A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Lamictal Indications, Dosage, Storage, Stability - Lamotrigine
Lamictal Indications, Dosage, Storage, Stability - Lamotrigine
INDICATIONS AND USAGE
Epilepsy:
Adjunctive Use: LAMICTAL is indicated as adjunctive
therapy for partial seizures in adults and pediatric patients (³2
years of age).
LAMICTAL is also indicated as adjunctive therapy for the generalized
seizures of Lennox-Gastaut syndrome in adult and pediatric patients (³2
years of age).
Monotherapy Use: LAMICTAL is indicated for conversion
to monotherapy in adults with partial seizures who are receiving treatment with
a single EIAED.
Safety and effectiveness of LAMICTAL have not been established
(1) as initial monotherapy, (2) for conversion to monotherapy from non enzyme-inducing
AEDs (e.g., valproate), or (3) for simultaneous conversion to monotherapy from
2 or more concomitant AEDs (see DOSAGE AND ADMINISTRATION).
Safety and effectiveness in patients below the age of 16 other
than those with partial seizures and the generalized seizures of Lennox-Gastaut
syndrome have not been established (see BOX WARNING).
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 patients 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 of 18 months duration in patients
with Bipolar I Disorder as defined by DSM-IV (see CLINICAL
STUDIES, Bipolar Disorder). The physician who elects to use LAMICTAL for
periods extending beyond 18 months should periodically re-evaluate the long-term
usefulness of the drug for the individual patient.
DOSAGE AND ADMINISTRATION
Epilepsy:
Adjunctive Use: LAMICTAL is indicated as adjunctive
therapy for partial seizures in adults and pediatric patients (³2
years of age). LAMICTAL is also indicated as adjunctive therapy for the generalized
seizures of Lennox-Gastaut syndrome in adult and pediatric patients (³2
years of age).
Monotherapy Use: LAMICTAL is indicated for conversion
to monotherapy in adults with partial seizures who are receiving treatment with
a single EIAED (e.g., carbamazepine, phenytoin, phenobarbital, etc.).
Safety and effectiveness of LAMICTAL have not been established
(1) as initial monotherapy, (2) for conversion to monotherapy from non enzyme-inducing
AEDs (e.g., valproate), or (3) for simultaneous conversion to monotherapy from
2 or more concomitant AEDs.
Safety and effectiveness in pediatric patients below the age
of 16 years other than those with partial seizures and the generalized seizures
of Lennox-Gastaut syndrome have not been established (see BOX
WARNING).
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 patients treated for acute
mood episodes with standard therapy. The effectiveness of LAMICTAL in the acute
treatment of mood episodes has not been established.
General Dosing Considerations for Epilepsy and Bipolar Disorder
Patients: The risk of nonserious rash is increased when the recommended
initial dose and/or the rate of dose escalation of LAMICTAL is exceeded. 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 been reported in the absence
of these factors (see BOX WARNING). Therefore,
it is important that the dosing recommendations be followed closely.
It is recommended that LAMICTAL not be restarted in patients
who discontinued due to rash associated with prior treatment with LAMICTAL,
unless the potential benefits clearly outweigh the risks. If the decision is
made to restart a patient who has discontinued LAMICTAL, 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 LAMICTAL for a period of more than 5 half-lives, it is recommended
that initial dosing recommendations and guidelines be followed. The half-life
of LAMICTAL is affected by other concomitant medications (see CLINICAL
PHARMACOLOGY: Pharmacokinetics and Drug Metabolism).
Patients With Hepatic Impairment: Experience in patients
with hepatic impairment is limited. Based on a clinical pharmacology study in
24 patients with moderate to severe liver dysfunction (see CLINICAL
PHARMACOLOGY), the following general recommendations can be made. Initial,
escalation, and maintenance doses should generally be reduced by approximately
50% in patients with moderate (Child-Pugh Grade B) and 75% in patients with
severe (Child-Pugh Grade C) hepatic impairment. Escalation and maintenance doses
should be adjusted according to clinical response.
Patients With Renal Functional Impairment: Initial doses
of LAMICTAL should be based on patients' AED regimen (see above); reduced maintenance
doses may be effective for patients with significant renal functional impairment
(see CLINICAL PHARMACOLOGY). Few patients
with severe renal impairment have been evaluated during chronic treatment with
LAMICTAL. Because there is inadequate experience in this population, LAMICTAL
should be used with caution in these patients.
