Lamictal

Pronunciation

Generic Name: Lamotrigine
Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine
Molecular Formula: C9H7Cl2N5
CAS Number: 84057-84-1

Warning(s)

  • Dermatologic Reactions
  • Can cause serious and potentially life-threatening rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and/or rash-related death.1 6 9 11 43 a (See Dermatologic Reactions under Cautions.)

  • Risk of serious rash is greater in pediatric patients than in adults (see Pediatric Use under Cautions) and may be increased by concomitant use of valproic acid (valproate, divalproex sodium)a 43 or by exceeding the recommended initial dosage or dosage escalation schedule for lamotrigine.1 5 9 43

  • Cases of life-threatening rash associated with immediate-release lamotrigine almost always have occurred within 2–8 weeks of treatment initiation;1 43 however, isolated cases have been reported following prolonged treatment (e.g., 6 months).1 43

  • Can also cause benign rashes; however, it is not possible to predict which rashes will become serious or life-threatening.43 Discontinue therapy at the first sign of rash (unless the rash is clearly not drug related).1 43

  • Discontinuance of therapy may not prevent rash from becoming life-threatening or permanently disabling or disfiguring.1 43

REMS:

FDA approved a REMS for lamotrigine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Phenyltriazine anticonvulsant;1 2 4 5 6 7 10 13 14 20 structurally unrelated to other currently available anticonvulsants.1 3 4 5 6 9 10 12 13 14 15 17 20

Uses for Lamictal

Seizure Disorders

Immediate-release formulations (e.g., conventional tablets, chewable/dispersible tablets, orally disintegrating tablets): Management (in combination with other anticonvulsants) of partial seizures, with or without secondary generalization, or primary generalized tonic-clonic seizures in adults and children ≥2 years of age.2 6 9 10 11 12 20 38 39 45

Adults and adolescents ≥16 years of age with partial seizures who are receiving a hepatic enzyme-inducing anticonvulsant (e.g., carbamazepine, phenobarbital, phenytoin, primidone) or valproic acid as monotherapy may be converted to immediate-release lamotrigine monotherapy.2 6 9 10 11 12 20 38 45

Slideshow: Flashback: FDA Drug Approvals 2013

Extended-release tablets: Management (in combination with other anticonvulsants) of partial seizures, with or without secondary generalization, or primary generalized tonic-clonic seizures in adults and adolescents ≥13 years of age.43 52

Immediate-release formulations: Management (in combination with other anticonvulsants) of generalized seizures associated with Lennox-Gastaut syndrome in adults and children ≥2 years of age.28 38 45

Safety and efficacy of lamotrigine not established as initial monotherapy; for conversion from monotherapy with anticonvulsants other than hepatic enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin, primidone) or valproic acid; or for simultaneous conversion to monotherapy from ≥2 concomitant anticonvulsants.38 45

Bipolar Disorder

Immediate-release formulations: Maintenance therapy of bipolar 1 disorder to prevent or attenuate recurrences of bipolar episodes in adult patients who remain at high risk of relapse following treatment of an acute depressive or manic episode.30 38 40 41 45 Considered by the American Psychiatric Association (APA) to be an alternative to first-line maintenance therapies (e.g., lithium, valproic acid, divalproex).30 May be more effective in preventing depressive episodes than manic episodes.30

Efficacy in the acute treatment of mood episodes has yet to be fully established,38 45 but lamotrigine is considered a first-line agent by the APA for the management of acute depressive episodes in patients with bipolar disorder and an alternative to lithium, valproic acid, or divalproex in the management of patients with rapid cycling bipolar disorder, particularly in those with the bipolar 2 form of rapid cycling.30

Lamictal Dosage and Administration

General

  • Therapeutic plasma concentration range has not been established for treatment of seizure disorders; base dosage on clinical response.a

  • To minimize the possibility of developing a serious rash, adhere to manufacturer-recommended initial dosages and dosage escalation regimens.1 2 3 6 9 Discontinue therapy at the first sign of rash (unless the rash is known not to be drug related).1 (See Boxed Warning and see also Dermatologic Reactions under Cautions.)

  • Do not discontinue abruptly, particularly in patients with preexisting seizure disorders.1 2 4 9 10 31 43 To minimize the possibility of increasing seizure frequency, reduce dosage in a step-wise fashion over ≥2 weeks (e.g., achieving a 50% reduction in the daily dosage of lamotrigine each week) unless safety concerns require more rapid withdrawal.1 2 10 43

  • Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.35 36 37 38 42 43 (See Suicidality Risk under Cautions.)

Administration

Oral Administration

Conventional Tablets

Administer orally in 1 dose or 2 divided doses daily without regard to meals.1 2 3 4 5 6 9 10 12

Swallow whole.38

Chewable/Dispersible Tablets

Administer orally in 1 dose or 2 divided doses daily without regard to meals.1 2 3 4 5 6 9 10 12

May be swallowed whole, chewed (and consumed with a small amount of water or diluted fruit juice to aid swallowing), or dispersed in water or diluted fruit juice.1

To disperse the tablets, add to a small volume (i.e., 5 mL or enough to cover the tablet) of liquid and allow to disperse completely (over approximately 1 minute); swirl the solution and consume immediately.1

Do not administer partial quantities of chewable/dispersible tablets; calculated doses that do not correspond to available strength of whole tablets should be rounded down to the nearest whole tablet.1 The smallest commercially available strength of chewable/dispersible tablets is 2 mg.1

Extended-release Tablets

Administer orally once daily without regard to meals.43

Swallow whole; do not chew, crush, or divide.43

Orally-disintegrating Tablets

Administer orally in 1 dose or 2 divided doses daily without regard to meals.38

Place orally disintegrating tablet on tongue and move around in mouth to disintegrate; then swallow with or without water.38

Dosage

When adding lamotrigine to an existing anticonvulsant regimen, add gradually while maintaining or gradually adjusting dosage of the other anticonvulsant(s).1 4 21

Addition of other anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin, primidone, valproic acid) to, or their discontinuance from, an anticonvulsant regimen including lamotrigine may require modification of the dosage of lamotrigine and/or the other anticonvulsant(s).1 4 a (See Specific Drugs under Interactions.)

