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Lamotrigine: Drug information

Lamotrigine: Drug information
(For additional information see "Lamotrigine: Patient drug information" and see "Lamotrigine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Serious skin rashes:

Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.3% to 0.8% in pediatric patients (2 to 17 years of age) and 0.08% to 0.3% in adults receiving lamotrigine. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (2 to 16 years of age) with epilepsy taking lamotrigine immediate-release as adjunctive therapy. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adults and pediatric patients, but those numbers are too few to permit a precise estimate of the rate.

The risk of serious rash caused by treatment with lamotrigine ER is not expected to differ from that with the immediate-release formulation of lamotrigine. However, the relatively limited treatment experience with lamotrigine ER makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with lamotrigine ER.

Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash caused by lamotrigine. There are suggestions, yet to be proven, that the risk of rash may also be increased by coadministration of lamotrigine with valproate (includes valproic acid and divalproex sodium), exceeding the recommended initial dose of lamotrigine, or exceeding the recommended dose escalation for lamotrigine. However, cases have been reported in the absence of these factors.

Nearly all cases of life-threatening rashes caused by lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have been reported after prolonged treatment (eg, 6 months). Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash.

Although benign rashes are also caused by lamotrigine, it is not possible to predict reliably which rashes will prove to be serious or life-threatening. Accordingly, lamotrigine should ordinarily be discontinued at the first sign of rash unless the rash is clearly not drug-related. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.

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;
  • TEVA-LamoTRIgine
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous
Dosing: Adult

Dosage guidance:

Safety: Adhere strictly to recommended initial dose, titration schedules, and adjustments to reduce the risk of severe, including potentially fatal, cutaneous reactions and other hypersensitivity reactions.

Dosing: Dosing recommendations are expressed as the total daily dose (ie, per 24 hours) unless stated otherwise. The IR tablets and compounded suspension (not commercially available) are dosed once daily when the total daily dose is ≤25 mg, and twice daily if the total daily dose is >25 mg. ER tablets are dosed once daily.

Bipolar disorder, maintenance treatment and acute bipolar major depression

Bipolar disorder, maintenance treatment (labeled use) and acute bipolar major depression (alternative agent; off-label use): Note: Not effective for treating acute bipolar mania or hypomania (Ref).

Patients not taking interacting medications: Oral: Initial: Weeks 1 and 2: 25 mg once daily; increase based on response and tolerability as follows: Weeks 3 and 4: 50 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5: 100 mg/day in 1 to 2 divided doses based on chosen formulation; Week 6: 200 mg/day in 1 to 2 divided doses based on chosen formulation (recommended maximum dose per manufacturer's labeling); however, further increases up to 400 mg/day may be necessary in some patients for optimal response (Ref). Some experts titrate more gradually (ie, by 25 to 50 mg/day each week) from week 5 until effective maintenance (or maximum) dose is reached (Ref). Also see "Dosing" above.

Patients taking valproate (inhibits lamotrigine metabolism): Oral: Initial: Weeks 1 and 2: 25 mg every other day; increase based on response and tolerability as follows: Weeks 3 and 4: 25 mg once daily; Week 5: 50 mg/day in 1 to 2 divided doses based on chosen formulation; Week 6 and maintenance: 100 mg/day in 1 to 2 divided doses based on chosen formulation. Also see “Dosing” above.

Patients taking drug(s) that induce lamotrigine metabolism (eg, carbamazepine, phenytoin, others) but not taking valproate: Note: Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism but separate recommendations apply. See manufacturer's labeling for specific dosing recommendations with estrogen derivatives.

Oral: Initial: Weeks 1 and 2: 50 mg/day in 1 to 2 divided doses based on chosen formulation; increase based on response and tolerability as follows: Weeks 3 and 4: 100 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5: 200 mg/day in 1 to 2 divided doses based on chosen formulation; Week 6: 300 mg/day in 1 to 2 divided doses based on chosen formulation; Maintenance: ≤400 mg/day in 1 to 2 divided doses based on chosen formulation. Also see “Dosing” above.

Discontinuation of concomitant interacting therapy (eg, discontinuing valproate or carbamazepine): Note: Gradual adjustments may decrease risk of serious cutaneous hypersensitivity reactions, loss of control of bipolar disorder, and withdrawal symptoms. The following recommendations are based on manufacturer labeling; alterations may be needed based on clinical response and other factors.

Valproate and other inhibitors of lamotrigine metabolism: Discontinue valproate (or other inhibitor) and begin to increase the dose of lamotrigine, with the goal of doubling the dose of lamotrigine over a 2-week interval (using equal weekly increments) based upon response, to a recommended maximum dose of 200 mg/day in 1 to 2 divided doses based on chosen formulation. Also see “Dosing” above.

Inducers of lamotrigine metabolism (eg, carbamazepine, phenytoin, others): Note: Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism, but separate recommendations apply. See manufacturer's labeling for recommendations for discontinuation of estrogen derivatives.

Discontinue the inducer drug and keep lamotrigine dose unchanged for 1 week, then decrease lamotrigine dose by one-half over a 2-week interval (using equal weekly increments). After 2 weeks, may adjust lamotrigine dose as needed based on response and tolerability to a recommended maximum dose of 200 mg/day in 1 to 2 divided doses based on chosen formulation. Also see “Dosing” above.

Focal onset seizures and generalized onset seizures

Focal (partial) onset seizures and generalized onset seizures: Note: FDA-approved for Lennox-Gastaut syndrome (adjunctive therapy only), primary generalized tonic-clonic seizures (adjunctive therapy only), and focal onset seizures (monotherapy or adjunctive therapy); may be used off-label for other seizure types.

Patients not taking interacting medications: Oral: Initial: Weeks 1 and 2: 25 mg once daily; increase based on response and tolerability as follows: Weeks 3 and 4: 50 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5 and beyond: increase by 50 mg/day every 1 to 2 weeks. Usual maintenance dose: 225 to 375 mg/day in 2 divided doses (immediate release) or 300 to 400 mg once daily (extended release). Also see “Dosing” above.

Patients taking valproate (inhibits lamotrigine metabolism): Oral: Initial: Weeks 1 and 2: 12.5 to 25 mg every other day; increase based on response and tolerability as follows: Weeks 3 and 4: 25 mg once daily; Week 5 and beyond: increase by 25 to 50 mg/day every 1 to 2 weeks. Usual maintenance dose: 100 to 200 mg/day in 2 divided doses (immediate release) or 200 to 250 mg once daily (extended release). In patients taking both valproate and a drug that induces lamotrigine metabolism, the usual maintenance dose range is 100 to 400 mg/day in 2 divided doses (immediate release) (Ref). Also see “Dosing” above.

Patients taking drug(s) that induce lamotrigine metabolism (eg, carbamazepine, phenytoin, others) but not taking valproate: Note: Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism, but separate recommendations apply. See manufacturer's labeling for dosing recommendations with estrogen derivatives.

Oral: Initial: Weeks 1 and 2: 50 mg/day in 1 to 2 divided doses based on chosen formulation; increase based on response and tolerability as follows: Weeks 3 and 4: 100 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5 and beyond: increase by 100 mg/day every 1 to 2 weeks. Usual maintenance dose: 300 to 500 mg/day in 2 divided doses (immediate release) or 400 to 600 mg once daily (extended release). Also see “Dosing” above.