Epilepsy:
Adjunctive Therapy With LAMICTAL for Epilepsy: This
section provides specific dosing recommendations for patients 2 to 12 years
of age and patients greater than 12 years of age. Within each of these age-groups,
specific dosing recommendations are provided depending upon whether or not the
patient is receiving valproate (Tables 9 and 10 for patients 2 to 12 years of
age, Tables 11 and 12 for patients greater than 12 years of age). In addition,
the section provides a discussion of dosing for those patients receiving concomitant
AEDs that have not been systematically evaluated in combination with LAMICTAL.
For dosing guidelines for LAMICTAL below, enzyme-inducing antiepileptic
drugs (EIAEDs) include phenytoin, carbamazepine, phenobarbital, and primidone.
Patients 2 to 12 Years of Age: Recommended dosing guidelines
for LAMICTAL added to an antiepileptic drug (AED) regimen containing valproate
are summarized in Table 9. Recommended dosing guidelines for LAMICTAL added
to EIAEDs are summarized in Table 10.
LAMICTAL Added to Antiepileptic Drugs Other Than Enzyme-Inducing
Antiepileptic Drugs and Valproate: The effect of AEDs other than EIAEDs
and valproate on the metabolism of LAMICTAL is not currently known. Therefore,
no specific dosing guidelines can be provided in that situation. Conservative
starting doses and dose escalations (as with concomitant valproate) would be
prudent; maintenance dosing would be expected to fall between the maintenance
dose with valproate and the maintenance dose without valproate, but with an
EIAED.
Note that the starting doses and dose escalations listed in
Tables 9 and 10 are different than those used in clinical trials; however, the
maintenance doses are the same as in clinical trials. Smaller starting doses
and slower dose escalations than those used in clinical trials are recommended
because of the suggestions that the risk of rash may be decreased by smaller
starting doses and slower dose escalations. Therefore, maintenance doses will
take longer to reach in clinical practice than in clinical trials. It may take
several weeks to months to achieve an individualized maintenance dose. Maintenance
doses in patients weighing less than 30 kg, regardless of age or concomitant
AED, may need to be increased as much as 50%, based on clinical response.
The smallest available strength of LAMICTAL Chewable Dispersible
Tablets is 2 mg, and only whole tablets should be administered. If the calculated
dose cannot be achieved using whole tablets, the dose should be rounded down
to the nearest whole tablet (see HOW SUPPLIED
and PATIENT INFORMATION for a description of
the available sizes of LAMICTAL Chewable Dispersible Tablets).
|
Table 9. LAMICTAL Added to an Antiepileptic Regimen Containing
Valproate in Patients 2 to 12 Years of Age
|
|
Weeks 1 and 2
|
0.15 mg/kg/day in 1 or 2 divided doses, rounded down
to the nearest whole tablet. Only whole tablets should be sed for dosing.
|
|
Weeks 3 and 4
|
0.3 mg/kg/day in 1 or 2 divided doses, rounded down to
the nearest whole tablet.
|
|
Weight based dosing can be achieved by using the following
guide:
|
|
If the patient s weight is
|
Give this daily dose, using the most appropriate combination
of LAMICTAL 2-mg and 5-mg tablets
|
|
Greater than
|
And less than Weeks 1 and 2 Weeks 3 and 4
|
|
6.7 kg
|
14 kg
|
2 mg every other day 2 mg every day
|
|
14.1 kg
|
27 kg
|
2 mg every day 4 mg every day
|
|
27.1 kg
|
34 kg
|
4 mg every day 8 mg every day
|
|
34.1 kg
|
40 kg
|
5 mg every day 10 mg every day
|
|
Usual maintenance dose: 1 to 5 mg/kg/day (maximum 200
mg/day in 1 or 2 divided doses). To achieve the usual maintenance dose,
subsequent doses should be increased every 1 to 2 weeks as follows: calculate
0.3 mg/kg/day, round this amount down to the nearest whole tablet, and
add this amount to the previously administered daily dose. The usual maintenance
dose in patients adding LAMICTAL to valproate alone ranges from 1 to 3
mg/kg/day. Maintenance doses in patients weighing less than 30 kg may
need to be increased by as much as 50%, based on clinical response.
|
|
|
|
|
|
|
|
Table 10. LAMICTAL Added to Enzyme-Inducing Antiepileptic
Drugs (Without Valproate) in Patients 2 to 12 Years of Age
|
|
Weeks 1 and 2
|
0.6 mg/kg/day in 2 divided doses, rounded down to the
nearest whole tablet.
|
|
Weeks 3 and 4
|
1.2 mg/kg/day in 2 divided doses, rounded down to the
nearest whole tablet.
