may

cause side effects (such as dizziness, lack of coordination, or double vision). Starting these medicines

may lessen how well LAMICTAL XR works.

are pregnant or plan to become pregnant. It is not known if LAMICTAL XR may harm your unborn

baby. If you become pregnant while taking LAMICTAL XR, talk to your healthcare provider about

registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this

registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the

safety of antiepileptic drugs during pregnancy.

are breastfeeding. LAMICTAL XR passes into breast milk and may cause side effects in a breastfed

baby. If you breastfeed while taking LAMICTAL XR, watch your baby closely for trouble breathing,

episodes of temporarily stopping breathing, sleepiness, or poor sucking. Call your baby’s healthcare

provider right away if you see any of these problems. Talk to your healthcare provider about the best

way to feed your baby if you take LAMICTAL XR.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter

medicines, vitamins, and herbal supplements. LAMICTAL XR and certain other medicines may interact

with each other. This may cause serious side effects.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when

you get a new medicine.

How should I take LAMICTAL XR?

Take LAMICTAL XR exactly as prescribed.

Your healthcare provider may change your dose. Do not change your dose without talking to your

healthcare provider.

Do not stop taking LAMICTAL XR without talking to your healthcare provider. Stopping

LAMICTAL XR suddenly may cause serious problems. For example, if you have epilepsy and you

stop taking LAMICTAL XR suddenly, you may have seizures that do not stop. Talk with your

healthcare provider about how to stop LAMICTAL XR slowly.

If you miss a dose of LAMICTAL XR, take it as soon as you remember. If it is almost time for your

next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the

same time.

If you take too much LAMICTAL XR, call your healthcare provider or your local Poison Control

Center or go to the nearest hospital emergency room right away.

You may not feel the full effect of LAMICTAL XR for several weeks.

If you have epilepsy, tell your healthcare provider if your seizures get worse or if you have any new

types of seizures.

LAMICTAL XR can be taken with or without food.

Do not chew, crush, or divide LAMICTAL XR.

Swallow LAMICTAL XR tablets whole.

If you have trouble swallowing LAMICTAL XR tablets, tell your healthcare provider because there

may be another form of LAMICTAL you can take.

If you receive LAMICTAL XR in a blister pack, examine the blister pack before use. Do not use if

blisters are torn, broken, or missing.

What should I avoid while taking LAMICTAL XR?

Do not drive, operate machinery, or do other dangerous activities until you know how LAMICTAL XR

affects you.

What are the possible side effects of LAMICTAL XR?

LAMICTAL XR can cause serious side effects.

See “What is the most important information I should know about LAMICTAL XR?”

Common side effects of LAMICTAL XR include:

dizziness vomiting

tremor trouble with balance and coordination

double vision anxiety

nausea

Other common side effects that have been reported with another form of LAMICTAL include headache,

sleepiness, blurred vision, runny nose, and rash.

These are not all the possible side effects of LAMICTAL XR.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-

1088.

How should I store LAMICTAL XR?

Store LAMICTAL XR at room temperature between 59°F and 86°F (15°C and 30°C).

Keep LAMICTAL XR and all medicines out of the reach of children.

General information about the safe and effective use of LAMICTAL XR.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

LAMICTAL XR for a condition for which it was not prescribed. Do not give LAMICTAL XR to other

people, even if they have the same symptoms that you have. It may harm them.

If you take a urine drug screening test, LAMICTAL XR may make the test result positive for another drug.

If you require a urine drug screening test, tell the healthcare professional administering the test that you are

taking LAMICTAL XR.

You can ask your healthcare provider or pharmacist for information about LAMICTAL XR that is written

for health professionals.

What are the ingredients in LAMICTAL XR?

Active ingredient: lamotrigine.

Inactive ingredients: glycerol monostearate, hypromellose, lactose monohydrate, magnesium stearate,

methacrylic acid copolymer dispersion, polyethylene glycol 400, polysorbate 80, silicon dioxide (25- and

50-mg tablets only), titanium dioxide, triethyl citrate, carmine (250-mg tablet only), iron oxide black (50-,

250-, and 300-mg tablets only), iron oxide yellow (25-, 50-, and 100-mg tablets only), iron oxide red (100-

mg tablet only), FD&C Blue No. 2 Aluminum Lake (200- and 250-mg tablets only). Tablets are printed with

edible black ink.

For more information about LAMICTAL XR, call 1-888-825-5249.

LAMICTAL XR is a trademark owned by or licensed to the GSK group of companies. The other brands

listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to the

GSK group of companies. The makers of these brands are not affiliated with and do not endorse the GSK

group of companies or its products.

Distributed by GlaxoSmithKline, Research Triangle Park, NC 27709

©2019 GSK group of companies or its licensor.

LXR:18MG

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised:

August 2019

Revised: 9/2019

Document Id: c81a4880-a40c-426a-8fb8-b4651d8a2132

34391-3

Set id: 3e2c9a35-6a39-41d7-ad84-3c0bb8894b09

Version: 32

Effective Time: 20190925

GlaxoSmithKline LLC

LAMICTAL XR- lamotrigine tablet, film coated, extended release

LAMICTAL XR- lamotrigine

GlaxoSmithKline LLC

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use LAMICTAL XR safely and effectively. See

full prescribing information for LAMICTAL XR.

LAMICTAL XR (lamotrigine) extended-release tablets, for oral use

Initial U.S. Approval: 1994

WARNING: SERIOUS SKIN RASHES

See full prescribing information for complete boxed warning.

RECENT MAJOR CHANGES

Warnings and Precautions, Hemophagocytic Lymphohistiocytosis (5.2)

8/2019

INDICATIONS AND USAGE

LAMICTAL XR is indicated for:

Limitation of use: Safety and effectiveness in patients younger than 13 years have not been established. (1.3)

DOSAGE AND ADMINISTRATION

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

inc lude :

coadministration with valproate.

exceeding recommended initial dose of LAMICTAL XR.

exceeding recommended dose escalation for LAMICTAL XR. (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. LAMICTAL XR should be discontinued at the first sign of

rash, unless the rash is clearly not drug related. (5.1)

adjunctive therapy for primary generalized tonic-clonic seizures 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. (1.2)

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 LAMICTAL XR: The initial dose of LAMICTAL XR 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 LAMICTAL XR 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 oral

contraceptives. (2.1, 5.8)

DOSAGE FORMS AND STRENGTHS

Extended-release tablets: 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, and 300 mg. (3.1, 16)

CONTRAINDICATIONS

Hypersensitivity to the drug or its ingredients. (Boxed Warning, 4)

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-

FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: SERIOUS SKIN RASHES

Discontinuation: Taper over a period of at least 2 weeks (approximately 50% dose reduction per week). (2.1, 5.9)

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 LAMICTAL XR if an alternative etiology is not established.

(5.2)

Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as drug reaction

with eosinophilia and systemic symptoms, may be fatal or life threatening. Early signs may include rash, fever, and

lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic

failure, blood dyscrasias, or acute multiorgan failure. LAMICTAL XR should be discontinued if alternate etiology for

this reaction is not found. (5.3)

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. (5.4)

Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors. (5.5)

Aseptic meningitis: Monitor for signs of meningitis. (5.6)

Medication errors due to product name confusion: Strongly advise patients to visually inspect tablets to verify the

received drug is correct. (5.7, 16, 17)

Most common adverse reactions with use as adjunctive therapy (treatment difference between LAMICTAL XR 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 LAMICTAL XR. (6.1)

Valproate increases lamotrigine concentrations more than 2-fold. (7, 12.3)

Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by

approximately 40%. (7, 12.3)

Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%. (7, 12.3)

Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50%

and 32%, respectively. (7, 12.3)

Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended (7,

12.3)

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)

1 INDICATIONS AND USAGE

1.1 Adjunctive Therapy

1.2 Monotherapy

1.3 Limitation of Use

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Considerations

2.2 Adjunctive Therapy for Primary Generalized Tonic-Clonic and Partial-Onset Seizures

2.3 Conversion from Adjunctive Therapy to Monotherapy

2.4 Conversion from Immediate-Release Lamotrigine Tablets to LAMICTAL XR

3 DOSAGE FORMS AND STRENGTHS

3.1 Extended-Release Tablets

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Serious Skin Rashes [see Boxed Warning]

5.2 Hemophagocytic Lymphohistiocytosis

5.3 Multiorgan Hypersensitivity Reactions and Organ Failure

5.4 Blood Dyscrasias

5.5 Suicidal Behavior and Ideation

5.6 Aseptic Meningitis

5.7 Potential Medication Errors

5.8 Concomitant Use with Oral Contraceptives

5.9 Withdrawal Seizures

5.10 Status Epilepticus

5.11 Sudden Unexplained Death in Epilepsy (SUDEP)

5.12 Addition of LAMICTAL XR to a Multidrug Regimen that Includes Valproate

5.13 Binding in the Eye and Other Melanin-Containing Tissues

5.14 Laboratory Tests

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience with LAMICTAL XR for Treatment of Primary Generalized Tonic-

Clonic and Partial-Onset Seizures

6.2 Other Adverse Reactions Observed during the Clinical Development of Immediate-Release

Lamotrigine

6.3 Postmarketing Experience with Immediate-Release Lamotrigine

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

10 OVERDOSAGE

10.1 Human Overdose Experience

10.2 Management of Overdose

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures

14.2 Adjunctive Therapy for Partial-Onset Seizures

14.3 Conversion to Monotherapy for Partial-Onset Seizures

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

WARNING: SERIOUS SKIN RASHES

LAMICTAL XR can cause serious rashes requiring hospitalization and discontinuation of

treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome,

is approximately 0.8% (8 per 1,000) in pediatric patients (aged 2 to 16 years) receiving

immediate-release lamotrigine as adjunctive therapy for epilepsy and 0.3% (3 per 1,000) in

adults on adjunctive therapy for epilepsy. In a prospectively followed cohort of 1,983

pediatric patients (aged 2 to 16 years) with epilepsy taking adjunctive immediate-release

lamotrigine, there was 1 rash-related death. LAMICTAL XR is not approved for patients

younger than 13 years. In worldwide postmarketing experience, rare cases of toxic

epidermal necrolysis and/or rash-related death have been reported in adult and pediatric

patients, but their numbers are too few to permit a precise estimate of the rate.

The risk of serious rash caused by treatment with LAMICTAL XR is not expected to differ

from that with immediate-release lamotrigine. However, the relatively limited treatment

experience with LAMICTAL XR makes it difficult to characterize the frequency and risk of

serious rashes caused by treatment with LAMICTAL XR.

Other than age, there are as yet no factors identified that are known to predict the risk of

occurrence or the severity of rash caused by LAMICTAL XR. There are suggestions, yet

to be proven, that the risk of rash may also be increased by (1) coadministration of

LAMICTAL XR with valproate (includes valproic acid and divalproex sodium), (2)

exceeding the recommended initial dose of LAMICTAL XR, or (3) exceeding the

recommended dose escalation for LAMICTAL XR. 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 LAMICTAL XR, it is not possible to predict

reliably which rashes will prove to be serious or life threatening. Accordingly, LAMICTAL

XR 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)].

1 INDICATIONS AND USAGE

1.1 Adjunctive Therapy

LAMICTAL XR is indicated as adjunctive therapy for primary generalized tonic-clonic (PGTC)

seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years

Sections or subsections omitted from the full prescribing information are not listed.

and older.

1.2 Monotherapy

LAMICTAL XR is indicated for conversion to monotherapy in patients aged 13 years and older with

partial-onset seizures who are receiving treatment with a single antiepileptic drug (AED).

Safety and effectiveness of LAMICTAL XR have not been established (1) as initial monotherapy or (2)

for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.

1.3 Limitation of Use

Safety and effectiveness of LAMICTAL XR for use in patients younger than 13 years have not been

established.

2 DOSAGE AND ADMINISTRATION

LAMICTAL XR extended-release tablets are taken once daily, with or without food. Tablets must be

swallowed whole and must not be chewed, crushed, or divided.

2.1 General Dosing Considerations

Rash

There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be

increased by (1) coadministration of LAMICTAL XR with valproate, (2) exceeding the recommended

initial dose of LAMICTAL XR, or (3) exceeding the recommended dose escalation for LAMICTAL

XR. 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 LAMICTAL XR is exceeded and in patients with a history of allergy or rash to

other AEDs.

LAMICTAL XR Patient Titration Kits provide LAMICTAL XR at doses consistent with the

recommended titration schedule for the first 5 weeks of treatment, based upon concomitant medications,

for patients with partial-onset seizures and are intended to help reduce the potential for rash. The use of

LAMICTAL XR Patient Titration Kits is recommended for appropriate patients who are starting or

restarting LAMICTAL XR [see How Supplied/Storage and Handling (16)].