If lamotrigine therapy is interrupted for >5 half-lives (see Half-life under Pharmacokinetics) for any reason and reinitiation of the drug is not contraindicated, resume therapy using recommended initial dosage and dosage escalation regimens.a

Pediatric Patients

Seizure Disorders
Adjunctive Therapy with Immediate-release Formulations
Oral

Recommended initial dosages and dosage escalations for lamotrigine given as immediate-release formulations (e.g., conventional tablets, chewable/dispersible tablets, orally disintegrating tablets) when added to an anticonvulsant regimen containing valproic acid; containing anticonvulsant(s) other than carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid); or containing carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid) are summarized in Table 1, Table 2, and Table 3, respectively.38 45

May take several weeks to months to achieve an individualized maintenance dosage.38 May need to increase maintenance dosage by as much as 50%, based on clinical response, in patients weighing <30 kg, regardless of age or concomitant anticonvulsant(s).38 45

Round dosage down to the nearest whole tablet.38 45

May need to increase maintenance dosage by as much as 50%, based on clinical response, in patients weighing <30 kg, regardless of age or concomitant anticonvulsant(s).38 45

Table 1: Recommended Pediatric Dosages of Immediate-release Lamotrigine When Added to Anticonvulsant Regimens Containing Valproic Acid3845

Week of Therapy

Children 2–12 Years of Age

Children >12 Years of Age

Weeks 1 and 2

0.15 mg/kg daily in 1 dose or 2 divided doses

25 mg every other day

Weeks 3 and 4

0.3 mg/kg daily in 1 dose or 2 divided doses

25 mg daily

Week 5 onward

Increase dosage in increments of 0.3 mg/kg daily every 1–2 weeks until an effective maintenance dosage is reached

Increase dosage in increments of 25–50 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Usual maintenance dosage

1–5 mg/kg daily (maximum 200 mg daily in 1 dose or 2 divided doses)

100–400 mg daily in 1 dose or 2 divided doses

 

1–3 mg/kg daily if added to anticonvulsant regimen containing valproic acid alone

100–200 mg daily if added to anticonvulsant regimen containing valproic acid alone

Round dosage down to the nearest whole tablet.38 45

May need to increase maintenance dosage by as much as 50%, based on clinical response, in patients weighing <30 kg, regardless of age or concomitant anticonvulsant(s).38 45

Table 2: Recommended Pediatric Dosages of Immediate-release Lamotrigine When Added to Anticonvulsant Regimens Containing Anticonvulsants Other Than Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)3845

Week of Therapy

Children 2–12 Years of Age

Children >12 Years of Age

Weeks 1 and 2

0.3 mg/kg daily in 1 dose or 2 divided doses

25 mg daily

Weeks 3 and 4

0.6 mg/kg daily in 2 divided doses

50 mg daily

Week 5 onward

Increase dosage in increments of 0.6 mg/kg daily every 1–2 weeks until an effective maintenance dosage is reached

Increase dosage in increments of 50 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Usual maintenance dosage

4.5–7.5 mg/kg daily (maximum 300 mg daily in 2 divided doses)

225–375 mg daily in 2 divided doses

Round dosage down to the nearest whole tablet.38 45

May need to increase maintenance dosage by as much as 50%, based on clinical response, in patients weighing <30 kg, regardless of age or concomitant anticonvulsant(s).38 45

Table 3: Recommended Pediatric Dosages of Immediate-release Lamotrigine When Added to Anticonvulsant Regimens Containing Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)3845

Week of Therapy

Children 2–12 Years of Age

Children >12 Years of Age

Weeks 1 and 2

0.6 mg/kg daily in 2 divided doses

50 mg daily

Weeks 3 and 4

1.2 mg/kg daily in 2 divided doses

100 mg daily in 2 divided doses

Week 5 onward

Increase dosage in increments of 1.2 mg/kg daily every 1–2 weeks until an effective maintenance dosage is reached

Increase dosage in increments of 100 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Usual maintenance dosage

5–15 mg/kg daily (maximum 400 mg daily in 2 divided doses)

300–500 mg daily in 2 divided doses

Patients receiving rifampin or other drugs that induce lamotrigine glucuronidation and increase clearance, but not receiving valproic acid, should receive lamotrigine dosages recommended for individuals receiving carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid).38 45 For dosage adjustments in patients receiving other concomitant therapy, including estrogen-containing oral contraceptives, see Interactions.

Adjunctive Therapy with Extended-release Formulations
Oral

Adolescents ≥13 years of age should receive extended-release dosage recommended for adults.43 (See Adults under Dosage and Administration.)

Conversion to Immediate-release Lamotrigine Monotherapy
Oral

Adolescents ≥16 years of age should receive immediate-release dosage recommended for adults.a (See Adults under Dosage and Administration.)

Conversion from Immediate-release Lamotrigine to Extended-release Lamotrigine
Oral

May convert patients directly from immediate-release formulations to extended-release tablets (Lamictal XR).43 Initial dosage of extended-release lamotrigine should be the same as the total daily dosage of immediate-release lamotrigine.43

Monitor all patients closely for effective seizure control following conversion, particularly those receiving concomitant therapy with enzyme-inducing drugs since they may have lower plasma lamotrigine concentrations.43

Depending on therapeutic response following conversion, adjust total daily dosage of extended-release lamotrigine within recommended dosing guidelines if necessary.43

Adults

Seizure Disorders
Adjunctive Therapy with Immediate-release Formulations
Oral

Recommended initial dosages and dosage escalations for lamotrigine given as immediate-release formulations (e.g., conventional tablets, chewable/dispersible tablets, orally disintegrating tablets) when added to an anticonvulsant regimen containing valproic acid; containing anticonvulsant(s) other than carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid); or containing carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid) are summarized in Table 4.38 45

Maintenance dosages usually are achieved after several weeks to months of therapy and should be individualized.1

Table 4: Recommended Adult Dosage of Immediate-release Lamotrigine When Added to Existing Anticonvulsant Regimens3845

Week of Therapy

Regimens Containing Valproic Acid

Regimens Containing Anticonvulsants Other Than Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)

Regimens Containing Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)

Weeks 1 and 2

25 mg every other day

25 mg daily

50 mg daily

Weeks 3 and 4

25 mg daily

50 mg daily

100 mg daily in 2 divided doses

Week 5 onward

Increase dosage in increments of 25–50 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Increase dosage in increments of 50 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Increase dosage in increments of 100 mg daily every 1–2 weeks until an effective maintenance dosage is reached

Usual maintenance dosage

100–400 mg daily in 1 dose or 2 divided doses (100–200 mg daily if added to anticonvulsant regimen containing valproic acid alone)

225–375 mg daily in 2 divided doses

300–500 mg daily in 2 divided doses

Patients receiving rifampin or other drugs that induce lamotrigine glucuronidation and increase clearance, but not receiving valproic acid, should receive lamotrigine dosages recommended for individuals receiving carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid).38 45 For dosage adjustments in patients receiving other concomitant therapy, including estrogen-containing oral contraceptives, see Interactions.