Discontinuation of concomitant interacting therapy : Note: Gradual adjustments may decrease the risk of serious cutaneous hypersensitivity reactions, loss of seizure control, and withdrawal symptoms. The following recommendations are based on manufacturer labeling; alterations may be needed based on clinical response and other factors.

For discontinuation of valproate and other inhibitors of lamotrigine metabolism:

Immediate release:

- Step 1: Gradually increase lamotrigine dose to 200 mg/day in 2 divided doses following standard escalation schedule for cotherapy with valproate. Maintain current valproate dose.

- Step 2: While maintaining lamotrigine 200 mg/day in 2 divided doses, decrease valproate dose in decrements of ≤500 mg/day once every week to a dose of 500 mg/day; maintain this valproate dosage for 1 week.

- Step 3: If needed based on response and tolerability, increase lamotrigine to 300 mg/day in 2 divided doses while simultaneously decreasing valproate to 250 mg/day; maintain both dosing regimens for 1 week.

- Step 4: Discontinue valproate. Increase lamotrigine as needed based on response and tolerability in increments of 100 mg/day every week to maintenance dose range for no interacting medications (manufacturer's labeling suggests ≤500 mg/day in 2 divided doses).

Extended release:

- Step 1: Gradually increase lamotrigine dose to 150 mg once daily following standard escalation schedule for cotherapy with valproate. Maintain current valproate dose.

- Step 2: While maintaining lamotrigine dose of 150 mg once daily, decrease valproate dose in decrements of ≤500 mg/day once every week to a dose of 500 mg/day; maintain this valproate dosage for 1 week.

- Step 3: If needed based on response and tolerability, increase lamotrigine to 200 mg once daily while simultaneously decreasing valproate to 250 mg/day; maintain both dosing regimens for 1 week.

- Step 4: Discontinue valproate. Increase lamotrigine as needed based on response and tolerability to maintenance dose range for no interacting medications (manufacturer's labeling suggests 250 to 300 mg once daily).

For discontinuation of inducers of lamotrigine metabolism (eg, carbamazepine, phenytoin, others): Note: Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism, but separate recommendations apply. See manufacturer's labeling for dosing recommendations with estrogen derivatives.

Immediate or extended release:

- Step 1: Maintain lamotrigine dose unchanged while withdrawing the concomitant enzyme-inducing drug in 5 equal steps (20% decrease per step) over a 4-week period.

- Step 2: The lamotrigine dose should then be decreased beginning 2 weeks after completion of withdrawal of the enzyme-inducing drug; decrease lamotrigine dose no faster than 100 mg/day each week to the maintenance dose range for no interacting medications (manufacturer's labeling suggests 250 to 300 mg once daily for extended release).

For discontinuation of antiseizure drugs that do not affect lamotrigine metabolism:

Immediate release: There are no specific dosing guidelines in the manufacturer's labeling.

Extended release:

- Step 1: Gradually increase lamotrigine dose based on response and tolerability following standard escalation schedule without interacting drugs to the maintenance dose range for no interacting concomitant medications (manufacturer's labeling suggests 250 to 300 mg once daily).

- Step 2: Concomitant antiseizure drug should then be withdrawn in 5 equal steps (20% decrease per step) over a 4-week period. Once concomitant antiseizure drug has been discontinued, no adjustment to the lamotrigine dose is needed, unless clinically warranted.

Short-lasting unilateral neuralgiform headache attacks, prophylaxis

Short-lasting unilateral neuralgiform headache attacks, prophylaxis (off-label use): Oral: Initial: Weeks 1 and 2: 25 mg once daily; Weeks 3 and 4: 50 mg/day in 1 to 2 divided doses based on chosen formulation; beginning with week 5, may increase based on response and tolerability in increments of 50 mg/day every 1 to 2 weeks. Usual maintenance dose: 200 mg/day in 1 to 2 divided doses based on chosen formulation; doses up to 400 mg/day may be needed for optimal response in some patients (Ref). Also see “Dosing” above.

Adjustments for interacting medications: Dosing of lamotrigine with concomitant valproate (inhibits lamotrigine metabolism) or inducers (eg, carbamazepine, others) has not been well studied for conditions other than bipolar disorder and seizures; may consider gradual adjustment schedules described for bipolar disorder or seizure indications to avoid increased risk of serious cutaneous hypersensitivity reactions.

Trigeminal neuralgia

Trigeminal neuralgia (alternative agent) (off-label use):

Note: Consider use in patients who do not respond or with intolerance or contraindications to carbamazepine and/or oxcarbazepine; titration time to effective dose may limit use in patients with severe pain (Ref).

Patients not taking interacting medications: Oral: Initial: Weeks 1 and 2: 25 mg once daily; increase as needed based on response and tolerability as follows: Weeks 3 and 4: 50 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5 and beyond: Increase daily dose by 50 mg every 1 to 2 weeks to a maximum of 400 mg/day in 1 to 2 divided doses based on chosen formulation (Ref). Also see "Dosing" above.

Patients taking valproate (inhibits lamotrigine metabolism): Oral: Initial: Weeks 1 and 2: 12.5 to 25 mg every other day; increase as needed based on response and tolerability as follows: Weeks 3 and 4: 25 mg once daily; Week 5 and beyond: Increase daily dose by 25 mg every 2 weeks to a maximum of 200 mg/day in 1 to 2 divided doses based on chosen formulation (Ref). Also see "Dosing" above.

Patients taking drug(s) that induce lamotrigine metabolism (eg, carbamazepine, phenytoin, others) but not taking valproate: Note: Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism, but separate recommendations apply. See manufacturer's labeling for dosing recommendations with estrogen derivatives.

Oral: Initial: Weeks 1 and 2: 50 mg in 1 to 2 divided doses based on chosen formulation; increase as needed based on response and tolerability as follows: Weeks 3 and 4: 100 mg/day in 1 to 2 divided doses based on chosen formulation; Week 5 and beyond: Increase daily dose by 100 mg every week to a maximum of 400 mg/day in 1 to 2 divided doses based on chosen formulation (Ref). Also see "Dosing" above.

Discontinuation of lamotrigine therapy: In chronic therapy, withdraw gradually to minimize the potential of increased seizure frequency (in patients with epilepsy) and withdrawal symptoms (eg, dysphoria, hallucinations, headache, insomnia, tremor) unless safety concerns require more rapid withdrawal. In clinical trials of bipolar disorder, doses were withdrawn by decreasing in weekly intervals by 50% over at least 2 weeks. If discontinuing all pharmacotherapy for bipolar disorder, patients are monitored for several weeks to months for re-emergence of mania/hypomania (Ref). For seizure disorders, some experts suggest withdrawing lamotrigine over a few to several (eg, 2 to 6) months (Ref).