It is recommended that LAMICTAL XR 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 LAMICTAL XR, 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)].

LAMICTAL XR 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 oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir.

Valproate inhibits glucuronidation. For dosing considerations for LAMICTAL XR in patients on

estrogen-containing contraceptives and atazanavir/ritonavir, see below and Table 5. For dosing

considerations for LAMICTAL XR 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 of

LAMICTAL XR should be based on therapeutic response [see Clinical Pharmacology (12.3)].

Women Taking Estrogen-Containing Oral Contraceptives

Starting LAMICTAL XR in Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-

containing oral contraceptives have been shown to increase the clearance of lamotrigine [see Clinical

Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for LAMICTAL

XR should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore,

dose escalation should follow the recommended guidelines for initiating adjunctive therapy with

LAMICTAL XR based on the concomitant AED or other concomitant medications (see Table 1). See

below for adjustments to maintenance doses of LAMICTAL XR in women taking estrogen-containing

oral contraceptives.

Adjustments to the Maintenance Dose of LAMICTAL XR in Women Taking Estrogen-Containing Oral

Contraceptives:

(1) Taking Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin,

phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir

and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical

Pharmacology (12.3)], the maintenance dose of LAMICTAL XR will in most cases need to be increased

by as much as 2-fold over the recommended target maintenance dose to maintain a consistent lamotrigine

plasma level.

(2) Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of LAMICTAL XR

and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and

the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine

glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in

most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level.

The dose increases should begin at the same time that the oral contraceptive is introduced and continue,

based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should

not exceed the recommended rate (see Table 1) unless lamotrigine plasma levels or clinical response

support larger increases. Gradual transient increases in lamotrigine plasma levels may occur during the

week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose

increases are made in the days before or during the week of inactive hormonal preparation. Increased

lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and

diplopia. If adverse reactions attributable to LAMICTAL XR consistently occur during the pill-free

week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to

the pill-free week are not recommended. For women taking LAMICTAL XR in addition to

carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease

inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug

Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of LAMICTAL XR should be

necessary.

(3) Stopping Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin,

phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir

and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical

Pharmacology (12.3)], the maintenance dose of LAMICTAL XR will in most cases need to be decreased

by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of

LAMICTAL XR should not exceed 25% of the total daily dose per week over a 2-week period, unless

clinical response or lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. In

women taking LAMICTAL XR in addition to carbamazepine, phenytoin, phenobarbital, primidone, or

other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that

induce lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no

adjustment to the dose of LAMICTAL XR should be necessary.

adjustment to the dose of LAMICTAL XR should be necessary.

Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy

The effect of other hormonal contraceptive preparations or hormone replacement therapy on the

pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that

ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the

progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of

LAMICTAL XR in the presence of progestogens alone will likely not be needed.

Patients Taking Atazanavir/Ritonavir

While atazanavir/ritonavir does reduce the lamotrigine plasma concentration, no adjustments to the

recommended dose-escalation guidelines for LAMICTAL XR should be necessary solely based on the

use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines for initiating

adjunctive therapy with LAMICTAL XR based on concomitant AED or other concomitant medications

(see Tables 1 and 5). In patients already taking maintenance doses of LAMICTAL XR and not taking

glucuronidation inducers, the dose of LAMICTAL XR may need to be increased if atazanavir/ritonavir

is added or decreased if atazanavir/ritonavir is discontinued [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment

Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24

subjects with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical

Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is

needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally

be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites

and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be

adjusted according to clinical response.

Patients with Renal Impairment

Initial doses of LAMICTAL XR should be based on patients’ concomitant medications (see Table 1);

reduced maintenance doses may be effective for patients with significant renal impairment [see Use in

Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have

been evaluated during chronic treatment with immediate-release lamotrigine. Because there is

inadequate experience in this population, LAMICTAL XR should be used with caution in these patients.

Discontinuation Strategy

For patients receiving LAMICTAL XR in combination with other AEDs, a re-evaluation of all AEDs in

the regimen should be considered if a change in seizure control or an appearance or worsening of

adverse reactions is observed.

If a decision is made to discontinue therapy with LAMICTAL XR, a step-wise reduction of dose over

at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more

rapid withdrawal [see Warnings and Precautions (5.9)].

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and

the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine

glucuronidation should prolong the half-life of lamotrigine; discontinuing valproate should shorten the

half-life of lamotrigine.

2.2 Adjunctive Therapy for Primary Generalized Tonic-Clonic and Partial-Onset Seizures

This section provides specific dosing recommendations for patients aged 13 years and older. Specific

dosing recommendations are provided depending upon concomitant AEDs or other concomitant

medications.

Table 1. Escalation Regimen for LAMICTAL XR in Patients Aged 13 Years and Older

Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of

lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)].

Drugs that induce lamotrigine glucuronidation and increase clearance, other than the specified

antiepileptic drugs, include estrogen-containing oral contraceptives, rifampin, and the protease

inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Dosing recommendations for oral contraceptives

and the protease inhibitor atazanavir/ritonavir can be found in General Dosing Considerations [see

Dosage and Administration (2.1)]. Patients on rifampin and the protease inhibitor lopinavir/ritonavir

should follow the same dosing titration/maintenance regimen used with antiepileptic drugs that induce

glucuronidation and increase clearance [see Dosage and Administration (2.1), Drug Interactions (7),

Clinical Pharmacology (12.3)].

Dose increases at week 8 or later should not exceed 100 mg daily at weekly intervals.

In Patients TAKING

Valproate

In Patients NOT

TAKING

Carbamazepine,

Phenytoin,

Phenobarbital,

Primidone,

or

Valproate

In Patients TAKING

Carbamazepine,

Phenytoin,

Phenobarbital, or

Primidone and NOT

TAKING Valproate

Weeks 1 and 2

25 mg every other day

25 mg every day

50 mg every day

Weeks 3 and 4

25 mg every day

50 mg every day

100 mg every day

Week 5

50 mg every day

100 mg every day

200 mg every day

Week 6

100 mg every day

150 mg every day

300 mg every day

Week 7

150 mg every day

200 mg every day

400 mg every day

Maintenance range (week

8 and onward)

200 to 250 mg

every day

300 to 400 mg

every day

400 to 600 mg

every day

2.3 Conversion from Adjunctive Therapy to Monotherapy

The goal of the transition regimen is to attempt to maintain seizure control while mitigating the risk of

serious rash associated with the rapid titration of LAMICTAL XR.

To avoid an increased risk of rash, the recommended maintenance dosage range of LAMICTAL XR as

monotherapy is 250 to 300 mg given once daily.

The recommended initial dose and subsequent dose escalations for LAMICTAL XR should not be

exceeded [see Boxed Warning].

Conversion from Adjunctive Therapy with Carbamazepine, Phenytoin, Phenobarbital, or Primidone to

Monotherapy with LAMICTAL XR

After achieving a dose of 500 mg/day of LAMICTAL XR using the guidelines in Table 1, the

concomitant enzyme-inducing AED should be withdrawn by 20% decrements each week over a 4-week

period. Two weeks after completion of withdrawal of the enzyme-inducing AED, the dosage of

LAMICTAL XR may be decreased no faster than 100 mg/day each week to achieve the monotherapy

maintenance dosage range of 250 to 300 mg/day.

The regimen for the withdrawal of the concomitant AED is based on experience gained in the

controlled monotherapy clinical trial using immediate-release lamotrigine.

Conversion from Adjunctive Therapy with Valproate to Monotherapy with LAMICTAL XR

The conversion regimen involves the 4 steps outlined in Table 2.

Table 2. Conversion from Adjunctive Therapy with Valproate to Monotherapy with LAMICTAL

XR in Patients Aged 13 Years and Older with Epilepsy

a

b

a

b

a

LAMICTAL XR

Valproate

Step 1

Achieve a dose of 150 mg/day according to

guidelines in Table 1.

Maintain established stable dose.

Step 2

Maintain at 150 mg/day.

Decrease dose by decrements no greater than

500 mg/day/week to 500 mg/day and then

maintain for 1 week.

Step 3

Increase to 200 mg/day.

Simultaneously decrease to 250 mg/day and

maintain for 1 week.

Step 4

Increase to 250 or 300 mg/day.

Discontinue.

Conversion from Adjunctive Therapy with Antiepileptic Drugs other than Carbamazepine, Phenytoin,

Phenobarbital, Primidone, or Valproate to Monotherapy with LAMICTAL XR

After achieving a dosage of 250 to 300 mg/day of LAMICTAL XR using the guidelines in Table 1, the

concomitant AED should be withdrawn by 20% decrements each week over a 4-week period. No

adjustment to the monotherapy dose of LAMICTAL XR is needed.

2.4 Conversion from Immediate-Release Lamotrigine Tablets to LAMICTAL XR

Patients may be converted directly from immediate-release lamotrigine to LAMICTAL XR extended-

release tablets. The initial dose of LAMICTAL XR should match the total daily dose of immediate-

release lamotrigine. However, some subjects on concomitant enzyme-inducing agents may have lower

plasma levels of lamotrigine on conversion and should be monitored [see Clinical Pharmacology (12.3)].

Following conversion to LAMICTAL XR, all patients (but especially those on drugs that induce

lamotrigine glucuronidation) should be closely monitored for seizure control [see Drug Interactions

(7)]. Depending on the therapeutic response after conversion, the total daily dose may need to be

adjusted within the recommended dosing instructions (see Table 1).

3 DOSAGE FORMS AND STRENGTHS

3.1 Extended-Release Tablets

25-mg, yellow with white center, round, biconvex, film-coated tablets printed with “LAMICTAL” and

“XR 25.”

50-mg, green with white center, round, biconvex, film-coated tablets printed with “LAMICTAL” and

“XR 50.”

100-mg, orange with white center, round, biconvex, film-coated tablets printed with “LAMICTAL” and

“XR 100.”

200-mg, blue with white center, round, biconvex, film-coated tablets printed with “LAMICTAL” and

“XR 200.”

250-mg, purple with white center, caplet-shaped, film-coated tablets printed with “LAMICTAL” and

“XR 250.”

300-mg, gray with white center, caplet-shaped, film-coated tablets printed with “LAMICTAL” and “XR

300.”

4 CONTRAINDICATIONS

LAMICTAL XR 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)].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Skin Rashes [see Boxed Warning]

The risk of serious rash caused by treatment with LAMICTAL XR is not expected to differ from that

with immediate-release lamotrigine [see Boxed Warning]. However, the relatively limited treatment

experience with LAMICTAL XR makes it difficult to characterize the frequency and risk of serious

rashes caused by treatment with LAMICTAL XR.

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, one 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.

LAMICTAL XR 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 a precise estimate of the rate.

Among the rashes leading to hospitalization were Stevens-Johnson syndrome, toxic epidermal

necrolysis, angioedema, and those associated with multiorgan hypersensitivity [see Warnings and

Precautions (5.3)].

There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious,

potentially life-threatening rash in adults. Specifically, of 584 patients administered immediate-release

lamotrigine with valproate in epilepsy clinical trials, 6 (1%) were hospitalized in association with rash;

in contrast, 4 (0.16%) of 2,398 clinical trial patients and volunteers administered immediate-release

lamotrigine in the absence of valproate were hospitalized.

Patients with History of Allergy or Rash to Other Antiepileptic Drugs

The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of

dose escalation for LAMICTAL XR is exceeded and in patients with a history of allergy or rash to

other AEDs.

5.2 Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) has occurred in pediatric and adult patients taking

LAMICTAL XR for various indications. HLH is a life-threatening syndrome of pathologic immune

activation characterized by clinical signs and symptoms of extreme systemic inflammation. It is

associated with high mortality rates if not recognized early and treated. Common findings include fever,

hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin,

hypertriglyceridemia, and liver function and coagulation abnormalities. In cases of HLH reported with

LAMICTAL XR, patients have presented with signs of systemic inflammation (fever, rash,

hepatosplenomegaly, and organ system dysfunction) and blood dyscrasias. Symptoms have been

reported to occur within 8 to 24 days following the initiation of treatment. Patients who develop early

manifestations of pathologic immune activation should be evaluated immediately, and a diagnosis of

HLH should be considered. LAMICTAL XR should be discontinued if an alternative etiology for the

signs or symptoms cannot be established.

5.3 Multiorgan Hypersensitivity Reactions and Organ Failure

Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic

symptoms (DRESS), have occurred with lamotrigine. Some have been fatal or life threatening. DRESS

typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association

with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities,

myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present.