|
|
Usual maintenance dose: 5 to 15 mg/kg/day (maximum 400
mg/day in 2 divided doses). To achieve the usual maintenance dose, subsequent
doses should be increased every 1 to 2 weeks as follows: calculate 1.2
mg/kg/day, round this amount down to the nearest whole tablet, and add
this amount to the previously administered daily dose. Maintenance doses
in patients weighing less than 30 kg may need to be increased by as much
as 50%, based on clinical response.
|
Patients Over 12 Years of Age: Recommended dosing guidelines
for LAMICTAL added to valproate are summarized in Table 11. Recommended dosing
guidelines for LAMICTAL added to EIAEDs are summarized in Table 12.
LAMICTAL Added to Antiepileptic Drugs Other Than Enzyme-Inducing
Antiepileptic Drugs and Valproate: The effect of AEDs other than EIAEDs
and valproate on the metabolism of LAMICTAL is not currently known. Therefore,
no specific dosing guidelines can be provided in that situation. Conservative
starting doses and dose escalations (as with concomitant valproate) would be
prudent; maintenance dosing would be expected to fall between the maintenance
dose with valproate and the maintenance dose without valproate, but with an
EIAED.
|
Table 11. LAMICTAL Added to an Antiepileptic Drug Regimen
Containing Valproate in Patients Over 12 Years of Age
|
|
Weeks 1 and 2
|
25 mg every other day
|
|
Weeks 3 and 4
|
25 mg every day
|
|
Usual maintenance dose: 100 to 400 mg/day (1 or 2 divided
doses). To achieve maintenance, doses may be increased by 25 to 50 mg/day
every 1 to 2 weeks. The usual maintenance dose in patients adding LAMICTAL
to valproate alone ranges from 100 to 200 mg/day.
|
|
Table 12. LAMICTAL Added to Enzyme-Inducing Antiepileptic
Drugs (Without Valproate) in Patients Over 12 Years of Age
|
|
Weeks 1 and 2
|
50 mg/day
|
|
Weeks 3 and 4
|
100 mg/day in 2 divided doses
|
|
Usual maintenance dose: 300 to 500 mg/day (in 2 divided
doses). To achievemaintenance, doses may be increased by 100 mg/day every
1 to 2 weeks.
|
Conversion From a Single Enzyme-Inducing Antiepileptic Drug
to Monotherapy With LAMICTAL in Patients ³16
Years of Age With Epilepsy: The goal of the transition regimen is to effect
the conversion to monotherapy with LAMICTAL under conditions that ensure adequate
seizure control while mitigating the risk of serious rash associated with the
rapid titration of LAMICTAL.
The conversion regimen involves 2 steps. In the first, LAMICTAL
is titrated to the targeted dose while maintaining the dose of the EIAED at
a fixed level; in the second step, the EIAED is gradually withdrawn over a period
of 4 weeks.
The recommended maintenance dose of LAMICTAL as monotherapy
is 500 mg/day given in 2 divided doses.
LAMICTAL should be added to an EIAED to achieve a dose of 500
mg/day according to the guidelines in Table 12. The regimen for the withdrawal
of the concomitant EIAED is based on experience gained in the controlled monotherapy
clinical trial. In that trial, the concomitant EIAED was withdrawn by 20% decrements
each week over a 4-week period.
Because of an increased risk of rash, the recommended initial
dose and subsequent dose escalations of LAMICTAL should not be exceeded (see
BOX WARNING).
Conversion from the Combination of LAMICTAL and Valproate
to Monotherapy With LAMICTAL in Patients = 16 Years of Age With Epilepsy:
Discontinuing valproate is known to shorten the half-life of lamotrigine. However,
there is insufficient information to provide dosing guidelines for this conversion.
The safety and effectiveness of LAMICTAL has not been established for the conversion
to monotherapy from the 2 drug combination of LAMICTAL and valproate in patients
with epilepsy.
Usual Maintenance Dose for Epilepsy: The usual maintenance
doses identified in Tables 9-12 are derived from dosing regimens employed in
the placebo-controlled adjunctive studies in which the efficacy of LAMICTAL
was established. In patients receiving multidrug regimens employing EIAEDs without
valproate, maintenance doses of adjunctive LAMICTAL as high as 700 mg/day
have been used. In patients receiving valproate alone, maintenance doses
of adjunctive LAMICTAL as high as 200 mg/day have been used. The advantage of
using doses above those recommended in Tables 9-12 has not been established
in controlled trials.