Restarting therapy after treatment interruption or discontinuation: If lamotrigine has been withheld for ≥5 half-lives (ie, >6 days in most patients), restart according to initial dose and dose escalation schedule. If lamotrigine has been withheld for <5 half-lives (ie, ≤6 days), consider restarting at a low dose and increasing to the previous dose gradually. When restarting therapy after treatment interruption, consider the previous daily dose and any concomitant medications that are known to prolong (eg, valproate) or decrease (eg, carbamazepine) half-life of lamotrigine. If treatment was discontinued due to rash, do not resume lamotrigine.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref). In patients with CrCl <30 mL/minute, some pharmacokinetic parameters (eg, half-life) may vary considerably; titrate with caution (Ref).

Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (17% ± 10% (Ref)): No dosage adjustment necessary; supplemental doses are generally not required; titrate with caution (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzable (Ref): No dosage adjustment necessary; titrate with caution (Ref).

CRRT: Some dialyzability expected but no specific data available: No initial dosage adjustment necessary; consider therapeutic drug monitoring (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Some dialyzability expected, but no specific data available: No initial dosage adjustment necessary; consider therapeutic drug monitoring (Ref).

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: Older Adult

Refer to adult dosing.

Dosing: Pediatric

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

Dosage guidance:

Safety: Adhere strictly to recommended initial dose, titration schedules, and adjustments to reduce the risk of severe, including potentially fatal, cutaneous reactions and other hypersensitivity reactions.

Dosing: 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.

Seizures; adjunctive therapy, Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, or focal seizures

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

Immediate-release formulations (eg, Lamictal, Subvenite):

Infants and Children <24 months: Adjunctive therapy; partial seizures: Limited data available (Ref): 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 antiseizure drug regimens containing valproic acid or nonenzyme-inducing antiseizure drugs :

Initiation: Note: Studies excluded patients <6.7 kg:

Weeks 1 and 2: Oral: 0.15 mg/kg/day.

Weeks 3 and 4: Oral: 0.3 mg/kg/day.

Maintenance dose: Oral: Titrate dose to effect; after week 4, increase dose every week by no more than 0.3 mg/kg/day; maximum maintenance daily 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 (Ref).

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

Initiation:

Weeks 1 and 2: Oral: 0.6 mg/kg/day.

Weeks 3 and 4: Oral: 1.2 mg/kg/day.

Maintenance dose: Oral: Titrate dose to effect; after week 4, increase dose every week by no more than 1.2 mg/kg/day; maximum maintenance daily 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 (Ref).

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 antiseizure drugs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid:

Initiation:

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

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

Maintenance dose: Oral: 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 antiseizure drug regimens containing valproic acid:

Initiation:

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

Maintenance dose: Oral: 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 antiseizure drug regimens (eg, carbamazepine, phenytoin, phenobarbital, primidone) without valproic acid:

Initiation:

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

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

Maintenance dose: Oral: 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 antiseizure drugs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproic acid:

Initiation:

Weeks 1 and 2: Oral: 25 mg every day.

Weeks 3 and 4: Oral: 50 mg every day.

Maintenance dose: Oral: 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 antiseizure drug regimens containing valproic acid:

Initiation:

Weeks 1 and 2: Oral: 25 mg every other day.

Weeks 3 and 4: Oral: 25 mg every day.

Maintenance dose: Oral: 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 antiseizure drug regimens (eg, carbamazepine, phenytoin, phenobarbital, primidone) without valproic acid:

Initiation:

Weeks 1 and 2: Oral: 50 mg/day once daily.

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

Maintenance dose: Oral: 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 (eg, Lamictal XR):

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; dose increases after week 8 should not exceed 100 mg/day at weekly intervals. 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; dose increases after week 8 should not exceed 100 mg/day at weekly intervals. 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; dose increases after week 8 should not exceed 100 mg/day at weekly intervals. 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 antiseizure drug agents. Adjust dose as needed within the recommended dosing guidelines.

Seizures; monotherapy, focal seizures

Seizures; monotherapy, focal (partial-onset) seizures:

Immediate-release formulations (eg, Lamictal, Subvenite):

Adolescents ≥16 years:

Conversion from adjunctive therapy with a single enzyme-inducing antiseizure drug (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 antiseizure drug at a fixed level; then gradually taper the enzyme-inducing antiseizure drug by 20% decrements each week to fully withdraw over a 4-week period.

Initiation:

Weeks 1 and 2: Oral: 50 mg/day once daily.

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

Maintenance dose: Oral: 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: Lamotrigine:

Weeks 1 and 2: Oral: 25 mg every other day.

Weeks 3 and 4: Oral: 25 mg every day.

Then increase dose every 1 to 2 weeks by 25 to 50 mg/day to a dose of 200 mg/day in 1 or 2 divided doses.

Second: Oral: Keep lamotrigine dose at 200 mg/day; slowly taper valproate dose in decrements of ≤500 mg/day per week, to a valproate dose of 500 mg/day; maintain this dose for 1 week.

Third: Oral: Increase lamotrigine to 300 mg/day and decrease valproate to 250 mg/day; maintain this dose for 1 week.

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

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

Extended-release formulation (eg, Lamictal XR):

Adolescents:

Conversion from adjunctive therapy with antiseizure drugs other than enzyme-inducing antiseizure drugs 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 antiseizure drug at a fixed level; then gradually taper the concomitant antiseizure drug by 20% decrements each week to fully withdraw over a 4-week period.

Weeks 1 and 2: Oral: 25 mg once daily.

Weeks 3 and 4: Oral: 50 mg once daily.

Week 5: Oral: 100 mg once daily.

Week 6: Oral: 150 mg once daily.

Week 7: Oral: 200 mg once daily.

Maintenance: Oral: 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: Oral: 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: Lamotrigine:

Weeks 1 and 2: Oral: 25 mg every other day.

Weeks 3 and 4: Oral: 25 mg once daily.

Week 5: Oral: 50 mg once daily.

Week 6: Oral: 100 mg once daily.

Week 7: Oral: 150 mg once daily.

Second: Oral: Maintain 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: Oral: Increase lamotrigine to 200 mg/day and decrease valproate to 250 mg/day; maintain this dose for 1 week.

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

Conversion from adjunctive therapy with a single enzyme-inducing antiseizure drug (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 antiseizure drug at a fixed level; then gradually taper the enzyme-inducing antiseizure drug by 20% decrements each week to fully withdraw over a 4-week period. Two weeks following withdrawal of the enzyme-inducing antiseizure drug, 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: Oral: 50 mg once daily.

Weeks 3 and 4: Oral: 100 mg once daily.

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

Seizures, absence; monotherapy

Seizures, absence; monotherapy: Limited data available; efficacy results variable, optimal dose and titration not defined:

Immediate-release formulations (eg, Lamictal, Subvenite):

Children and Adolescents 2.5 to 13 years: Oral: 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) (Ref). 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 (Ref). Another titration strategy based on 2 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 (Ref). 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) (Ref). 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) (Ref).