This disorder is variable in its expression and other organ systems not noted here may be involved.

Fatalities associated with acute multiorgan failure and various degrees of hepatic failure have been

reported in 2 of 3,796 adult patients and 4 of 2,435 pediatric patients who received lamotrigine in

epilepsy clinical trials. Rare fatalities from multiorgan failure have also been reported in postmarketing

use.

Isolated liver failure without rash or involvement of other organs has also been reported with

lamotrigine.

It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be

present even though a rash is not evident. If such signs or symptoms are present, the patient should be

evaluated immediately. LAMICTAL XR should be discontinued if an alternative etiology for the signs

or symptoms cannot be established.

Prior to initiation of treatment with LAMICTAL XR, the patient should be instructed that a rash or other

signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical

event and that the patient should report any such occurrence to a healthcare provider immediately.

5.4 Blood Dyscrasias

There have been reports of blood dyscrasias with immediate-release lamotrigine that may or may not be

associated with multiorgan hypersensitivity (also known as DRESS) [see Warnings and Precautions

(5.3)]. These have included neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and,

rarely, aplastic anemia and pure red cell aplasia.

5.5 Suicidal Behavior and Ideation

AEDs, including LAMICTAL XR, increase the risk of suicidal thoughts or behavior in patients taking

these drugs for any indication. Patients treated with any AED for any indication should be monitored for

the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes

in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (monotherapy and adjunctive therapy) of 11

different AEDs showed that patients randomized to 1 of the AEDs had approximately twice the risk

(adjusted Relative Risk 1.8, 95% CI: 1.2, 2.7) of suicidal thinking or behavior compared with patients

randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated

incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared

with 0.24% among 16,029 placebo-treated patients, representing an increase of approximately 1 case of

suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated

patients in the trials and none in placebo-treated patients, but the number of events is too small to allow

any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after

starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials

included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior

beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.

The finding of increased risk with AEDs of varying mechanism of action and across a range of

indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary

substantially by age (5 to 100 years) in the clinical trials analyzed.

Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis

Indication

Placebo Patients

with Events per

1,000 Patients

Drug Patients

with Events per

1,000 Patients

Relative Risk:

Incidence of Events

in Drug Patients/

Incidence in

Placebo Patients

Risk Difference:

Additional Drug Patients

with Events per 1,000

Patients

Epilepsy

Psychiatric

Other

Total

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in

clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the

epilepsy and psychiatric indications.

Anyone considering prescribing LAMICTAL XR or any other AED must balance the risk of suicidal

thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which

AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of

suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the

prescriber needs to consider whether the emergence of these symptoms in any given patient may be

related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal

thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of

the signs and symptoms of depression, any unusual changes in mood or behavior, the emergence of

suicidal thoughts or suicidal behavior, or thoughts about self-harm. Behaviors of concern should be

reported immediately to healthcare providers.

5.6 Aseptic Meningitis

Therapy with lamotrigine increases the risk of developing aseptic meningitis. Because of the potential

for serious outcomes of untreated meningitis due to other causes, patients should also be evaluated for

other causes of meningitis and treated as appropriate.

Postmarketing cases of aseptic meningitis have been reported in pediatric and adult patients taking

lamotrigine for various indications. Symptoms upon presentation have included headache, fever, nausea,

vomiting, and nuchal rigidity. Rash, photophobia, myalgia, chills, altered consciousness, and

somnolence were also noted in some cases. Symptoms have been reported to occur within 1 day to one

and a half months following the initiation of treatment. In most cases, symptoms were reported to

resolve after discontinuation of lamotrigine. Re-exposure resulted in a rapid return of symptoms (from

within 30 minutes to 1 day following re-initiation of treatment) that were frequently more severe. Some

of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of

systemic lupus erythematosus or other autoimmune diseases.

Cerebrospinal fluid (CSF) analyzed at the time of clinical presentation in reported cases was

characterized by a mild to moderate pleocytosis, normal glucose levels, and mild to moderate increase

in protein. CSF white blood cell count differentials showed a predominance of neutrophils in a majority

of the cases, although a predominance of lymphocytes was reported in approximately one third of the

cases. Some patients also had new onset of signs and symptoms of involvement of other organs

(predominantly hepatic and renal involvement), which may suggest that in these cases the aseptic

meningitis observed was part of a hypersensitivity reaction [see Warnings and Precautions (5.3)].

5.7 Potential Medication Errors

Medication errors involving LAMICTAL XR have occurred. In particular, the names LAMICTAL or

lamotrigine can be confused with the names of other commonly used medications. Medication errors

may also occur between the different formulations of LAMICTAL. To reduce the potential of

medication errors, write and say LAMICTAL XR clearly. Depictions of the LAMICTAL XR extended-

release tablets can be found in the Medication Guide. Each LAMICTAL XR tablet has a distinct color

and white center, and is printed with “LAMICTAL XR” and the tablet strength. These distinctive

features serve to identify the different presentations of the drug and thus may help reduce the risk of

medication errors. LAMICTAL XR is supplied in round, unit-of-use bottles with orange caps

containing 30 tablets. The label on the bottle includes a depiction of the tablets that further

communicates to patients and pharmacists that the medication is LAMICTAL XR and the specific tablet

strength included in the bottle. The unit-of-use bottle with a distinctive orange cap and distinctive bottle

label features serves to identify the different presentations of the drug and thus may help to reduce the

risk of medication errors. To avoid the medication error of using the wrong drug or formulation,

patients should be strongly advised to visually inspect their tablets to verify that they are

LAMICTAL XR each time they fill their prescription.

5.8 Concomitant Use with Oral Contraceptives

Some estrogen-containing oral contraceptives have been shown to decrease serum concentrations of

lamotrigine [see Clinical Pharmacology (12.3)]. Dosage adjustments will be necessary in most patients

who start or stop estrogen-containing oral contraceptives while taking LAMICTAL XR [see Dosage

and Administration (2.1)]. During the week of inactive hormone preparation (pill-free week) of oral

contraceptive therapy, plasma lamotrigine levels are expected to rise, as much as doubling at the end of

the week. Adverse reactions consistent with elevated levels of lamotrigine, such as dizziness, ataxia,

and diplopia, could occur.

5.9 Withdrawal Seizures

As with other AEDs, LAMICTAL XR should not be abruptly discontinued. In patients with epilepsy

there is a possibility of increasing seizure frequency. Unless safety concerns require a more rapid

withdrawal, the dose of LAMICTAL XR should be tapered over a period of at least 2 weeks

(approximately 50% reduction per week) [see Dosage and Administration (2.1)].

5.10 Status Epilepticus

Valid estimates of the incidence of treatment-emergent status epilepticus among patients treated with

immediate-release lamotrigine are difficult to obtain because reporters participating in clinical trials did

not all employ identical rules for identifying cases. At a minimum, 7 of 2,343 adult patients had episodes

that could unequivocally be described as status epilepticus. In addition, a number of reports of variably

defined episodes of seizure exacerbation (e.g., seizure clusters, seizure flurries) were made.

5.11 Sudden Unexplained Death in Epilepsy (SUDEP)

During the premarketing development of immediate-release lamotrigine, 20 sudden and unexplained

deaths were recorded among a cohort of 4,700 patients with epilepsy (5,747 patient-years of exposure).

Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at

night. This represents an incidence of 0.0035 deaths per patient-year. Although this rate exceeds that

expected in a healthy population matched for age and sex, it is within the range of estimates for the

incidence of sudden unexplained death in epilepsy (SUDEP) in patients not receiving lamotrigine

(ranging from 0.0005 for the general population of patients with epilepsy, to 0.004 for a recently

studied clinical trial population similar to that in the clinical development program for immediate-

release lamotrigine, to 0.005 for patients with refractory epilepsy). Consequently, whether these

figures are reassuring or suggest concern depends on the comparability of the populations reported

upon with the cohort receiving immediate-release lamotrigine and the accuracy of the estimates

provided. Probably most reassuring is the similarity of estimated SUDEP rates in patients receiving

immediate-release lamotrigine and those receiving other AEDs, chemically unrelated to each other, that

underwent clinical testing in similar populations. This evidence suggests, although it certainly does not

prove, that the high SUDEP rates reflect population rates, not a drug effect.

5.12 Addition of LAMICTAL XR to a Multidrug Regimen that Includes Valproate

Because valproate reduces the clearance of lamotrigine, the dosage of lamotrigine in the presence of

valproate is less than half of that required in its absence [see Dosage and Administration (2.1, 2.2), Drug

Interactions (7)].

5.13 Binding in the Eye and Other Melanin-Containing Tissues

Because lamotrigine binds to melanin, it could accumulate in melanin-rich tissues over time. This raises

the possibility that lamotrigine may cause toxicity in these tissues after extended use. Although

ophthalmological testing was performed in 1 controlled clinical trial, the testing was inadequate to

exclude subtle effects or injury occurring after long-term exposure. Moreover, the capacity of

available tests to detect potentially adverse consequences, if any, of lamotrigine’s binding to melanin is

unknown.

Accordingly, although there are no specific recommendations for periodic ophthalmological

monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects.

5.14 Laboratory Tests

False-Positive Drug Test Results

Lamotrigine has been reported to interfere with the assay used in some rapid urine drug screens, which

can result in false-positive readings, particularly for phencyclidine (PCP). A more specific analytical

method should be used to confirm a positive result.

Plasma Concentrations of Lamotrigine

The value of monitoring plasma concentrations of lamotrigine in patients treated with LAMICTAL XR

has not been established. Because of the possible pharmacokinetic interactions between lamotrigine and

other drugs, including AEDs (see Table 6), monitoring of the plasma levels of lamotrigine and

concomitant drugs may be indicated, particularly during dosage adjustments. In general, clinical

judgment should be exercised regarding monitoring of plasma levels of lamotrigine and other drugs and

whether or not dosage adjustments are necessary.

Effect on Leukocytes

Treatment with LAMICTAL XR caused an increased incidence of subnormal (below the reference

range) values in some hematology analytes (e.g., total white blood cells, monocytes). The treatment

effect (LAMICTAL XR % - Placebo %) incidence of subnormal counts was 3% for total white blood

cells and 4% for monocytes.

6 ADVERSE REACTIONS

The following serious adverse reactions are described in more detail in the Warnings and Precautions

section of the labeling:

6.1 Clinical Trial Experience with LAMICTAL XR 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 LAMICTAL XR. Dizziness was the most common reason

for withdrawal in the group receiving LAMICTAL XR (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

Epileps y

Body System/Adverse Reaction

Percent of Patients Receiving

Adjunctive LAMICTAL XR

(n = 190)

Percent of Patients

Receiving Adjunctive

Placebo

(n = 195)

Ear and labyrinth disorders

Vertigo

<1

Eye disorders

Diplopia

<1

Vision blurred

Gastrointestinal disorders

Nausea

Vomiting

Diarrhea

Constipation

<1

Dry mouth

General disorders and administration

site conditions

Asthenia and fatigue

Infections and infestations

Sinusitis

Metabolic and nutritional disorders

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)]

Blood Dyscrasias [see Warnings and Precautions (5.4)]

Suicidal Behavior and Ideation [see Warnings and Precautions (5.5)]

Aseptic Meningitis [see Warnings and Precautions (5.6)]

Withdrawal Seizures [see Warnings and Precautions (5.9)]

Status Epilepticus [see Warnings and Precautions (5.10)]

Sudden Unexplained Death in Epilepsy [see Warnings and Precautions (5.11)]

a

Adverse reactions that occurred in at least 2% of patients treated with LAMICTAL XR and at a

greater incidence than placebo.

Anorexia

Musculoskeletal and connective tissue

disorder

Myalgia

Nervous system

Dizziness

Tremor and intention tremor

Somnolence

Cerebellar coordination and balance

disorder

Nystagmus

<1

Psychiatric disorders

Depression

<1

Anxiety

Respiratory, thoracic, and mediastinal

disorders

Pharyngolaryngeal pain

Vascular disorder

Hot flush

Note: In these trials the incidence of nonserious rash was 2% for LAMICTAL XR 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 in the titration phase persisted

in the maintenance phase.

The incidence for many adverse reactions caused by treatment with LAMICTAL XR was increased

relative to placebo (i.e., treatment difference between LAMICTAL XR and placebo ≥2%) in either the

titration or maintenance phases of the trial. During the titration phase, an increased incidence (shown in

descending order of percent treatment difference) was observed for diarrhea, nausea, vomiting,

somnolence, vertigo, myalgia, hot flush, and anxiety. During the maintenance phase, an increased

incidence was observed for dizziness, tremor, and diplopia. Some adverse reactions developing in the

titration phase were notable for persisting (>7 days) into the maintenance phase. These persistent

adverse reactions included somnolence and dizziness.