Discontinuation Strategy for Patients With Epilepsy: For
patients receiving LAMICTAL in combination with other AEDs, a reevaluation of
all AEDs in the regimen should be considered if a change in seizure control
or an appearance or worsening of adverse experiences is observed.
If a decision is made to discontinue therapy with LAMICTAL,
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 PRECAUTIONS).
Discontinuing an EIAED should prolong the half-life of lamotrigine;
discontinuing valproate should shorten the half-life of lamotrigine.
Target Plasma Levels for Patients With Epilepsy: A therapeutic
plasma concentration range has not been established for lamotrigine. Dosing
of LAMICTAL should be based on therapeutic response.
Bipolar Disorder: The goal of maintenance treatment
with LAMICTAL is to delay the time to occurrence of mood episodes (depression,
mania, hypomania, mixed episodes) in patients treated for acute mood episodes
with standard therapy. The target dose of LAMICTAL is 200 mg/day (100 mg/day
in combination with valproate and 400 mg/day in combination with carbamazepine
or other enzyme-inducing drugs). In the clinical trials, doses up to 400 mg/day
as monotherapy were evaluated, however, no additional benefit was seen at 400
mg/day compared to 200 mg/day (see CLINICAL STUDIES:
Bipolar Disorder). Accordingly, doses above 200 mg/day are not recommended.
Treatment with LAMICTAL is introduced, based on concurrent medications, according
to the regimen outlined in Table 13. If other psychotropic medications are withdrawn
following stabilization, the dose of LAMICTAL should be adjusted. For patients
discontinuing valproate, the dose of LAMICTAL should be doubled over a 2-week
period in equal weekly increments (see Table 14). For patients
discontinuing carbamazepine or other enzyme inducing agents, the dose of LAMICTAL
should remain constant for the first week and then should be decreased by half
over a 2-week period in equal weekly decrements (see Table 14). The dose of
LAMICTAL may then be further adjusted to the target dose (200 mg) as clinically
indicated.
If other drugs are subsequently introduced, the dose of LAMICTAL
may need to be adjusted. In particular, the introduction of valproate requires
reduction in the dose of LAMICTAL (see CLINICAL
PHARMACOLOGY: Drug Interactions).
Because of an increased risk of rash, the recommended initial
dose and subsequent dose escalations of LAMICTAL should not be exceeded (see
BOX WARNING).
|
Table 13. Escalation Regimen for LAMICTAL for Patients
With Bipolar Disorder
|
|
|
For Patients Not Taking Carbamazepine (or Other Enzyme-
Inducing Drugs) or Valproate
|
For Patients Taking Valproate
|
For Patients Taking Carbamazepine (or Other Enzyme-Inducing
Drugs) and Not Taking Valproate
|
|
Weeks 1 and 2
|
25 mg daily
|
25 mg every other day
|
50 mg daily
|
|
Weeks 3 and 4
|
50 mg daily
|
25 mg daily
|
100 mg daily, in divided doses
|
|
Week 5
|
100 mg daily
|
50 mg daily
|
200 mg daily, in divided doses
|
|
Week 6
|
200 mg daily
|
100 mg daily
|
300 mg daily, in divided doses
|
| |
|
Week 7
|
200 mg daily
|
100 mg daily
|
up to 400 mg daily, in divided doses
|
|
Table 14. Adjustments to LAMICTAL Dosing
for Patients With Bipolar Disorder Following Discontinuation of Psychotropic
Medications
|
|
|
Discontinuation of Psychotropic Drugs excluding Valproate,
Carbamazepine, or Other Enzyme-Inducing Drugs
|
After Discontinuation of Valproate
|
After Discontinuation of Carbamazepine or Other Enzyme-Inducing
Drugs
|
|
Current LAMICTAL Dose (mg/day) 100
|
Current LAMICTAL dose (mg/day) 400
|
|
Week 1
|
Maintain current LAMICTAL dose
|
150
|
400
|
|
Week 2
|
Maintain current LAMICTAL dose
|
200
|
300
|
|
Week 3 onward
|
Maintain current LAMICTAL dose
|
200
|
200
|
There is no body of evidence available to answer the question
of how long the patient should remain on LAMICTAL therapy. Systematic evaluation
of the efficacy of LAMICTAL in patients with either depression or mania who
responded to standard therapy during an acute 8 to 16 week treatment phase and
were then randomized to LAMICTAL or placebo for up to 76 weeks of observation
for affective relapse demonstrated a benefit of such maintenance treatment (see
CLINICAL STUDIES: Bipolar Disorder). Nevertheless,
patients should be periodically reassessed to determine the need for maintenance
treatment.
