LamoTRIgine (Lexi-Drugs)

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Pronunciation

(la MOE tri jeen)

Brand Names: US

LaMICtal; LaMICtal ODT; LaMICtal Starter; LaMICtal XR; Subvenite; Subvenite Starter Kit-Blue; Subvenite Starter Kit-Green; Subvenite Starter Kit-Orange

Brand Names: Canada

APO-LamoTRIgine; Auro-LamoTRIgine; LaMICtal; LamoTRIgine-100; LamoTRIgine-150; LamoTRIgine-25; MYLAN-LamoTRIgine; PMS-LamoTRIgine; RATIO-LamoTRIgine [DSC]; TEVA-LamoTRIgine

Pharmacologic Category

Anticonvulsant, Miscellaneous

Dosing: Adult

Note: Drugs that induce lamotrigine glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and atazanavir/ritonavir. Valproic acid inhibits lamotrigine glucuronidation. Whole tablets should be used for dosing, round calculated dose down to the nearest whole tablet. Alternatively, a suspension may be prepared using immediate release tablets (see also Extemporaneous Prepared).

Lennox-Gastaut (adjunctive): Oral:

Immediate release formulation:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 3 and 4: 50 mg once daily; Week 5 and beyond: Increase by 50 mg daily every 1 to 2 weeks; Usual maintenance: 225 to 375 mg daily in 2 divided doses

Regimens containing valproic acid: Initial: Weeks 1 and 2: 25 mg every other day; Weeks 3 and 4: 25 mg once daily; Week 5 and beyond: Increase by 25 to 50 mg daily every 1 to 2 weeks; Usual maintenance: 100 to 200 mg daily (valproic acid alone) or 100 to 400 mg daily (valproic acid and other drugs that induce glucuronidation) in 1 or 2 divided doses

Regimens containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and without valproic acid: Initial: Weeks 1 and 2: 50 mg once daily; Weeks 3 and 4: 100 mg daily in 2 divided doses; Week 5 and beyond: Increase by 100 mg daily every 1 to 2 weeks; Usual maintenance: 300 to 500 mg daily in 2 divided doses (doses as high as 700 mg/day have been used)

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

Immediate release formulation:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 3 and 4: 50 mg once daily; Week 5 and beyond: Increase by 50 mg daily every 1 to 2 weeks; Usual maintenance: 225 to 375 mg daily in 2 divided doses

Regimens containing valproic acid: Initial: Weeks 1 and 2: 25 mg every other day; Weeks 3 and 4: 25 mg once daily; Week 5 and beyond: Increase by 25 to 50 mg daily every 1 to 2 weeks; Usual maintenance: 100 to 200 mg daily (valproic acid alone) or 100 to 400 mg daily (valproic acid and other drugs that induce glucuronidation) in 1 or 2 divided doses

Regimens containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and without valproic acid: Initial: Weeks 1 and 2: 50 mg once daily; Weeks 3 and 4: 100 mg daily in 2 divided doses; Week 5 and beyond: Increase by 100 mg daily every 1 to 2 weeks; Usual maintenance: 300 to 500 mg daily in 2 divided doses (doses as high as 700 mg/day have been used)

Extended release formulation:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 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; Week 8 and beyond: Dose increases should not exceed 100 mg daily at weekly intervals; Usual maintenance: 300 to 400 mg once daily

Regimens containing valproic acid: Initial: Weeks 1 and 2: 25 mg every other day; Weeks 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; Week 8 and beyond: Dose increases should not exceed 100 mg daily at weekly intervals; Usual maintenance: 200 to 250 mg once daily

Regimens containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and without valproic acid: Initial: Weeks 1 and 2: 50 mg once daily; Weeks 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; Week 8 and beyond: Dose increases should not exceed 100 mg daily at weekly intervals; Usual maintenance: 400 to 600 mg once daily

Conversion strategy from adjunctive therapy with valproic acid to monotherapy with lamotrigine:

Immediate release formulation:

– Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 200 mg daily.

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

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

Extended release formulation:

– Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 150 mg daily.

– Then taper valproic acid dose in decrements of not >500 mg/day/week to a valproic acid dose of 500 mg daily; this dosage should be maintained for 1 week. The lamotrigine dosage should then be increased to 200 mg daily while valproic acid is simultaneously decreased to 250 mg daily; 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 to 300 mg once daily.

Conversion strategy from adjunctive therapy with drugs that induce lamotrigine glucuronidation (carbamazepine, phenytoin, phenobarbital, primidone) to monotherapy with lamotrigine:Immediate release formulation and extended release formulation:

– Initiate and titrate as per escalation recommendations for adjunctive therapy to a lamotrigine dose of 500 mg daily

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

– Two weeks after withdrawal of the enzyme-inducing drug, 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 to 300 mg once daily; no further dosage reduction is required for lamotrigine immediate release.

Conversion strategy from adjunctive therapy with drugs that do not inhibit or induce lamotrigine glucuronidation to monotherapy with lamotrigine:

Immediate release formulation: No specific guidelines available

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

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.

Bipolar I disorder (maintenance): Oral:

Immediate release formulation:

Regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 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: Weeks 1 and 2: 25 mg every other day; Weeks 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, primidone, rifampin, or lopinavir/ritonavir, and without valproic acid: Initial: Weeks 1 and 2: 50 mg once daily; Weeks 3 and 4: 100 mg daily in divided doses; Week 5: 200 mg daily in divided doses; Week 6: 300 mg daily in divided doses; Maintenance: Up to 400 mg daily in divided doses

Adjustment following discontinuation of drugs that inhibit or induce lamotrigine glucuronidation:

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

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

Bipolar depression (acute treatment) (off-label use): Oral: Immediate release formulation: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 3 and 4: 50 mg once daily; Week 5: 100 mg once daily; Week 6 and maintenance: 200 mg once daily. Doses up to 400 mg/day have been evaluated in clinical trials; however, guidelines recommend dose ranges of 50 to 200 mg/day (Geddes 2009; van der Loos 2009; WFSBP [Grunze 2010]). Note: Concurrent psychoactive drugs were excluded in monotherapy clinical trials (Geddes 2009); this titration reflects product labeling recommendations for regimens not containing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or valproic acid.

Additional considerations:

Discontinuing therapy: Decrease dose by ~50% per week, over at least 2 weeks unless safety concerns require a more rapid withdrawal. Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or atazanavir/ritonavir 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. If lamotrigine has been withheld for <5 half-lives, consider restarting at a low dose and increasing to the previous dose gradually, based on the duration of treatment interruption, half-life of lamotrigine, and previous daily dose. Note: Concomitant medications may affect the half-life of lamotrigine; consider pharmacokinetic interactions when restarting therapy.

Concomitant therapy:

Dosage adjustment with atazanavir/ritonavir: Follow initial lamotrigine dosing guidelines, maintenance dose should be adjusted as follows:

Patients not taking concomitant carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing contraceptives, or lopinavir/ritonavir: Lamotrigine maintenance dose may need to be increased if atazanavir/ritonavir is added or decreased if atazanavir/ritonavir is discontinued.

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, rifampin, lopinavir/ritonavir, or atazanavir/ritonavir: No dosing adjustment required

Patients not taking concomitant carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, or atazanavir/ritonavir: 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 to 100 mg daily 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: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. Decreased maintenance dosage may be effective in patients with significant renal impairment; has not been adequately studied; use with caution.

Dosing: Hepatic Impairment: Adult

Mild impairment: No dosage adjustment necessary.

Moderate to severe impairment without ascites: Decrease initial, escalation, and maintenance doses by ~25%; adjust according to clinical response and tolerance.

Moderate to severe impairment with ascites: Decrease initial, escalation, and maintenance doses by ~50%; adjust according to clinical response and tolerance.

Dosing: Pediatric

Note: Tablets should not be split to achieve dose; whole tablets should be used for dosing; round calculated dose down to the nearest whole tablet. Alternatively, a suspension may be prepared using immediate release tablets (see Extemporaneous Preparations). Dosage depends on patient’s concomitant medications [ie, valproic acid; enzyme-inducing AEDs (specifically phenytoin, phenobarbital, carbamazepine, and primidone); or other AEDs not previously mentioned. Patients receiving concomitant rifampin or other drugs that induce lamotrigine glucuronidation and increase clearance should follow the same dosing regimen as that used with anticonvulsants that have similar effects (eg, phenytoin, phenobarbital, carbamazepine, and primidone).

Anticonvulsant: Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, or partial seizures; adjunctive (add-on) therapy: Oral:

Immediate-release formulations:

Infants and Children <24 months: Adjunctive therapy; partial seizures: Limited data available (Piña-Garza 2008; Piña-Garza 2008a): Note: As reported in the trials, initial doses were administered every other day if necessary due to limited strengths of commercially available products; use of an extemporaneously compounded suspension may allow for more frequent dosing; usually, daily doses are divided into 1 to 2 doses per day; daily doses in these trials were divided 3 times daily once sufficiently large enough to utilize commercially available products; this was done due to the possible increased clearance of lamotrigine in this age group.