There were inadequate data to evaluate the effect of dose and/or concentration on the incidence of

adverse reactions because, although patients were randomized to different target doses based upon

concomitant AEDs, the plasma exposure was expected to be generally similar among all patients

receiving different doses. However, in a randomized, parallel trial comparing placebo with 300 and 500

mg/day of immediate-release lamotrigine, the incidence of the most common adverse reactions (>5%)

such as ataxia, blurred vision, diplopia, and dizziness were dose related. Less common adverse

reactions (<5%) were not assessed for dose-response relationships.

Monotherapy in Patients with Epilepsy: Adverse reactions observed in this trial were generally similar to

those observed and attributed to drug in adjunctive and monotherapy immediate-release lamotrigine and

adjunctive LAMICTAL XR placebo-controlled trials. Only 2 adverse events, nasopharyngitis and upper

respiratory tract infection, were observed at a rate of >3% and not reported at a similar rate in previous

trials. Because this trial did not include a placebo control group, causality could not be established [see

Clinical Studies (14.3)].

6.2 Other Adverse Reactions Observed during the Clinical Development of Immediate-Release

Lamotrigine

All reported reactions are included except those already listed in the previous tables or elsewhere in

the labeling, those too general to be informative, and those not reasonably associated with the use of the

drug.

Adjunctive Therapy in Adults with Epilepsy

In addition to the adverse reactions reported above from the development of LAMICTAL XR, the

following adverse reactions with an uncertain relationship to lamotrigine were reported during the

clinical development of immediate-release lamotrigine for treatment of epilepsy in adults. These

reactions occurred in ≥2% of patients receiving immediate-release lamotrigine and more frequently than

in the placebo group.

Body as a Whole: Headache, flu syndrome, fever, neck pain.

Musculoskeletal: Arthralgia.

Nervous: Insomnia, convulsion, irritability, speech disorder, concentration disturbance.

Respiratory: Pharyngitis, cough increased.

Skin and Appendages: Rash, pruritus.

Urogenital (female patients only): Vaginitis, amenorrhea, dysmenorrhea.

Monotherapy in Adults with Epilepsy

In addition to the adverse reactions reported above from the development of LAMICTAL XR, the

following adverse reactions with an uncertain relationship to lamotrigine were reported during the

clinical development of immediate-release lamotrigine for treatment of epilepsy in adults. These

reactions occurred in >2% of patients receiving immediate-release lamotrigine and more frequently than

in the placebo group.

Body as a Whole: Chest pain.

Digestive: Rectal hemorrhage, peptic ulcer.

Metabolic and Nutritional: Weight decrease, peripheral edema.

Nervous: Hypesthesia, libido increase, decreased reflexes.

Respiratory: Epistaxis, dyspnea.

Skin and Appendages: Contact dermatitis, dry skin, sweating.

Special Senses: Vision abnormality.

Urogenital (female patients only): Dysmenorrhea.

Other Clinical Trial Experience

Immediate-release lamotrigine has been administered to 6,694 individuals for whom complete adverse

reaction data was captured during all clinical trials, only some of which were placebo controlled.

Adverse reactions are further classified within body system categories and enumerated in order of

decreasing frequency using the following definitions: frequent adverse reactions are defined as those

occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to

1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients.

Cardiovascular System: Infrequent: Hypertension, palpitations, postural hypotension, syncope,

tachycardia, vasodilation.

Dermatological: Infrequent: Acne, alopecia, hirsutism, maculopapular rash, urticaria.

Rare: Leukoderma, multiforme erythema, petechial rash, pustular rash.

Digestive System: Infrequent: Dysphagia, liver function tests abnormal, mouth ulceration.

Rare: Gastrointestinal hemorrhage, hemorrhagic colitis, hepatitis, melena, stomach ulcer.

Endocrine System: Rare: Goiter, hypothyroidism.

Hematologic and Lymphatic System: Infrequent: Ecchymosis, leukopenia.

Rare: Anemia, eosinophilia, fibrin decrease, fibrinogen decrease, iron deficiency anemia, leukocytosis,

lymphocytosis, macrocytic anemia, petechia, thrombocytopenia.

Metabolic and Nutritional Disorders: Infrequent: Aspartate transaminase increased.

Rare: Alcohol intolerance, alkaline phosphatase increase, alanine transaminase increase, bilirubinemia,

gamma glutamyl transpeptidase increase, hyperglycemia.

Musculoskeletal System: Rare: Muscle atrophy, pathological fracture, tendinous contracture.

Nervous System: Frequent: Confusion.

Infrequent: Akathisia, apathy, aphasia, depersonalization, dysarthria, dyskinesia, euphoria, hallucinations,

hostility, hyperkinesia, hypertonia, libido decreased, memory decrease, mind racing, movement

disorder, myoclonus, panic attack, paranoid reaction, personality disorder, psychosis, stupor.

Rare: Choreoathetosis, delirium, delusions, dysphoria, dystonia, extrapyramidal syndrome, hemiplegia,

hyperalgesia, hyperesthesia, hypokinesia, hypotonia, manic depression reaction, neuralgia, paralysis,

peripheral neuritis.

Respiratory System: Rare: Hiccup, hyperventilation.

Special Senses: Frequent: Amblyopia.

Infrequent: Abnormality of accommodation, conjunctivitis, dry eyes, ear pain, photophobia, taste

perversion, tinnitus.

Rare: Deafness, lacrimation disorder, oscillopsia, parosmia, ptosis, strabismus, taste loss, uveitis,

visual field defect.

Urogenital System: Infrequent: Abnormal ejaculation, hematuria, impotence, menorrhagia, polyuria,

urinary incontinence.

Rare: Acute kidney failure, breast neoplasm, creatinine increase, female lactation, kidney failure, kidney

pain, nocturia, urinary retention, urinary urgency.

6.3 Postmarketing Experience with Immediate-Release Lamotrigine

The following adverse reactions have been identified during postapproval use of immediate-release

lamotrigine. Because these reactions are reported voluntarily from a population of uncertain size, it is

not always possible to reliably estimate their frequency or establish a causal relationship to drug

exposure.

Blood and Lymphatic

Agranulocytosis, hemolytic anemia, lymphadenopathy not associated with hypersensitivity disorder.

Gastrointestinal

Esophagitis.

Hepatobiliary Tract and Pancreas

Pancreatitis.

Immunologic

Hypogammaglobulinemia, lupus-like reaction, vasculitis.

Lower Respiratory

Apnea.

Musculoskeletal

Rhabdomyolysis has been observed in patients experiencing hypersensitivity reactions.

Nervous System

Aggression, exacerbation of Parkinsonian symptoms in patients with pre-existing Parkinson’s disease,

tics.

Non-site Specific

Progressive immunosuppression.

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 [see Dosage and Administration (2.1)].

Table 5. Established and Other Potentially Significant Drug Interactions

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

Decreased lamotrigine

concentrations approximately

50%.

↓ levonorgestrel

Decrease in levonorgestrel

component by 19%.

Carbamazepine and

carbamazepine epoxide

↓ lamotrigine

Addition of carbamazepine

decreases lamotrigine

concentration approximately 40%.

? carbamazepine epoxide

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

↓ = Decreased (induces lamotrigine glucuronidation).

↑ = Increased (inhibits lamotrigine glucuronidation).

? = Conflicting data.

approximately 40%.

Valproate

↑ lamotrigine

Increased lamotrigine

concentrations slightly more than

2-fold.

? valproate

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 LAMICTAL XR 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 LAMICTAL XR with OCT2 substrates with a

narrow therapeutic index (e.g., dofetilide) is not recommended.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs,

including LAMICTAL XR, during pregnancy. Encourage women who are taking LAMICTAL XR

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).

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. 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

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 exposure in pregnancy compared with healthy and disease-matched controls. No patterns of

specific malformation types were observed.

The same meta-analyses evaluated the risk of additional maternal and infant outcomes including fetal

death, stillbirth, preterm birth, small for gestational age, and neurodevelopmental delay. Although there

are no data suggesting an increased risk of these outcomes with lamotrigine monotherapy exposure,

differences in outcome definition, ascertainment methods, and comparator groups limit the conclusions

that can be drawn.

Animal Data: When lamotrigine was administered to pregnant mice, rats, or rabbits during the period of

organogenesis (oral doses of up to 125, 25, and 30 mg/kg, respectively), reduced fetal body weight and

increased incidences of fetal skeletal variations were seen in mice and rats at doses that were also

maternally toxic. The no-effect doses for embryofetal developmental toxicity in mice, rats, and rabbits

(75, 6.25, and 30 mg/kg, respectively) are similar to (mice and rabbits) or less than (rats) the human dose

of 400 mg/day on a body surface area (mg/m ) basis.

In a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during

the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities

were observed in exposed offspring at both doses. The lowest effect dose for developmental

neurotoxicity in rats is less than the human dose of 400 mg/day on a mg/m basis. Maternal toxicity was

observed at the higher dose tested.

When pregnant rats were administered lamotrigine (oral doses of 0, 5, 10, or 20 mg/kg) during the latter

part of gestation and throughout lactation, increased offspring mortality (including stillbirths) was seen

at all doses. The lowest effect dose for pre- and post-natal developmental toxicity in rats is less than the

human dose of 400 mg/day on a mg/m basis. Maternal toxicity was observed at the 2 highest doses

tested.

When administered to pregnant rats, lamotrigine decreased fetal folate concentrations at doses greater

than or equal to 5 mg/kg/day, which is less than the human dose of 400 mg/day on a mg/m basis.

8.2 Lactation

Risk Summary

Lamotrigine is present in milk from lactating women taking LAMICTAL XR (see Data). Neonates and

young infants are at risk for high serum levels because maternal serum and milk levels can rise to high

levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after

delivery to the pre-pregnancy dosage. Glucuronidation is required for drug clearance. Glucuronidation

capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure.

Events including rash, apnea, drowsiness, poor sucking, and poor weight gain (requiring hospitalization

in some cases) have been reported in infants who have been human milk-fed by mothers using

lamotrigine; whether or not these events were caused by lamotrigine is unknown. No data are available

on the effects of the drug on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s

clinical need for LAMICTAL XR and any potential adverse effects on the breastfed infant from

LAMICTAL XR or from the underlying maternal condition.

Clinical Considerations

Human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine.

Measurement of infant serum levels should be performed to rule out toxicity if concerns arise. Human

milk-feeding should be discontinued in infants with lamotrigine toxicity.

Data

Data from multiple small studies indicate that lamotrigine plasma levels in nursing infants have been

reported to be as high as 50% of maternal plasma concentrations.

8.4 Pediatric Use

LAMICTAL XR 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 LAMICTAL

XR 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 basis.

8.5 Geriatric Use

Clinical trials of LAMICTAL XR 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.

8.6 Hepatic Impairment

Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study with

immediate-release lamotrigine in 24 subjects with mild, moderate, and severe liver impairment [see

Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage

adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses

should generally be reduced by approximately 25% in patients with moderate and severe liver

impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and

maintenance doses may be adjusted according to clinical response [see Dosage and Administration (2.1)].

8.7 Renal Impairment

Lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites

being recovered in the urine. In a small study comparing a single dose of immediate-release lamotrigine

in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of

lamotrigine was approximately twice as long in the subjects with chronic renal failure [see Clinical

Pharmacology (12.3)].

Initial doses of LAMICTAL XR should be based on patients’ AED regimens; reduced maintenance

doses may be effective for patients with significant renal impairment. Few patients with severe renal

impairment have been evaluated during chronic treatment with lamotrigine. Because there is inadequate

experience in this population, LAMICTAL XR should be used with caution in these patients [see

Dosage and Administration (2.1)].

10 OVERDOSAGE

10.1 Human 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.

10.2 Management 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 LAMICTAL XR.

11 DESCRIPTION

LAMICTAL XR (lamotrigine), 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 H N Cl

, and its molecular weight is 256.09. Lamotrigine is a white to pale cream-

colored powder and has a pK of 5.7. Lamotrigine is very slightly soluble in water (0.17 mg/mL at

25°C) and slightly soluble in 0.1 M HCl (4.1 mg/mL at 25°C). The structural formula is:

LAMICTAL XR extended-release tablets are supplied for oral administration as 25-mg (yellow with

white center), 50-mg (green with white center), 100-mg (orange with white center), 200-mg (blue with

white center), 250-mg (purple with white center), and 300-mg (gray with white center) tablets. Each

tablet contains the labeled amount of lamotrigine and the following inactive ingredients: glycerol

monostearate, hypromellose, lactose monohydrate; magnesium stearate; methacrylic acid copolymer

dispersion, polyethylene glycol 400, polysorbate 80, silicon dioxide (25- and 50-mg tablets only),

titanium dioxide, triethyl citrate, carmine (250-mg tablet only), iron oxide black (50-, 250-, and 300-mg

tablets only), iron oxide yellow (25-, 50-, and 100-mg tablets only), iron oxide red (100-mg tablet only),

FD&C Blue No. 2 Aluminum Lake (200- and 250-mg tablets only). Tablets are printed with edible black

ink.

