Specific Dosages ;

Dosing: Adult

Note: Only whole tablets should be used for dosing, round calculated dose down to the nearest whole tablet. Enzyme-inducing regimens specifically refer to those containing carbamazepine, phenytoin, phenobarbital, or primidone.

Lennox-Gastaut (adjunctive), primary generalized tonic-clonic seizures (adjunctive) or partial seizures (adjunctive): Oral:

Immediate release formulations:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid: Initial: Week 1 and 2: 25 mg once daily; Week 3 and 4: 50 mg once daily; Week 5 and beyond: Increase by 50 mg/day every 1-2 weeks; Maintenance: 225-375 mg/day in 2 divided doses

Regimens containing valproic acid: Initial: Week 1 and 2: 25 mg every other day; Week 3 and 4: 25 mg once daily; Week 5 and beyond: Increase by 25-50 mg/day every 1-2 weeks; Maintenance: 100-200 mg/day (valproic acid alone) or 100-400 mg/day (valproic acid and other drugs that induce glucuronidation)

Regimens containing carbamazepine, phenytoin, phenobarbital, or primidone and without valproic acid: Initial: Week 1 and 2: 50 mg once daily; Week 3 and 4: 100 mg/day in 2 divided doses; Week 5 and beyond: Increase by 100 mg/day every 1-2 weeks; Maintenance: 300-500 mg/day in 2 divided doses; maximum daily dose: 700 mg

Partial seizures (adjunctive) and primary generalized tonic-clonic seizures (adjunctive):

Extended release formulation: Note: Dose increases after week 8 should not exceed 100 mg/day at weekly intervals:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid: Initial: Week 1 and 2: 25 mg once daily; Week 3 and 4: 50 mg once daily; Week 5: 100 mg once daily; Week 6: 150 mg once daily; Week 7: 200 mg once daily; Maintenance: 300-400 mg once daily

Regimens containing valproic acid: Initial: Week 1 and 2: 25 mg every other day; Week 3 and 4: 25 mg once daily; Week 5: 50 mg once daily; Week 6: 100 mg once daily; Week 7: 150 mg once daily; Maintenance: 200-250 mg once daily

Regimens containing carbamazepine, phenytoin, phenobarbital, or primidone and without valproic acid: Initial: Week 1 and 2: 50 mg once daily; Week 3 and 4: 100 mg once daily; Week 5: 200 mg once daily; Week 6: 300 mg once daily; Week 7: 400 mg once daily; Maintenance: 400-600 mg once daily

Conversion from adjunctive therapy with a single enzyme-inducing AED regimen for partial seizures to monotherapy with lamotrigine: Note: Goal is to achieve a lamotrigine monotherapy dose of 500 mg/day in 2 divided doses for immediate release formulations and a lamotrigine monotherapy dosage range of 250-300 mg once daily for the extended release formulation.

Conversion strategy from adjunctive therapy with valproic acid:

Immediate release formulations:

- Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 200 mg/day.

- Then taper valproic acid dose in decrements of not >500 mg/day/week to a valproic acid dosage of 500 mg/day; this dosage should be maintained for 1 week. The lamotrigine dosage should then be increased to 300 mg/day while valproic acid is simultaneously decreased to 250 mg/day; this dosage should be maintained for 1 week.

- Valproic acid may then be discontinued, while the lamotrigine dose is increased by 100 mg/day at weekly intervals to achieve a lamotrigine maintenance dose of 500 mg/day in 2 divided doses.

Extended release formulation:

- Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 150 mg/day.

- Then taper valproic acid dose in decrements of not >500 mg/day/week to a valproic acid dose of 500 mg/day; this dosage should be maintained for 1 week. The lamotrigine dosage should then be increased to 200 mg/day while valproic acid is simultaneously decreased to 250 mg/day; this dosage should be maintained for 1 week.

- Valproic acid may then be discontinued, while the lamotrigine dose is increased to achieve a maintenance dosage range of 250-300 mg once daily.

Conversion strategy from adjunctive therapy with carbamazepine, phenytoin, phenobarbital, or primidone: Immediate release formulations and extended release formulation:

- Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 500 mg/day.

- Concomitant enzyme-inducing AED should then be withdrawn by 20% decrements each week over a 4-week period.

- Following withdrawal of the enzyme-inducing AED, the dosage of lamotrigine extended release may be tapered in decrements of not >100 mg/day at intervals of 1 week to achieve a maintenance dosage range of 250-300 mg once daily; no further dosage reduction is required for lamotrigine immediate release formulations.

Conversion strategy from adjunctive therapy with AED other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid:

Immediate release formulations: No specific guidelines available

Extended release formulation: Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 250-300 mg/day. Concomitant AED should then be withdrawn by 20% decrements each week over a 4 week period.