Patients receiving AED regimens containing valproic acid or nonenzyme-inducing AEDs: Note: Studies excluded patients <6.7 kg:

Weeks 1 and 2: 0.15 mg/kg/day

Weeks 3 and 4: 0.3 mg/kg/day

Maintenance dose: Titrate dose to effect; after week 4, increase dose every week by no more than 0.3 mg/kg/day; maximum maintenance dose: 5.1 mg/kg/day in 3 divided doses not to exceed 200 mg/day; mean final dose required in open-label phase of trial was 3.1 mg/kg/day; n=51 (Piña-Garza 2008a)

Patients receiving enzyme-inducing AED regimens (eg, carbamazepine, phenytoin, phenobarbital, or primidone) without valproic acid:

Weeks 1 and 2: 0.6 mg/kg/day

Weeks 3 and 4: 1.2 mg/kg/day

Maintenance dose: Titrate dose to effect; after week 4, increase dose every week by no more than 1.2 mg/kg/day; maximum maintenance dose: 15.6 mg/kg/day in 3 divided doses not to exceed 400 mg/day; mean final dose required in open-label phase of trial was 8.9 mg/kg/day; n=126 (Piña-Garza 2008a)

Children 2 to 12 years: Note: Only whole tablets should be used for dosing; children 2 to 6 years will likely require maintenance doses at the higher end of recommended range; patients weighing <30 kg may need as much as a 50% increase in maintenance dose compared with patients weighing >30 kg; titrate dose to clinical effect

Patients receiving AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid:

Weeks 1 and 2: 0.3 mg/kg/day in 1 to 2 divided doses; round dose down to the nearest whole tablet

Weeks 3 and 4: 0.6 mg/kg/day in 2 divided doses; round dose down to the nearest whole tablet

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by a calculated increment; calculate increment as 0.6 mg/kg/day rounded down to the nearest whole tablet; add this amount to the previously administered daily dose; usual maintenance: 4.5 to 7.5 mg/kg/day in 2 divided doses; maximum daily dose: 300 mg/day

Patients receiving AED regimens containing valproic acid:

Weeks 1 and 2: 0.15 mg/kg/day in 1 to 2 divided doses; round dose down to the nearest whole tablet; use 2 mg every other day for patients weighing >6.7 kg and <14 kg

Weeks 3 and 4: 0.3 mg/kg/day in 1 to 2 divided doses; round dose down to the nearest whole tablet

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by a calculated increment; calculate increment as 0.3 mg/kg/day rounded down to the nearest whole tablet; add this amount to the previously administered daily dose; usual maintenance: 1 to 5 mg/kg/day in 1 to 2 divided doses; maximum daily dose: 200 mg/day. Note: Usual maintenance dose in children adding lamotrigine to valproic acid alone: 1 to 3 mg/kg/day

Patients receiving enzyme-inducing AED regimens (eg, carbamazepine, phenytoin, phenobarbital, or primidone) without valproic acid:

Weeks 1 and 2: 0.6 mg/kg/day in 2 divided doses; round dose down to the nearest whole tablet

Weeks 3 and 4: 1.2 mg/kg/day in 2 divided doses; round dose down to the nearest whole tablet

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by a calculated increment; calculate increment as 1.2 mg/kg/day rounded down to the nearest whole tablet; add this amount to the previously administered daily dose; usual maintenance: 5 to 15 mg/kg/day in 2 divided doses; maximum daily dose: 400 mg/day

Adolescents:

Patients receiving AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid:

Weeks 1 and 2: 25 mg every day

Weeks 3 and 4: 50 mg every day

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by 50 mg/day; usual maintenance: 225 to 375 mg/day in 2 divided doses

Patients receiving AED regimens containing valproic acid:

Weeks 1 and 2: 25 mg every other day

Weeks 3 and 4: 25 mg every day

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by 25 to 50 mg/day; usual maintenance in patients receiving valproic acid and other drugs that induce glucuronidation: 100 to 400 mg/day in 1 to 2 divided doses; usual maintenance in patients adding lamotrigine to valproic acid alone: 100 to 200 mg/day

Patients receiving enzyme-inducing AED regimens (eg, carbamazepine, phenytoin, phenobarbital, or primidone) without valproic acid:

Weeks 1 and 2: 50 mg/day

Weeks 3 and 4: 100 mg/day in 2 divided doses

Maintenance dose: Titrate dose to effect; after week 4, increase dose every 1 to 2 weeks by 100 mg/day; usual maintenance: 300 to 500 mg/day in 2 divided doses; doses as high as 700 mg/day in 2 divided doses have been used

Extended-release formulation: Adolescents: 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: Weeks 1 and 2: 25 mg once daily; Weeks 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 to 400 mg once daily

Regimens containing valproic acid: Initial: Weeks 1 and 2: 25 mg every other day; Weeks 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 to 250 mg once daily

Regimens containing carbamazepine, phenytoin, phenobarbital, or primidone and without valproic acid: Initial: Weeks 1 and 2: 50 mg once daily; Weeks 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 to 600 mg once daily

Conversion from immediate release to extended release (Lamictal XR): Initial dose of the extended release tablet (given once daily) should match the total daily dose of the immediate release formulation; monitor for seizure control, especially in patients on AED agents. Adjust dose as needed within the recommended dosing guidelines.

Anticonvulsant: Partial seizures; monotherapy: Oral:

Immediate-release formulations: Adolescents ≥16 years:

Conversion from adjunctive therapy with a single enzyme-inducing AED (eg, carbamazepine, phenytoin, phenobarbital, or primidone and not valproate) to lamotrigine immediate release monotherapy: Note: First add lamotrigine and titrate it (as outlined below) to the recommended maintenance monotherapy dose (500 mg/day in 2 divided doses), while maintaining the enzyme-inducing AED at a fixed level; then gradually taper the enzyme-inducing AED by 20% decrements each week to fully withdraw over a 4-week period.

Weeks 1 and 2: 50 mg/day

Weeks 3 and 4: 100 mg/day in 2 divided doses

Maintenance dose: After week 4, increase dose every 1 to 2 weeks by 100 mg/day; recommended maintenance monotherapy dose: 500 mg/day in 2 divided doses

Conversion from adjunctive therapy with valproate to lamotrigine immediate release monotherapy: Note: This is a 4-step conversion process to achieve the lamotrigine recommended monotherapy dose (500 mg/day in 2 divided doses).

First: Add lamotrigine and titrate it to a dose of 200 mg/day as follows (if not already receiving 200 mg/day), while maintaining the valproate dose at a fixed level:

Weeks 1 and 2: 25 mg every other day

Weeks 3 and 4: 25 mg every day

Then increase dose every 1 to 2 weeks by 25 to 50 mg/day

Second: Keep lamotrigine dose at 200 mg/day; slowly taper valproate dose in decrements of ≤500 mg/day per week, to a dose of 500 mg/day; maintain this dose for one week

Third: Increase lamotrigine to 300 mg/day and decrease valproate to 250 mg/day; maintain this dose for one week

Fourth: Discontinue valproate and increase lamotrigine by 100 mg/day at weekly intervals to achieve recommended maintenance monotherapy dose of 500 mg/day in 2 divided doses

Conversion from adjunctive therapy with AEDs other than enzyme-inducing AEDs or valproate to lamotrigine immediate release monotherapy: No specific guidelines available

Extended-release formulation: Adolescents:

Conversion from adjunctive therapy with AEDs other than enzyme-inducing AEDs or valproate to lamotrigine extended release monotherapy: First add lamotrigine and titrate it (as outlined below) to a recommended lamotrigine dose of 250 to 300 mg once daily, while maintaining the concomitant AED at a fixed level; then gradually taper the concomitant AED by 20% decrements each week to fully withdraw over a 4-week period.

Weeks 1 and 2: 25 mg once daily

Weeks 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: 250 to 300 mg once daily

Conversion from adjunctive therapy with valproate to lamotrigine extended release monotherapy: Note: This is a 4-step conversion process to achieve the lamotrigine recommended extended release monotherapy dose (250 to 300 mg once daily).