Discontinuation of antiseizure therapy: Children ≥2 years and Adolescents: There is currently no standard method for the withdrawal of antiseizure drugs in pediatric patients. Successful discontinuation of an antiseizure drug is dependent on several factors including but not limited to: Time of seizure freedom, underlying reason for the seizures, neuroimaging abnormalities, underlying neurodevelopmental status, and medication to be withdrawn (including dose, duration of therapy, and other pharmacokinetic/dynamic considerations) (Ref). Do not abruptly discontinue lamotrigine; 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 antiseizure drugs 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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents: Use with caution; has not been adequately studied; base initial dose on patient's antiseizure drug 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%

Adverse Reactions (Significant): Considerations
Aseptic meningitis

Lamotrigine is associated with rare reports of aseptic meningitis, with symptoms consistent with meningeal inflammation (headache, photophobia, nuchal rigidity, fever) while routine bacterial cultures are negative. Some cases have been associated with concurrent development of a rash and organ dysfunction, which suggests a broader hypersensitivity reaction (Ref).

Mechanism: Non-dose-related; immunologic (Ref).

Onset: Varied; occurs within 1 to 42 days following therapy initiation. In 40% of cases of rechallenge, recurrence often resulted in a more rapid onset (Ref). Recurrence has occurred as rapidly as 30 to 60 minutes following re-exposure (Ref).

Risk factors:

Collagen vascular disease (Ref)

Blood dyscrasias

Lamotrigine is associated with a range of hematologic adverse effects including agranulocytosis, neutropenia, pancytopenia, and pure red cell aplasia. Aplastic anemia has also been reported. At least one case of agranulocytosis was fatal, but it is not clear that lamotrigine was the causative agent, as this occurred in a patient receiving multiple medications with an association with blood dyscrasias (Ref). Blood dyscrasias may be associated with multiorgan hypersensitivity reactions (eg, drug reaction with eosinophilia and systemic symptoms [DRESS]).

Mechanism: Unknown; in cases which present as DRESS, a T-cell mediated drug-specific immune response is implicated (Ref).

Onset: Varied; between 2 weeks to 3 months (Ref).

Hypersensitivity reactions (delayed)

Lamotrigine is associated with a range of dermatologic adverse reactions in adult and pediatric patients. Mild skin rash (benign morbilliform rashes with or without pruritus) occur with a higher frequency, but rare serious skin rashes and other multiorgan hypersensitivity reactions have also been reported (Ref). Multiorgan hypersensitivity reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Some features of lamotrigine-associated DRESS have been noted to be milder than in DRESS observed with other medications, including a lower frequency of herpesvirus-6 reactivation (Ref).

Mechanism: Not clearly established; may be linked to drug concentrations (Ref). Severe cutaneous reactions, including SJS/TEN and DRESS, are delayed type IV hypersensitivity reaction involving a T-cell mediated drug-specific immune response (Ref).

Onset: Varied. Lamotrigine-induced skin eruptions generally occur between 5 days and 8 weeks after initiation of therapy (Ref). The manufacturer's labeling notes that nearly all cases of life-threatening rashes caused by lamotrigine have occurred within 2 to 8 weeks of treatment initiation, with only isolated cases occurring after prolonged treatment (eg, 6 months).

Risk factors:

Age <13 years (Ref)

Higher initial dose and/or rapid titration (Ref)

Concurrent therapy with inhibitors of lamotrigine metabolism (eg, valproate) (Ref)

Prior rash with other antiseizure medications (Ref)

Uridine diphosphate-glucuronosyltransferase (UGT) enzyme polymorphisms may contribute (Ref)

HLA molecular variants (specific to SJS/TEN in select populations) (Ref)

Hemophagocytic lymphohistiocytosis

Lamotrigine is associated with a rare syndrome, hemophagocytic lymphohistiocytosis (HLH), which is characterized by excessive and sustained immune activation with a natural killer cell count decreased (Ref). Symptoms may include fever, rash, hepatosplenomegaly, organ system dysfunction, and blood dyscrasias (Ref).

Mechanism: Unknown. There are primary (genetic) forms of this syndrome as well as secondary (associated with infectious, malignancy, autoimmune disorders, or drug exposures) (Ref). Stimuli are believed to activate circulating macrophages, which prompt phagocytosis of blood cells, leading to excessive release of cytokines (Ref).

Onset: Intermediate; typically within the first several weeks (17 to 24 days) after starting therapy (Ref).

Suicidal ideation/tendencies

Antiseizure medications have been associated with suicidal ideation and tendencies. However, the FDA meta-analysis has been criticized due to several limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some AEDs (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as postictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref).

Onset: Variable; peak incidence of suicidality across AEDs (not specific to individual agents) has been noted to occur between 1 and 12 weeks of drug therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.

Risk factors:

History of depression (Ref)

Use in conditions other than epilepsy, depression, or bipolar disorder (Ref)

Family and psychiatric history (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences 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%), edema (1% to 5%), peripheral edema (2% to 5%)

Dermatologic: Contact dermatitis (2% to 5%), diaphoresis (2% to 5%), skin rash (nonserious: 7%; requiring hospitalization: <1%) (table 1), xeroderma (2% to 5%)

Lamotrigine: Adverse Reaction: Skin Rash

Drug (Lamotrigine)

Placebo

Indication

Number of Patients (Lamotrigine)

Number of Patients (Placebo)

Comments

7%

5%

Bipolar I disorder

227

190

Nonserious

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

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

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

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

Infection: Infection (5%)

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

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

Ophthalmic: Amblyopia (≥1%), nystagmus disorder (2% to 5%), visual disturbance (2% to 5%)

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

Miscellaneous: Alcohol intolerance (1% to 5%), fever (1% to 5%)

<1%:

Cardiovascular: Flushing, hypertension, orthostatic hypotension, palpitations, syncope, tachycardia, vasodilation

Dermatologic: Acne vulgaris, alopecia, dermatitis (exfoliative, fungal), ecchymoses, erythema multiforme, erythema of skin, leukoderma, maculopapular rash, pruritus, pustular rash, skin discoloration, Stevens-Johnson syndrome (Bloom 2017), urticaria, vesicobullous dermatitis

Endocrine & metabolic: Decreased libido, decreased serum fibrinogen, goiter, heavy menstrual bleeding, hirsutism, hot flash, hyperglycemia, hypothyroidism, increased gamma-glutamyl transferase

Gastrointestinal: Ageusia, dysgeusia, dysphagia, eructation, gastric ulcer, gastritis, gastrointestinal hemorrhage, gingival hemorrhage, gingival hyperplasia, gingivitis, glossitis, hematemesis, hemorrhagic colitis, hiccups, increased appetite, melena, oral mucosa ulcer, sialorrhea, stomatitis

Genitourinary: Breast abscess, cystitis, dysuria, ejaculatory disorder, epididymitis, hematuria, impotence, lactation, nocturia, urinary incontinence, urinary retention, urinary urgency

Hematologic & oncologic: Anemia, breast neoplasm, decreased fibrin, eosinophilia, iron deficiency anemia, leukocytosis, leukopenia, lymphocytosis, macrocytic anemia, petechia, petechial rash, thrombocytopenia

Hepatic: Abnormal hepatic function tests, hepatitis, hyperbilirubinemia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase

Hypersensitivity: Angioedema, tongue edema

Immunologic: Drug reaction with eosinophilia and systemic symptoms (DRESS) (Lameiras 2019; Nathan 2015; Tashiro 2019)