Adjunctive Therapy with Extended-release Formulations
Oral

Recommended initial dosages and dosage escalations for lamotrigine given as extended-release tablets (e.g., Lamictal XR) when added to an anticonvulsant regimen containing valproic acid; containing anticonvulsant(s) other than carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid); or containing carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid) are summarized in Table 5.43

Dosage increases from week 8 or later should not exceed 100 mg daily at weekly intervals.43

Table 5: Recommended Adult Dosage of Extended-release Lamotrigine When Added to Existing Anticonvulsant Regimens43

Week of Therapy

Regimens Containing Valproic Acid

Regimens Containing Anticonvulsants Other Than Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)

Regimens Containing Carbamazepine, Phenobarbital, Phenytoin, or Primidone (Without Valproic Acid)

Weeks 1 and 2

25 mg every other day

25 mg daily

50 mg daily

Weeks 3 and 4

25 mg daily

50 mg daily

100 mg daily

Week 5

50 mg daily

100 mg daily

200 mg daily

Week 6

100 mg daily

150 mg daily

300 mg daily

Week 7

150 mg daily

200 mg daily

400 mg daily

Usual maintenance dosage (Week 8 onward)

200–250 mg daily

300–400 mg daily

400–600 mg daily

Patients receiving rifampin or other drugs that induce lamotrigine glucuronidation and increase clearance, but not receiving valproic acid, should receive lamotrigine dosages recommended for individuals receiving carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid).43 For dosage adjustments in patients receiving other concomitant therapy, including estrogen-containing oral contraceptives, see Interactions.

Conversion to Immediate-release Lamotrigine Monotherapy
Oral

Conversion from adjunctive therapy with carbamazepine, phenobarbital, phenytoin, or primidone: Titrate dosage until a maintenance lamotrigine dosage of 500 mg daily (given in 2 divided doses daily) is reached (see dosage guidelines in Table 4),38 45 then withdraw concomitant anticonvulsant by 20% decrements each week over a 4-week period.38 45

Conversion from adjunctive therapy with valproic acid: Follow the manufacturer-recommended 4-step conversion regimen in Table 6.38 45

Table 6: Conversion from Adjunctive Therapy with Valproic Acid to Immediate-release Lamotrigine Monotherapy3845

Step

Lamotrigine

Valproic Acid

1

Achieve a dosage of 200 mg daily according to guidelines in Table 4 (if not already receiving 200 mg daily)

Maintain previous stable dosage

2

Maintain at 200 mg daily

Decrease to 500 mg daily in decrements no greater than 500 mg daily every week and then maintain dosage of 500 mg daily for 1 week

3

Increase to 300 mg daily and maintain for 1 week

Simultaneously decrease to 250 mg daily and maintain for 1 week

4

Increase in increments of 100 mg daily every week to achieve maintenance dosage of 500 mg daily

Discontinue

Manufacturers make no specific dosage recommendations for conversion to lamotrigine monotherapy in patients receiving anticonvulsants other than carbamazepine, phenobarbital, phenytoin, primidone, or valproic acid.38 45

Conversion from Immediate-release Lamotrigine to Extended-release Lamotrigine
Oral

May convert patients directly from immediate-release formulations to extended-release tablets (Lamictal XR).43 Initial dosage of extended-release lamotrigine should be the same as the total daily dosage of immediate-release lamotrigine.43

Monitor all patients closely for effective seizure control following conversion, particularly those receiving concomitant therapy with enzyme-inducing drugs since they may have lower plasma lamotrigine concentrations.43

Depending on therapeutic response following conversion, adjust total daily dosage of extended-release lamotrigine within recommended dosing guidelines if necessary.43

Bipolar Disorder
Maintenance Therapy with Immediate-release Formulations
Oral

Recommended initial dosages and dosage escalations for immediate-release lamotrigine in patients not receiving carbamazepine, phenobarbital, phenytoin, primidone, rifampin, or valproic acid; receiving valproic acid; or receiving carbamazepine, phenobarbital, phenytoin, primidone, or rifampin (without valproic acid) are summarized in Table 7.38 45

Optimum duration of therapy has not been established; periodically reevaluate the usefulness of the drug during prolonged therapy (i.e., >18 months).38 45

Table 7: Immediate-release Lamotrigine Dosage Titration Regimen for Patients with Bipolar Disorder3845

Week of Therapy

For Patients Not Receiving Carbamazepine, Phenobarbital, Phenytoin, Primidone, Rifampin, or Valproic Acid

For Patients Receiving Valproic Acid

For Patients Receiving Carbamazepine, Phenobarbital, Phenytoin, Primidone, or Rifampin (Without Valproic Acid)

Weeks 1 and 2

25 mg daily

25 mg every other day

50 mg daily

Weeks 3 and 4

50 mg daily

25 mg daily

100 mg daily in divided doses

Week 5

100 mg daily

50 mg daily

200 mg daily in divided doses

Week 6

200 mg daily

100 mg daily

300 mg daily in divided doses

Week 7 (target dosages)

200 mg daily

100 mg daily

Up to 400 mg daily in divided doses

Recommended adjustments to lamotrigine dosage following discontinuance of rifampin or concomitantly administered psychotropic agents are summarized in Table 8.38 45

Table 8: Immediate-release Lamotrigine Dosage Adjustments for Patients with Bipolar Disorder following Discontinuance of Rifampin or Concomitantly Administered Psychotropic Agents3845

Week of Therapy

Lamotrigine Dosage after Discontinuance of Psychotropic Agents Excluding Carbamazepine, Phenobarbital, Phenytoin, Primidone, or Valproic Acid

Lamotrigine Dosage after Discontinuance of Valproic Acid (when current lamotrigine dosage = 100 mg daily)

Lamotrigine Dosage after Discontinuance of Carbamazepine, Phenobarbital, Phenytoin, Primidone, or Rifampin (when current lamotrigine dosage = 400 mg daily)

Week 1

Maintain current lamotrigine dosage

150 mg daily

400 mg daily

Week 2

Maintain current lamotrigine dosage

200 mg daily

300 mg daily

Week 3 onward

Maintain current lamotrigine dosage

200 mg daily

200 mg daily

Prescribing Limits

Pediatric Patients

Seizure Disorders
Adjunctive Therapy with Immediate-release Formulations
Oral

Children 2–12 years of age: Maximum 200 mg daily when added to an anticonvulsant regimen containing valproic acid.38 45

Children 2–12 years of age: Maximum 300 mg daily when added to an anticonvulsant regimen not containing carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid).38 45