LAMICTAL XR extended-release tablets contain a modified-release eroding formulation as the core.

The tablets are coated with a clear enteric coat and have an aperture drilled through the coats on both

faces of the tablet (DiffCORE) to enable a controlled release of drug in the acidic environment of the

stomach. The combination of this and the modified-release core 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism 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

for lamotrigine effects on NMDA-induced currents (in the presence of

3 µM of glycine) in cultured hippocampal neurons exceeded 100 µM.

12.2 Pharmacodynamics

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.

Cardiovascular

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. Similar cardiovascular effects 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).

12.3 Pharmacokinetics

In comparison with immediate-release lamotrigine, the plasma lamotrigine levels following

administration of LAMICTAL XR 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 LAMICTAL XR given once daily with those of lamotrigine immediate-release given twice daily. In

this study, the median time to peak concentration (T

) following administration of LAMICTAL XR

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

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

by 11% to 29% was observed for LAMICTAL XR 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

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. LAMICTAL XR 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

LAMICTAL XR. Therefore, doses may need to be adjusted in some patients based on therapeutic

response.

Table 6. Steady-State Bioavailability of LAMICTAL XR Relative to Immediate-Release

Lamotrigine at Equivalent Daily Doses (Ratio of Extended-Release to Immediate-Release 90%

CI)

Enzyme-inducing antiepileptic drugs include carbamazepine, phenytoin, phenobarbital, and

Concomitant Antiepileptic Drug

AUC

C

C

Enzyme-inducing antiepileptic drugs

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 or valproate

1.00 (0.88,

1.14)

0.89 (0.78,

1.03)

1.14 (1.03,

1.25)

(0 -24 ss)

max

min

Enzyme-inducing antiepileptic drugs include carbamazepine, phenytoin, phenobarbital, and

primidone.

Dose Proportionality

In healthy volunteers not receiving any other medications and given LAMICTAL XR 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 1.3 L/kg. Vd/F is independent of dose and is similar following single

and multiple doses in both patients with epilepsy and in healthy volunteers.

Protein Binding

Data from in vitro studies indicate that lamotrigine is approximately 55% bound to human plasma

proteins at plasma lamotrigine concentrations from 1 to 10 mcg/mL (10 mcg/mL is 4 to 6 times the

trough plasma concentration observed in the controlled efficacy trials). Because lamotrigine is not

highly bound to plasma proteins, clinically significant interactions with other drugs through competition

for protein binding sites are unlikely. The binding of lamotrigine to plasma proteins did not change in

the presence of therapeutic concentrations of phenytoin, phenobarbital, or valproate. Lamotrigine did

not displace other AEDs (carbamazepine, phenytoin, phenobarbital) from protein-binding sites.

Metabolism

Lamotrigine is metabolized predominantly by glucuronic acid conjugation; the major metabolite is an

inactive 2-N-glucuronide conjugate. After oral administration of 240 mg of

C-lamotrigine (15 μCi) to

6 healthy volunteers, 94% was recovered in the urine and 2% was recovered in the feces. The

radioactivity in the urine consisted of unchanged lamotrigine (10%), the 2-N-glucuronide (76%), a 5-N-

glucuronide (10%), a 2-N-methyl metabolite (0.14%), and other unidentified minor metabolites (4%).

Enzyme Induction

The effects of lamotrigine on the induction of specific families of mixed-function oxidase isozymes

have not been systematically evaluated.

Following multiple administrations (150 mg twice daily) to normal volunteers taking no other

medications, lamotrigine induced its own metabolism, resulting in a 25% decrease in t

and a 37%

increase in CL/F at steady state compared with values obtained in the same volunteers following a

single dose. Evidence gathered from other sources suggests that self-induction by lamotrigine may not

occur when lamotrigine is given as adjunctive therapy in patients receiving enzyme-inducing drugs such

as carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease

inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation [see Drug

Interactions (7)].

Elimination

The elimination half-life and apparent clearance of lamotrigine following oral administration of

immediate-release lamotrigine to adult subjects with epilepsy and healthy volunteers is summarized in

Table 7. Half-life and apparent oral clearance vary depending on concomitant AEDs.

Since the half-life of lamotrigine following administration of single doses of immediate-release

lamotrigine is comparable with that observed following administration of LAMICTAL XR, similar

changes in the half-life of lamotrigine would be expected for LAMICTAL XR.

Table 7. Mean Pharmacokinetic Parameters

of Immediate-Release Lamotrigine in

Healthy Volunteers and Adult Subjects with Epilepsy

a

The majority of parameter means determined in each study had coefficients of variation

between 20% and 40% for half-life and CL/F and between 30% and 70% for T

. The overall

mean values were calculated from individual study means that were weighted based on the

number of volunteers/subjects in each study. The numbers in parentheses below each parameter

mean represent the range of individual volunteer/subject values across studies.

Carbamazepine, phenytoin, phenobarbital, and primidone have been shown to increase the

apparent clearance of lamotrigine. Estrogen-containing oral contraceptives and other drugs, such

as rifampin and protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir, that induce

lamotrigine glucuronidation have also been shown to increase the apparent clearance of

lamotrigine [see Drug Interactions (7)].

Adult Study Population

Number of

Subjects

t

:

Elimination

Half life (h)

CL/F:

Apparent Plasma

Clearance

(mL/min/kg)

Healthy volunteers taking no other

medications :

Single-dose lamotrigine

32.8

(14.0-103.0)

0.44

(0.12-1.10)

Multiple-dose lamotrigine

25.4

(11.6-61.6)

0.58

(0.24-1.15)

Healthy volunteers taking valproate:

Single-dose lamotrigine

48.3

(31.5-88.6)

0.30

(0.14-0.42)

Multiple-dose lamotrigine

70.3

(41.9-113.5)

0.18

(0.12-0.33)

Subjects with epilepsy taking

valproate only:

Single-dose lamotrigine

58.8

(30.5-88.8)

0.28

(0.16-0.40)

Subjects with epilepsy taking

carbamazepine, phenytoin,

phenobarbital, or primidone plus

valproate:

Single-dose lamotrigine

27.2

(11.2-51.6)

0.53

(0.27-1.04)

Subjects with epilepsy taking

carbamazepine, phenytoin,

phenobarbital, or primidone:

Single-dose lamotrigine

14.4

(6.4-30.4)

1.10

(0.51-2.22)

Multiple-dose lamotrigine

12.6

(7.5-23.1)

1.21

(0.66-1.82)

Drug Interactions

The apparent clearance of lamotrigine is affected by the coadministration of certain medications [see

Warnings and Precautions (5.8, 5.12), Drug Interactions (7)].

The net effects of drug interactions with lamotrigine, based on drug interaction studies using

immediate-release lamotrigine, are summarized in Tables 5 and 8, followed by details of the drug

interaction studies below.

½

b

b

Table 8. Summary of Drug Interactions with Lamotrigine

From adjunctive clinical trials and volunteer trials.

Net effects were estimated by comparing the mean clearance values obtained in adjunctive clinical

trials and volunteer trials.

The effect of other hormonal contraceptive preparations or hormone replacement therapy on the

pharmacokinetics of lamotrigine has not been systematically evaluated in clinical trials, although the

effect may be similar to that seen with the ethinylestradiol/levonorgestrel combinations.

Modest decrease in levonorgestrel.

Slight decrease, not expected to be clinically meaningful.

Compared with historical controls.

Not administered, but an active metabolite of carbamazepine.

Not administered, but an active metabolite of oxcarbazepine.

Not administered, but an active metabolite of risperidone.

Slight increase, not expected to be clinically meaningful.

↔ = No significant effect.

? = Conflicting data.

Drug

Drug Plasma

Concentration with

Adjunctive Lamotrigine

Lamotrigine Plasma

Concentration with

Adjunctive Drugs

Oral contraceptives (e.g.,

ethinylestradiol/levonorgestrel)

Aripiprazole

Not assessed

Atazanavir/ritonavir

Bupropion

Not assessed

Carbamazepine

Carbamazepine epoxide

Felbamate

Not assessed

Gabapentin

Not assessed

Lacosamide

Not assessed

Levetiracetam

Lithium

Not assessed

Lopinavir/ritonavir

Olanzapine

Oxcarbazepine

10-Monohydroxy oxcarbazepine

metabolite

Perampanel

Not assessed

Phenobarbital/primidone

Phenytoin

Pregabalin

Rifampin

Not assessed

Risperidone

Not assessed

9-Hydroxyrisperidone

Topiramate

Valproate

Valproate + phenytoin and/or

carbamazepine

Not assessed

Zonisamide

Not assessed

a

b

Estrogen-Containing Oral Contraceptives

In 16 female volunteers, an oral contraceptive preparation containing 30 mcg ethinylestradiol and

150 mcg levonorgestrel increased the apparent clearance of lamotrigine (300 mg/day) by approximately

2-fold with mean decreases in AUC of 52% and in C

of 39%. In this study, trough serum lamotrigine

concentrations gradually increased and were approximately 2-fold higher on average at the end of the

week of the inactive hormone preparation compared with trough lamotrigine concentrations at the end of

the active hormone cycle.

Gradual transient increases in lamotrigine plasma levels (approximate 2-fold increase) occurred during

the week of inactive hormone preparation (pill-free week) for women not also taking a drug that

increased the clearance of lamotrigine (carbamazepine, phenytoin, phenobarbital, primidone, or other

drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce

lamotrigine glucuronidation) [see Drug Interactions (7)]. The increase in lamotrigine plasma levels will

be greater if the dose of LAMICTAL XR is increased in the few days before or during the pill-free

week. Increases in lamotrigine plasma levels could result in dose-dependent adverse reactions.

In the same study, coadministration of lamotrigine (300 mg/day) in 16 female volunteers did not affect

the pharmacokinetics of the ethinylestradiol component of the oral contraceptive preparation. There

were mean decreases in the AUC and C

of the levonorgestrel component of 19% and 12%,

respectively. Measurement of serum progesterone indicated that there was no hormonal evidence of

ovulation in any of the 16 volunteers, although measurement of serum FSH, LH, and estradiol indicated

that there was some loss of suppression of the hypothalamic-pituitary-ovarian axis.

The effects of doses of lamotrigine other than 300 mg/day have not been systematically evaluated in

controlled clinical trials.

The clinical significance of the observed hormonal changes on ovulatory activity is unknown.

However, the possibility of decreased contraceptive efficacy in some patients cannot be excluded.

Therefore, patients should be instructed to promptly report changes in their menstrual pattern (e.g.,

break-through bleeding).

Dosage adjustments may be necessary for women receiving estrogen-containing oral contraceptive

preparations [see Dosage and Administration (2.1)].

Other Hormonal Contraceptives or Hormone Replacement Therapy

The effect of other hormonal contraceptive preparations or hormone replacement therapy on the

pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that

ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the

progestin-only pills had no effect on lamotrigine plasma levels. Therefore, adjustments to the dosage of

LAMICTAL XR in the presence of progestogens alone will likely not be needed.

Aripiprazole

In 18 patients with bipolar disorder on a stable regimen of 100 to 400 mg/day of lamotrigine, the

lamotrigine AUC and C

were reduced by approximately 10% in patients who received aripiprazole

10 to 30 mg/day for 7 days, followed by 30 mg/day for an additional 7 days. This reduction in

lamotrigine exposure is not considered clinically meaningful.

Atazanavir/Ritonavir

In a study in healthy volunteers, daily doses of atazanavir/ritonavir (300 mg/100 mg) reduced the plasma

AUC and C

of lamotrigine (single 100-mg dose) by an average of 32% and 6%, respectively, and

shortened the elimination half-lives by 27%. In the presence of atazanavir/ritonavir (300 mg/100 mg),

the metabolite-to-lamotrigine ratio was increased from 0.45 to 0.71 consistent with induction of

glucuronidation. The pharmacokinetics of atazanavir/ritonavir were similar in the presence of

concomitant lamotrigine to the historical data of the pharmacokinetics in the absence of lamotrigine.

