Trade Names:Lamictal- Tablets 25 mg- Tablets 100 mg- Tablets 150 mg- Tablets 200 mg- Tablets, chewable dispersible 2 mg- Tablets, chewable dispersible 5 mg- Tablets, chewable dispersible 25 mg- Tablets, orally disintegrating 25 mg- Tablets, orally disintegrating 50 mg- Tablets, orally disintegrating 100 mg- Tablets, orally disintegrating 200 mg
Trade Names:Lamictal XR- Tablets, ER 25 mg- Tablets, ER 50 mg- Tablets, ER 100 mg- Tablets, ER 200 mgApo-Lamotrigine (Canada)Gen-Lamotrigine (Canada)PMS-Lamotrigine (Canada)ratio-Lamotrigine (Canada)
Chemically unrelated to existing antiepileptic drugs (AEDs); precise mechanism(s) unknown. One proposed mechanism suggests inhibition of voltage-sensitive sodium channels, thereby stabilizing neuronal membranes that modulate presynaptic transmitter release of excitatory amino acids (eg, glutamate and aspartate).
Rapidly and completely absorbed after oral administration. Absolute bioavailability is 98%; not affected by food. T max is 1.4 to 4.8 h.
Mean Vd is 0.9 to 1.3 L/kg, independent of dose. Approximately 55% protein bound at concentrations from 1 to 10 mcg/mL.
Metabolized predominantly by glucuronic acid conjugation. Major metabolite is 2-N-glucuronide conjugate. Following multiple administrations (150 mg twice daily), lamotrigine induced its own metabolism, resulting in a 25% decrease in half-life and a 37% increase in Cl at steady state.
Elimination half-life is 25.4 to 32.8 h. Approximately 94% is excreted in urine and 2% in feces.
Plasma half-life is 42.9 h in patients with CrCl of 6 to 23 mL/min. In patients undergoing hemodialysis, half-life was 13 h during hemodialysis and 57.4 h between dialysis sessions. On average, approximately 20% of lamotrigine in the body is eliminated during a 4-h hemodialysis session.Hepatic Function Impairment
Mean half-life is 46, 72, 67, or 100 h in patients with Child-Pugh score A, B, C without ascites, or C with ascites, respectively.Elderly
Mean half-life was 31.2 h and mean Cl was 0.4 mL/min/kg in elderly patients after a single 150 mg dose.Children
The oral Cl of lamotrigine was higher, on a body-weight basis, in children than in adults. Weight-normalized Cl was higher in subjects weighing less than 30 kg, and the dose may need to be increased as much as 50% in these patients.Gender
Mean trough concentrations were 24% to 45% higher in women than men.Race
Oral Cl was 25% lower in nonwhite patients than in white patients.
Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy.Epilepsy
Adjunctive therapy for partial seizures, the generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in adults and children 2 yr of age and older (immediate-release); for partial-onset seizures with or without secondary generalization in patients at least 13 years of age (ER); conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenobarbital, phenytoin, primidone, or valproate as a single AED (immediate-release).
Management of children with absence seizures, juvenile myoclonic epilepsy, and temporal lobe seizures; postpoliomyelitis syndrome; prevention of migraines in adults; rectal administration.
PO Wk 1 and 2: 0.15 mg/kg/day in 1 to 2 divided doses. Wk 3 and 4: 0.3 mg/kg/day in 1 to 2 divided doses. Round down to the nearest whole tablet. In patients weighing less than 30 kg, may need to increase maintenance dose by as much as 50%, based on clinical response.Maintenance dose
1 to 5 mg/kg/day (max, 200 mg/day in 1 to 2 divided doses). For patients taking valproate alone, 1 to 3 mg/kg/day. To achieve, add 0.3 mg/kg/day, rounded down to the nearest whole tablet, to the previous daily dose every 1 to 2 weeks.Adults and Children older than 12 yr of age
PO Wk 1 and 2: 25 mg every other day. Wk 3 and 4: 25 mg/day.Maintenance dose
100 to 400 mg/day in 1 to 2 divided doses. 100 to 200 mg/day in patients using valproate alone. To achieve, escalate dose by 25 to 50 mg/day every 1 to 2 wk.Lamotrigine Immediate-Release Plus AEDs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate Children 2 to 12 yr of age
PO Wk 1 and 2: 0.3 mg/kg/day in 1 or 2 divided doses. Wk 3 and 4: 0.6 mg/kg/day in 2 divided doses. Round down to the nearest whole tablet.Maintenance dose