Children 2–12 years of age: Maximum 400 mg daily when added to an anticonvulsant regimen containing carbamazepine, phenobarbital, phenytoin, or primidone (without valproic acid).38 45

Children >12 years of age: See recommended dosage ranges in Pediatric Patients under Dosage. 38 45

Adults

Bipolar Disorder
Maintenance Therapy with Immediate-release Formulations
Oral

Maximum 200 mg daily in patients not receiving concomitant therapy with carbamazepine, phenobarbital, phenytoin, primidone, rifampin, or valproic acid.a

Special Populations

Hepatic Impairment

Manufacturers generally recommend reducing initial, escalation, and maintenance dosages by approximately 25% in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment without ascites and by 50% in patients with severe hepatic impairment with ascites.38 43 45 Adjust escalation and maintenance dosage according to clinical response.38 43 45 Dosage adjustment not necessary in patients with mild (Child-Pugh class A) hepatic impairment.38 43 45

Renal Impairment

In patients with renal impairment, base initial dosage on patient’s existing anticonvulsant drug regimen.10 38 43 45 (See Dosage under Dosage and Administration.) A reduced maintenance dosage may be effective in patients with substantial renal impairment;10 38 43 45 however, manufacturers make no specific recommendation for dosage adjustment in such patients.38 43 45

Geriatric Patients

Initiate therapy with dosages at the lower end of the usual range because of possible age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.38 43 45 Titrate dosage carefully.38 43 45

Cautions for Lamictal

Contraindications

  • Known hypersensitivity to lamotrigine or any ingredient in the formulation.38 43 45

Warnings/Precautions

Warnings

Acute Multiorgan Failure

Multiorgan failure, in some cases fatal or irreversible, reported rarely.1 2 6 13 22 24 43

Majority of deaths caused by multiorgan failure occurred in association with other serious medical events, including status epilepticus, overwhelming sepsis, and hantavirus infection, making it difficult to identify the initiating cause.1 43 a

Consider possibility of potentially fatal adverse effects in patients who exhibit signs and symptoms of multiorgan failure and/or hepatic impairment following initiation of lamotrigine.21 22

Blood Dyscrasias

Neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and, rarely, aplastic anemia and pure red cell aplasia have been reported.26 a Such blood dyscrasias may or may not be associated with a hypersensitivity syndrome.a (See Hypersensitivity Reactions under Cautions.)

Suicidality Risk

Increased risk of suicidality (suicidal ideation or behavior) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).35 36 37 38 43 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.35 36 37 38 43 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.35 37

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.35 36 37 38 42 Anxiety, agitation, hostility, hypomania, and mania may be precursors to emerging suicidality.35

Balance risk of suicidality with the risk of untreated illness.35 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.38 If suicidal thoughts or behavior emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.38 (See Advice to Patients.)

Aseptic Meningitis

Risk of aseptic meningitis.43 44 46 47 48 49 50 51 In postmarketing cases, symptoms included headache, fever, nausea, vomiting, and nuchal rigidity; rash, photophobia, myalgia, chills, altered consciousness, and somnolence also reported.43 44 46 47 48 49 50 In most cases, symptoms resolved following discontinuance of lamotrigine.43 44 46 47 48 49 50

Some patients had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases.43 44 47 48 50 Some patients also had new onset of signs and symptoms of other organ involvement (predominantly hepatic and renal), possibly suggesting that the aseptic meningitis was part of a hypersensitivity or generalized drug reaction.43 44 46 47 48 50 (See Sensitivity Reactions under Cautions.)

Because of the potential for serious outcomes with untreated meningitis due to other causes, evaluate patients for other causes of meningitis and treat appropriately.43 44 Discontinue lamotrigine if no other clear cause of meningitis is identified.43 44

Withdrawal Seizures

Abrupt withdrawal may result in increased seizure frequency, particularly in patients with preexisting seizure disorders;1 2 31 43 withdraw gradually (e.g., over a period of ≥2 weeks) and slowly reduce dosage unless safety concerns dictate more rapid withdrawal of the drug.1 2 43 (See General under Dosage and Administration.)

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of Lamictal (lamotrigine), Lamisil (terbinafine hydrochloride), lamivudine, labetalol hydrochloride, Lomotil (the fixed combination of atropine sulfate and diphenoxylate hydrochloride), and Ludiomil (maprotiline hydrochloride; no longer commercially available under this trade name in the US) may result in errors.27 29 Medication errors also may occur between the different formulations of lamotrigine.38 43 45 Advise patients to visually inspect their tablets to verify that they are lamotrigine as well as the correct formulation of the drug each time they fill their prescription.38 43 45

Sensitivity Reactions

Dermatologic Reactions

Rashes severe enough to result in discontinuance of therapy and hospitalization (e.g., Stevens-Johnson syndrome,1 3 5 6 9 11 43 toxic epidermal necrolysis,1 5 6 9 43 angioedema,1 3 5 6 9 43 rash associated with systemic manifestations)1 5 6 9 43 reported in adults and pediatric patients receiving immediate-release lamotrigine.1 6 9 11 43 Risk caused by extended-release lamotrigine not fully characterized but not expected to differ from risk associated with immediate-release formulations.43 (See Boxed Warning and see Pediatric Use under Cautions.)

Discontinue therapy at the first sign of rash (unless the rash is known not to be drug related).1

Hypersensitivity Reactions

Potentially fatal or life-threatening hypersensitivity reactions may occur; manifestations may include multiorgan failure or dysfunction, including hepatic abnormalities and disseminated intravascular coagulation.1 43

If early signs of a possible hypersensitivity reaction (e.g., fever and lymphadenopathy, with or without rash) occur, immediately evaluate the patient.1 43 Unless another cause for the signs or symptoms is found, discontinue lamotrigine.1 43

General Precautions

REMS Program

FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for lamotrigine.54 55 Goal is to inform patients about serious risks (e.g., suicidality) associated with use of the drug.54 55 (See Cautions.) The REMS program consists of a medication guide.54 55 (See Advice to Patients.)