Bupropion

The pharmacokinetics of a 100-mg single dose of lamotrigine in healthy volunteers (n = 12) were not

changed by coadministration of bupropion sustained-release formulation (150 mg twice daily) starting

11 days before lamotrigine.

Carbamazepine

Lamotrigine has no appreciable effect on steady-state carbamazepine plasma concentration. Limited

clinical data suggest there is a higher incidence of dizziness, diplopia, ataxia, and blurred vision in

patients receiving carbamazepine with lamotrigine than in patients receiving other AEDs with

lamotrigine [see Adverse Reactions (6.1)]. The mechanism of this interaction is unclear. The effect of

lamotrigine on plasma concentrations of carbamazepine-epoxide is unclear. In a small subset of patients

(n = 7) studied in a placebo-controlled trial, lamotrigine had no effect on carbamazepine-epoxide plasma

concentrations, but in a small, uncontrolled study (n = 9), carbamazepine-epoxide levels increased.

The addition of carbamazepine decreases lamotrigine steady-state concentrations by approximately

40%.

Esomeprazole

In a study of 30 subjects, coadministration of LAMICTAL XR with esomeprazole resulted in no

significant change in lamotrigine levels and a small decrease in T

. The levels of gastric pH were

not altered compared with pre-lamotrigine dosing.

Felbamate

In a trial in 21 healthy volunteers, coadministration of felbamate (1,200 mg twice daily) with lamotrigine

(100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the

pharmacokinetics of lamotrigine.

Folate Inhibitors

Lamotrigine is a weak inhibitor of dihydrofolate reductase. Prescribers should be aware of this action

when prescribing other medications that inhibit folate metabolism.

Gabapentin

Based on a retrospective analysis of plasma levels in 34 subjects who received lamotrigine both with

and without gabapentin, gabapentin does not appear to change the apparent clearance of lamotrigine.

Lacosamide

Plasma concentrations of lamotrigine were not affected by concomitant lacosamide (200, 400, or 600

mg/day) in placebo-controlled clinical trials in patients with partial-onset seizures.

Levetiracetam

Potential drug interactions between levetiracetam and lamotrigine were assessed by evaluating serum

concentrations of both agents during placebo-controlled clinical trials. These data indicate that

lamotrigine does not influence the pharmacokinetics of levetiracetam and that levetiracetam does not

influence the pharmacokinetics of lamotrigine.

Lithium

The pharmacokinetics of lithium were not altered in healthy subjects (n = 20) by coadministration of

lamotrigine (100 mg/day) for 6 days.

Lopinavir/Ritonavir

The addition of lopinavir (400 mg twice daily)/ritonavir (100 mg twice daily) decreased the AUC,

and elimination half-life of lamotrigine by approximately 50% to 55.4% in 18 healthy subjects.

The pharmacokinetics of lopinavir/ritonavir were similar with concomitant lamotrigine, compared with

that in historical controls.

Olanzapine

max,

The AUC and C

of olanzapine were similar following the addition of olanzapine (15 mg once daily)

to lamotrigine (200 mg once daily) in healthy male volunteers (n = 16) compared with the AUC and

in healthy male volunteers receiving olanzapine alone (n = 16).

In the same trial, the AUC and C

of lamotrigine were reduced on average by 24% and 20%,

respectively, following the addition of olanzapine to lamotrigine in healthy male volunteers compared

with those receiving lamotrigine alone. This reduction in lamotrigine plasma concentrations is not

expected to be clinically meaningful.

Oxcarbazepine

The AUC and C

of oxcarbazepine and its active 10-monohydroxy oxcarbazepine metabolite were

not significantly different following the addition of oxcarbazepine (600 mg twice daily) to lamotrigine

(200 mg once daily) in healthy male volunteers (n = 13) compared with healthy male volunteers

receiving oxcarbazepine alone (n = 13).

In the same trial, the AUC and C

of lamotrigine were similar following the addition of

oxcarbazepine (600 mg twice daily) to lamotrigine in healthy male volunteers compared with those

receiving lamotrigine alone. Limited clinical data suggest a higher incidence of headache, dizziness,

nausea, and somnolence with coadministration of lamotrigine and oxcarbazepine compared with

lamotrigine alone or oxcarbazepine alone.

Perampanel

In a pooled analysis of data from 3 placebo-controlled clinical trials investigating adjunctive perampanel

in patients with partial-onset and primary generalized tonic-clonic seizures, the highest perampanel dose

evaluated (12 mg/day) increased lamotrigine clearance by <10%. An effect of this magnitude is not

considered to be clinically relevant.

Phenobarbital, Primidone

The addition of phenobarbital or primidone decreases lamotrigine steady-state concentrations by

approximately 40%.

Phenytoin

Lamotrigine has no appreciable effect on steady-state phenytoin plasma concentrations in patients with

epilepsy. The addition of phenytoin decreases lamotrigine steady-state concentrations by approximately

40%.

Pregabalin

Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin

(200 mg 3 times daily) administration. There are no pharmacokinetic interactions between lamotrigine

and pregabalin.

Rifampin

In 10 male volunteers, rifampin (600 mg/day for 5 days) significantly increased the apparent clearance

of a single 25-mg dose of lamotrigine by approximately 2-fold (AUC decreased by approximately

40%).

Risperidone

In a 14 healthy volunteers study, multiple oral doses of lamotrigine 400 mg daily had no clinically

significant effect on the single-dose pharmacokinetics of risperidone 2 mg and its active metabolite 9-

OH risperidone. Following the coadministration of risperidone 2 mg with lamotrigine, 12 of the 14

volunteers reported somnolence compared with 1 out of 20 when risperidone was given alone, and none

when lamotrigine was administered alone.

Topiramate

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine

resulted in a 15% increase in topiramate concentrations.

Valproate

When lamotrigine was administered to healthy volunteers (n = 18) receiving valproate, the trough

steady-state valproate plasma concentrations decreased by an average of 25% over a 3-week period, and

then stabilized. However, adding lamotrigine to the existing therapy did not cause a change in valproate

plasma concentrations in either adult or pediatric patients in controlled clinical trials.

The addition of valproate increased lamotrigine steady-state concentrations in normal volunteers by

slightly more than 2-fold. In 1 trial, maximal inhibition of lamotrigine clearance was reached at

valproate doses between 250 and 500 mg/day and did not increase as the valproate dose was further

increased.

Zonisamide

In a study in 18 patients with epilepsy, coadministration of zonisamide (200 to 400 mg/day) with

lamotrigine (150 to 500 mg/day for 35 days) had no significant effect on the pharmacokinetics of

lamotrigine.

Known Inducers or Inhibitors of Glucuronidation

Drugs other than those listed above have not been systematically evaluated in combination with

lamotrigine. Since lamotrigine is metabolized predominately by glucuronic acid conjugation, drugs that

are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine, and

doses of LAMICTAL XR may require adjustment based on clinical response.

Other

In vitro assessment of the inhibitory effect of lamotrigine at OCT2 demonstrate that lamotrigine, but not

the N(2)-glucuronide metabolite, is an inhibitor of OCT2 at potentially clinically relevant

concentrations, with IC

value of 53.8 µM [see Drug Interactions (7)].

Results of in vitro experiments suggest that clearance of lamotrigine is unlikely to be reduced by

concomitant administration of amitriptyline, clonazepam, clozapine, fluoxetine, haloperidol, lorazepam,

phenelzine, sertraline, or trazodone.

Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs

eliminated predominantly by CYP2D6.

Specific Populations

Patients with Renal Impairment: Twelve volunteers with chronic renal failure (mean creatinine

clearance: 13 mL/min, range: 6 to 23) and another 6 individuals undergoing hemodialysis were each

given a single 100-mg dose of immediate-release lamotrigine. The mean plasma half-lives determined

in the study were 42.9 hours (chronic renal failure), 13.0 hours (during hemodialysis), and 57.4 hours

(between hemodialysis) compared with 26.2 hours in healthy volunteers. On average, approximately

20% (range: 5.6 to 35.1) of the amount of lamotrigine present in the body was eliminated by

hemodialysis during a 4-hour session [see Dosage and Administration (2.1)].

Patients with Hepatic Impairment: The pharmacokinetics of lamotrigine following a single 100-mg dose

of immediate-release lamotrigine were evaluated in 24 subjects with mild, moderate, and severe hepatic

impairment (Child-Pugh classification system) and compared with 12 subjects without hepatic

impairment. The subjects with severe hepatic impairment were without ascites (n = 2) or with ascites

(n = 5). The mean apparent clearances of lamotrigine in subjects with mild (n = 12), moderate (n = 5),

severe without ascites (n = 2), and severe with ascites (n = 5) liver impairment were 0.30 ± 0.09,

0.24 ± 0.1, 0.21 ± 0.04, and 0.15 ± 0.09 mL/min/kg, respectively, as compared with 0.37 ± 0.1

mL/min/kg in the healthy controls. Mean half-lives of lamotrigine in subjects with mild, moderate,

severe without ascites, and severe with ascites hepatic impairment were 46 ± 20, 72 ± 44, 67 ± 11, and

100 ± 48 hours, respectively, as compared with 33 ± 7 hours in healthy controls [see Dosage and

Administration (2.1)].

Geriatric Patients: The pharmacokinetics of lamotrigine following a single 150-mg dose of immediate-

release lamotrigine were evaluated in 12 elderly volunteers between the ages of 65 and 76 years (mean

creatinine clearance: 61 mL/min, range: 33 to 108 mL/min). The mean half-life of lamotrigine in these

subjects was 31.2 hours (range: 24.5 to 43.4 hours), and the mean clearance was 0.40 mL/min/kg (range:

0.26 to 0.48 mL/min/kg).

Male and Female Patients: The clearance of lamotrigine is not affected by gender. However, during

dose escalation of immediate-release lamotrigine in 1 clinical trial in patients with epilepsy on a stable

dose of valproate (n = 77), mean trough lamotrigine concentrations unadjusted for weight were 24% to

45% higher (0.3 to 1.7 mcg/mL) in females than in males.

Racial or Ethnic Groups: The apparent oral clearance of lamotrigine was 25% lower in non-Caucasians

than Caucasians.

Pediatric Patients: Safety and effectiveness of LAMICTAL XR for use in patients younger than 13 years

have not been established.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, 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 ) 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 basis.

14 CLINICAL STUDIES

14.1 Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures

The effectiveness of LAMICTAL XR as adjunctive therapy in subjects with PGTC seizures was

established in a 19-week, international, multicenter, double-blind, randomized, placebo-controlled trial

in 143 patients aged 13 years and older (n = 70 on LAMICTAL XR, n = 73 on placebo). Patients with at

least 3 PGTC seizures during an 8-week baseline phase were randomized to 19 weeks of treatment with

LAMICTAL XR or placebo added to their current AED regimen of up to 2 drugs. Patients were dosed

on a fixed-dose regimen, with target doses ranging from 200 to 500 mg/day of LAMICTAL XR based

on concomitant AEDs (target dose = 200 mg for valproate, 300 mg for AEDs not altering plasma

lamotrigine levels, and 500 mg for enzyme-inducing AEDs).

The primary efficacy endpoint was percent change from baseline in PGTC seizure frequency during the

double-blind treatment phase. For the intent-to-treat population, the median percent reduction in PGTC

seizure frequency was 75% in patients treated with LAMICTAL XR and 32% in patients treated with

placebo, a difference that was statistically significant, defined as a 2-sided P value <0.05.

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 LAMICTAL

XR compared with the placebo group. For example, 70% of patients randomized to LAMICTAL XR

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 LAMICTAL XR and Placebo Group

(Primary Generalized Tonic-Clonic Seizures Study)

14.2 Adjunctive 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 LAMICTAL XR 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 LAMICTAL XR (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 LAMICTAL XR 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 baseline was 2.3 for LAMICTAL XR and 2.1

for placebo.

The primary endpoint was the median percent change from baseline in partial-onset seizure frequency

during the entire double-blind treatment phase. The median percent reductions in weekly partial-onset

seizures were 47% in patients treated with LAMICTAL XR and 25% on placebo, a difference that was

statistically significant, defined as a 2-sided P value ≤0.05.

Figure 2 presents the percentage of patients (X-axis) with a percent reduction in partial-onset seizure

frequency (responder rate) from baseline through the entire treatment period at least as great as that

represented on the Y-axis. The proportion of patients achieving any particular level of reduction in

partial-onset seizure frequency was consistently higher for the group treated with LAMICTAL XR

compared with the placebo group. For example, 44% of patients randomized to LAMICTAL XR

experienced a 50% or greater reduction in partial-onset seizure frequency compared with 21% of

patients randomized to placebo.