First: Add lamotrigine and titrate it to a dose of 150 mg/day as follows (if not already receiving 150 mg/day), while maintaining the valproate dose at a fixed level:

Weeks 1 and 2: 25 mg every other day

Weeks 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

Second: Keep lamotrigine dose at 150 mg/day; slowly taper valproate dose in decrements of ≤500 mg/day per week, to a dose of 500 mg/day; maintain this dose for 1 week

Third: Increase lamotrigine to 200 mg/day and decrease valproate to 250 mg/day; maintain this dose for 1 week

Fourth: Discontinue valproate and increase lamotrigine to a maintenance dose of 250 to 300 mg/day

Conversion from adjunctive therapy with a single enzyme-inducing AED (eg, carbamazepine, phenytoin, phenobarbital, or primidone and not valproate) to lamotrigine extended release monotherapy in patients with partial seizures: Note: First add lamotrigine and titrate it (as outlined below) to a recommended lamotrigine dose of 500 mg/day, while maintaining the enzyme-inducing AED at a fixed level; then gradually taper the enzyme-inducing AED by 20% decrements each week to fully withdraw over a 4-week period. Two weeks following withdrawal of the enzyme-inducing AED, the dosage of lamotrigine extended release may be tapered in decrements of ≤100 mg/day at intervals of 1 week to achieve a maintenance dosage range of 250 to 300 mg/day

Weeks 1 and 2: 50 mg once daily

Weeks 3 and 4: 100 mg once daily

Maintenance: After week 4, increase dose every 1 week by 100 mg/day to a lamotrigine dose of 500 mg once daily

Anticonvulsant: Absence seizures; monotherapy: Oral: Limited data available; efficacy results variable, optimal dose and titration not defined:

Immediate-release formulations: Children and Adolescents 2.5 to 13 years: Initial: 0.3 mg/kg/day in 2 divided doses for 2 weeks; then 0.6 mg/kg/day for 2 weeks; titrate weekly to effect/tolerability to a maximum daily dose of 12 mg/kg/day or 600 mg/day (whichever is less) (Glauser 2010; Glauser 2013). Multiple titration strategies have been reported. In the largest trial (n=453), the efficacy of lamotrigine (n=149) was compared with valproic acid (n=148) and ethosuximide (n=156); the initial lamotrigine dose was 0.3 mg/kg/day for 2 weeks, followed by 0.6 mg/kg/day for 2 weeks, then the dose was increased at weekly intervals until efficacy or intolerability in 0.6 mg/kg/day increments up to 3 mg/kg/day for 1 week (week 8), then increased to 4.5 mg/kg/day for 2 weeks, then 7 mg/kg/day for 2 weeks, then 9 mg/kg/day for 2 weeks, and then finally 12 mg/kg/day (week 15); mean final dose reported was 9.7 ± 6.3 mg/kg/day. Results showed the lamotrigine treatment arm had a treatment failure rate of 71%, compared to 47% failure with ethosuximide and 42% failure with valproic acid; the superior efficacy of valproic acid and ethosuximide persisted at 12 months (Glauser 2010; Glauser 2013). Another titration strategy based on two smaller studies used a higher initial dose of 0.5 mg/kg/day in 2 divided doses for 2 weeks, increased to 1 mg/kg/day for 2 weeks, then increased by 1 mg/kg/day increments every 5 days (or as clinically indicated) to a maximum of 12 mg/kg/day (Coppola 2004; Frank 1999). In one dose-escalation trial of 45 patients (2 to 15 years old), the median effective dose required was 5 mg/kg/day (range: 2 to 15 mg/kg/day) (Frank 1999). The other study was an open-label trial comparing lamotrigine (n=19) to valproic acid (n=19) in 3 to 13 year olds; the mean lamotrigine dose required at 3 months was 6.5 mg/kg/day (range: 2 to 11.5 mg/kg/day) (Coppola 2004).

Bipolar disorder: Oral: Immediate-release formulation: Adolescents ≥18 years:

Patients not receiving enzyme-inducing drugs (eg, carbamazepine, phenytoin, phenobarbital, primidone, rifampin) or valproate:

Weeks 1 and 2: 25 mg/day

Weeks 3 and 4: 50 mg/day

Week 5: 100 mg/day

Week 6 and thereafter: 200 mg/day

Patients receiving valproate:

Weeks 1 and 2: 25 mg every other day

Weeks 3 and 4: 25 mg/day

Week 5: 50 mg/day

Week 6 and thereafter: 100 mg/day

Note: If valproate is discontinued, increase daily lamotrigine dose in 50 mg increments at weekly intervals until dosage of 200 mg/day is attained.

Patients receiving enzyme-inducing drugs (eg, carbamazepine, phenytoin, phenobarbital, primidone, rifampin) without valproate:

Weeks 1 and 2: 50 mg/day

Weeks 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

Week 7 and thereafter: May increase to 400 mg/day in divided doses

Note: If carbamazepine (or other enzyme-inducing drug) is discontinued, maintain current lamotrigine dose for 1 week, then decrease daily lamotrigine dose in 100 mg increments at weekly intervals until dosage of 200 mg/day is attained.

Dosing adjustment with concomitant atazanavir/ritonavir: Adolescents: Follow initial lamotrigine dosing guidelines, maintenance dose should be adjusted as follows:

Patients not taking concomitant carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen-containing contraceptives, or lopinavir/ritonavir: Lamotrigine maintenance dose may need to be increased if atazanavir/ritonavir is added or decreased if atazanavir/ritonavir is discontinued.

Dosing adjustment with concomitant estrogen-containing oral contraceptives: Adolescents: Follow initial lamotrigine dosing guidelines, maintenance dose should be adjusted as follows:

Patients taking concomitant carbamazepine, phenytoin, phenobarbital, primidone, or other drugs, such as rifampin, that induce lamotrigine glucuronidation: No dosing adjustment required

Patients not taking concomitant carbamazepine, phenytoin, phenobarbital, primidone, or other drugs, such as rifampin, that induce lamotrigine glucuronidation: If already taking estrogen-containing oral contraceptives, the maintenance dose of lamotrigine may need to be increased by as much as twofold over the target maintenance dose listed above. If already taking a stable dose of lamotrigine and starting an oral contraceptive agent, the lamotrigine maintenance dose may need to be increased by as much as twofold. Dose increases should start when contraceptive agent is started and titrated to clinical response increasing no more rapidly than 50 to 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 dose adjustments may be required. Dose adjustments during “pill-free” week are not recommended. When discontinuing combination 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.

Additional considerations:

Discontinuing therapy: Children ≥2 years and Adolescents: Do not abruptly discontinue; when discontinuing lamotrigine therapy, gradually decrease the dose by ~50% per week and taper over at least 2 weeks unless safety concerns require a more rapid withdrawal. Note: If discontinuing other anticonvulsants and maintaining lamotrigine therapy, keep in mind that discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs, such as rifampin, that induce lamotrigine glucuronidation should prolong the half-life of lamotrigine; discontinuing valproic acid should shorten the half-life of lamotrigine; monitor patient closely; dosage change may be needed.

Restarting therapy after discontinuation: Children ≥2 years and Adolescents: If lamotrigine has been withheld for >5 half-lives, restart according to initial dosing recommendations. If lamotrigine has been withheld for <5 half-lives, consider restarting at a low dose and increasing to the previous dose gradually, based on the duration of treatment interruption, half-life of lamotrigine, and previous daily dose. Note: Concomitant medications may affect the half-life of lamotrigine; consider pharmacokinetic interactions when restarting therapy.

Dosing: Renal Impairment: Pediatric

Children ≥2 years and Adolescents: Use with caution; has not been adequately studied; base initial dose on patient’s AED regimen; decreased maintenance dosage may be effective in patients with significant renal impairment; during a 4-hour hemodialysis period, ~20% is removed.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents: Adjust escalation and maintenance doses by clinical response.

Mild hepatic impairment: No dosage adjustment required

Moderate and severe hepatic impairment without ascites: Reduce initial, escalation, and maintenance doses by ~25%

Severe hepatic impairment with ascites: Reduce initial, escalation, and maintenance doses by 50%

Use: Labeled Indications

Bipolar I disorder (immediate release only): 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.

Epilepsy:

Adjunctive therapy:

Immediate release: Adjunctive therapy for partial-onset seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in adults and children 2 years and older.

Extended release: Adjunctive therapy for primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization in patients 13 years and older.

Monotherapy:

Immediate release: Conversion to monotherapy in adults (16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).

Extended release: Conversion to monotherapy in patients 13 years and older with partial-onset seizures who are receiving treatment with a single AED.

Use: Off-Label: Adult

  Bipolar depressionLevel of Evidence [B, G]

Data from four meta-analyses supports the use of lamotrigine in the acute treatment of bipolar depression, however, the effects are modest, especially for severely depressed patients Ref. Additional trials may be necessary to further define the role of lamotrigine in this condition.

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the treatment of acute bipolar depression, lamotrigine given for acute bipolar depression may be effective and is suggested (particularly in severely depressed patients) as monotherapy or in combination with lithium in patients who are non- or partially responsive to other therapies. However in contrast, based the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines for the management of patients with bipolar disorder, lamotrigine given for acute bipolar I depression is effective and monotherapy is recommended as a first-line option. Combination therapy with lithium or divalproex is recommended as a second-line option. In addition for acute bipolar II depression, lamotrigine may be effective and monotherapy is recommended as a second-line option.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Bipolar Disorder:

American Psychiatric Association. “Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision),” 2002

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health, “Bipolar Disorder: The Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care,” 2014

“The Texas Implementation of Medication Algorithms: Update to the Algorithms for Treatment of Bipolar I Disorder,” July 2005

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the Long-term Treatment of Bipolar Disorder,” 2013

Drug-Induced Liver Injury:

American College of Gastroenterology (ACG), “2014 ACG Guideline for Idiosyncratic Drug-induced Liver Injury,” July 2014

Seizure Disorders:

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy,” 2018

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy, “ 2018

Administration: Oral

Doses should be rounded down to the nearest whole tablet.