Suicide

Attendant risk with bipolar disorder; closely supervise patients and prescribe drug in the smallest quantity consistent with good patient management to reduce the risk of overdosage.a Overdosages of lamotrigine (including fatalities) have been reported.a

Nervous System Effects

Seizure exacerbation and/or treatment-emergent status epilepticus have been reported in patients receiving lamotrigine as adjunctive therapy for seizure disorders; the incidence has been difficult to determine conclusively.1 21

If a change in seizure control or appearance or worsening of adverse effects occurs, reevaluate the use and dosage of all anticonvulsants in the regimen.1

Sudden, Unexplained Deaths in Epilepsy

Higher incidence of sudden and unexplained deaths reported with immediate-release lamotrigine than would be expected in a healthy (nonepileptic) population; however, incidence is within range of estimates for patients with epilepsy or refractory epilepsy receiving a chemically unrelated anticonvulsant drug.1 6 43

Concomitant Diseases

Experience in patients with concomitant diseases is limited.a Use with caution in patients with conditions that could affect metabolism or elimination of the drug (e.g., renal, hepatic, or cardiac impairment).22 a

Binding To Melanin-Rich Tissues

Potential accumulation of lamotrigine in melanin-rich tissues (e.g., eye, pigmented skin) over time, resulting in potential toxicity in these tissues with extended use.1

Manufacturers make no specific recommendations for periodic ophthalmologic monitoring; however, clinicians should be aware of possible long-term adverse ophthalmologic effects.1 43 45

Specific Populations

Pregnancy

Category C.1 43 45

Lamotrigine pregnancy registry (for clinicians) at 800-336-2176.38 43 North American Antiepileptic Drug (NAAED) pregnancy registry (for patients) at 888-233-2334 or .38 43

Decreases fetal folate concentrations in rats, an effect known to be associated with teratogenesis in animals and humans.1 43 (See Specific Drugs under Interactions.)

Possible association between lamotrigine exposure during the first trimester of pregnancy and cleft lip or cleft palate in infants.32 33 34

Physiologic changes during pregnancy may affect plasma lamotrigine concentrations and/or therapeutic effect.1 43 (See Absorption: Special Populations, under Pharmacokinetics.) Adjust dosage to maintain clinical response if necessary.1 43

Lactation

Distributed into milk.1 43 53 Discontinue nursing or drug.1 43

Pediatric Use

Safety and efficacy of immediate-release formulations of lamotrigine not established for any indication in pediatric patients <2 years of age.38 43 45 Safety and efficacy of immediate-release lamotrigine in children 2–16 years of age have not been established for uses other than adjunctive therapy of partial seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome.38 43 45

Safety and efficacy of extended-release lamotrigine for adjunctive treatment of partial seizures and primary generalized tonic-clonic seizures not established in children <13 years of age.43

Safety and efficacy of immediate-release lamotrigine for the management of bipolar disorder not established in children <18 years of age.38 45

Incidence of serious rash, including Stevens-Johnson syndrome, requiring hospitalization and discontinuance of immediate-release lamotrigine appears to be higher in pediatric patients <16 years of age (0.8%) than in adults (0.3%) receiving lamotrigine as adjunctive therapy for seizure disorders.38 43 45 (See Boxed Warning and see also Dermatologic Reactions under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently or exhibit a different safety profile than younger adults.38 43 45 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.1 Adjust dosage in patients with moderate to severe hepatic impairment.38 43 45 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution in patients with severe renal impairment.38 43 45 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Immediate-release lamotrigine as adjunctive therapy in adults with seizure disorders: dizziness,1 2 3 5 6 10 11 12 15 16 17 23 ataxia,1 2 3 5 6 10 11 12 15 16 17 23 somnolence,1 3 5 6 10 15 16 23 headache,1 2 3 5 6 10 12 15 16 17 23 diplopia,1 2 3 5 6 10 11 12 15 16 17 23 blurred vision,1 2 5 6 10 11 15 16 nausea,1 2 5 6 10 11 12 15 17 vomiting,1 10 11 15 17 rash.1 5 6 10 11 15 16 17

Immediate-release lamotrigine as adjunctive therapy in children with seizure disorders: infection,1 vomiting,1 rash,1 fever,1 somnolence,1 accidental injury,1 dizziness,1 diarrhea,1 abdominal pain,1 nausea,1 ataxia,1 tremor,1 asthenia,1 bronchitis,1 flu syndrome,1 diplopia.1

Extended-release lamotrigine as adjunctive therapy in adults and children ≥13 years of age with seizure disorders: dizziness,43 tremor/intention tremor,43 nausea,43 vomiting,43 diarrhea,43 diplopia,43 asthenia and fatigue,43 somnolence.43

Immediate-release lamotrigine as monotherapy in adults with seizure disorders: vomiting,1 coordination abnormality,1 dyspepsia,1 nausea,1 dizziness,1 rhinitis,1 anxiety,1 insomnia,1 infection,1 pain,1 weight decrease,1 chest pain,1 dysmenorrhea.1

Immediate-release lamotrigine as monotherapy in adults with bipolar disorder: nausea,a insomnia,a somnolence,a back pain,a fatigue,a rhinitis,a rash (nonserious),a abdominal pain,a xerostomia,a constipation,a vomiting,a exacerbation of cough,a pharyngitis.a

Interactions for Lamictal

Metabolized principally by glucuronic acid conjugation.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Drugs that induce or inhibit glucuronidation may alter lamotrigine clearance.a

Lamotrigine does not appear to inhibit the metabolism of drugs eliminated predominantly by CYP2D6.a

Potential for lamotrigine to induce specific families of mixed-function oxidase isoenzymes not systematically evaluated to date.a

Specific Drugs

Drug

Interaction

Comment

Amitriptyline

Effect on plasma lamotrigine concentrations unlikelya

Bupropion

Effect on plasma lamotrigine concentrations unlikelya

Carbamazepine

Increased incidence of dizziness, headache, diplopia, blurred vision, ataxia, nausea, nystagmus1 2 3 4 6 9 10 13

Approximately 40% decrease in steady-state plasma lamotrigine concentrationsa

Generally does not appreciably alter steady-state plasma carbamazepine concentrations1 3 4 5 10 13 15 but may increase plasma concentrations of an active metabolite of carbamazepine (carbamazepine-10,11-epoxide)1 2 3 4 5 6 10 11 12 13 20

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Clonazepam

Effect on plasma lamotrigine concentrations unlikelya

Clozapine

Effect on plasma lamotrigine concentrations unlikelya

Felbamate

No clinically important effect on lamotrigine pharmacokinetics38 43 45

Fluoxetine

Effect on plasma lamotrigine concentrations unlikelya

Folate inhibitors

Possible increased inhibition of dihydrofolate reductase1

Decreased fetal folate concentrations associated with teratogenesis in humans1

Consider interaction when used concomitantly1

Gabapentin

Effect on lamotrigine clearance unlikely38 43 45

Haloperidol

Effect on plasma lamotrigine concentrations unlikelya

Hormonal contraceptives, oral

Approximately 52% decrease in lamotrigine AUC in women receiving ethinyl estradiol/levonorgestrel preparation; gradual, transient increases in plasma lamotrigine concentrations occur during hormone-free week of dosage cycle in women not receiving concomitant therapy with a drug that increases lamotrigine clearance (e.g., carbamazepine, phenobarbital, phenytoin, primidone, rifampin)38 43 45