Infection: Herpes zoster infection

Nervous system: Akathisia, altered sense of smell, anorgasmia, apathy, aphasia, central nervous system depression, chills, choreoathetosis, delirium, delusion, depersonalization, dysarthria, dysphoria, dystonia, euphoria, extrapyramidal reaction, hallucination, hemiplegia, hostility, hyperalgesia, hyperesthesia, hypertonia, hypotonia, malaise, manic depressive reaction, memory impairment, movement disorder, myasthenia, myoclonus, neuralgia, neurosis, panic attack, paralysis, paranoid ideation, peripheral neuritis, personality disorder, psychosis, racing mind, sleep disorder, status epilepticus, stupor, tonic clonic epilepsy (exacerbation), twitching, withdrawal syndrome, yawning

Neuromuscular & skeletal: Amyotrophy, arthritis, bursitis, dyskinesia, hyperkinetic muscle activity, hypokinesia, lower limb cramp, muscle spasm, pathological fracture, tendinous contracture

Ophthalmic: Abnormal lacrimation, accommodation disturbance, blepharoptosis, conjunctivitis, dry eye syndrome, oscillopsia, photophobia, strabismus, uveitis, visual field defect

Otic: Deafness, otalgia, tinnitus

Renal: Acute renal failure, increased serum creatinine, polyuria, renal pain

Respiratory: Hyperventilation

Postmarketing (any indication):

Cardiovascular: Vasculitis, disseminated intravascular coagulation (Chattergoon 1997)

Dermatologic: Toxic epidermal necrolysis (Bloom 2017)

Endocrine & metabolic: Hyponatremia (Nakamura 2019)

Gastrointestinal: Esophagitis (associated with DRESS) (Do-Pham 2011), pancreatitis (associated with DRESS) (Roquin 2010)

Hematologic & oncologic: Agranulocytosis (Ahn 2008; Nazer 2012), aplastic anemia, decreased serum immunoglobulins (subclass [IgA] deficiency) (Maruyama 2016), hemolytic anemia, hemophagocytic lymphohistiocytosis (Kim 2019; Zhou 2019), hypogammaglobulinemia (Smith 2004), lymphadenopathy (Pomeroy 2017), neutropenia (LeDrew 2005), pancytopenia (Chang 2018), pure red cell aplasia (Pulik 2000)

Hepatic: Hepatotoxicity (Moeller 2008)

Immunologic: Immunosuppression

Nervous system: Aggressive behavior (Beran 1998), aseptic meningitis (Green 2008; Simms 2012), exacerbation of Parkinson's disease (Sabolek 2010; Santens 2006), suicidal tendencies (Caley 2018), tic disorder (Centorino 2016; Thome-Souze 2012)

Neuromuscular & skeletal: Lupus-like syndrome (Chang 2014), rhabdomyolysis (Karaoulanis 2016)

Renal: Interstitial nephritis

Respiratory: Apnea (includes infant exposure through breast milk) (Nordmo 2009)

Miscellaneous: Multi-organ failure (Chattergoon 1997; Ferguson 2009)

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:

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

Disease-related concerns:

• Cardiovascular disease: Use caution in patients with structural or functional heart disease (ie, cardiac channelopathies [eg, Brugada syndrome], conduction system disease, congenital heart disease, heart failure, ischemic heart disease [significant], valvular heart disease, ventricular arrhythmias, or multiple risk factors for coronary artery disease); in vitro data have shown lamotrigine exhibits class Ib antiarrhythmic activity at normal concentrations, and therefore, may slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death. Proarrhythmic risk may also be increased with concomitant use of other sodium channel blockers. Consider additional cardiac monitoring in at-risk patients (French 2021).

• 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 due to large interindividual variability in half-life (Fillastre 1993; Wootton 1997).

Dosage form specific issues:

• Phenylalanine: Some products may contain phenylalanine.

• 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 mania or episodes with mixed features 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 antiseizure drugs other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid or conversion to monotherapy from two or more antiseizure drugs.

• Withdrawal: In chronic therapy, withdraw gradually to minimize the potential of increased seizure frequency (in patients with epilepsy) and withdrawal symptoms (eg, dysphoria, hallucinations, headache, insomnia, tremor) unless safety concerns require more rapid withdrawal.

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.

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(sunset yellow)alumin lake]

LaMICtal XR: Green Kit: 50 mg (14s) & 100 mg (14s) & 200 mg (7s) [contains fd&c blue #2 (indigo carm) 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), Blue Kit: 25 mg (35s), Green Kit: 25 mg (84s) & 100 mg (14s), Green Kit: 50 mg (42s) & 100 mg (14s), Orange Kit: 25 mg (14s) & 50 mg (14s) & 100 mg (7s), Orange Kit: 25 mg (42s) & 100 mg (7s)

Tablet, Oral:

LaMICtal: 25 mg [scored]

LaMICtal: 100 mg [scored; contains fd&c yellow #6(sunset yellow)alumin lake]

LaMICtal: 150 mg [scored]

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

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 (indigo carm) aluminum lake, polysorbate 80]

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

LaMICtal XR: 300 mg [contains polysorbate 80]

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

Generic Equivalent Available: US

Yes

Pricing: US

Chewable (LaMICtal Oral)

5 mg (per each): $18.48

25 mg (per each): $19.84

Chewable (lamoTRIgine Oral)

5 mg (per each): $3.05

25 mg (per each): $3.20

Kit (LaMICtal ODT Oral)

21 x 25 MG &7 x 50 MG (per each): $20.09

25 & 50 & 100 mg (per each): $22.95

42 x 50 MG &14x100 MG (per each): $28.69

Kit (LaMICtal Starter Oral)

35 x 25 mg (per each): $19.10

42 x 25 MG &7 x 100 MG (per each): $19.49

84 x 25 MG &14x100 MG (per each): $19.49

Kit (LaMICtal XR Oral)

21 x 25 MG &7 x 50 MG (per each): $21.00

25 & 50 & 100 mg (per each): $24.00

50 & 100 & 200 mg (per each): $47.99

Kit (lamoTRIgine Oral)

21 x 25 MG &7 x 50 MG (per each): $12.30

25 & 50 & 100 mg (per each): $14.05

42 x 50 MG &14x100 MG (per each): $17.57

Kit (Subvenite Starter Kit-Blue Oral)

35 x 25 mg (per each): $20.20

Kit (Subvenite Starter Kit-Green Oral)

84 x 25 MG &14x100 MG (per each): $20.20

Kit (Subvenite Starter Kit-Orange Oral)

42 x 25 MG &7 x 100 MG (per each): $21.00

Tablet, 24-hour (LaMICtal XR Oral)

25 mg (per each): $16.80

50 mg (per each): $33.60

100 mg (per each): $35.99

200 mg (per each): $38.38

250 mg (per each): $52.33

300 mg (per each): $57.57

Tablet, 24-hour (lamoTRIgine ER Oral)

25 mg (per each): $6.55 - $14.04

50 mg (per each): $13.09 - $28.07

100 mg (per each): $14.03 - $30.07

200 mg (per each): $14.96 - $32.07

250 mg (per each): $20.40 - $43.73

300 mg (per each): $22.44 - $48.10

Tablet, orally-disintegrating (LaMICtal ODT Oral)

25 mg (per each): $16.07

50 mg (per each): $17.21

100 mg (per each): $18.35

200 mg (per each): $21.90

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): $19.10

100 mg (per each): $21.82

150 mg (per each): $23.91

200 mg (per each): $26.03

Tablets (lamoTRIgine Oral)

25 mg (per each): $0.20 - $4.55

100 mg (per each): $0.17 - $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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

LaMICtal: 25 mg

LaMICtal: 100 mg [contains fd&c yellow #6(sunset yellow)alumin lake]

LaMICtal: 150 mg, 250 mg

Generic: 25 mg, 100 mg, 150 mg

Tablet Chewable, Oral:

LaMICtal: 2 mg, 5 mg [contains saccharin sodium]

Administration: Adult

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.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR tablet and cut tablets into smaller pieces; not recommended to crush due to bitter taste. Orally disintegrating tablet is also available.