Figure 2. Proportion of Patients by Responder Rate for LAMICTAL XR and Placebo Group

(Partial-Onset Seizure Study)

14.3 Conversion to Monotherapy for Partial-Onset Seizures

The effectiveness of LAMICTAL XR as monotherapy for partial-onset seizures was established in a

historical control trial in 223 adults with partial-onset seizures. The historical control methodology is

described in a publication by French, et al. [see References (15)]. Briefly, in this study, patients were

randomized to ultimately receive either LAMICTAL XR 300 or 250 mg once a day, and their responses

were compared with those of a historical control group. The historical control consisted of a pooled

analysis of the control groups from 8 studies of similar design, which utilized a subtherapeutic dose of

an AED as a comparator. Statistical superiority to the historical control was considered to be

demonstrated if the upper 95% confidence interval for the proportion of patients meeting escape criteria

in patients receiving LAMICTAL XR remained below the lower 95% prediction interval of 65.3%

derived from the historical control data.

In this study, patients aged 13 years and older experienced at least 4 partial-onset seizures during an 8-

week baseline period with at least 1 seizure occurring during each of 2 consecutive 4-week periods

while receiving valproate or a non–enzyme-inducing AED. LAMICTAL XR was added to either

valproate or a non–enzyme-inducing AED over a 6- to 7-week period followed by the gradual

withdrawal of the background AED. Patients were then continued on monotherapy with LAMICTAL XR

for 12 weeks. The escape criteria were 1 or more of the following: (1) doubling of average monthly

seizure count during any 28 consecutive days, (2) doubling of highest consecutive 2-day seizure

frequency during the entire treatment phase, (3) emergence of a new seizure type compared with

baseline (4) clinically significant prolongation of generalized tonic-clonic seizures or worsening of

seizure considered by the investigator to require intervention. These criteria were similar to those in

the 8 controlled trials from which the historical control group was constituted.

The upper 95% confidence limits of the proportion of subjects meeting escape criteria (40.2% at

300 mg/day and 44.5% at 250 mg/day) were below the threshold of 65.3% derived from the historical

control data.

Although the study population was not fully comparable with the historical control population and the

study was not fully blinded, numerous sensitivity analyses supported the primary results. Efficacy was

further supported by the established effectiveness of the immediate-release formulation as

monotherapy.

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.

16 HOW SUPPLIED/STORAGE AND HANDLING

LAMICTAL XR (lamotrigine) extended-release tablets

25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 25”, unit-of-use bottles of 30 with orange caps (NDC 0173-0754-00).

50-mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 50”, unit-of-use bottles of 30 with orange caps (NDC 0173-0755-00).

100-mg, orange with a white center, round, biconvex, film-coated tablets printed on one face in black

ink with “LAMICTAL” and “XR 100”, unit-of-use bottles of 30 with orange caps (NDC 0173-0756-

00).

200-mg, blue with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 200”, unit-of-use bottles of 30 with orange caps (NDC 0173-0757-00).

250-mg, purple with a white center, caplet-shaped, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 250”, unit-of-use bottles of 30 with orange caps (NDC 0173-0781-00).

300-mg, gray with a white center, caplet-shaped, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 300”, unit-of-use bottles of 30 with orange caps (NDC 0173-0761-00).

LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Taking Valproate (Blue XR Kit)

25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 25” and 50 mg, green with a white center, round, biconvex, film-coated

tablets printed on one face in black ink with “LAMICTAL” and “XR 50”; blister pack of 21/25-mg

tablets and 7/50-mg tablets (NDC 0173-0758-00).

LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Taking Carbamazepine, Phenytoin,

Phenobarbital, or Primidone, and Not Taking Valproate (Green XR Kit)

50-mg, green with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 50”; 100 mg, orange with a white center, round, biconvex, film-coated

tablets printed on one face in black ink with “LAMICTAL” and “XR 100”; and 200 mg, blue with a white

center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and

“XR 200”; blister pack of 14/50-mg tablets, 14/100-mg tablets, and 7/200-mg tablets (NDC 0173-0759-

00).

LAMICTAL XR (lamotrigine) Patient Titration Kit for Patients Not Taking Carbamazepine, Phenytoin,

Phenobarbital, Primidone, or Valproate (Orange XR Kit)

25-mg, yellow with a white center, round, biconvex, film-coated tablets printed on one face in black ink

with “LAMICTAL” and “XR 25”; 50 mg, green with a white center, round, biconvex, film-coated tablets

printed on one face in black ink with “LAMICTAL” and “XR 50”; and 100 mg, orange with a white

center, round, biconvex, film-coated tablets printed on one face in black ink with “LAMICTAL” and

“XR 100”; blister pack of 14/25-mg tablets, 14/50-mg tablets, and 7/100-mg tablets (NDC 0173-0760-

00).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room

Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Rash

Prior to initiation of treatment with LAMICTAL XR, inform patients that a rash or other signs or

symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and

instruct them to report any such occurrence to their healthcare providers immediately.

Hemophagocytic Lymphohistiocytosis

Prior to initiation of treatment with LAMICTAL XR, inform patients that excessive immune activation

may occur with LAMICTAL XR and that they should report signs or symptoms such as fever, rash, or

lymphadenopathy to a healthcare provider immediately.

Multiorgan Hypersensitivity Reactions, Blood Dyscrasias, and Organ Failure

Inform patients that multiorgan hypersensitivity reactions and acute multiorgan failure may occur with

LAMICTAL XR. Isolated organ failure or isolated blood dyscrasias without evidence of multiorgan

hypersensitivity may also occur. Instruct patients to contact their healthcare providers immediately if

they experience any signs or symptoms of these conditions [see Warnings and Precautions (5.3, 5.4)].

Suicidal Thinking and Behavior

Inform patients, their caregivers, and families that AEDs, including LAMICTAL XR, 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 LAMICTAL XR 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 LAMICTAL XR 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 antiepileptic drugs 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 LAMICTAL XR 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.

Oral Contraceptive Use

Instruct women to notify their healthcare providers if they plan to start or stop use of oral

contraceptives or other female hormonal preparations. Starting estrogen-containing oral contraceptives

may significantly decrease lamotrigine plasma levels and stopping estrogen-containing oral

contraceptives (including the pill-free week) may significantly increase lamotrigine plasma levels [see

Warnings and Precautions (5.8), Clinical Pharmacology (12.3)]. Also instruct women to promptly notify

their healthcare providers if they experience adverse reactions or changes in menstrual pattern (e.g.,

break-through bleeding) while receiving LAMICTAL XR in combination with these medications.

Discontinuing LAMICTAL XR

Instruct patients to notify their healthcare providers if they stop taking LAMICTAL XR for any reason

and not to resume LAMICTAL XR without consulting their healthcare providers.

Aseptic Meningitis

Inform patients that LAMICTAL XR may cause aseptic meningitis. Instruct them to notify their

healthcare providers immediately if they develop signs and symptoms of meningitis such as headache,

fever, nausea, vomiting, stiff neck, rash, abnormal sensitivity to light, myalgia, chills, confusion, or

drowsiness while taking LAMICTAL XR.

Potential Medication Errors

To avoid a medication error of using the wrong drug or formulation, strongly advise patients to visually

inspect their tablets to verify that they are LAMICTAL XR each time they fill their prescription [see

Dosage Forms and Strengths (3), How Supplied/Storage and Handling (16)]. Refer the patient to the

Medication Guide that provides depictions of the LAMICTAL XR extended-release tablets.

LAMICTAL XR is a trademark owned by or licensed to the GSK group of companies. The other brand

listed is a trademark owned by or licensed to its owner and is not owned by or licensed to the GSK

group of companies. The maker of this brand is not affiliated with and does not endorse the GSK group

of companies or its products.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2019 GSK group of companies or its licensor.

LXR:23PI

MEDICATION GUIDE

LAMICTAL (la-MIK-tal) XR (lamotrigine) extended-release tablets

What is the most important information I should know about LAMICTAL XR?

LAMICTAL XR may cause a serious skin rash that may cause you to be hospitalized or

even cause death.

There is no way to tell if a mild rash will become more serious. A serious skin rash can happen at

any time during your treatment with LAMICTAL XR, but is more likely to happen within the first

2 to 8 weeks of treatment. Children aged between 2 and 16 years have a higher chance of getting

this serious skin rash while taking LAMICTAL XR. LAMICTAL XR is not approved for use in

children younger than 13 years.

The risk of getting a serious skin rash is higher if you:

take LAMICTAL XR while taking valproate [DEPAKENE (valproic acid) or DEPAKOTE

(divalproex sodium)].

take a higher starting dose of LAMICTAL XR than your healthcare provider prescribed.

increase your dose of LAMICTAL XR faster than prescribed.

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 LAMICTAL XR.

Other serious reactions, including serious blood problems or liver problems. LAMICTAL

XR 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

weakness, fatigue

yellowing of your skin or the white part of your eyes

Like other antiepileptic drugs, LAMICTAL XR 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 LAMICTAL XR without first talking to a healthcare provider.

Stopping LAMICTAL XR suddenly can cause serious problems.

Suicidal thoughts or actions can be caused by things other than medicines. If you have

suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions in myself or a family

member?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about

symptoms.

LAMICTAL XR may cause aseptic meningitis, a serious inflammation of the protective

membrane that covers the brain and spinal cord.

Call your healthcare provider right away if you have any of the following symptoms:

headache

fever

nausea

vomiting

stiff neck

rash

unusual sensitivity to light

muscle pains

chills

confusion

drowsiness

Meningitis has many causes other than LAMICTAL XR, which your doctor would check for if

you developed meningitis while taking LAMICTAL XR.

LAMICTAL XR can cause other serious side effects. For more information ask your

healthcare provider or pharmacist. Tell your healthcare provider if you have any side effect that

bothers you. Be sure to read the section below entitled “What are the possible side effects of

LAMICTAL XR?”

People prescribed LAMICTAL XR have sometimes been given the wrong medicine

because many medicines have names similar to LAMICTAL XR, so always check that you

receive LAMICTAL XR.

Taking the wrong medication can cause serious health problems. When your healthcare provider

gives you a prescription for LAMICTAL XR:

Make sure you can read it clearly.

Talk to your pharmacist to check that you are given the correct medicine.

Each time you fill your prescription, check the tablets you receive against the pictures of

LAMICTAL XR (lamotrigine) extended-release tablets

25 mg, yellow

with white center

Imprinted with

LAMICTAL

XR 25

50 mg, green

with white center

Imprinted with

LAMICTAL

XR 50

100 mg, orange

with white center

Imprinted with

LAMICTAL

XR 100

200 mg, blue

with white center

Imprinted with

LAMICTAL

XR 200

250 mg, purple

with white center

Imprinted with

LAMICTAL

XR 250

300 mg, gray

with white center

Imprinted with

LAMICTAL

XR 300

What is LAMICTAL XR?

Do not take LAMICTAL XR:

Before taking LAMICTAL XR, tell your healthcare provider about all of your health conditions,

including if you:

the tablets below.

These pictures show the distinct wording, colors, and shapes of the tablets that help to identify

the right strength of LAMICTAL XR. Immediately call your pharmacist if you receive a

LAMICTAL XR tablet that does not look like one of the tablets shown below, as you may have

received the wrong medication.

LAMICTAL XR is a prescription medicine used:

together with other medicines to treat primary generalized tonic-clonic seizures and partial-

onset seizures in people aged 13 years and older.

alone when changing from 1 other medicine used to treat partial-onset seizures in people

aged 13 years and older.

It is not known if LAMICTAL XR is safe or effective in children younger than 13 years. Other

forms of LAMICTAL can be used in children aged 2 to 12 years.

It is not known if LAMICTAL XR is safe or effective when used alone as the first treatment of

seizures.

if you have had an allergic reaction to lamotrigine or to any of the inactive ingredients in

LAMICTAL XR. See the end of this leaflet for a complete list of ingredients in LAMICTAL XR.

have had a rash or allergic reaction to another antiseizure medicine.

have or have had depression, mood problems, or suicidal thoughts or behavior.

have had aseptic meningitis after taking LAMICTAL (lamotrigine) or LAMICTAL XR.

are taking oral contraceptives (birth control pills) or other female hormonal medicines. Do not

start or stop taking birth control pills or other female hormonal medicine until you have talked

Tell your healthcare provider about all the medicines you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements. LAMICTAL XR and certain other medicines may

interact with each other. This may cause serious side effects.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist

when you get a new medicine.

How should I take LAMICTAL XR?