Modest decrease in plasma levonorgestrel concentrations reported in women receiving ethinyl estradiol/levonorgestrel preparation; no evidence of ovulation, but serum FSH, LH, and estradiol concentrations indicated some loss of hypothalamic-pituitary-ovarian suppressiona

No adjustment of lamotrigine escalation dosages necessary based only on use of estrogen-containing oral contraceptives; follow dosage escalation guidelines based on whether lamotrigine is added to a regimen containing valproic acid or to a regimen containing carbamazepine, phenobarbital, phenytoin, primidone, or rifampin or is added in the absence of these agents38 43 45 (see Dosage under Dosage and Administration)

Up to twofold increase in lamotrigine target maintenance dosage may be required based on clinical response in women receiving oral contraceptives but not receiving carbamazepine, phenobarbital, phenytoin, primidone, or rifampin concomitantly; if oral contraceptive is discontinued in these women, up to 50% reduction in lamotrigine maintenance dosage may be required38 43 45

No adjustment of lamotrigine maintenance dosage should be necessary in women receiving oral contraceptives concomitantly with carbamazepine, phenobarbital, phenytoin, primidone, or rifampin38 43 45

If lamotrigine-associated adverse effects consistently occur during the “pill-free” week, adjust overall maintenance dosage as needed; however, dosage adjustments limited to the “pill-free” week are notrecommended38 43 45

Clinical importance of observed changes in hormone concentrations not determined; possibility of decreased contraceptive effectiveness cannot be excludeda

Hormonal contraceptives, other

Effects of other hormonal contraceptives on lamotrigine pharmacokinetics not evaluated; may be similar to those of oral contraceptivesa

Dosage adjustments similar to those required in women receiving oral contraceptives may be needed, based on clinical responsea

Hormone replacement therapy

Effects on lamotrigine pharmacokinetics not evaluated; may be similar to those of oral contraceptivesa

Dosage adjustments similar to those required in women receiving oral contraceptives may be needed based on clinical responsea

Levetiracetam

Pharmacokinetic interaction unlikelya

Lithium

No effect on lithium pharmacokinetics38 43 45

Lorazepam

Effect on lamotrigine clearance unlikelya

Olanzapine

Small decrease in AUC and peak plasma concentrations of lamotrigine; unlikely to be clinically important38 43 45

Effect on plasma olanzapine concentrations unlikely38 43 45

Oxcarbazepine

Possible increased incidence of dizziness, headache, nausea, somnolencea

No appreciable change in plasma concentrations of lamotrigine or of oxcarbazepine or its active metabolite 10-monohydroxy oxcarbazepinea

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Phenelzine

Effect on plasma lamotrigine concentrations unlikelya

Phenobarbital

Approximately 40% decrease in steady-state plasma lamotrigine concentrationsa

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Phenytoin

Approximately 40% decrease in steady-state plasma lamotrigine concentrationsa

Generally does not appreciably alter steady-state plasma phenytoin concentrations1 3 4 5 10 13 15

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Pregabalin

Steady-state trough plasma concentrations of lamotrigine not affected; no pharmacokinetic interaction38 43 45

Primidone

Approximately 40% decrease in steady-state plasma lamotrigine concentrationsa

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Rifampin

Approximately 40% decrease in lamotrigine AUCa

Adjust dosages accordingly (see Dosage under Dosage and Administration)

Risperidone

Effect on lamotrigine clearance unlikelya

Sertraline

Effect on lamotrigine clearance unlikelya

Topiramate

No appreciable change in plasma concentrations of lamotrigine; 15% increase in plasma topiramate concentrations38 43 45

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Trazodone

Effect on lamotrigine clearance unlikelya

Valproic acid

Increased risk of serious, potentially life-threatening rasha

Approximately 25% decrease in steady-state trough plasma concentrations of valproic acid1 2 3 4 6 10 11 12

Reduces lamotrigine clearance and increases steady-state plasma lamotrigine concentrations by slightly more than 50% whether or not carbamazepine, phenobarbital, phenytoin, or primidone is given concomitantly1 2 3 4 6 8 9 10 18 20

Adjust dosages accordingly1 (see Dosage under Dosage and Administration)

Zonisamide

No substantial effect on lamotrigine pharmacokinetics during multiple-dose administration of both drugs38 43 45

Lamictal Pharmacokinetics

Absorption

Bioavailability

Immediate-release lamotrigine formulations: Rapidly and completely absorbed after oral administration, with peak plasma concentrations usually attained within approximately 1–5 hours.1 43

Extended-release lamotrigine tablets: Median time to attain peak plasma concentrations was 4–6 hours in patients receiving carbamazepine, phenytoin, phenobarbital, or primidone; 9–11 hours in patients receiving valproic acid; and 6–10 hours in patients receiving other anticonvulsants.43 Steady-state trough concentrations were similar to or higher than those of immediate-release lamotrigine depending on concomitant anticonvulsant therapy.43

Absolute bioavailability of immediate-release lamotrigine is 98%.1 AUCs of extended-release and immediate-release regimens were similar in patients receiving anticonvulsants not known to induce lamotrigine metabolism; relative bioavailability was approximately 21% lower with extended-release lamotrigine compared with immediate-release lamotrigine in individuals receiving enzyme-inducing anticonvulsants.43 However, reduction in lamotrigine exposure of ≤70% was observed in some individuals when switched from immediate-release lamotrigine to extended-release lamotrigine.43

Commercially available chewable/dispersible tablets, whether administered dispersed in water, chewed and swallowed, or swallowed whole, are bioequivalent to conventional tablets.1

Rate and extent of lamotrigine absorption from commercially available orally disintegrating tablets, whether administered disintegrated in the mouth or swallowed whole with water, are bioequivalent to conventional tablets.38

Food

Food does not affect bioavailability.1 43

Special Populations

During pregnancy, lamotrigine concentrations may be decreased; restoration of prepartum concentrations occurs after delivery.1

Distribution

Extent

Distributed into milk.1 43 53

Plasma Protein Binding

Approximately 55% at plasma lamotrigine concentrations of 1–10 mcg/mL.1 43

Elimination

Metabolism

Metabolized mainly by glucuronic acid conjugation; the major metabolite is an inactive 2-N-glucuronide conjugate.1

Reported to induce its own metabolism when given as monotherapy; some evidence suggests that self-induction may not occur when used concomitantly with carbamazepine, phenobarbital, phenytoin, primidone, or rifampin.a

Elimination Route

Eliminated principally in urine as glucuronide conjugates.1

Half-life

In healthy adults, the elimination half-life following single or multiple doses of immediate-release lamotrigine is approximately 33 or 25 hours, respectively.38 After single or multiple doses of immediate-release lamotrigine in addition to valproic acid, elimination half-life was approximately 48 or 70 hours, respectively.38

Clearance in children 2–18 years of age is influenced mainly by the patient’s total body weight and concurrent anticonvulsant drug therapy.a Children weighing <30 kg have a higher weight-normalized lamotrigine clearance than those weighing >30 kg;a after accounting for body weight, lamotrigine clearance is not significantly influenced by age.a

Estimates of elimination half-life of immediate-release lamotrigine when administered concomitantly with other anticonvulsants in adults and children 10 months to 11 years of age are summarized in Table 9.