Discontinuation Strategy in Bipolar Disorder: As with
other AEDs, LAMICTAL should not be abruptly discontinued. In the controlled
clinical trials, there was no increase in the incidence, type, or severity of
adverse experiences following abrupt termination of LAMICTAL. In clinical trials
in patients with bipolar disorder, 2 patients experienced seizures shortly after
abrupt withdrawal of LAMICTAL. However, there were confounding factors that
may have contributed to the occurrence of seizures in these bipolar patients.
Discontinuation of LAMICTAL should involve a step-wise reduction of dose over
at least 2 weeks (approximately 50% per week) unless safety concerns require
a more rapid withdrawal.
Administration of LAMICTAL Chewable Dispersible Tablets:
LAMICTAL Chewable Dispersible Tablets may be swallowed whole, chewed, or dispersed
in water or diluted fruit juice. If the tablets are chewed, consume a small
amount of water or diluted fruit juice to aid in swallowing.
To disperse LAMICTAL Chewable Dispersible Tablets, add the
tablets to a small amount of liquid (1 teaspoon, or enough to cover the medication).
Approximately 1 minute later, when the tablets are completely dispersed, swirl
the solution and consume the entire quantity immediately.
No attempt should be made to administer partial quantities
of the dispersed tablets.
HOW SUPPLIED
LAMICTAL Tablets, 25-mg
White, scored, shield-shaped tablets debossed with "LAMICTAL"
and "25", bottles of 100 (NDC 0173-0633-02).
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature] in a dry place.
LAMICTAL Tablets, 100-mg
Peach, scored, shield-shaped tablets debossed with "LAMICTAL"
and "100", bottles of 100 (NDC 0173-0642-55).
LAMICTAL Tablets, 150-mg
Cream, scored, shield-shaped tablets debossed with "LAMICTAL"
and "150", bottles of 60 (NDC 0173-0643-60).
LAMICTAL Tablets, 200-mg
Blue, scored, shield-shaped tablets debossed with "LAMICTAL"
and "200", bottles of 60 (NDC 0173-0644-60).
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature] in a dry place and protect from light.
LAMICTAL Chewable Dispersible Tablets, 2-mg
White to off-white, round tablets debossed with LTG over 2
, bottles of 30 (NDC 0173-0699-00). ORDER DIRECTLY FROM GlaxoSmithKline 1-800-334-4153.
LAMICTAL Chewable Dispersible Tablets, 5-mg
White to off-white, caplet-shaped tablets debossed with GX
CL2 , bottles of 100 (NDC 0173-0526-00).
LAMICTAL Chewable Dispersible Tablets, 25-mg
White, super elliptical-shaped tablets debossed with GX CL5
, bottles of 100 (NDC 0173-0527-00).
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature] in a dry place.
LAMICTAL Starter Kit for Patients Taking Valproate
25-mg, white, scored, shield-shaped tablets debossed
with "LAMICTAL" and "25", blisterpack of 35 tablets (NDC 0173-0633-10).
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86F)
[see USP Controlled Room Temperature] in a dry place.
LAMICTAL Starter Kit for Patients Taking Enzyme-Inducing
Drugs and Not Taking Valproate 25-mg, white, scored, shield-shaped tablets
debossed with "LAMICTAL" and "25" and 100-mg, peach, scored, shield-shaped
tablets debossed with "LAMICTAL" and 100 , blisterpack of 84, 25-mg tablets
and 14, 100-mg tablets (NDC 0081-0594-01)
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature] in a dry place and protect from light.
LAMICTAL Starter Kit for Patients Not Taking Enzyme-Inducing
Drugs or Valproate [FOR USE IN BIPOLAR PATIENTS ONLY] 25-mg, white, scored,
shield-shaped tablets debossed with "LAMICTAL" and "25" and 100-mg, peach,
scored, shield-shaped tablets debossed with "LAMICTAL" and 100 , blisterpack
of 42, 25-mg tablets and 7, 100-mg tablets (NDC 0173-0594-02).
Store at 25°C (77°F);
excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature] in a dry place and protect from light.
Manufactured for GlaxoSmithKline
Research Triangle Park, NC 27709 by DSM Pharmaceuticals,
Inc. Greenville, NC 27834 or GlaxoSmithKline Research Triangle Park, NC 27709
DEPAKENE and DEPAKOTE are registered trademarks
of Abbott Laboratories. _ 2003, GlaxoSmithKline. All rights reserved. June 2003 RL-2011
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