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.

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 CD, Lamictal ODT: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020241s064,020764s057,022251s028lbl.pdf#page=65

Lamictal XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022115s029lbl.pdf#page=51

Use: Labeled Indications

Bipolar disorder: Maintenance treatment of bipolar disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, episodes with mixed features), as monotherapy or adjunctive therapy.

Focal (partial) onset seizures and generalized onset seizures: Treatment of Lennox-Gastaut syndrome (adjunctive therapy only), primary generalized tonic-clonic seizures (adjunctive therapy only), and focal onset seizures (monotherapy or adjunctive therapy). May be used off-label for other seizure types.

Use: Off-Label: Adult

Bipolar major depression; Short-lasting unilateral neuralgiform headache attacks, prophylaxis; Trigeminal neuralgia

Medication Safety Issues
Sound-alike/look-alike issues:

LamoTRIgine may be confused with labetalol, LamISIL, lamiVUDine, levETIRAcetam, levothyroxine, Lomotil

LaMICtal may be confused with labetalol, LamISIL, Lomotil

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Pediatric patients: High-risk medication:

KIDs List: Lamotrigine, when used in pediatric patients <18 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of serious skin rashes; titration needed (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).

Administration issues:

Potential exists for medication errors to occur among different formulations of LaMICtal (tablets, extended release tablets, orally disintegrating tablets, and chewable/dispersible tablets). Patients should be instructed to visually inspect tablets dispensed to verify receiving the correct medication and formulation. The medication guide includes illustrations to aid in tablet verification.

International issues:

Lamictal [US, Canada, and multiple international markets] may be confused with Ludiomil brand name for maprotiline [multiple international markets]

Lamotrigine [US, Canada, and multiple international markets] may be confused with Ludiomil brand name for maprotiline [multiple international markets]

Metabolism/Transport Effects

Substrate of OCT1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Antiseizure Agents (Sodium Channel Blockers): May enhance the arrhythmogenic effect of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Risk D: Consider therapy modification

Atazanavir: May decrease the serum concentration of LamoTRIgine. Specifically, the use of ritonavir-boosted atazanavir may decrease the serum concentration of lamotrigine. Risk C: Monitor therapy

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

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

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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: May enhance the adverse/toxic effect of LamoTRIgine. Specifically, the risk for hematologic toxicities may be increased. CarBAMazepine may enhance the arrhythmogenic effect of LamoTRIgine. CarBAMazepine may decrease the serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus benefit of this combination. For patients taking carbamazepine without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. See full interact monograph for details. Risk D: Consider therapy modification

Cenobamate: May enhance the arrhythmogenic effect of LamoTRIgine. Cenobamate may decrease the serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. If combined, monitor for reduced lamotrigine efficacy and increase lamotrigine dose if needed. 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

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

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. 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

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. 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: Larger doses of lamotrigine may be needed when combined with estrogens. Specific dosing recommendations vary based on other concomitant medications and which medication is being initiated or discontinued. See interaction monograph for details. Risk D: Consider therapy modification

Ethinyl Estradiol-Containing Products: May decrease the serum concentration of LamoTRIgine. Management: Larger doses of lamotrigine may be needed when combined with ethinyl estradiol. Specific dosing recommendations vary based on other concomitant medications and which medication is being initiated or discontinued. See interaction monograph for details. Risk D: Consider therapy modification

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

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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fosphenytoin: May enhance the arrhythmogenic effect of LamoTRIgine. Fosphenytoin may decrease the serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus benefit of this combination. For patients taking fosphenytoin without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. See full interact monograph for details. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

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

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

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

Lacosamide: Antiseizure 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

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

LevETIRAcetam: May enhance the CNS depressant effect of LamoTRIgine. Risk C: Monitor therapy

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

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

Lopinavir: May decrease the serum concentration of LamoTRIgine. Management: For patients taking lopinavir/ritonavir without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Risk D: Consider therapy modification

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

Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

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

MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. 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 Antiseizure Agents. Risk C: Monitor therapy

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

Nirmatrelvir and Ritonavir: May decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy

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

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 Antiseizure Agents. 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

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

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. Risk C: Monitor therapy

PHENobarbital: May enhance the adverse/toxic effect of LamoTRIgine. Specifically, the risk for hematologic toxicities may be increased. PHENobarbital may decrease the serum concentration of LamoTRIgine. Management: For patients taking phenobarbital without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Risk D: Consider therapy modification

Phenytoin: May enhance the arrhythmogenic effect of LamoTRIgine. Phenytoin may decrease the serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus benefit of this combination. For patients taking phenytoin without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. See full interact monograph for details. 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: LamoTRIgine may enhance the adverse/toxic effect of Primidone. Specifically, the risk for hematologic toxicities may be increased. Primidone may decrease the serum concentration of LamoTRIgine. Management: For patients taking primidone without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. 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

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

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

RifAMPin: May decrease the serum concentration of LamoTRIgine. Management: For patients taking rifampin without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Risk D: Consider therapy modification

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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). 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 arrhythmogenic effect of LamoTRIgine. LamoTRIgine may enhance the CNS depressant effect of Rufinamide. Specifically, sleepiness and dizziness may be enhanced. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Additionally, if combined, caution patients that sleepiness and dizziness may be increased. 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

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

Topiramate: May enhance the arrhythmogenic effect of LamoTRIgine. LamoTRIgine may enhance the CNS depressant effect of Topiramate. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Additionally, if combined, caution patients that CNS depressant effects may be increased. Risk D: Consider therapy modification

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

Valerian: 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. Management: Lamotrigine dose reductions are needed when combined with valproate. See full interaction monograph for details. Increase monitoring for lamotrigine toxicity (eg, rash, hematologic toxicities) when these agents are combined. 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

Zonisamide: May enhance the arrhythmogenic effect of LamoTRIgine. LamoTRIgine may enhance the CNS depressant effect of Zonisamide. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Additionally, if combined, caution patients that CNS depressant effects may be increased. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Food Interactions

Food has no effect on absorption.

Reproductive Considerations

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 (Patsalos 2008; Patsalos 2018).

Potentially significant interactions may exist with hormone-containing contraceptives.