4.5 to 7.5 mg/kg/day (max, 300 mg/day) in 2 divided doses. To achieve, add 0.6 mg/kg/day, rounded to the nearest whole tablet, to the previous daily dose every 1 to 2 wk. In patients weighing less than 30 kg, may need to increase maintenance dose by as much as 50%, based on clinical response.Adults and Children older than 12 yr of age
PO Wk 1 and 2: 25 mg every day. Wk 3 and 4: 50 mg/day. Maintenance dose: 225 to 375 mg/day in 2 divided doses. To achieve, escalate dose by 50 mg/day every 1 to 2 wk.Lamotrigine Immediate-Release Plus Enzyme-Inducing Antiepileptic Drugs (EIAEDs) Without Valproate Children 2 to 12 yr of age
PO Wk 1 and 2: 0.6 mg/kg/day in 2 divided doses. Wk 3 and 4: 1.2 mg/kg/day in 2 divided doses. Round down to the nearest whole tablet.Maintenance dose
5 to 15 mg/kg/day (max, 400 mg/day in 2 divided doses). To achieve, add 1.2 mg/kg/day, rounded to the nearest whole tablet, to the previous daily dose every 1 to 2 wk. In patients weighing less than 30 kg, may need to increase maintenance dose by as much as 50%, based on clinical response.Adults and Children older than 12 yr of age
PO Wk 1 and 2: 50 mg/day. Wk 3 and 4: 100 mg/day in 2 divided doses.Maintenance dose
300 to 500 mg/day in 2 divided doses. To achieve, escalate dose by 100 mg/day every 1 to 2 wk. Patients receiving multidrug regimens employing EIAEDs without valproic acid can have a maintenance dose of lamotrigine as high as 700 mg/day.Conversion From Carbamazepine, Phenobarbital, Phenytoin, or Primidone to Monotherapy With Lamotrigine Immediate-Release Adults and Children 16 yr of age and older
PO 500 mg/day given as 2 divided doses. Begin conversion by titrating lamotrigine to the target dose (500 mg in 2 divided doses) while maintaining the dose of the EIAED at a fixed level, then withdraw concomitant EIAED by 20% decrements each week over a 4-wk period.Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine Immediate-Release Adults and Children older than 16 yr of age
PO Conversion involves 4 steps. Step 1: While maintaining valproate at stable dose, achieve lamotrigine dose of 200 mg/day (if not already on 200 mg/day) as follows: Wk 1 and 2: 25 mg every other day. Wk 3 and 4: 25 mg every day. Wk 5 onwards to maintenance (200 mg/day): increase by 25 to 50 mg/day every 1 to 2 weeks. Step 2: Maintain lamotrigine at 200 mg/day and decrease valproate to 500 mg/day by decrements no greater than 500 mg/day per week, then maintain valproate dose at 500 mg/day for 1 wk. Step 3: Increase lamotrigine to 300 mg/day for 1 wk while simultaneously decreasing valproate to 250 mg/day for 1 wk. Step 4: Increase lamotrigine by 100 mg/day every week to achieve maintenance dose of 500 mg/day and discontinue valproate.Lamotrigine ER Plus AED Regimen Containing ValproateAdults and Children 13 yr of age and older
PO Wk 1 and 2: 25 mg every other day. Wk 3 and 4: 25 mg/day. Wk 5: 50 mg/day. Wk 6: 100 mg/day. Wk 7: 150 mg/day.Maintenance dose
200 to 250 mg/day.Lamotrigine ER Plus AEDs Other than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or ValproateAdults and Children 13 yr of age and older
PO Wk 1 and 2: 25 mg/day. Wk 3 and 4: 50 mg/day. Wk 5: 100 mg/day. Wk 6: 150 mg/day. Wk 7: 200 mg/day.Maintenance dose
300 to 400 mg/day.Lamotrigine ER Plus EIAEDs Without ValproateAdults and Children 13 yr of age and older
PO Wk 1 and 2: 50 mg/day. Wk 3 and 4: 100 mg/day. Wk 5: 200 mg/day. Wk 6: 300 mg/day. Wk 7: 400 mg/day.Maintenance dose
400 to 600 mg/day.Lamotrigine Immediate-Release Escalation Regimen for Patients with Bipolar DisorderPatients Not Taking Carbamazepine (or Other Enzyme-Inducing Drugs) or Valproate Adults (18 yr of age and older)
PO Wk 1 and 2: 25 mg/day. Wk 3 and 4: 50 mg/day. Wk 5: 100 mg/day. Wk 6 and 7: 200 mg/day.Patients Taking Valproate Adults (18 yr of age and older)
PO Wk 1 and 2: 25 mg every other day. Wk 3 and 4: 25 mg/day. Wk 5: 50 mg/day. Wk 6 and 7: 100 mg/day.Patients Taking Carbamazepine (or Other Enzyme-Inducing Drugs) and Not Taking Valproate Adults (18 yr of age and older)