Bipolar disorder: Immediate release formulations:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid: Initial: Week 1 and 2: 25 mg once daily; Week 3 and 4: 50 mg once daily; Week 5: 100 mg once daily; Week 6 and maintenance: 200 mg once daily

Regimens containing valproic acid: Initial: Week 1 and 2: 25 mg every other day; Week 3 and 4: 25 mg once daily; Week 5: 50 mg once daily; Week 6 and maintenance: 100 mg once daily

Regimens containing carbamazepine, phenytoin, phenobarbital, or primidone and without valproic acid: Initial: Week 1 and 2: 50 mg once daily; Week 3 and 4: 100 mg/day in divided doses; Week 5: 200 mg/day in divided doses; Week 6: 300 mg/day in divided doses; Maintenance: up to 400 mg/day in divided doses

Adjustment following discontinuation of psychotropic medication:

Discontinuing valproic acid with current dose of lamotrigine 100 mg/day: 150 mg/day for week 1, then increase to 200 mg/day beginning week 2

Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or rifampin with current dose of lamotrigine 400 mg/day: 400 mg/day for week 1, then decrease to 300 mg/day for week 2, then decrease to 200 mg/day beginning week 3

Conversion from immediate release to extended release (Lamictal® XR™): Initial dose of the extended release tablet should match the total daily dose of the immediate-release formulation. Adjust dose as needed within the recommended dosing guidelines.

Discontinuing therapy: Children and Adults: Decrease dose by ~50% per week, over at least 2 weeks unless safety concerns require a more rapid withdrawal. Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or rifampin should prolong the half-life of lamotrigine; discontinuing valproic acid should shorten the half-life of lamotrigine

Restarting therapy after discontinuation: If lamotrigine has been withheld for >5 half-lives, consider restarting according to initial dosing recommendations. Note: Concomitant medications may affect the half-life of lamotrigine; consider pharmacokinetic interactions when restarting therapy.

Dosage adjustment with estrogen-containing hormonal contraceptives: Follow initial lamotrigine dosing guidelines, maintenance dose should be adjusted as follows, based on concomitant medications:

Patients taking concomitant carbamazepine, phenytoin, phenobarbital, primidone or rifampin: No dosing adjustment required

Patients not taking concomitant carbamazepine, phenytoin, phenobarbital, primidone or rifampin: Lamotrigine maintenance dose may need increased by twofold over target dose. If already taking a stable dose of lamotrigine and starting contraceptive, maintenance dose may need increased by twofold. Dose increases should start when contraceptive is started and titrated to clinical response increasing no more rapidly than 50-100 mg/day every week. Gradual increases of lamotrigine plasma levels may occur during the inactive “pill-free” week and will be greater when dose increases are made the week before. If increased adverse events consistently occur during “pill-free” week, overall maintenance dose adjustments may be required. When discontinuing estrogen-containing hormonal contraceptive, dose of lamotrigine may need decreased by as much as 50%; do not decrease by more than 25% of total daily dose over a 2-week period unless clinical response or plasma levels indicate otherwise. Dose adjustments during “pill-free” week are not recommended.

Dosing: Pediatric

(For additional information see "Lamotrigine: Pediatric drug information" )

Note: Only whole tablets should be used for dosing, round calculated dose down to the nearest whole tablet. Extended release tablets not approved for use in children ≤12 years of age. Enzyme-inducing regimens specifically refer to those containing carbamazepine, phenytoin, phenobarbital, or primidone.

Lennox-Gastaut (adjunctive), primary generalized tonic-clonic seizures (adjunctive), or partial seizures (adjunctive): Oral: Note: Children <30 kg will likely require maintenance doses to be increased as much as 50% based on clinical response regardless of regimen below:

Immediate release formulations:

Children 2-12 years:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid: Initial: Week 1 and 2: 0.3 mg/kg/day in 1-2 divided doses; Week 3 and 4: 0.6 mg/kg/day in 2 divided doses; Week 5 and beyond: Increase by 0.6 mg/kg/day every 1-2 weeks; Maintenance: 4.5-7.5 mg/kg/day (maximum: 300 mg/day) in 2 divided doses

Regimens containing valproic acid : Initial: Week 1 and 2: 0.15 mg/kg/day in 1-2 divided doses; Week 3 and 4: 0.3 mg/kg/day in 1-2 divided doses; Week 5 and beyond: Increase by 0.3 mg/kg/day every 1-2 weeks; Maintenance: 1-5 mg/kg/day (maximum: 200 mg/day) in 1 or 2 divided doses or 1-3 mg/kg/day (maximum: 200 mg/day) (valproic acid alone)

Regimens containing carbamazepine, phenytoin, phenobarbital, or primidone and without valproic acid: Initial: Week 1 and 2: 0.6 mg/kg/day in 2 divided doses; Week 3 and 4: 1.2 mg/kg/day in 2 divided doses; Week 5 and beyond: Increase by 1.2 mg/kg/day every 1-2 weeks; Maintenance: 5-15 mg/kg/day (maximum: 400 mg/day) in 2 divided doses

Children ≥13 years: Refer to adult dosing.

Conversion from adjunctive therapy with a single enzyme-inducing AED regimen for partial seizures to monotherapy with lamotrigine:

Immediate release formulations: Children ≥16 years: Refer to adult dosing.

Extended release formulation: Children ≥13 years: Refer to adult dosing.

Discontinuing therapy: Refer to adult dosing.

Restarting therapy after discontinuation: Refer to adult dosing.

Dosage adjustment with estrogen-containing hormonal contraceptives: Refer to adult dosing.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Decreased maintenance dosage may be effective in patients with significant renal impairment; has not been adequately studied; use with cautio