Lamictal chewable/dispersible tablets: May be chewed, dispersed in water or diluted fruit juice, or swallowed whole. To disperse tablets, add to a small amount of liquid (just enough to cover tablet); let sit ~1 minute until dispersed; swirl solution and consume immediately. Do not administer partial amounts of liquid. If tablets are chewed, a small amount of water or diluted fruit juice should be used to aid in swallowing.

Lamictal ODT: Place tablets on tongue and move around in the mouth. Tablets will dissolve rapidly and can be swallowed with or without food or water.

Lamictal XR: Administer without regard to meals. Swallow whole; do not chew, crush, or cut.

Administration: Pediatric

Oral: Doses should be rounded down to the nearest whole tablet. May be administered without regard to food. If medication is received in blisterpack, examine blisterpack before use; do not use if blisters are broken, torn, or missing.

Immediate release:

Regular tablet: Do not chew, as a bitter taste may result; swallow tablet whole

Chewable, dispersible tablet: Only whole tablets should be administered (tablets should not be cut or divided); may swallow whole, chew, or disperse in water or diluted fruit juice; if chewed, administer a small amount of water or diluted fruit juice to help in swallowing. If dispersed in a small amount of liquid, swirl the solution after tablet completely dispersed and administer entire amount immediately. Do not attempt to administer partial quantities of dispersed tablets.

Orally disintegrating tablet (Lamictal ODT): Place tablet on tongue and move around in the mouth. Tablet will dissolve rapidly and can be swallowed with or without food or water.

Extended release tablet (Lamictal XR): May be administered without regard to meals. Swallow tablet whole; do not chew, crush, or break.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Protect from light.

Preparation for Administration: Pediatric

Oral: Chewable, dispersible tablet: To disperse, add tablets to a small amount of liquid (~5 mL or enough to cover the medication); tablets should be completely dispersed in about 1 minute.

Extemporaneously Prepared

A 1 mg/mL oral suspension may be made with tablets and one of two different vehicles (a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus). Crush one 100 mg tablet in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 100 mL; transfer to a graduated cylinder, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Label “shake well” and “protect from light”. Stable for 91 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.

Nahata M, Morosco R, Hipple T. “Stability of Lamotrigine in Two Extemporaneously Prepared Oral Suspensions at 4 and 25 Degrees C,” Am J Health Syst Pharm, 1999, 56(3):240-2.[PubMed 10030509]

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, vomiting, tremors, insomnia, rhinitis, pharyngitis, constipation, weight loss, dry mouth, back pain, or diarrhea. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), mood changes, agitation, panic attacks, behavioral changes, shortness of breath, excessive weight gain, swelling of arms or legs, swollen glands, seizures, severe muscle weakness, severe muscle pain, severe joint pain, severe joint edema, bruising, bleeding, severe loss of strength and energy, vision changes, severe dizziness, passing out, change in balance, involuntary eye movements, angina, flu-like symptoms, menstrual changes, painful periods, or signs of aseptic meningitis (headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to lights, fatigue, or confusion) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Administration issues:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information, and as follows, must be dispensed with this medication:

Lamictal, Lamictal ODT: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020764s050lbl.pdf#page=63

Lamictal XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022115s011s018lbl.pdf#page=46

Contraindications

Hypersensitivity (eg, rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to lamotrigine or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Aseptic meningitis: Increased risk of developing aseptic meningitis has been reported; symptoms (eg, headache, nuchal rigidity, fever, nausea/vomiting, rash, photophobia) have generally occurred within 1 to 45 days following therapy initiation. In some cases, new onset hepatic, renal and/or other organ involvement has also occurred with symptoms, possibly suggesting aseptic meningitis is associated with a hypersensitivity reaction (eg, anticonvulsant hypersensitivity syndrome). Symptoms of aseptic meningitis generally resolve following discontinuation. In some cases, re-exposure has resulted in a rapid return of symptoms (often more severe).

• Blood dyscrasias: A spectrum of hematologic effects have been reported with use (eg, neutropenia, leukopenia, thrombocytopenia, pancytopenia, anemias, and rarely, aplastic anemia and pure red cell aplasia); patients with a previous history of adverse hematologic reaction to any drug may be at increased risk. Early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage. May be associated with hypersensitivity syndrome.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hemophagocytic lymphohistiocytosis: Hemophagocytic lymphohistiocytosis (HLH), a rare but life-threatening immune system reaction, has been reported with lamotrigine use. Symptoms may include fever, rash, hepatosplenomegaly, organ system dysfunction, and blood dyscrasias. Onset usually occurs within the first several weeks after starting therapy. Patients with HLH symptoms should be evaluated promptly; discontinuation and conversion to alternate therapy may be required.

• Multiorgan hypersensitivity reactions (drug reaction with eosinophilia and systemic symptoms [DRESS]): Potentially serious, sometimes fatal, multiorgan hypersensitivity reactions (DRESS) have been reported with some antiepileptic drugs (rare). Symptoms may include fever, rash, and/or lymphadenopathy; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems. Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinuation and conversion to alternate therapy may be required.

• Skin reactions: [US Boxed Warning]: Serious skin rashes requiring hospitalization and discontinuation of treatment have been reported; incidence of serious rash is higher in pediatric patients than adults; risk may be increased by coadministration with valproic acid, higher than recommended initial doses, exceeding recommended initial dose titration, or exceeding the recommended dose escalation for lamotrigine. One rash-related death was reported in a pediatric patients taking lamotrigine immediate-release as adjunctive therapy. Nearly all cases of life-threatening rashes associated with lamotrigine have occurred within 2 to 8 weeks of treatment initiation; however, isolated cases may occur after prolonged treatment (eg, 6 months) or in patients without these risk factors; discontinue at first sign of rash and do not reinitiate therapy unless rash is clearly not drug related. Rare cases of toxic epidermal necrolysis and/or rash-related death have been reported. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment may be required.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Children are at increased risk for developing serious skin rashes during therapy; lower starting doses and slower dose escalations may decrease the risk of rash.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Bipolar disorder use: Patients treated for bipolar disorder should be monitored closely for clinical worsening or suicidality; reassess patients to determine the need for maintenance treatment if on therapy >16 weeks. Prescriptions should be written for the smallest quantity consistent with good patient care. Treatment of acute manic or mixed episodes is not recommended; efficacy has not been established and slow titration limits use.

• Medication error potential: Medication errors have occurred; potential for medication errors with similar-sounding medications and between different lamotrigine formulations.

• Melanin binding: Binds to melanin and may accumulate in the eye and other melanin-rich tissues; the clinical significance of this is not known.

• Monotherapy: Epilepsy: Safety and efficacy have not been established for use as initial monotherapy, conversion to monotherapy from antiepileptic drugs (AED) other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid or conversion to monotherapy from two or more AEDs.

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Taper over at least 2 weeks if possible.

Geriatric Considerations

No pharmacokinetic differences noted between young adults and the elderly. Use with caution in the elderly with significant renal decline.

Warnings: Additional Pediatric Considerations

Incidence of serious rash is higher in pediatric patients than adults. Serious skin rashes (including Stevens-Johnson syndrome) occur in 0.8% of pediatric epilepsy patients (2 to 16 years of age) and 0.3% of adult epilepsy patients and in up to 0.13% of adult patients treated for bipolar and other mood disorders; rare cases of toxic epidermal necrolysis and angioedema have been reported; rash-related deaths have occurred in pediatric and adult patients. In addition to pediatric age, the risk of rash may be increased in patients receiving valproic acid, high initial doses, or with rapid dosage increases; however, rash has been reported in patients without risk factors. Rash usually appears in the first 2 to 8 weeks of therapy, but may occur after prolonged treatment (eg, 6 months). Benign rashes may occur, but one cannot predict which rashes will become serious or life-threatening; the manufacturer recommends (ordinarily) discontinuation of lamotrigine at the first sign of rash (unless rash is clearly not drug related); discontinuation of lamotrigine may not prevent rash from becoming life-threatening or permanently disfiguring or disabling. Risk of nonserious rash may also be increased when the initial recommended dose or dose escalation rate is exceeded in patients with a history of rash or allergy to other AEDs.

Do not abruptly discontinue; when discontinuing therapy, gradually reduce the dose by ~50% per week and taper over at least 2 weeks unless safety concerns require a more rapid withdrawal. Lamotrigine should not be restarted in patients who discontinued therapy due to lamotrigine-associated rash, unless benefits clearly outweigh risks; if restarting lamotrigine after withholding for >5 half-lives, use the initial dosing recommendations and titrate dosage accordingly (ie, do not restart at the previous maintenance dose).

