Lamotrigine (Page 3 of 19)

Bipolar Disorder

In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of lamotrigine tablets. In the clinical development program in adults with bipolar disorder, two patients experienced seizures shortly after abrupt withdrawal of lamotrigine tablets. Discontinuation of lamotrigine tablets 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 [see Warnings and Precautions (5.8)].

2.2 Epilepsy – Adjunctive Therapy

This section provides specific dosing recommendations for patients older than 12 years and patients aged 2 to 12 years. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AEDs or other concomitant medications (see Table 1 for patients older than 12 years and Table 2 for patients aged 2 to 12 years). A weight-based dosing guide for patients aged 2 to 12 years on concomitant valproate is provided in Table 3.

Patients Older than 12 Years

Recommended dosing guidelines are summarized in Table 1.

Table 1. Escalation Regimen for Lamotrigine Tablets in Patients Older than 12 Years with Epilepsy
*
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), and Clinical Pharmacology (12.3)].

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/day

Weeks 3 and 4

25 mg every day

50 mg/day

100 mg/day (in 2 divided doses)

Week 5 onward

to maintenance

Increase by 25 to 50 mg/day every 1 to 2 weeks.

Increase by 50 mg/day every 1 to 2 weeks.

Increase by 100 mg/day every 1 to 2 weeks.

Usual maintenance dose

100 to 200 mg/day with valproate alone 100 to 400 mg/day with valproate and other drugs that induce glucuronidation

(in 1 or 2 divided doses)

225 to 375 mg/day (in 2 divided doses)

300 to 500 mg/day (in 2 divided doses)

Patients Aged 2 to 12 Years

Recommended dosing guidelines are summarized in Table 2. Recommended dosing guidelines are summarized in Table 2.

Lower starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by lower 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. Lower starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by lower 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.

Table 2. Escalation Regimen for Lamotrigine Tablets in Patients Aged 2 to 12 Years with Epilepsy
Note: Only whole tablets should be used for dosing.
*
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), and Clinical Pharmacology (12.3)].

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 2Weeks 1 and 2

in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide) 0.15 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide)

in 1 or 2 divided doses, rounded down to the nearest whole tablet 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet

in 2 divided doses, rounded down to the nearest whole tablet 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet

Weeks 3 and 4Weeks 3 and 4

0.3 mg/kg/day

in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide)in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight-based dosing guide)

in 2 divided doses, rounded down to the nearest whole tablet 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet

in 2 divided doses, rounded down to the nearest whole tablet 1.2 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet

Week 5 Week 5

onward toonward to

maintenancemaintenance

The dose 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 dose 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 dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose.The dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose.

The dose 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.The dose 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.

UsualUsual

maintenancemaintenance

dosedose

(maximum 200 mg/day in 1 or 2 divided doses) with valproate alone 1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses) 1 to 3 mg/kg/day with valproate alone

(maximum 300 mg/day in 2 divided doses) 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses)

(maximum 400 mg/day in 2 divided doses) 5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided doses)

MaintenanceMaintenance

dose indose in

patients lesspatients less

than 30 kgthan 30 kg

May need to be increased by as much as 50%, based on clinical response. May need to be increased by as much as 50%, based on clinical response.

May need to be increased by as much as 50%, based on clinical response.May need to be increased by as much as 50%, based on clinical response.

May need to be increased by as much as 50%, based on clinical response.May need to be increased by as much as 50%, based on clinical response.

Table 3. The Initial Weight-Based Dosing Guide for Patients Aged 2 to 12 Years Taking Valproate (Weeks 1 to 4) with Epilepsy

If the patient’s weight is

Give this daily dose, using the most appropriate combination of lamotrigine 2 mg and 5 mg tablets

Greater than

And less than

Weeks 1 and 2

Weeks 3 and 4

6.7 kg 6.7 kg

14 kg 14 kg

2 mg every day 2 mg every other day

2 mg every day2 mg every day

14.1 kg 14.1 kg

27 kg 27 kg

2 mg every day2 mg every day

4 mg every day4 mg every day

27.1 kg 27.1 kg

34 kg 34 kg

4 mg every day4 mg every day

8 mg every day8 mg every day

34.1 kg 34.1 kg

40 kg 40 kg

5 mg every day5 mg every day

10 mg every day10 mg every day

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