Lamotrigine

Seizure Disorder

With enzyme-inducing AEDs but without valproic acid

• Initial: 50 mg PO qDay for 2 weeks, THEN
• 100 mg/day divided q12hr for 2 weeks
• At week 5 and beyond, may increase by 100 mg/day PO q1-2Week to 300-500 mg/day PO divided q12hr
• Lamotrigine XR: Start 50 mg PO qDay (weeks 1 and 2), THEN 100 mg qDay (weeks 3 and 4), THEN increase by 100 mg/day PO qWeek through week 7 (400 mg qDay); maintenance dose (week 8+): 400-600 mg PO qDay

With valproic acid

• Initial: 25 mg PO qODay for 2 weeks, THEN
• 25 mg PO qDay for 2 weeks
• At 5 weeks may increase by 25-50 mg/day q1-2Week to 100-400 mg/day qDay or divided q12hr
• With valproate alone: 100-200 mg/day PO
• Lamotrigine XR: Start 25 mg PO qODay for 2 weeks, THEN 25 mg PO qDay for 2 weeks, THEN 50 mg PO qDay (week 5), 100 mg PO qDay (week 6), 150 mg PO qDay (week 7), to maintenance (200-250 mg PO qDay)

Without enzyme-inducing AEDs or valproic acid

• Initial: 25 mg PO qDay for 2 weeks, THEN
• 50 mg/day PO for 2 weeks
• After 4 weeks may increase by 50 mg/day q1-2Week to 225-375 mg/day divided q12hr
• Lamotrigine XR: Start 25 mg PO qDay for 2 weeks, THEN 50 mg PO qDay for 2 weeks, THEN 100 mg qDay (week 5), 150 mg qDay (week 6), 200 mg qDay (week 7), to maintenance (300-400 mg PO qDay)

Partial-Onset Seizures (Conversion to Monotherapy)

Taking valproic acid, conversion to immediate-release lamotrigine

• Initiate and titrate to lamotrigine dose of 200 mg/day, THEN
• Decrease valproic acid dose by 500 mg/day at intervals of 1 week or longer to valproic acid dose of 500 mg/day; maintain this dose for 1 week, THEN
• Increase lamotrigine dose to 300 mg while valproic acid is decreased to 250 mg/day; maintain this dose for 1 week, THEN
• Discontinue valproic acid
• Increase lamotrigine dose by 100 mg/day at weekly intervals to achieve a maintenance dose of 500 mg/day

Taking valproic acid, conversion to extended-release lamotrigine

• Conversion to monotherapy for patients taking 1 anticonvulsant drug
• Weeks 1-2: 25 mg PO qODay
• Weeks 3-4: 25 mg PO qDay
• Week 5: 50 mg PO qDay
• Week 6: 100 mg PO qDay
• Weeks 7-10: 150 mg PO qDay; begin valproic acid withdrawal over 5-7 weeks to 500mg/day and maintain for 1 week
• Week 11: 200 mg PO qDay; decrease valproic acid dose to 250 mg/day for 1 week
• Weeks 12-23: 250-300 mg PO qDay; discontinue valproic acid

Taking carbamazepine, phenytoin, phenobarbital, or primidone (conversion to immediate-release lamotrigine)

• Initiate and titrate to lamotrigine dose of 500 mg/day as per recommendations
• Decrease concomitant enzyme-inducing AED by 20% each week over a 4-week period and then withdraw

Taking neutral AED, conversion to extended-release lamotrigine

• Conversion to monotherapy for patients taking 1 anticonvulsant drug
• Weeks 1-2: 25 mg PO qDay
• Weeks 3-4: 50 mg PO qDay
• Week 5: 100 mg PO qDay
• Week 6: 150-200 mg PO qDay
• Weeks 7-23: 250-300 mg PO qDay; begin AED withdrawal over 5-week period by weekly 20% decreases in daily dose

Conversion from immediate-release to extended-release lamotrigine

• Dose of extended-release lamotrigine should equal the total daily dose of the immediate-release formulation
• Adjust dose as needed within recommended dosing

Bipolar Disorder

Indicated for 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

Efficacy and safety have not been established for treatment of acute manic or mixed episodes

Monotherapy or without enzyme inducers or valproic acid

• Initial: 25 mg PO qDay for 2 weeks, THEN
• 50 mg PO qDay for 2 weeks
• 100 mg PO qDay for 1 week
• Double dose qWeek to maintenance at 200 mg/day PO

With AED regimen without valproic acid

• Initial: 50 mg PO qDay for 2 weeks, THEN
• 100 mg/day PO divided q12hr for 2 weeks
• Increase by 100 mg qWeek to 400 mg/day PO divided q12hr

With valproic acid

• Initial: 25 mg PO qODay for 2 weeks, THEN
• 25 mg PO qDay for 2 weeks
• Double dose qWeek to maintenance at 100 mg/day PO

Dosing Modifications

Renal impairment

• Use caution; may consider reduce the dose in significant renal impairment

Hepatic impairment

• Limited data, various recommendations
• Manufacturer: Decrease dose by 25% (moderate-severe without ascites) or by 50% (severe with ascites)
• Other (eg, AHSP): Decrease dose by 50% (Child-Pugh class B) or by 75% (Child-Pugh class C)