PO Wk 1 and 2: 50 mg/day. Wk 3 and 4: 100 mg/day in divided doses. Wk 5: 200 mg/day in divided doses. Wk 6: 300 mg/day in divided doses. Wk 7: up to 400 mg/day in divided doses.Lamotrigine Dosing Adjustments for Patients with Bipolar Disorder Following Discontinuation of PsychotropicsAfter Discontinuation of Valproate (Current Lamotrigine Dose 100 mg/day) Adults (18 yr of age and older)
PO Wk 1: 150 mg/day. Wk 2: 200 mg/day. Wk 3 and onward: 200 mg/day.After Discontinuation of Carbamazepine or Other Enzyme-Inducing Drugs (Current Lamotrigine Dose 400 mg/day) Adults (18 yr of age and older)
PO Wk 1: 400 mg/day. Wk 2: 300 mg/day. Wk 3 and onward: 200 mg/day.Adjustments to Maintenance Dose of Lamotrigine in Patients Taking Oral ContraceptivesTaking or Starting Oral Contraceptives in Patients Not Taking Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Rifampin Adults
PO Maintenance dose of lamotrigine may need to be increased 2î“¸fold over recommended target maintenance dose, according to clinical response. If a patient is starting oral contraceptives, the dose increase should start at the same time the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week.Stopping Oral Contraceptives in Patients Not Taking Carbamazepine, Phenobarbital, Phenytoin, Primidone, or Rifampin Adults
PO Maintenance dose of lamotrigine may need to be decreased 50%, according to clinical response. Decrease in lamotrigine dose should not exceed 25% of total daily dose per week over a 2-wk period.Conversion to ER Formulation Adults and Children 13 yr of age and older
Should match the total daily dose of the immediate-release, given once daily. Monitor patients closely for seizure control and adjust based on clinical response.Discontinuation of Lamotrigine
PO Lamotrigine should not be abruptly discontinued. A step-wise dose reduction over at least 2 weeks (approximately 50% per week) is recommended, unless safety concerns require a more rapid withdrawal.Hepatic Function Impairment
PO Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and by 50% in patients with severe liver impairment with ascites. Adjust escalation and maintenance doses according to clinical response.Renal Function Impairment
PO Reduced maintenance doses may be effective for patients with significant renal impairment.
Store at controlled room temperature (59° to 86°F). Protect from light and moisture.
Lamotrigine plasma levels may be reduced by these agents, decreasing the therapeutic effect.Carbamazepine
The risk of carbamazepine toxicity may be increased.Folate inhibitors
Lamotrigine is an inhibitor of dihydrofolate reductase. Use caution with other agents that inhibit folate metabolism.Levonorgestrel
Levonorgestrel plasma levels may be decreased.Topiramate
Topiramate plasma levels may be increased.Valproic acid
Plasma levels may be reduced by lamotrigine, decreasing the therapeutic effect. Valproate increases lamotrigine levels.
None well documented.
Chest pain (5%); hot flush (3%); hemorrhage (2%); vasculitis (postmarketing).
Dizziness (54%); headache (29%); ataxia (28%); somnolence (17%); insomnia, tremor (10%); asthenic conditions (asthenia, fatigue, malaise) (9%); asthenia, fatigue (8%); abnormal coordination (7%); incoordination (6%); anxiety, cerebellar condition/balance disorder, mania (including hypomania and mixed mood episodes) (5%); depression, emotional lability, gait abnormality (4%); abnormal thinking, convulsions, irritability, nystagmus, speech disorder, vertigo (3%); amnesia, hypesthesia, increased libido, increased or decreased reflexes, suicidal ideation (2% to 5%); concentration disturbance, nervousness, seizure exacerbation (2%); abnormal dreams, agitation, dyspraxia, hypoesthesia, migraine (1% to 5%); confusion, paresthesias (at least 1%); exacerbation of Parkinsonian symptoms in patients with preexisting Parkinson disease (postmarketing).
Rash (14%); pruritus (3%); eczema, photosensitivity (2%); contact dermatitis, dry skin, sweating (2% to 5%); alopecia (2%); Stevens-Johnson syndrome, toxic epidermal necrolysis.
Diplopia (49%); blurred vision (25%); pharyngitis, rhinitis (14%); dry mouth (6%); abnormal vision, pharyngolaryngeal pain (3%); epistaxis (2%); amblyopia (at least 1%).
