GlaxoSmithKline LLC
LAMICTAL- lamotrigine tablet
LAMICTAL- lamotrigine tablet, chewable
LAMICTAL ODT- lamotrigine tablet, orally disintegrating
LAMICTAL- lamotrigine
LAMICTAL ODT- lamotrigine
GlaxoSmithKline LLC
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use LAMICTAL safely and effectively. See full prescribing information for LAMICTAL.
LAMICTAL (lamotrigine) Tablets
LAMICTAL (lamotrigine) Chewable Dispersible Tablets
LAMICTAL ODT (lamotrigine) Orally Disintegrating Tablets
Initial U.S. Approval: 1994
WARNING: SERIOUS SKIN RASHES
See full prescribing information for complete boxed warning.
Cases of life-threatening serious rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and/or rash-related death, have been caused by LAMICTAL. The rate of serious rash is greater in pediatric patients than in adults. Additional factors that may increase the risk of rash include (5.1):
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coadministration with valproate
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exceeding recommended initial dose of LAMICTAL
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exceeding recommended dose escalation of LAMICTAL
Benign rashes are also caused by LAMICTAL; however, it is not possible to predict which rashes will prove to be serious or life threatening. LAMICTAL should be discontinued at the first sign of rash, unless the rash is clearly not drug related. (5.1)
INDICATIONS AND USAGE
LAMICTAL is an antiepileptic drug (AED) indicated for: (1)
Epilepsy—adjunctive therapy in patients ≥2 years of age: (1.1) (1)
•
partial seizures
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primary generalized tonic-clonic seizures
•
generalized seizures of Lennox-Gastaut syndrome
Epilepsy—monotherapy in patients ≥16 years of age: conversion to monotherapy in patients with partial seizures who are receiving treatment with carbamazepine, phenobarbital, phenytoin, primidone, or valproate as the single AED. (1.1) (1)
Bipolar Disorder in patients ≥18 years of age: maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2) (1)
DOSAGE AND ADMINISTRATION
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Dosing is based on concomitant medications, indication, and patient age. (2.2, 2.4)
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To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. LAMICTAL Starter Kits and LAMICTAL ODT Patient Titration Kits are available for the first 5 weeks of treatment. (2.1, 16)
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Do not restart LAMICTAL in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. (2.1)
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Adjustments to maintenance doses will in most cases be required in patients starting or stopping estrogen-containing oral contraceptives. (2.1, 5.8)
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LAMICTAL should be discontinued over a period of at least 2 weeks (approximately 50% reduction per week). (2.1, 5.9)
Epilepsy (2)
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Adjunctive therapy—See Table 1 for patients >12 years of age and Tables 2 and 3 for patients 2 to 12 years. (2.2)
•
Conversion to monotherapy—See Table 4. (2.3)
Bipolar Disorder: See Tables 5 and 6. (2.4) (2)
DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 100 mg, 150 mg, and 200 mg scored. (3.1, 16) (3)
Chewable Dispersible Tablets: 2 mg, 5 mg, and 25 mg. (3.2, 16) (3)
Orally Disintegrating Tablets: 25 mg, 50 mg, 100 mg, and 200 mg. (3.3, 16) (3)
CONTRAINDICATIONS
Hypersensitivity to the drug or its ingredients. (Boxed Warning, 4) (4)
WARNINGS AND PRECAUTIONS
•
Life-threatening serious rash and/or rash-related death may result. (Boxed Warning, 5.1)
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Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), may be fatal or life threatening. Early signs may include rash, fever, and lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic failure, blood dyscrasias, or acute multiorgan failure. LAMICTAL should be discontinued if alternate etiology for this reaction is not found. (5.2)
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Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): May occur, either with or without an associated hypersensitivity syndrome. (5.3)
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Suicidal behavior and ideation. (5.4)
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Clinical worsening, emergence of new symptoms, and suicidal ideation/behaviors may be associated with treatment of bipolar disorder. Patients should be closely monitored, particularly early in treatment or during dosage changes. (5.5)
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Aseptic meningitis reported in pediatric and adult patients. (5.6)
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Medication errors involving LAMICTAL have occurred. In particular the names LAMICTAL or lamotrigine can be confused with names of other commonly used medications. Medication errors may also occur between the different formulations of LAMICTAL. (3.4, 5.7, 16, 17.10)
ADVERSE REACTIONS
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Most common adverse reactions (incidence ≥10%) in adult epilepsy clinical studies were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children in epilepsy clinical studies included vomiting, infection, fever, accidental injury, pharyngitis, abdominal pain, and tremor. (6.1)
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Most common adverse reactions (incidence >5%) in adult bipolar clinical studies were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia. (6.1)
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
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Valproate increases lamotrigine concentrations more than 2-fold. (7, 12.3)
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Carbamazepine, phenytoin, phenobarbital, and primidone decrease lamotrigine concentrations by approximately 40%. (7, 12.3)
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Oral estrogen-containing contraceptives and rifampin also decrease lamotrigine concentrations by approximately 50%. (7, 12.3)