What should I avoid while taking LAMICTAL XR?

Do not drive, operate machinery, or do other dangerous activities until you know how LAMICTAL XR

affects you.

What are the possible side effects of LAMICTAL XR?

LAMICTAL XR can cause serious side effects.

with your healthcare provider. Tell your healthcare provider if you have any changes in your

menstrual pattern such as breakthrough bleeding. Stopping these medicines while you are taking

LAMICTAL XR may cause side effects (such as dizziness, lack of coordination, or double

vision). Starting these medicines may lessen how well LAMICTAL XR works.

are pregnant or plan to become pregnant. It is not known if LAMICTAL XR may harm your unborn

baby. If you become pregnant while taking LAMICTAL XR, talk to your healthcare provider

about registering with the North American Antiepileptic Drug Pregnancy Registry. You can

enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect

information about the safety of antiepileptic drugs during pregnancy.

are breastfeeding. LAMICTAL XR passes into breast milk and may cause side effects in a

breastfed baby. If you breastfeed while taking LAMICTAL XR, watch your baby closely for

trouble breathing, episodes of temporarily stopping breathing, sleepiness, or poor sucking. Call

your baby’s healthcare provider right away if you see any of these problems. Talk to your

healthcare provider about the best way to feed your baby if you take LAMICTAL XR.

Take LAMICTAL XR exactly as prescribed.

Your healthcare provider may change your dose. Do not change your dose without talking to your

healthcare provider.

Do not stop taking LAMICTAL XR without talking to your healthcare provider. Stopping

LAMICTAL XR suddenly may cause serious problems. For example, if you have epilepsy and

you stop taking LAMICTAL XR suddenly, you may have seizures that do not stop. Talk with your

healthcare provider about how to stop LAMICTAL XR slowly.

If you miss a dose of LAMICTAL XR, take it as soon as you remember. If it is almost time for

your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2

doses at the same time.

If you take too much LAMICTAL XR, call your healthcare provider or your local Poison Control

Center or go to the nearest hospital emergency room right away.

You may not feel the full effect of LAMICTAL XR for several weeks.

If you have epilepsy, tell your healthcare provider if your seizures get worse or if you have any

new types of seizures.

LAMICTAL XR can be taken with or without food.

Do not chew, crush, or divide LAMICTAL XR.

Swallow LAMICTAL XR tablets whole.

If you have trouble swallowing LAMICTAL XR tablets, tell your healthcare provider because

there may be another form of LAMICTAL you can take.

If you receive LAMICTAL XR in a blister pack, examine the blister pack before use. Do not use

if blisters are torn, broken, or missing.

See “What is the most important information I should know about LAMICTAL XR?”

Common side effects of LAMICTAL XR include:

dizziness vomiting

tremor trouble with balance and coordination

double vision anxiety

nausea

Other common side effects that have been reported with another form of LAMICTAL include

headache, sleepiness, blurred vision, runny nose, and rash.

These are not all the possible side effects of LAMICTAL XR.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

How should I store LAMICTAL XR?

Keep LAMICTAL XR and all medicines out of the reach of children.

General information about the safe and effective use of LAMICTAL XR.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use LAMICTAL XR for a condition for which it was not prescribed. Do not give LAMICTAL XR to

other people, even if they have the same symptoms that you have. It may harm them.

If you take a urine drug screening test, LAMICTAL XR may make the test result positive for another

drug. If you require a urine drug screening test, tell the healthcare professional administering the test

that you are taking LAMICTAL XR.

You can ask your healthcare provider or pharmacist for information about LAMICTAL XR that is

written for health professionals.

What are the ingredients in LAMICTAL XR?

Active ingredient: lamotrigine.

Inactive ingredients: glycerol monostearate, hypromellose, lactose monohydrate, magnesium stearate,

methacrylic acid copolymer dispersion, polyethylene glycol 400, polysorbate 80, silicon dioxide (25-

and 50-mg tablets only), titanium dioxide, triethyl citrate, carmine (250-mg tablet only), iron oxide black

(50-, 250-, and 300-mg tablets only), iron oxide yellow (25-, 50-, and 100-mg tablets only), iron oxide

red (100-mg tablet only), FD&C Blue No. 2 Aluminum Lake (200- and 250-mg tablets only). Tablets are

printed with edible black ink.

For more information about LAMICTAL XR, call 1-888-825-5249.

LAMICTAL XR is a trademark owned by or licensed to the GSK group of companies. The other brands

listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed

to the GSK group of companies. The makers of these brands are not affiliated with and do not endorse

the GSK group of companies or its products.

Distributed by GlaxoSmithKline, Research Triangle Park, NC 27709

©2019 GSK group of companies or its licensor.

LXR:18MG

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised:

August 2019

PRINCIPAL DISPLAY PANEL

NDC 0173-0754-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

25 mg

Store LAMICTAL XR at room temperature between 59°F and 86°F (15°C and 30°C).

®

TM

Once A Day

R only

CAUTION: Verify Product Dispensed

30 Tablets

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

RTP, NC 27709

Made in India

Rev. 5/17

10000000146294

PRINCIPAL DISPLAY PANEL

NDC 0173-0755-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

50 mg

Once A Day

R only

X

®

TM

x

CAUTION: Verify Product Dispensed

30 tablets

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

RTP, NC 27709

Made in India

Rev. 5/17

10000000146295

PRINCIPAL DISPLAY PANEL

NDC 0173-0756-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

100 mg

Once A Day

R only

CAUTION: Verify Product Dispensed

30 tablets

®

TM

x

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

RTP, NC 27709

Made in India

Rev. 4/17

10000000146292

PRINCIPAL DISPLAY PANEL

NDC 0173-0757-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

200 mg

Once A Day

R only

CAUTION: Verify Product Dispensed

30 tablets

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

®

TM

x

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

RTP, NC 27709

Made in India

Rev. 4/17

10000000146293

PRINCIPAL DISPLAY PANEL

NDC 0173-0781-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED- RELEASE TABLETS

250 mg

Once A Day

R only

CAUTION: Verify Product Dispensed

30 tablets

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

®

TM

x

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

RTP, NC 27709

Made in India

Rev. 4/17

10000000146235

PRINCIPAL DISPLAY PANEL

NDC 0173-0761-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED- RELEASE TABLETS

300 mg

Once A Day

R only

CAUTION: Verify Product Dispensed

30 tablets

Dispense the accompanying Medication Guide to each patient.

See prescribing information for dosage information.

Do not use if printed safety seal under cap is broken or missing.

Store at 25 C (77 F); excursions permitted to 15 C to 30 C (59 F to 86 F) [see USP Controlled Room

Temperature].

GlaxoSmithKline

®

TM

x

RTP, NC 27709

Made in India

Rev. 5/17

10000000146291

PRINCIPAL DISPLAY PANEL

NDC 0173-0758-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

R only

For patients TAKING valproate

See prescribing information for other drugs that may affect dosing of LAMICTAL XR.

PATIENT TITRATION KIT:

21 25-mg Tablets

Each tablet contains 25 mg of lamotrigine

7 50-mg Tablets

Each tablet contains 50 mg of lamotrigine

Please check with your physician about proper maintenance dose before week 5.

Weeks

Tablets per day

1 & 2

Take 1 (25mg) tablet every OTHER day

3 &4

Take 1 (25mg) tablet ONCE a DAY

Take 1 (50mg) tablet ONCE a DAY

®

TM

x

*

Dispense the accompanying Medication Guide to each patient.

CAUTION: Verify Product Dispensed

GlaxoSmithKline

Research Triangle Park, NC 27709

Made in India

©2017 the GSK group of companies

546721-01 Rev. 11/17

PRINCIPAL DISPLAY PANEL

NDC 0173-0759-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

R only

For patients TAKING carbamazepine, phenytoin, phenobarbital, or primidone and NOT

TAKING valproate

See prescribing information for other drugs that may affect dosing of LAMICTAL XR.

PATIENT TITRATION KIT:

14 50-mg Tablets

Each tablet contains 50 mg of lamotrigine

14 100-mg Tablets

Each tablet contains 100 mg of lamotrigine

7 200-mg Tablets

Each tablet contains 200 mg of lamotrigine

Please check with your physician about proper maintenance dose before week 5.

Weeks

Tablets per day

1 & 2

Take 1 (50mg) tablet ONCE a DAY

3 &4

Take 1 (100mg) tablet ONCE a DAY

Take 1 (200mg) tablet ONCE a DAY

Dispense the accompanying Medication Guide to each patient.

CAUTION: Verify Product Dispensed

Made in India

©2017 the GSK group of companies

®

TM

x

*

546720-01 Rev. 11/17

PRINCIPAL DISPLAY PANEL

NDC 0173-0760-00

LAMICTAL XR

(LAMOTRIGINE)

EXTENDED-RELEASE TABLETS

R only

For patients NOT TAKING carbamazepine, phenytoin, phenobarbital, primidone, or valproate

See prescribing information for other drugs that may affect dosing of LAMICTAL XR.

®

TM

x

*

PATIENT TITRATION KIT:

14 25-mg Tablets

Each tablet contains 25 mg of lamotrigine

14 50-mg Tablets

Each tablet contains 50 mg of lamotrigine

7 100-mg Tablets

Each tablet contains 100 mg of lamotrigine

Please check with your physician about proper maintenance dose before week 5.

Weeks

Tablets per day

1 & 2

Take 1 (25mg) tablet ONCE a DAY

3 & 4

Take 1 (50mg) tablet ONCE a DAY

Take 1 (100mg) tablet ONCE a DAY

Dispense the accompanying Medication Guide to each patient.

CAUTION: Verify Product Dispensed

Made in India

©2017 the GSK group of companies

546722-01 Rev. 11/17

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 754

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

25 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

YELLOW (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;25

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 754-0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 755

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

GREEN (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;50

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 755-0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 756

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

Product Characteristics

Color

ORANGE (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

LAMICTAL;XR;10 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 756 -0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 757

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

20 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

Product Characteristics

Color

BLUE (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

LAMICTAL;XR;20 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 757-0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine kit

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 758

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 758 -0 0

1 in 1 PACKAGE, COMBINATION

0 7/0 6 /20 0 9

1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

Pa rt 2

Part 1 of 2

LAMITCAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

25 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

YELLOW (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;25

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Part 2 of 2

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

GREEN (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;50

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine kit

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 76 0

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 76 0 -0 0

1 in 1 PACKAGE, COMBINATION

0 7/0 6 /20 0 9

1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

Pa rt 2

Pa rt 3

Part 1 of 3

LAMITCAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

25 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

YELLOW (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;25

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Part 2 of 3

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

GREEN (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;50

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Part 3 of 3

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

Product Characteristics

Color

ORANGE (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

LAMICTAL;XR;10 0

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine kit

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 759

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 759 -0 0

1 in 1 PACKAGE, COMBINATION

0 7/0 6 /20 0 9

1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

Pa rt 2

Pa rt 3

Part 1 of 3

LAMITCAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

20 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

Product Characteristics

Color

BLUE (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

LAMICTAL;XR;20 0

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Part 2 of 3

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

Product Characteristics

Color

GREEN (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

LAMICTAL;XR;50

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Part 3 of 3

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

Product Characteristics

Color

ORANGE (with a white center)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

LAMICTAL;XR;10 0

Contains

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 7/0 6 /20 0 9

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 76 1

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

30 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

Product Characteristics

Color

GRAY (with a white center)

S core

no sco re

S hap e

OVAL (caplet-shaped)

S iz e

15mm

Flavor

Imprint Code

LAMICTAL;XR;30 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 76 1-0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/31/20 11

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 3/31/20 11

LAMICTAL XR

lamotrigine tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 173-0 78 1

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LAMO TRIGINE (UNII: U3H2749 8 KS) (LAMOTRIGINE - UNII:U3H2749 8 KS)

LAMOTRIGINE

250 mg

Inactive Ingredients

Ingredient Name

Stre ng th

GLYCERYL MO NO STEARATE (UNII: 230 OU9 XXE4)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

METHACRYLIC ACID (UNII: 1CS0 2G8 6 56 )

Po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

CO CHINEAL (UNII: TZ8 Z31B35M)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

GlaxoSmithKline LLC

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

Product Characteristics

Color

PURPLE (with a white center)

S core

no sco re

S hap e

OVAL (caplet-shaped)

S iz e

14mm

Flavor

Imprint Code

LAMICTAL;XR;250

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 173-0 78 1-0 0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /15/20 11

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 22115

0 8 /15/20 11

Labeler -

GlaxoSmithKline LLC (167380711)

Revised: 9/2019

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