A small randomized, double-blind, placebo-controlled study in pediatric patients 1 to 24 months of age did not demonstrate safety and efficacy of immediate release lamotrigine when used as adjunctive treatment for partial seizures; lamotrigine was associated with an increased risk for infectious and respiratory adverse reactions.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Lamotrigine crosses the human placenta and can be measured in the plasma of exposed newborns (Harden and Pennell 2009; Ohman 2000). An overall increase in the risk for major congenital malformations has not been observed in available studies; however, an increased risk for cleft lip or cleft palate has not been ruled out (Cunnington 2011; Hernández-Díaz 2012; Holmes 2012). An increased risk of malformations following maternal lamotrigine use may be associated with larger doses (Cunnington 2007; Tomson 2011). Polytherapy may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended (Harden and Meader 2009).

Due to pregnancy-induced physiologic changes, women who are pregnant may require dose adjustments of lamotrigine in order to maintain clinical response; monitoring during pregnancy should be considered (Harden and Pennell 2009). For women with epilepsy who are planning a pregnancy in advance, baseline serum concentrations should be measured once or twice prior to pregnancy during a period when seizure control is optimal. Monitoring can then be continued up to once a month during pregnancy and every second day during the first week postpartum (Patsalos 2008). In women taking lamotrigine who are trying to avoid pregnancy, potentially significant interactions may exist with hormone-containing contraceptives; consult drug interactions database for more detailed information.

Pregnancy registries are available for women who have been exposed to lamotrigine. Patients may enroll themselves in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling (888) 233-2334. Additional information is available at www.aedpregnancyregistry.org.

Breast-Feeding Considerations

Lamotrigine is present in breast milk.

The relative infant dose (RID) of lamotrigine reported in the literature is variable. One study reported a mean RID of 9.2% (95% CI: 7.4% to 10.9%; range: 3.1% to 21.1%) when calculated using mean breast milk concentrations and compared to patient-specific, weight-adjusted maternal doses (range: 50 to 800 mg/day) (Newport 2008).

In general, breastfeeding is considered acceptable when the RID of a medication is <10%; when the RID is >25% breastfeeding should be avoided (Anderson 2016; Ito 2000).

The RID of lamotrigine was calculated using an average milk concentration of 3.38 mcg/mL, providing an estimated daily infant dose via breast milk of 0.51 mg/kg/day. This mean milk concentration was calculated following maternal administration of oral lamotrigine in doses that ranged from 50 to 800 mg/day in 25 women between 7.6 and 18.4 weeks’ postpartum (Newport 2008).

Lamotrigine can be detected in the serum of breastfed infants; the manufacturer reports that infant lamotrigine plasma concentrations may be as high as 50% of the maternal serum concentration. Neonates and young infants are at an increased risk for high serum concentrations due to a decreased capacity for glucuronidation needed for drug clearance, especially if the maternal lamotrigine dose is not returned to the prepregnancy dosage (maternal doses are often increased during pregnancy).

Adverse events observed in breastfed infants include apnea, drowsiness, poor sucking, thrombocytosis, and rash (Newport 2008; Nordmo 2009; Soussan 2014; Wakil 2009). Symptoms of withdrawal may occur if breastfeeding is abruptly discontinued (Popescu 2005).

The manufacturer recommends that caution be exercised when administering lamotrigine to breastfeeding women. Monitor the infant for signs and symptoms of lamotrigine toxicity; obtain infant serum lamotrigine concentrations if symptoms of toxicity occur.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Percentages reported in adults on monotherapy for epilepsy or bipolar disorder.

>10%: Gastrointestinal: Nausea (7% to 14%)

1% to 10%:

Cardiovascular: Chest pain (2% to 5%), peripheral edema (2% to 5%), edema (1% to 5%)

Central nervous system: Insomnia (5% to 10%), drowsiness (9%), fatigue (8%), dizziness (7%), ataxia (2% to 7%), anxiety (5%), pain (5%), irritability (2% to 5%), suicidal ideation (2% to 5%), abnormal dreams (1% to 5%), abnormality in thinking (1% to 5%), agitation (1% to 5%), amnesia (1% to 5%), depression (1% to 5%), emotional lability (1% to 5%), hypoesthesia (1% to 5%), migraine (1% to 5%), neurologic abnormality (dyspraxia) (1% to 5%), hyperreflexia (>2% to <5%), hyporeflexia (>2% to <5%), confusion (≥1%), paresthesia (≥1%)

Dermatologic: Skin rash (nonserious 7%; requiring hospitalization ≤1%), contact dermatitis (2% to 5%), diaphoresis (2% to 5%), xeroderma (2% to 5%)

Endocrine & metabolic: Increased libido (2% to 5%), weight loss (2% to 5%), weight gain (1% to 5%)

Gastrointestinal: Vomiting (5% to 9%), dyspepsia (7%), abdominal pain (6%), xerostomia (2% to 6%), constipation (5%), anorexia (2% to 5%), peptic ulcer (2% to 5%), flatulence (1% to 5%)

Genitourinary: Dysmenorrhea (2% to 5%), urinary frequency (1% to 5%)

Hematologic & oncologic: Rectal hemorrhage (2% to 5%)

Infection: Infection (5%)

Neuromuscular & skeletal: Back pain (8%), asthenia (2% to 5%), arthralgia (1% to 5%), myalgia (1% to 5%), neck pain (1% to 5%)

Ophthalmic: Nystagmus (2% to 5%), visual disturbance (2% to 5%), amblyopia (≥1%)

Respiratory: Rhinitis (7%), cough (5%), pharyngitis (5%), bronchitis (2% to 5%), dyspnea (2% to 5%), epistaxis (2% to 5%), sinusitis (1% to 5%), nasopharyngitis (≥3%), upper respiratory tract infection (≥3%)

Miscellaneous: Fever (1% to 5%)

<1%, postmarketing and/or case reports (any indication): Abnormal hepatic function tests, abnormal lacrimation, accommodation disturbance, acne vulgaris, acute renal failure, ageusia, aggressive behavior, agranulocytosis, akathisia, alcohol intolerance, alopecia, altered sense of smell, amyotrophy, anemia, angina pectoris, angioedema, anorgasmia, apathy, aphasia, aplastic anemia, apnea, arthritis, aseptic meningitis, blepharoptosis, breast abscess, breast neoplasm, bursitis, central nervous system depression, chills, choreoathetosis, conjunctivitis, cystitis, deafness, decreased fibrin, decreased libido, decreased serum fibrinogen, delirium, delusions, depersonalization, dermatitis (exfoliative, fungal), dry eye syndrome, dysarthria, dysgeusia, dyskinesia, dysphagia, dysphoria, dystonia, dysuria, ecchymosis, ejaculatory disorder, eosinophilia, epididymitis, eructation, erythema, erythema multiforme, esophagitis, euphoria, exacerbation of Parkinson disease, extrapyramidal reaction, flushing, gastric ulcer, gastritis, gastrointestinal hemorrhage, gingival hemorrhage, gingival hyperplasia, gingivitis, glossitis, goiter, hallucination, hematemesis, hematuria, hemiplegia, hemolytic anemia, hemorrhagic colitis, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014), herpes zoster infection, hiccups, hirsutism, hostility, hot flash, hyperalgesia, hyperbilirubinemia, hyperesthesia, hyperglycemia, hyperkinesia, heavy menstrual bleeding, hypersensitivity reaction, hypertension, hypertonia, hyperventilation, hypokinesia, hypothyroidism, hypotonia, immunosuppression (progressive), impotence, increased appetite, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum creatinine, iron deficiency anemia, lactation, leukocytosis, leukoderma, leukopenia, lower limb cramp, lupus-like syndrome, lymphadenopathy, lymphocytosis, macrocytic anemia, maculopapular rash, malaise, manic depressive reaction, melena, memory impairment, movement disorder, multiorgan failure, muscle spasm, myasthenia, myoclonus, neuralgia, neutropenia, nocturia, oral mucosa ulcer, orthostatic hypotension, oscillopsia, otalgia, palpitations, pancreatitis, pancytopenia, panic attack, paralysis, paranoia, pathological fracture, peripheral neuritis, personality disorder, petechia, petechial rash, photophobia, polyuria, pruritus, psychoneurosis, psychosis, pure red cell aplasia, pustular rash, racing mind, renal pain, rhabdomyolysis, sialorrhea, skin discoloration, sleep disorder, status epilepticus, Stevens-Johnson syndrome, stomatitis, strabismus, stupor, suicidal tendencies, syncope, tachycardia, tendinous contracture, thrombocytopenia, tics, tinnitus, tongue edema, tonic-clonic seizures (exacerbation), toxic epidermal necrolysis, twitching, urinary incontinence, urinary retention, urinary urgency, urticaria, uveitis, vasculitis, vasodilation, vesiculobullous dermatitis, visual field defect, withdrawal syndrome (seizures with abrupt withdrawal), yawning

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Inhibits OCT2

Drug Interactions 

Acetaminophen: May decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Atazanavir: May decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Barbiturates: May decrease the serum concentration of LamoTRIgine. Management: See lamotrigine prescribing information for specific age-dependent dosing guidelines regarding concurrent use with a barbiturate, as well as for adjusting lamotrigine dosing if concurrent barbiturate therapy is discontinued. Risk D: Consider therapy modification