Nausea (25%); vomiting (20%); diarrhea (11%); abdominal pain (10%); dyspepsia (7%); constipation (5%); anorexia, peptic ulcer, rectal hemorrhage (2% to 5%); flatulence (1% to 5%); esophagitis, pancreatitis (postmarketing).
Dysmenorrhea (7%); vaginitis (4%); UTI (3%); amenorrhea (2%); urinary frequency (1% to 5%).
Lymphadenopathy (2%); agranulocytosis, hemolytic anemia (postmarketing).
Weight loss (5%); peripheral edema (2% to 5%); edema, weight gain (2%).
Back pain (8%); myalgia (3%); arthralgia, neck pain (2%); rhabdomyolysis (postmarketing).
Increased cough (8%); bronchitis (7%); sinusitis (3%); dyspnea (2% to 5%); bronchospasm (2%); apnea (postmarketing).
Infection (20%); fever (15%); accidental injury (14%); flu syndrome (7%); pain (5%); facial edema (2%); hypersensitivity reaction, lupus-like reaction, multiorgan failure, progressive immunosuppression (postmarketing).
Serious rashes (including Stevens-Johnson syndrome) requiring hospitalization and discontinuation of treatment have been reported in 0.8% of children receiving lamotrigine as adjunctive therapy for epilepsy, 0.3% of adults receiving lamotrigine as adjunctive therapy for epilepsy, 0.08% of adults receiving lamotrigine as initial monotherapy for bipolar and other mood disorders, and 0.13% of adults receiving lamotrigine as adjunctive therapy for bipolar and other mood disorders. Other than age (children are at greatest risk), there are no other identified risk factors. There are suggestions that the risk of rash may be increased by coadministration of lamotrigine with valproate, exceeding recommended initial dose of lamotrigine, or exceeding recommended dose escalation for lamotrigine. Almost all life-threatening cases have occurred within the first 2 to 8 wk of therapy, but isolated cases have been reported after prolonged (eg, 6 mo) use. Discontinue lamotrigine at the first sign of rash, unless the rash is clearly not drug related.
Because of possible pharmacokinetic interactions between lamotrigine and other AEDs, monitoring of plasma levels may be indicated, particularly during dosage adjustments. Closely monitor patients for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of treatment or at the time of dose changes.
Category C .
Excreted in breast milk.
For the treatment of partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures, safety and efficacy not established for children younger than 2 yr of age. Safety and efficacy not established in patients younger than 18 yr of age with bipolar disorder. For ER formulation, safety and efficacy is not established in patients younger than 13 yr of age as adjunctive therapy for partial-onset seizures.
Cautiously select dosage, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function, and of comorbidity.
Fatal or life-threatening hypersensitivity reactions may occur. Early manifestations of hypersensitivity (eg, fever, lymphadenopathy) may be present even though a rash is not evident. Immediately evaluate patient if such signs or symptoms are present and discontinue lamotrigine if an alternative etiology for the signs and symptoms cannot be established.
Use with caution; reduce maintenance doses for patients with significant impairment.
Reduce initial, escalation, and maintenance doses approximately 25% in patients with moderate (Child-Pugh score B) and severe (Child-Pugh score B) impairment without ascites and 50% in patients with severe impairment (Child-Pugh score C) with ascites.
Use with caution in patients with diseases or conditions that could affect metabolism or elimination of the drug (eg, renal, hepatic, cardiac impairment).
May cause drowsiness or dizziness.
Multiorgan failure, which has been fatal or irreversible in some cases, has been observed.
Blood dyscrasias have been reported that may or may not be associated with the hypersensitivity syndrome. These include neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and, rarely, aplastic anemia and pure red cell aplasia.
Closely monitor patients for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of treatment and at the time of dose changes (either increase or decrease). Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening and/or emergence of suicidal ideation/behavior, especially if symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Prescribe the smallest quantity of medication consistent with good patient management.
Lamotrigine binds to melanin and may cause toxicity with possibility of long-term ophthalmologic effects.
Do not restart lamotrigine in patients who discontinued because of rash with prior treatment unless potential benefits clearly outweigh risk. If decision is made to restart lamotrigine, assess the initial dosing recommendations. The greater the interval since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period greater than 5 half-lives, follow initial dosing recommendations and guidelines.
During premarketing development of lamotrigine, 20 sudden and unexplained deaths were recorded among a cohort of 4,700 patients with epilepsy (5,747 patient-years of exposure).
Do not abruptly discontinue AEDs because of possibility of increasing seizure frequency. Taper dose over a 2-wk period.
Ataxia, coma, decreased levels of consciousness, increased seizures, intraventricular conduction delay, nystagmus.
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