Pregnancy Considerations

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). 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; Patsalos 2018).

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.

Breastfeeding 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).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Monitor the infant for signs and symptoms of lamotrigine toxicity; obtain infant serum lamotrigine concentrations if symptoms of toxicity occur.

Dietary Considerations

Some products may contain phenylalanine.

Monitoring Parameters

Serum levels of concurrent antiseizure medications, LFTs, renal function, hypersensitivity reactions (especially rash), including signs and symptoms of DRESS (eg. lymphadenopathy, fever, rash, possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems); ECG (prior to initiation in patients ≥60 years of age or in patients <60 years of age with concurrent sodium channel blocker or cardiac conduction-impairing substance use, with known cardiac disease or major cardiovascular risk factors [diabetes, hypertension, familial hypercholesterolemia, smoking], or with sudden onset syncope or presyncope without clear cause; repeat in at-risk patients when target dose or serum level is reached) (French 2021); suicidality (eg, suicidal thoughts, depression, behavioral changes); clinical worsening in bipolar disorder; signs/symptoms of aseptic meningitis; signs and symptoms of blood dyscrasias (eg, fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage).

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)

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.

Pharmacokinetics (Adult Data Unless Noted)

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

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%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Older adult: Clearance was 0.3 to 0.5 mL/minute/kg.