Table 9: Immediate-release Lamotrigine Elimination Half-life in Epileptic Adults and Children Receiving Concomitant Anticonvulsants38

Concomitant Anticonvulsant(s)

Epileptic Adults

Epileptic Children 10 Months to 5.3 Years of Age

Epileptic Children 5–11 Years of Age

Carbamazepine, phenobarbital, phenytoin, or primidone

14 or 13 hours with single or multiple doses of lamotrigine, respectively

8 hours

7 hours

Carbamazepine, phenobarbital, phenytoin, or primidone given with valproic acid and a single dose of lamotrigine

27 hours

Not estimated

19 hours

Valproic acid

59 hours

45 hours

66 hours

Anticonvulsants with no known effect on lamotrigine clearance

Not estimated

19 hours

Not estimated

Special Populations

Patients with renal impairment: Mean plasma elimination half-life of immediate-release lamotrigine is approximately 43 hours in chronic renal failure (mean Clcr = 13 mL/minute; range: 6–23 mL/minute), 13 hours during hemodialysis session, and 57 hours between hemodialysis sessions, compared with 26 hours in healthy individuals.1 On average, approximately 20% (range: 6–35%) of the amount of lamotrigine present in the body is eliminated during a 4-hour hemodialysis session.1

Patients with hepatic impairment: Mean half-life of immediate-release lamotrigine is 46, 72, 67, or 100 hours in patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), severe (Child-Pugh class C) hepatic impairment without ascites, or severe hepatic impairment with ascites, respectively, compared with 33 hours in healthy individuals.38 43 45

Increased plasma concentrations of 2-N-methyl metabolite may occur in patients with liver disease.1 45 (See Actions.)

Stability

Storage

Oral

Tablets, conventional

25°C (may be exposed to 15–30°C).1 45 Protect from moisture and light.1 45

Tablets, chewable/dispersible

25°C (may be exposed to 15–30°C).38 Protect from moisture.38

Tablets, extended-release, film-coated

25°C (may be exposed to 15–30°C).43

Tablets, orally disintegrating

20–25°C (may be exposed to 15–30°C).38

Actions

  • Exact mechanism of anticonvulsant action is unknown1 6 11 but may involve inhibition of voltage-sensitive sodium channels, which stabilizes neuronal membranes and consequently modulates the release of excitatory amino acid neurotransmitters (e.g., glutamate, aspartate) that play a role in the generation and spread of epileptic seizures.1 2 3 4 5 6 7 8 9 10 11 13 14 15 16 17 20

  • Exhibits anticonvulsant activity similar to that of phenytoin,2 3 4 5 9 11 14 15 16 18 phenobarbital,10 and carbamazepine.2 3 4 9 10 11 14 15 16 18

  • May be effective in the management of tonic-clonic (grand mal), absence (petit mal),1 2 3 4 5 6 7 9 10 14 15 16 and simple or complex partial seizures.1 4 6 9 10

  • Mechanisms of action in bipolar disorder have not been established.a

  • Weakly inhibits dihydrofolate reductase1 4 6 9 and type 3 serotonergic (5-HT3) receptors;1 has weak agonist effects at opiate Σ receptors.1

  • Does not exhibit high affinity for type 2 serotonergic (5-HT2), adenosine A1 or A2, α1- or α2-adrenergic, β-adrenergic, dopamine D1 or D2, GABA A or B, histamine H1, opiate κ, or cholinergic muscarinic receptors.1

  • Has no effect on dihydropyridine-sensitive calcium channels or N-methyl-d-aspartate (NMDA) receptors.1 4 5 6 Does not inhibit the uptake of norepinephrine, dopamine, serotonin, or aspartic acid.1 4 5 6

  • Dose-dependent prolongation of PR interval,1 9 widening of QRS complex,1 9 and at high dosages, complete AV block1 associated with formation of 2-N-methyl metabolite1 9 in dogs.1 Similar cardiovascular effects are not anticipated in humans because only trace amounts of the 2-N-methyl metabolite (<0.6% of lamotrigine dose) have been found in human urine.1

Advice to Patients

  • Under the REMS approved by FDA for lamotrigine, a medication guide must be dispensed with every prescription for the drug; importance of patient reading this information prior to taking the drug.38 43 45 54 55 (See REMS Program under Cautions.)

  • Importance of informing patients prior to initiation of therapy that a rash or other manifestations of hypersensitivity (e.g., fever, hives, mouth and periorbital ulceration, facial edema, lymphadenopathy) may herald a serious medical event and of instructing patients to contact a clinician immediately if such effects occur.38 43

  • Risk of suicidality (anticonvulsants, including lamotrigine, may increase risk of suicidal thoughts or actions in about 1 in 500 people).35 38 42 43 Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).35 38 43

  • Risk of dizziness or drowsiness; avoid driving, operating machinery, or performing hazardous tasks until effects on the individual are known.1 43 45

  • Risk of aseptic meningitis;43 44 46 47 48 49 50 51 importance of instructing patients to immediately contact their clinician if they experience headache, fever, chills, nausea, vomiting, stiff neck, rash, unusual sensitivity to light, muscle pain, drowsiness, and/or confusion.43 44

  • Importance of instructing patients to report immediately any worsening of seizure control or appearance of any new types of seizures.38 43 45

  • Importance of informing patients that it may take several weeks to feel the full effects of lamotrigine therapy.38 43

  • Importance of taking only as prescribed; do not abruptly discontinue therapy unless otherwise instructed by a clinician.38 43 45 Advise patients to notify their clinician of any interruptions in therapy and to not resume therapy without first consulting their clinician.38 43 45

  • For patients taking chewable/dispersible tablets, importance of instructing patients that tablets may be swallowed whole, chewed, or mixed in water or diluted fruit juice to help in swallowing.38 (See Chewable/Dispersible Tablets under Administration.)