USE IN SPECIFIC POPULATIONS
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Hepatic impairment: Dosage adjustments required. (2.1)
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Healthcare professionals can enroll patients in the Lamotrigine Pregnancy Registry (1-800-336-2176). Patients can enroll themselves in the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334). (8.1)
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Efficacy of LAMICTAL, used as adjunctive treatment for partial seizures, was not demonstrated in a small, randomized, double-blind, placebo-controlled study in very young pediatric patients (1 to 24 months). (8.4)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 09/2012
FULL PRESCRIBING INFORMATION: CONTENTS *
WARNING: SERIOUS SKIN RASHES
1 INDICATIONS AND USAGE
1.1 Epilepsy
1.2 Bipolar Disorder
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Considerations
2.2 Epilepsy – Adjunctive Therapy
2.3 Epilepsy – Conversion From Adjunctive Therapy to Monotherapy
2.4 Bipolar Disorder
2.5 Administration of LAMICTAL Chewable Dispersible Tablets
2.6 Administration of LAMICTAL ODT Orally Disintegrating Tablets
3 DOSAGE FORMS AND STRENGTHS
3.1 Tablets
3.2 Chewable Dispersible Tablets
3.3 Orally Disintegrating Tablets
3.4 Potential Medication Errors
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Serious Skin Rashes [see Boxed Warning]
5.2 Multiorgan Hypersensitivity Reactions and Organ Failure
5.3 Blood Dyscrasias
5.4 Suicidal Behavior and Ideation
5.5 Use in Patients With Bipolar Disorder
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 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 Trials
6.2 Other Adverse Reactions Observed in All Clinical Trials
6.3 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients With Hepatic Impairment
8.7 Patients With 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 Epilepsy
14.2 Bipolar Disorder
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Rash
17.2 Multiorgan Hypersensitivity Reactions, Blood Dyscrasias, and Organ Failure
17.3 Suicidal Thinking and Behavior
17.4 Worsening of Seizures
17.5 Central Nervous System Adverse Effects
17.6 Pregnancy and Nursing
17.7 Oral Contraceptive Use
17.8 Discontinuing LAMICTAL
17.9 Aseptic Meningitis
17.10 Potential Medication Errors
*
Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
1WARNING: SERIOUS SKIN RASHES
LAMICTAL® 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 (2 to 16 years of age) receiving LAMICTAL as adjunctive therapy for epilepsy and 0.3% (3 per 1,000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08% (0.8 per 1,000) in adult patients receiving LAMICTAL as initial monotherapy and 0.13% (1.3 per 1,000) in adult patients receiving LAMICTAL as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients (2 to 16 years of age) with epilepsy taking adjunctive LAMICTAL, there was 1 rash-related death. 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.
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. There are suggestions, yet to be proven, that the risk of rash may also be increased by (1) coadministration of LAMICTAL with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of LAMICTAL, or (3) exceeding the recommended dose escalation for LAMICTAL. However, cases have occurred in the absence of these factors.
Nearly all cases of life-threatening rashes caused by LAMICTAL 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, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, LAMICTAL 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)].
11 INDICATIONS AND USAGE
1.11.1 Epilepsy
Adjunctive Therapy: LAMICTAL is indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age:
-
•
-
partial seizures
-
•
-
primary generalized tonic-clonic seizures
-
•
-
generalized seizures of Lennox-Gastaut syndrome
Monotherapy: LAMICTAL is indicated for conversion to monotherapy in adults (≥16 years of age) with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).
Safety and effectiveness of LAMICTAL have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.
1.21.2 Bipolar Disorder
LAMICTAL is indicated for the maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults (≥18 years of age) treated for acute mood episodes with standard therapy. The effectiveness of LAMICTAL in the acute treatment of mood episodes has not been established.
The effectiveness of LAMICTAL as maintenance treatment was established in 2 placebo-controlled trials in patients with Bipolar I Disorder as defined by DSM-IV [see Clinical Studies (14.2)]. The physician who elects to prescribe LAMICTAL for periods extending beyond 16 weeks should periodically re-eva luate the long-term usefulness of the drug for the individual patient.
22 DOSAGE AND ADMINISTRATION
2.12.1 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 with valproate, (2) exceeding the recommended initial dose of LAMICTAL, or (3) exceeding the recommended dose escalation for LAMICTAL. 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 of LAMICTAL is exceeded and in patients with a history of allergy or rash to other AEDs.
LAMICTAL Starter Kits and LAMICTAL® ODT™ Patient Titration Kits provide LAMICTAL at doses consistent with the recommended titration schedule for the first 5 weeks of treatment, based upon concomitant medications, for patients with epilepsy (>12 years of age) and Bipolar I Disorder (≥18 years of age) and are intended to help reduce the potential for rash. The use of LAMICTAL Starter Kits and LAMICTAL ODT Patient Titration Kits is recommended for appropriate patients who are starting or restarting LAMICTAL [see How Supplied/Storage and Handling (16)].
It is recommended that LAMICTAL not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine, unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine, 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 Added to Drugs Known to Induce or Inhibit Glucuronidation: Drugs other than those listed in the Clinical Pharmacology section [see Clinical Pharmacology (12.3)] have not been systematically eva luated in combination with lamotrigine. 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 and doses of LAMICTAL may require adjustment based on clinical response.
