DOSAGE AND ADMINISTRATION
EPILEPSY:
Adjunctive Use: LAMICTAL is indicated as adjunctive therapy for partial seizures in adults and pediatric patients (>/=2 years of age). LAMICTAL is also indicated as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (>/=2 years of age). Monotherapy Use: LAMICTAL is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single 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. 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. Patients 2 to 12 Years of Age: LAMICTAL Added to an Antiepileptic Drug Regimen Containing Valproate: Recommended dosing guidelines are summarized in Table 9.
LAMICTAL Added to Carbamazepine, Phenytoin, Phenobarbital, or Primidone: Recommended dosing guidelines are summarized in Table 10.
LAMICTAL Added to Oxcarbazepine or Levetiracetam, or to Antiepileptic Drugs for Which the Interaction With Lamotrigine is Not Known: Oxcarbazepine and levetiracetam do not affect the apparent clearance of lamotrigine. Specific dosing guidelines for the addition of LAMICTAL to oxcarbazepine or levetiracetam have not been studied in clinical trials. The effect of AEDs other than those already specified on the metabolism of LAMICTAL is not currently known. Therefore, no specific dosing guidelines can be provided. 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, which decreases the apparent clearance of lamotrigine, and the maintenance dose without valproate, but with carbamazepine, phenytoin, phenobarbital, or primidone, which increase the apparent clearance of lamotrigine.
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 used 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 Carbamazepine, Phenytoin, Phenobarbital, or Primidone * (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.
|
|
*Rifampin has also been shown to increase the apparent clearance of lamotrigine (see PRECAUTIONS: Drug Interactions)
|
|
Patients Over 12 Years of Age: LAMICTAL Added to an Antiepileptic Drug Regimen Containing Valproate: Recommended dosing guidelines are summarized in Table 11.
LAMICTAL Added to Carbamazepine, Phenytoin, Phenobarbital, or Primidone: Recommended dosing guidelines are summarized in Table 12.
LAMICTAL Added to Oxcarbazepine or Levetiracetam, or to Antiepileptic Drugs for Which the Interaction With Lamotrigine is Not Known: Oxcarbazepine and levetiracetam do not affect the apparent clearance of lamotrigine. Specific dosing guidelines for the addition of LAMICTAL to oxcarbazepine or levetiracetam have not been studied in clinical trials. The effect of AEDs other than those already specified on the metabolism of LAMICTAL is not currently known. Therefore, no specific dosing guidelines can be provided. 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, which decreases the apparent clearance of lamotrigine, and the maintenance dose without valproate, but with carbamazepine, phenytoin, phenobarbital, or primidone, which increase the apparent clearance of lamotrigine.
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 Carbamazepine, Phenytoin, Phenobarbital, or Primidone * (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 achieve maintenance, doses may be increased by 100 mg/day every 1 to 2 weeks.
|
|
*Rifampin has also been shown to increase the apparent clearance of lamotrigine (see PRECAUTIONS: Drug Interactions)
|
|
Conversion From Adjunctive Therapy With Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate as the Single AED to Monotherapy With LAMICTAL in Patients >/=16 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 recommended maintenance dose of LAMICTAL as monotherapy is 500 mg/day given in 2 divided doses.
To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of LAMICTAL should not be exceeded (see BOX WARNING).
Conversion From Adjunctive Therapy With Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy With LAMICTAL: After achieving a dose of 500 mg/day of LAMICTAL according to the guidelines in Table 12, the concomitant AED should be withdrawn by 20% decrements each week over a 4-week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.
Conversion From Adjunctive Therapy With Valproate to Monotherapy With LAMICTAL: The conversion regimen involves 4 steps. First, achieve a dose of 200 mg/day of LAMICTAL according to the guidelines in Table 11. Second, while keeping the LAMICTAL dose at 200 mg/day, valproate should be gradually decreased to a dose of 500 mg/day by decrements no greater than 500 mg/day per week. This dosage regimen is then maintained for 1 week. Third, LAMICTAL should then be increased to 300 mg/day while valproate is simultaneously decreased to 250 mg/day. This regimen should be maintained for 1 week. Fourth, valproate should then be discontinued completely and LAMICTAL increased by 100 mg/day every week until the recommended monotherapy dose of 500 mg/day is reached (see Table 13).
Table 13. Conversion From Adjunctive Therapy With Valproate to Monotherapy With LAMICTAL in Patients >/=16 Years of Age.
|
|
LAMICTAL
|
Valproate
|
|
Step 1
|
Achieve a dose of 200 mg/day according to guidelines in Table 11 (if not already on 200 mg/day). |
Maintain previous stable dose.
|
|
Step 2
|
Maintain at
200 mg/day. |
Decrease to 500 mg/day by decrements no greater than 500 mg/day per week and then maintain the dose of 500 mg/day for 1 week. |
|
Step 3
|
Increase to 300 mg/day and maintain for
1 week. |
Simultaneously decrease to 250 mg/day and maintain for
1 week. |
|
Step 4
|
Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. |
Discontinue. |
|
Conversion From Adjunctive Therapy With Antiepileptic Drugs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With LAMICTAL: No specific dosing guidelines can be provided for conversion to monotherapy with LAMICTAL with AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate.. 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 carbamazepine, phenytoin, phenobarbital, or primidone 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 9-13 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 carbamazepine, phenytoin, phenobarbital, or primidone 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 patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or rifampin, which increase the apparent clearance of lamotrigine). 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 14. 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 15). For patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or rifampin, 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 15). 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).
To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of LAMICTAL should not be exceeded (see BOX WARNING).
Table 14. Escalation Regimen for LAMICTAL for Patients With Bipolar Disorder *
|
|
For Patients Not
Taking Carbamazepine,
Phenytoin,
Phenobarbital,
Primidone, or
Rifampin **/*
and Not
Taking Valproate **/** |
For Patients
Taking
Valproate
|
For Patients Taking
Carbamazepine, Phenytoin,
Phenobarbital, Primidone,
or Rifampin **/*
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
|
|
*See CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions for a description of known drug interactions.
|
| **/* Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin have been shown to increase the apparent clearance of lamotrigine.
|
| **/** Valporate has been shown to decrease the apparent clearance of lamotrigine.
|
|
Table 15. Adjustments to LAMICTAL Dosing for Patients With Bipolar Disorder Following Discontinuation of Psychotropic Medications *
|
|
Discontinuation of
Psychotropic Drugs
(excluding Carbamazepine,
Phenytoin, Phenobarbital,
Primidone, Rifampin **/*,
or Valproate **/**)
|
After Discontinuation
of Valproate **/** |
After Discontinuation of
Carbamazepine,
Phenytoin, Phenobarbital,
Primidone, or Rifampin **/* |
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
|
|
*See CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions for a description of known drug interactions.
|
| **/* Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin have been shown to increase the apparent clearance of lamotrigine.
|
| **/** Valporate has been shown to decrease the apparent clearance of lamotrigine.
|
|
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 (59-86°F) [see USP Controlled Room Temperature] in a dry place. LAMICTAL Starter Kit for Patients
Taking
Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Rifampin 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 0173-0594-01) 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
Carbamazepine, Phenytoin, Phenobarbital, Primidone, Rifampin, 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.
|