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

CarBAMazepine: LamoTRIgine may enhance the adverse/toxic effect of CarBAMazepine. CarBAMazepine may increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Desmopressin: LamoTRIgine may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dofetilide: LamoTRIgine may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Estrogen Derivatives: May decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Estrogen Derivatives (Contraceptive): May decrease the serum concentration of LamoTRIgine. Management: Monitor for increased serum concentrations/effects of lamotrigine in patients in whom a hormonal contraceptive is discontinued/dose decreased (this includes during a pill-free week). A reduced dosage of lamotrigine may be needed. Risk D: Consider therapy modification

Ezogabine: May decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Fosphenytoin: May decrease the serum concentration of LamoTRIgine. Risk D: Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lacosamide: Antiepileptic Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

MetFORMIN: LamoTRIgine may increase the serum concentration of MetFORMIN. Management: The lamotrigine Canadian product monograph states that coadministration of these drugs is not recommended. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

OLANZapine: LamoTRIgine may enhance the sedative effect of OLANZapine. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Phenytoin: May decrease the serum concentration of LamoTRIgine. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: May decrease the serum concentration of LamoTRIgine. Management: Adjust dose per lamotrigine prescribing information guidelines during primidone treatment. Monitor for decreased concentration/effect if primidone is initiated/dose increased or increased concentration/effect if primidone is discontinued/dose decreased. Risk D: Consider therapy modification

Procainamide: LamoTRIgine may increase the serum concentration of Procainamide. Management: Consider monitoring for increased procainamide concentrations and/or systemic effects in patients receiving procainamide with lamotrigine. The lamotrigine Canadian product monograph states that coadministration of these agents is not recommended. Risk C: Monitor therapy

Progestins (Contraceptive): LamoTRIgine may decrease the serum concentration of Progestins (Contraceptive). Risk C: Monitor therapy

RifAMPin: May increase the metabolism of LamoTRIgine. Risk C: Monitor therapy

Ritonavir: May decrease the serum concentration of LamoTRIgine. Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

Sulthiame: May increase the serum concentration of LamoTRIgine. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valproate Products: May enhance the adverse/toxic effect of LamoTRIgine. Valproate Products may increase the serum concentration of LamoTRIgine. Risk D: Consider therapy modification

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

Food has no effect on absorption.

Test Interactions

May interfere with some rapid urine drug screens, particularly phencyclidine (false-positives).

Monitoring Parameters

Serum levels of concurrent anticonvulsants, LFTs, renal function, hypersensitivity reactions (especially rash); seizure, frequency and duration; suicidality (eg, suicidal thoughts, depression, behavioral changes); signs/symptoms of aseptic meningitis

Reference Range

Timing of serum samples: Draw trough just before next dose.

Laboratory alert level: 20 mcg/mL (SI: 78 mcmol/L)

Therapeutic reference range: Note: Dosing should be based on therapeutic response as opposed to serum concentrations (Hiemke 2018).

Bipolar disorder: 1 to 6 mcg/mL (SI: 3.9 to 23.4 mcmol/L)

Epilepsy: 3 to 15 mcg/mL (SI: 11.7 to 58.5 mcmol/L)

Advanced Practitioners Physical Assessment/Monitoring

Obtain liver function, renal function tests, serum levels of concurrent anticonvulsants. Assess for signs of hypersensitivity, especially for skin rash. Discontinue at the first sign of rash, unless clearly not drug-related. Assess for suicide ideation, depression, unusual behavior changes, or signs of aseptic meningitis. Observe and teach seizure/safety precautions. Assess for therapeutic response.

Nursing Physical Assessment/Monitoring

Check labs results and report abnormalities. Monitor therapeutic response (seizure activity, type, duration) at beginning of therapy and periodically throughout. Report presence of skin rash or hypersensitivity immediately. Monitor for suicide ideation, depression, unusual behavior changes or signs of aseptic meningitis (headache, nuchal rigidity, fever, nausea, vomiting, rash, or photophobia). Observe and teach seizure/safety precautions.

Dosage Forms Considerations

LaMICtal Kits are available as follows:

Blue – for patients already taking valproate

LaMICtal Starter: 25 mg (35s)

LaMICtal ODT (Titration): 25 mg (21s) and 50 mg (7s)

LaMICtal XR (Titration): 25 mg (21s) and 50 mg (7s)

Green- for patients already taking carbamazepine, phenytoin, phenobarbital, or primidone, and not taking valproate

LaMICtal Starter: 25 mg (84s) and 100 mg (14s)

LaMICtal ODT (Titration): 50 mg (42s) and 100 mg (14s)

LaMICtal XR (Titration): 50 mg (14s) and 100 mg (14s) and 200 mg (7s)

Orange – for patients not taking carbamazepine, phenytoin, phenobarbital, primidone, or valproate

LaMICtal Starter: 25 mg (42s) and 100 mg (7s)

LaMICtal ODT (Titration): 25 mg (14s) and 50 mg (14s) and 100 mg (7s)

LaMICtal XR (Titration): 25 mg (14s) and 50 mg (14s) and 100 mg (7s)

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Oral:

LaMICtal ODT: Blue Kit: 25 mg (21s) & 50 mg (7s), Orange Kit: 25 mg (14s) & 50 mg (14s) & 100 mg (7s), Green Kit: 50 mg (42s) & 100 mg (14s)

LaMICtal Starter: Blue Kit: 25 mg (35s)

LaMICtal Starter: Green Kit: 25 mg (84s) & 100 mg (14s), Orange Kit: 25 mg (42s) & 100 mg (7s) [contains fd&c yellow #6 aluminum lake]

LaMICtal XR: Green Kit: 50 mg (14s) & 100 mg (14s) & 200 mg (7s) [contains fd&c blue #2 aluminum lake, polysorbate 80]

LaMICtal XR: Blue Kit: 25 mg (21s) & 50 mg (7s), Orange Kit: 25 mg (14s) & 50 mg (14s) & 100 mg (7s) [contains polysorbate 80]

Subvenite Starter Kit-Blue: Blue Kit: 25 mg (35s)

Subvenite Starter Kit-Green: Green Kit: 25 mg (84s) & 100 mg (14s)

Subvenite Starter Kit-Orange: Orange Kit: 25 mg (42s) & 100 mg (7s)

Generic: Blue Kit: 25 mg (21s) & 50 mg (7s) [DSC], Blue Kit: 25 mg (35s), Green Kit: 25 mg (84s) & 100 mg (14s), Green Kit: 50 mg (42s) & 100 mg (14s) [DSC], Orange Kit: 25 mg (14s) & 50 mg (14s) & 100 mg (7s) [DSC], Orange Kit: 25 mg (42s) & 100 mg (7s)

Tablet, Oral:

LaMICtal: 25 mg [scored]

LaMICtal: 100 mg [scored; contains fd&c yellow #6 aluminum lake]

LaMICtal: 150 mg [scored]

LaMICtal: 200 mg [scored; contains fd&c blue #2 (indigotine)]

Subvenite: 25 mg, 100 mg, 150 mg, 200 mg [scored]

Generic: 25 mg, 100 mg, 150 mg, 200 mg

Tablet Chewable, Oral:

LaMICtal: 5 mg [scored; berry flavor]

LaMICtal: 25 mg [berry flavor]

Generic: 5 mg, 25 mg

Tablet Disintegrating, Oral:

LaMICtal ODT: 25 mg, 50 mg, 100 mg, 200 mg

Generic: 25 mg, 50 mg, 100 mg, 200 mg

Tablet Extended Release 24 Hour, Oral:

LaMICtal XR: 25 mg, 50 mg, 100 mg [contains polysorbate 80]

LaMICtal XR: 200 mg [contains fd&c blue #2 aluminum lake, polysorbate 80]

LaMICtal XR: 250 mg [contains fd&c blue #2 aluminum lake]

LaMICtal XR: 300 mg [contains polysorbate 80]

Generic: 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

LaMICtal: 25 mg, 50 mg [DSC]

LaMICtal: 100 mg [contains FD&C YELLOW #6 ALUMINUM LAKE]

LaMICtal: 150 mg, 250 mg

Generic: 25 mg, 100 mg, 150 mg

Tablet Chewable, Oral:

LaMICtal: 2 mg, 5 mg [contains SACCHARIN SODIUM]

Anatomic Therapeutic Chemical (ATC) Classification
  • N03AX09
Generic Available (US)

Yes

Pricing: US

Chewable (LaMICtal Oral)

5 mg (per each): $14.83

25 mg (per each): $15.92

Chewable (lamoTRIgine Oral)

5 mg (per each): $3.05 – $4.36

25 mg (per each): $3.20 – $4.68

Kit (LaMICtal ODT Oral)

25 (21)-50 (7) mg (per each): $16.12

25 & 50 & 100 mg (per each): $18.42

50 (42)-100(14) mg (per each): $23.02

Kit (LaMICtal Starter Oral)