  • For patients taking extended-release tablets, importance of instructing patients to swallow tablet whole and not to chew, crush, or divide the tablets.43

  • For patients taking orally disintegrating tablets, importance of instructing patients to place tablet onto tongue and to move it around in the mouth, where it will disintegrate rapidly and can be swallowed with or without water.38

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 38 45 Importance of women who are pregnant not to begin or discontinue lamotrigine therapy without first talking to their clinician.32 34 Importance of clinicians informing women about the existence of and encouraging enrollment in pregnancy registries (see Pregnancy under Cautions).38 43 45

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.38 43 45 Instruct women to consult with their clinician prior to initiating or discontinuing use of hormonal contraceptives or hormone replacement therapy and to promptly notify their clinician of any changes in menstrual pattern (e.g., breakthrough bleeding) during concomitant therapy with these agents.38 43 45

  • Importance of informing patients of other important precautionary information.38 43 45 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Lamotrigine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Lamictal (scored)

GlaxoSmithKline

Lamotrigine Tablets

100 mg*

Lamictal (scored)

GlaxoSmithKline

Lamotrigine Tablets

150 mg*

Lamictal (scored)

GlaxoSmithKline

Lamotrigine Tablets

200 mg*

Lamictal (scored)

GlaxoSmithKline

Lamotrigine Tablets

Tablets, chewable/dispersible

2 mg

Lamictal

GlaxoSmithKline

5 mg

Lamictal

GlaxoSmithKline

25 mg

Lamictal

GlaxoSmithKline

Tablets, extended-release, film-coated

25 mg

Lamictal XR

GlaxoSmithKline

50 mg

Lamictal XR

GlaxoSmithKline

100 mg

Lamictal XR

GlaxoSmithKline

200 mg

Lamictal XR

GlaxoSmithKline

Tablets, orally disintegrating

25 mg

Lamictal ODT

GlaxoSmithKline

50 mg

Lamictal ODT

GlaxoSmithKline

100 mg

Lamictal ODT

GlaxoSmithKline

200 mg

Lamictal ODT

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

LaMICtal 100MG Tablets (GLAXO SMITH KLINE): 60/$343.99 or 180/$1,012.97

LaMICtal 150MG Tablets (GLAXO SMITH KLINE): 60/$374.99 or 180/$1,096.97

LaMICtal 200MG Tablets (GLAXO SMITH KLINE): 60/$409.99 or 180/$1,187.96

LaMICtal 25MG Chewable Tablets (GLAXO SMITH KLINE): 30/$176.99 or 100/$564.99

LaMICtal 25MG Tablets (GLAXO SMITH KLINE): 60/$304.99 or 180/$892.96

LaMICtal ODT 100MG Dispersible Tablets (GLAXO SMITH KLINE): 30/$199.98 or 90/$575.97

LaMICtal ODT 25MG Dispersible Tablets (GLAXO SMITH KLINE): 30/$165.99 or 90/$459.97

LaMICtal XR 100MG 24-hr Tablets (GLAXO SMITH KLINE): 30/$357.99 or 90/$1,037.98

LaMICtal XR 200MG 24-hr Tablets (GLAXO SMITH KLINE): 30/$365.98 or 90/$1,085.95

LaMICtal XR 300MG 24-hr Tablets (GLAXO SMITH KLINE): 30/$589.98 or 90/$1,699.98

LamoTRIgine 100MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 100/$29.99 or 200/$49.98

LamoTRIgine 150MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$31.99 or 120/$39.98

LamoTRIgine 200MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$31.99 or 120/$39.98

LamoTRIgine 25MG Chewable Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$89.99 or 90/$244.94

LamoTRIgine 25MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 100/$29.99 or 200/$49.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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21. Burroughs Wellcome, Research Triangle Park, NC: Personal communication.

22. Makin AJ, Fitt S, Williams R et al. Fulminant hepatic failure induced by lamotrigine. BMJ. 1995; 311:292. [IDIS 351601] [PubMed 7633236]

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27. Sykes NS. Dear pharmacist letter: Dispensing errors alert. Research Triangle Park, NC: Glaxo Wellcome, Inc; 2000 Jun 6.

28. Motte J, Trevathan E, Arvidsson JFV et al. Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. N Engl J Med. 1997; 337:1807-12. [IDIS 401164] [PubMed 9400037]

29. Kent RS. Dear health professional letter: Dispensing errors alert. Research Triangle Park, NC: Glaxo Wellcome, Inc; 2000 Aug.

30. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002; 159(Suppl):1-50.

31. GlaxoSmithKline. Lamictal (lamotrigine) tablets and chewable dispersible tablets prescribing information. Research Triangle Park, NC; 2003 Jun.

32. Food and Drug Administration. Lamictal (lamotrigine) [September 28, 2006]. Medwatch alert. Rockville, MD; September 2006. From FDA website.

33. Food and Drug Administration. Information for healthcare professionals: Lamotrigine (marketed as Lamictal). Rockville, MD; 2006 Sep 28. From the FDA website.

34. Food and Drug Administration. Patient information sheet: Lamotrigine (marketed as Lamictal). Rockville, MD; 2006 Sep 28. From the FDA website.

35. Food and Drug Administration. FDA Alert: Information for healthcare professionals: suicidality and antiepileptic drugs. Rockville, MD; 2008 Jan 31. From the FDA website.

36. Food and Drug Administration. FDA News: FDA alerts health care providers to risk of suicidal thoughts and behavior with antiepileptic medications. Rockville, MD; 2008 Jan 31. From the FDA website.

37. Food and Drug Administration. FDA Alert: Suicidality and antiepileptic drugs. Rockville, MD; 2008 Jan 31. From the FDA website.

38. GlaxoSmithKline. Lamictal (lamotrigine) tablets, chewable dispersible tablets, and orally disintegrating tablets prescribing information. Research Triangle Park, NC; 2009 Sep.

39. Biton V, Sackellares JC, Vuong A et al. Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures. Neurology. 2005; 65:1737-43. [PubMed 16344515]

40. Hirschfeld RMA. Guideline watch: Practice guideline for the treatment of patients with bipolar disorder, 2nd edition. Arlington, VA; 2005 Nov. From the American Psychiatric Association website.

41. Calabrese JR, Bowden CL, Sachs G et al and the Lamictal 605 Study Group. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar disorder. J Clin Psychiatry. 2003; 64:1013-24. [PubMed 14628976]

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b. GlaxoSmithKline, Research Triangle Park, NC: Personal communication.

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