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

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Lamictal;
  • (AR) Argentina: Dafex | Epilepax | Lagotran | Lamictal | Lamirax | Lamocas xr;
  • (AT) Austria: Lamictal | Lamotribene | Lamotrigin | Lamotrigin genericon | Lamotrigin ratiopharm | Lamotrigin sandoz;
  • (AU) Australia: Apo lamotrigine | Elmendos | Lamictal | Lamidus | Lamitan | Lamitrin | Lamogine | Lamotrigine an | Lamotrigine Generic Health | Lamotrigine ps | Lamotrigine Sandoz | Lamotrigine-GA | Lamotrust | Logem | Munatrep | Noumed lamotrigine | Reedos | Seaze | Torlemo;
  • (BD) Bangladesh: Lameptil | Lamicet | Lamictal | Lamitrin | Lamogin;
  • (BE) Belgium: Doclamotri | Lambipol | Lamictal | Lamotrigine EG | Lamotrigine mylan | Lamotrigine ratiopharm | Lamotrigine Teva;
  • (BG) Bulgaria: Epitrigine | Gerolamic | Lamal | Lamictal | Lamotren | Lamotrix;
  • (BR) Brazil: Bipogine | Forlut | Lamictal | Lamitor | Lamitor cd | Lamoctril | Lamotrigina | Lamotrix | Neural | Neurium | Nortrigin;
  • (CH) Switzerland: Lamictal | Lamotrigin actavis | Lamotrigin desitin | Lamotrigin Helvepharm | Lamotrigin sandoz | Lamotrine;
  • (CL) Chile: Daksol | Flamus | Lafigin | Lafigin dt | Lafigin xr | Lamictal | Lamitrin | Letico | Lomarin | Meganox | Tradox | Trigilab | Trizol;
  • (CN) China: An xian | Lamictal;
  • (CO) Colombia: Fenebra | Lafigin | Lafigin dt | Lamep | Lamez | Lamictal | Lamogin | Lamolet | Lamotrigina | Lamotrigina humax | Latrimed | Normatrin;
  • (CZ) Czech Republic: Epimil | Epiral | Lamictal | Lamogine | Lamolep | Lamotax | Lamotrigin aurobindo | Lamotrigin ratiopharm | Lamotrigine Farmax | Lamotrigine Teva | Lamotrix | Plexxo;
  • (DE) Germany: Elmendos | Espa-trigin | Lamictal | Lamo | Lamotriax | Lamotrig-Isis | Lamotrigin 1 a pharma | Lamotrigin Aaa-Ph | Lamotrigin Acis | Lamotrigin actavis | Lamotrigin al | Lamotrigin Aristo | Lamotrigin Atid | Lamotrigin aurobindo | Lamotrigin Axcount | Lamotrigin basics | Lamotrigin Beta | Lamotrigin desitin | Lamotrigin dura | Lamotrigin heumann | Lamotrigin heunet | Lamotrigin hexal | Lamotrigin Holsten | Lamotrigin Hormosan | Lamotrigin neuraxpharm | Lamotrigin Real | Lamotrigin sandoz | Lamotrigin teva | Lamotrigin winthrop | Lamotrigin-ratiopharm;
  • (DK) Denmark: Lamotrigin actavis | Lamotrigin copyfarm | Lamotrigin gsk | Lamotrigin hexal | Lamotrigin ratiopharm | Lamotrigin stada;
  • (DO) Dominican Republic: Clarus | Flamus | Lafigin dt | Lamictal | Lamocas | Lamotrigina | Lamtox | Leumont;
  • (EC) Ecuador: Ginacross | Lafigin | Lafigin dt | Lamictal | Lamotrigina | Latrigin | Latrimed | Latrin | Leumont | Trimolep;
  • (EE) Estonia: Lamepil | Lamictal | Lamorin | Lamotrigin sandoz;
  • (EG) Egypt: Controlepsy | Labileno | Lamictal | Lamotrine | Lamotrotic | Larogen | Leptrogine | Motrigine | Rowatrigin;
  • (ES) Spain: Crisomet | Labileno | Lamictal | Lamomylan | Lamotrigina Aurobindo | Lamotrigina aurovitas | Lamotrigina bexal | Lamotrigina Combix | Lamotrigina davur | Lamotrigina edigen | Lamotrigina kern pharma | Lamotrigina korhis | Lamotrigina normon | Lamotrigina Qualigen | Lamotrigina Ratiopharm | Lamotrigina sandoz | Lamotrigina Stada | Lamotrigina Tevagen | Lamotrigina urquima | Lamotrigina Winthrop | Lavinol | Simolan;
  • (ET) Ethiopia: Lamotrix;
  • (FI) Finland: Lamictal | Lamotrigin actavis | Lamotrigin hexal | Lamotrigin ratiopharm | Lamotrigin sandoz;
  • (FR) France: Lamicstart | Lamictal | Lamotrigine Almus | Lamotrigine Arrow | Lamotrigine arrow lab | Lamotrigine Biogaran | Lamotrigine EG | Lamotrigine Qualimed | Lamotrigine Ranbaxy | Lamotrigine ratiopharm | Lamotrigine Sandoz | Lamotrigine Teva;
  • (GB) United Kingdom: Lamictal | Lamotrigine milpharm;
  • (GR) Greece: Dezepil | Isleton | Lamictal | Lamot | Lamotrigine mylan | Lamotrix;
  • (HK) Hong Kong: Apo lamotrigine | Lamictal;
  • (HR) Croatia: Arvind | Lamal | Lameptil | Lamictal | Lamotrigin genericon | Lamox;
  • (HU) Hungary: Gerolamic | Lamictal | Lamitrin | Lamolep | Lamotrigin aurobindo | Lamotrigin ratiopharm | Lamotrigine Orion | Lamotrigine pliva | Latrigil | Plexxo;
  • (ID) Indonesia: Lamictal | Lamiros;
  • (IE) Ireland: Lamictal | Lamoro | Lamot | Larig;
  • (IL) Israel: Lamictal | Lamodex | Lamogine;
  • (IN) India: Epilam | Epitic | Favlam | Lamepil | Lametec | Lamez | Lamictal | Lamictin | Lamidus | Lamitor | Lamogin | Lamogine | Lamokem | Lamorig | Lamosyn | Lamotem | Lamriga | Lemit | Monolam | Motrigin | Nombre Od | Voltrigin;
  • (IT) Italy: Lamictal | Lamotrigina | Lamotrigina Arrow | Lamotrigina Aurobindo | Lamotrigina Breath | Lamotrigina eg | Lamotrigina Ranbaxy;
  • (JO) Jordan: Epictal | Lamictal | Loxol;
  • (JP) Japan: Lamictal | Lamotrigine towa;
  • (KR) Korea, Republic of: Labicitin | Lameptil | Lamiart | Lamictal | Lamogine | Lamostal | Lamotigin | Lamotrizin | Lathrizin | Lavicitin | Ramozin | Teva lamotrigine;
  • (KW) Kuwait: Lamictal;
  • (LB) Lebanon: Lamictal | Lamotrigine arrow lab | Lamotrigine Biogaran | Lepigine | Pms lamotrigine;
  • (LT) Lithuania: Lamepil | Lamictal | Lamorin | Lamotrigine Ranbaxy | Latrigil | Triginet;
  • (LU) Luxembourg: Lambipol | Lamictal | Lamotrigin ratiopharm | Lamotrigine EG;
  • (LV) Latvia: Lamictal | Lamorin | Lamotrigin sandoz | Lamotrigine Ranbaxy | Lamotrix | Lamox | Triginet;
  • (MA) Morocco: Lamictal | Synnax;
  • (MX) Mexico: Damotip | Fenebra | Lamdra | Lamictal | Lamotrigina | Latrigin | Motricord | Neuxitab | Prilkenzide | Protalgine | Ramitrine | Torlamo DT | Triland | Trimolep | Ximolatrim | Yamoyoung;
  • (MY) Malaysia: Apo-Lamotrigine | Epsylam dt | Lamictal | Lamitor | Lamotaxyl | Lamotrigine normon | Lamotrix;
  • (NG) Nigeria: Lamocan;
  • (NL) Netherlands: Lamictal | Lamotrigine A | Lamotrigine Actavis | Lamotrigine Aurobindo | Lamotrigine PCH | Lamotrigine ratiopharm | Lamotrigine Sandoz;
  • (NO) Norway: Lamictal | Lamotrigin | Lamotrigin 1 a pharma | Lamotrigin Arrow | Lamotrigin hexal;
  • (NZ) New Zealand: Lamictal | Lamotrigine Arrow | Mogine | Motrig | Noumed lamotrigine;
  • (PE) Peru: Lafigin | Lamez | Lamictal | Lamosyn | Lamotaxyl | Lamotrigina | Lamotrine | Lamotriptal | Leumont | Peratil | Trimolep;
  • (PH) Philippines: Lamictal | Lamitor | Lamosyn | Lamotrix;
  • (PK) Pakistan: Lagintal | Lagotran | Lamepil | Lamgin | Lamictal | Lamitor | Lamomed | Lamomet | Lamonil | Lamot | Lamotrin | Lamprene | Limgit | Lojin | Lomogin | Longtel | Lupin | Morigin | Motrig | Novogin | Xamogine | Zitrigine;
  • (PL) Poland: Danoptin | Epilactal | Epitrigine | Lameptil | Lamexim | Lamilept | Lamitrin | Lamotrigine Farmax | Lamotrigine ratiopharm | Lamotrihexal | Lamotrix | Lamox | Lamozor | Plexxo | Symla | Triginet | Trogine | Verpin;
  • (PR) Puerto Rico: Lamictal | Subvenite;
  • (PT) Portugal: Lamictal | Lamotrigina arrowblue | Lamotrigina Aurobindo | Lamotrigina aurovitas | Lamotrigina azevedos | Lamotrigina Labesfal | Lamotrigina wynn;
  • (PY) Paraguay: Dafex | Flamus | Lafigin | Lafigin dt | Lamictal | Lamotrigina celsius | Lamotrigina heisecke | Lamotrigina imedic | Lamotrigina intas | Lamotrigina prosalud | Lamotrigina quimfa;
  • (RO) Romania: Epimil | Epiral | Lamictal | Lamolep;
  • (RU) Russian Federation: Convulsan | Lameptil | Lamictal | Lamitor | Lamolep | Lamotrigine canon | Lamotrix | Sazar | Triginet | Vero lamotrigine;
  • (SA) Saudi Arabia: Apo lamotrigine | Lamictal | Lamira | Lamotrix | Loxol | Pms lamotrigine | Seizet;
  • (SE) Sweden: Lamictal | Lamocare | Lamotrigin | Lamotrigin 1a farma | Lamotrigin abacus medicine | Lamotrigin actavis | Lamotrigin amneal | Lamotrigin Arrow | Lamotrigin aurobindo | Lamotrigin bmm pharma | Lamotrigin Ebb | Lamotrigin eql | Lamotrigin medartuum | Lamotrigin mylan | Lamotrigin omnia | Lamotrigin orifarm | Lamotrigin ratiopharm | Lamotrigin teva;
  • (SG) Singapore: Apo lamotrigine | Lamictal | Lamotrix;
  • (SI) Slovenia: Lamal | Lameptil | Lamictal | Lamitrin | Lamotrigin | Triginet;
  • (SK) Slovakia: Lamepil | Lamictal | Lamotrigin | Lamotrigine Farmax | Medotrigin | Plexxo | Triginet;
  • (TH) Thailand: Lamictal | Lamoga 25 | Lamogine | Neumogine;
  • (TN) Tunisia: Lamictal | Lamilep | Lamotrin | Thymoreg 100 | Thymoreg 200 | Thymoreg 25 | Thymoreg 50;
  • (TR) Turkey: Lamictal | Latrigal | Pinral;
  • (TW) Taiwan: Lamictal | Lamidus | Lamogin | Lamotrix | Lamta | Latrigine;
  • (UA) Ukraine: Epimil | Lamal | Lamictal | Lamidum | Lamitril | Lamotridex | Lamotrigin | Lamotrigine pliva | Lamotrin | Lanistor | Latrigil;
  • (UG) Uganda: Lamictal | Lamitor;
  • (UY) Uruguay: Lamictal | Lamirax | Lamocas | Lamogin | Lamotrina | Lamotrine | Lamotrix | Latrigin | Ltg;
  • (VE) Venezuela, Bolivarian Republic of: Epifon | Epitral | Lamictal | Lamocris | Lamolet | Lamotrigil | Lamotrigina | Lamtox | Laspen | Nakimal | Traminal;
  • (ZA) South Africa: Aspen Lamotrigine | Dyna Lamotrigine | Epitec | Girotec | Lameptil | Lamictin | Lamidus | Serinem;
  • (ZM) Zambia: Lamitor;
  • (ZW) Zimbabwe: Lamictin | Lamitor
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