25 (35) mg (per each): $15.33

25 (42)-100 (7) mg (per each): $15.64

25 (84)-100(14) mg (per each): $15.64

Kit (LaMICtal XR Oral)

25 (21)-50 (7) mg (per each): $16.85

25 & 50 & 100 mg (per each): $19.25

50 & 100 & 200 mg (per each): $38.51

Kit (Subvenite Starter Kit-Blue Oral)

25 (35) mg (per each): $17.00

Kit (Subvenite Starter Kit-Green Oral)

25 (84)-100(14) mg (per each): $15.71

Kit (Subvenite Starter Kit-Orange Oral)

25 (42)-100 (7) mg (per each): $15.29

Tablet, 24-hour (LaMICtal XR Oral)

25 mg (per each): $13.48

50 mg (per each): $26.96

100 mg (per each): $28.88

200 mg (per each): $30.79

250 mg (per each): $41.99

300 mg (per each): $46.19

Tablet, 24-hour (lamoTRIgine ER Oral)

25 mg (per each): $6.55

50 mg (per each): $13.09

100 mg (per each): $14.03

200 mg (per each): $14.96

250 mg (per each): $20.40 – $32.05

300 mg (per each): $22.44

Tablet, orally-disintegrating (LaMICtal ODT Oral)

25 mg (per each): $12.89

50 mg (per each): $13.81

100 mg (per each): $14.73

200 mg (per each): $17.57

Tablet, orally-disintegrating (lamoTRIgine Oral)

25 mg (per each): $8.88 – $8.95

50 mg (per each): $9.51 – $9.58

100 mg (per each): $10.14 – $10.22

200 mg (per each): $12.10 – $12.19

Tablets (LaMICtal Oral)

25 mg (per each): $15.33

100 mg (per each): $17.51

150 mg (per each): $19.19

200 mg (per each): $20.89

Tablets (lamoTRIgine Oral)

25 mg (per each): $0.25 – $4.55

100 mg (per each): $2.48 – $5.19

150 mg (per each): $5.19 – $5.69

200 mg (per each): $5.65 – $6.20

Tablets (Subvenite Oral)

25 mg (per each): $4.16

100 mg (per each): $4.75

150 mg (per each): $5.00

200 mg (per each): $5.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

A triazine derivative which inhibits release of glutamate (an excitatory amino acid) and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membranes. Lamotrigine has weak inhibitory effect on the 5-HT3 receptor; in vitro inhibits dihydrofolate reductase.

Pharmacodynamics/Kinetics

Absorption: Immediate release: Rapid and complete, 97.6% absorbed; Note: Orally disintegrating tablets (either swallowed whole with water or disintegrated in the mouth) are equivalent to regular tablets (swallowed whole with water) in terms of rate and extent of absorption.

Distribution: Vd: 1.1 L/kg; range: 0.9 to 1.3 L/kg

Protein binding: ~55% (primarily albumin)

Metabolism: Hepatic and renal; >75% metabolized via glucuronidation; autoinduction may occur

Bioavailability: Immediate release: 98%; Note: AUCs were similar for immediate release and extended release preparations in patients receiving nonenzyme-inducing AEDs. In subjects receiving concomitant enzyme-inducing AEDs, bioavailability of extended release product was ~21% lower than immediate release product; in some of these subjects, a decrease in AUC of up to 70% was observed when switching from immediate release to extended release tablets.

Half-life elimination:

Pediatric patients:

No concomitant enzyme-inducing AED (ie, phenytoin, phenobarbital, carbamazepine, primidone): Infants and Children 10 months to 5 years: 19 hours (range: 13 to 27 hours)

Concomitant valproate derivative therapy:

Infants and Children 10 months to 5 years: 45 hours (range: 30 to 52 hours)

Children 5 to 11 years: 66 hours (50 to 74 hours)

Concomitant enzyme-inducing AEDs (ie, phenytoin, phenobarbital, carbamazepine, primidone):

Infants and Children 10 months to 5 years: 7.7 hours (range: 6 to 11 hours)

Children 5 to 11 years: 7 hours (range: 4 to 10 hours)

Concomitant enzyme-inducing AEDs plus valproate derivative therapy: Children 5 to 11 years: 19 hours (range: 7 to 31 hours)

Adults:

Immediate release: 25 to 33 hours, Elderly: 25 to 43 hours; Extended release: Similar to immediate release

Concomitant valproic acid therapy: 48 to 70 hours

Concomitant phenytoin, phenobarbital, primidone, or carbamazepine therapy: 13 to 14 hours

Concomitant phenytoin, phenobarbital, primidone, or carbamazepine plus valproate therapy: 27 hours

Chronic renal failure: 43 hours

Hemodialysis: 13 hours during dialysis; 57 hours between dialysis (~20% of a dose is eliminated in a 4-hour dialysis session)

Hepatic impairment:

Mild: 46 ± 20 hours

Moderate: 72 ± 44 hours

Severe without ascites: 67 ± 11 hours

Severe with ascites: 100 ± 48 hours

Time to peak, plasma: Immediate release: ~1 to 5 hours (dependent on adjunct therapy); Extended release: 4 to 11 hours (dependent on adjunct therapy)

Excretion: Urine (94%, ~90% as glucuronide conjugates and ~10% unchanged); feces (2%)

Pharmacodynamics/Kinetics: Additional Considerations

Geriatric: Clearance was 0.3 to 0.5 mL/minute/kg.

Gender: Mean trough concentrations were 24% to 45% higher in women than men.

Race: Oral clearance was 25% lower in nonwhite patients than in white patients.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

Thrombocytopenia and anemia have been reported in <1% of patients.

Index Terms

BW-430C; LTG

FDA Approval Date
December 27, 1994
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Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172.[PubMed 10985636]

Messenheimer JA, “Lamotrigine,” Epilepsia, 1995, 36(Suppl 2):87-94.[PubMed 8784217]

Messenheimer J, “Efficacy and Safety of Lamotrigine in Pediatric Patients,” J Child Neurol, 2002, 17(Suppl 2):34-42.[PubMed 11952035]

Myllynen PK, Pienimaki PK, and Vahakangas KH, “Transplacental Passage of Lamotrigine in a Human Placental Perfusion System in vitro and in Maternal and Cord Blood in vivo,” Eur J Clin Pharmacol, 2003, 58(10):677-82.[PubMed 12610744]

Newport DJ, Pennell PB, Calamaras MR, et al. Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics. 2008;122(1):e223-231.[PubMed 18591203]

Nordmo E, Aronsen L, Wasland K, Småbrekke L, Vorren S. Severe apnea in an infant exposed to lamotrigine in breast milk. Ann Pharmacother. 2009;43(11):1893-1897.[PubMed 19826099]

Ohman I, Vitols S, and Tomson T, “Lamotrigine in Pregnancy: Pharmacokinetics During Delivery, in the Neonate, and During Lactation,” Epilepsia, 2000, 41(6):709-13.[PubMed 10840403]

Patsalos PN, Berry DJ, Bourgeois BF, et al, “Antiepileptic Drugs-Best Practice Guidelines for Therapeutic Drug Monitoring: A Position Paper by the Subcommission on Therapeutic Drug Monitoring, ILAE Commission on Therapeutic Strategies,” Epilepsia, 2008, 49(7):1239-76.[PubMed 18397299]

Popescu L, Marceanu M, Moleavin I. Withdrawal of lamotrigine caused by sudden weaning of a newborn: a case report. Epilepsia 2005;46 (Suppl 6):407. (Abstract p. 1351.)

Sabers A, Buchholt JM, Uldall P, et al, “Lamotrigine Plasma Levels Reduced by Oral Contraceptives,” Epilepsy Res, 2001, 47(1-2):151-4.[PubMed 11673029]

Schirop TH, Lufft H, Winkler M, et al, “Bronchial Mucosa Reaction in Lyell-Stevens-Johnson Syndrome Following Lamotrigine,” Intensivmedizin und Notfallmedizin, 1994, 31:343.

Selle V, Schalkwijk S, Vázquez GH, Baldessarini RJ. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics. Pharmacopsychiatry. 2014;47(2):43-52.[PubMed 24549862]

Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313.[PubMed 7746084]

Soussan C, Gouraud A, Portolan G, et al. Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database. Eur J Clin Pharmacol. 2014;70(11):1361-1366.[PubMed 25183382]

Suppes T, Dennehy EB, Hirschfeld RMA, et al, “The Texas Implementation of Medication Algorithms: Update to the Algorithms for the Treatment of Bipolar I Disorder,” J Clin Psychiatry, 2005, 66(7):870-86.[PubMed 16013903]

Taylor DM, Cornelius V, Smith L, Young AH. Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis. Acta Psychiatr Scand. 2014;130(6):452-469.[PubMed 25283309]

Tomson T, Battino D, Bonizzoni E, et al, “Dose-Dependent Risk of Malformations With Antiepileptic Drugs: An Analysis of Data From the EURAP Epilepsy and Pregnancy Registry,” Lancet Neurol, 2011, 10(7):609-17.

van der Loos ML, Mulder PG, Hartong EG, et al; LamLit Study Group. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70(2):223-231.[PubMed 19200421]

Vieta E, Locklear J, Günther O, et al. Treatment options for bipolar depression: a systematic review of randomized, controlled trials. J Clin Psychopharmacol. 2010;30(5):579-590.[PubMed 20814319]

Wakil L, Epperson CN, Gonzalez J, O’Reardon JP, Kim DR. Neonatal outcomes with the use of lamotrigine for bipolar disorder in pregnancy and breastfeeding: a case series and review of the literature. Psychopharmacol Bull. 2009;42(3):91-98.[PubMed 19752842]

Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013 Feb;15(1):1-44.[PubMed 23237061]

Brand Names: International

Arvind (HR); Controlepsy (EG); Epictal (JO); Epileptal (UA); Labicitin (KR); Lafigin (PY); Lambipol (BE); Lamdra SBK (MX); Lamepil (IN); Lameptil (BD); Lametec (CO); Lamicet (BD); Lamictal (AE, AR, AT, AU, BB, BD, BE, BG, BH, BM, BO, BR, BS, BZ, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IQ, IR, IS, IT, JM, JO, JP, KR, KW, LB, LT, LU, LV, LY, MT, MX, MY, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, SY, TH, TR, TT, TW, UA, UY, VE, VN, YE); Lamictin (ZW); Lamidus (AU, TW); Lamidus DT (LK); Lamiros (ID); Lamitor (AE, PH); Lamitor DT-25 (ET); Lamitor-25 (ZW); Lamitor-50 (ZW); Lamitrin (BD); Lamodex (IL); Lamoga (TH); Lamogin (CO, TW); Lamogine (IL); Lamor (JO); Lamoro (IE); Lamostad (VN); Lamosyn (PH); Lamotrin (HK, UA); Lamotrix (LK, LV, MY, PH, SG, TW, VN); Lamox (HR); Larig (IE); Larogen (EG); Latrigine (TW); Latrin (EC); Lepigine (LB); Logem (AU); Lojin (LK); Loxol (BH, JO); Mibedos (VN); Mogine (NZ); Motrigine (PH); Protalgine (MX); Seaze (AU); Tevalamotrigine Chew Tab (KR)

Lamotrigine (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(la MOE tri jeen)

Brand Names: US

LaMICtal; LaMICtal ODT; LaMICtal Starter; LaMICtal XR; Subvenite; Subvenite Starter Kit-Blue; Subvenite Starter Kit-Green; Subvenite Starter Kit-Orange

Brand Names: Canada

Lamictal

Warning
  • All products:
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • The chance of a skin reaction is raised in children between 2 and 17 years old. It may also be raised if you take valproic acid or divalproex sodium with this drug, if you start taking this drug at too high of a dose, or if your dose is raised too fast. Skin reactions have also happened without any of these. Talk with your doctor.
  • Most cases of skin reactions have happened within 2 to 8 weeks of starting this drug, but some show up after longer treatment like 6 months. Talk with the doctor.
  • Extended-release tablets:
  • This drug is not approved for use in children younger than 13 years old. Talk with the doctor.
What is this drug used for?
  • It is used to help control certain kinds of seizures.
  • It is used to treat bipolar problems.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to lamotrigine or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking dofetilide.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • It may take several weeks to see the full effects.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • If you stop taking this drug, talk with your doctor. You may need to be restarted at a lower dose and raise the dose slowly.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • A very bad and sometimes deadly reaction has happened with this drug. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • Use with care in children. Talk with the doctor.
  • Some drugs may look the same as this drug or may have names that sound like this drug. Always check to make sure you have the right product. If you see any change in the way this drug looks like shape, color, size, or wording, check with your pharmacist.
  • Birth control pills and other hormone-based birth control may change how much of this drug is in your body. Talk to your doctor before you start or stop any hormone-based birth control. The chance of side effects may be raised when taking birth control pills during the week that the pills are not active. Talk with your doctor.
  • Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this drug.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • For all uses of this drug:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Swollen gland.
  • Very bad muscle pain or weakness.
  • Very bad joint pain or swelling.
  • Any unexplained bruising or bleeding.
  • Feeling very tired or weak.
  • Change in eyesight.
  • Very bad dizziness or passing out.
  • Change in balance.
  • Not able to control eye movements.
  • Chest pain or pressure.
  • Flu-like signs.
  • Painful periods.
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call your doctor right away if you have a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother your eyes, feeling sleepy, or feeling confused.
  • For seizures:
  • If seizures are worse or not the same after starting this drug.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Upset stomach or throwing up.
  • Feeling tired or weak.
  • Shakiness.
  • Not able to sleep.
  • Nose or throat irritation.
  • Diarrhea.
  • Constipation.
  • Weight loss.
  • Dry mouth.
  • Back pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Do not change the dose or stop this drug. This could cause seizures. Talk with your doctor.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Tablets:
  • Swallow whole. Do not chew, break, or crush.
  • If you have trouble swallowing, talk with your doctor.
  • Chewable dispersible tablet:
  • It may be swallowed whole, chewed, or mixed in water or fruit juice.
  • If chewed, drink a little water or fruit juice to help swallow.
  • You may break up tablet by adding liquid to cover tablet in a glass or spoon. Wait at least 1 minute until fully broken up, then mix and drink.
  • Oral-disintegrating tablet:
  • Place on your tongue and let it dissolve. Water is not needed. Do not swallow it whole. Do not chew, break, or crush it.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Lamotrigine (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(la MOE tri jeen)

Brand Names: US

LaMICtal; LaMICtal ODT; LaMICtal Starter; LaMICtal XR; Subvenite; Subvenite Starter Kit-Blue; Subvenite Starter Kit-Green; Subvenite Starter Kit-Orange

Brand Names: Canada

Lamictal

Warning
  • All products:
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
  • The chance of a skin reaction is raised in children between 2 and 17 years old. It may also be raised if your child takes valproic acid or divalproex sodium with this drug, if your child starts taking this drug at too high of a dose, or if your child’s dose is raised too fast. Skin reactions have also happened without any of these. Talk with the doctor.
  • Most cases of skin reactions have happened within 2 to 8 weeks of starting this drug, but some show up after longer treatment like 6 months. Talk with the doctor.
  • Extended-release tablets:
  • This drug is not approved for use in children younger than 13 years old. Talk with the doctor.
What is this drug used for?
  • It is used to help control certain kinds of seizures.
  • It is used to treat bipolar problems.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking dofetilide.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • It may take several weeks to see the full effects.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Have your child’s blood work checked often. Talk with your child’s doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • If you stop giving this drug, talk with the doctor. Your child may need to be restarted at a lower dose and raise the dose slowly.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your child’s doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • A very bad and sometimes deadly reaction has happened with this drug. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • Some drugs may look the same as this drug or may have names that sound like this drug. Always check to make sure you have the right product. If you see any change in the way this drug looks like shape, color, size, or wording, check with your pharmacist.
  • Birth control pills and other hormone-based birth control may change how much of this drug is in the body. Talk to the doctor before your child starts or stops any hormone-based birth control. The chance of side effects may be raised when taking birth control pills during the week that the pills are not active. Talk with the doctor.
  • If your child is or may be sexually active:
  • Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Be sure your child uses some other kind of birth control also, like a condom, when taking this drug.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • For all uses of this drug:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Swollen gland.
  • Very bad muscle pain or weakness.
  • Change in eyesight.
  • Any unexplained bruising or bleeding.
  • Feeling very tired or weak.
  • Very bad joint pain or swelling.
  • Very bad dizziness or passing out.
  • Change in balance.
  • Not able to control eye movements.
  • Chest pain or pressure.
  • Flu-like signs.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call the doctor right away if your child has a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother the eyes, feeling sleepy, or feeling confused.
  • If your child has menstrual periods:
  • Painful periods.
  • Period (menstrual) changes. These include spotting or bleeding between cycles.
  • For seizures:
  • If seizures are worse or not the same after starting this drug.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Upset stomach or throwing up.
  • Feeling tired or weak.
  • Shakiness.
  • Not able to sleep.
  • Nose or throat irritation.
  • Diarrhea.
  • Constipation.
  • Weight loss.
  • Dry mouth.
  • Back pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Do not change the dose or stop your child’s drug. This could cause seizures. Talk with your child’s doctor.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Tablets:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • If your child has trouble swallowing, talk with the doctor.
  • Chewable dispersible tablet:
  • It may be swallowed whole, chewed, or mixed in water or fruit juice.
  • If chewed, have your child drink a little water or fruit juice to help swallow it.
  • You may break up tablet by adding liquid to cover tablet in a glass or spoon. Wait at least 1 minute until fully broken up, then mix and have your child drink.
  • Oral-disintegrating tablet:
  • Place on your child’s tongue and let it dissolve. Water is not needed. Do not let your child swallow it whole. Do not let your child chew, break, or crush it.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.