lamotrigine
lamotrigine
[lah-mo´trĭ-jēn]lamotrigine
Pharmacologic class: Phenyltriazine
Therapeutic class: Anticonvulsant
Pregnancy risk category C
FDA Box Warning
• Lamotrigine has caused life-threatening serious rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and rash-related death. Rate of serious rash is greater in children than in adults. Additional factors that may increase risk of rash include concurrent use with valproate, exceeding lamotrigine recommended initial dose, or exceeding lamotrigine recommended dosage escalation.
• Drug also causes benign rashes; however, it's impossible to predict which rashes will prove to be serious or life-threatening. Discontinue drug at first sign of rash, unless rash is clearly not drug-related.
Action
Unknown. Thought to block sodium channel membranes, which in turn inhibits release of the neurotransmitters glutamate and aspartate in brain.
Availability
Tablets: 25 mg, 100 mg, 150 mg, 200 mg
Tablets (chewable): 2 mg, 5 mg, 25 mg
Tablets (extended-release): 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg
Tablets (orally disintegrating): 25 mg, 50 mg, 100 mg, 200 mg
Indications and dosages
➣ Partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in patients receiving valproate
Adults and children ages 12 and older: 25 mg immediate-release P.O. every other day during weeks 1 and 2; then 25 mg daily during weeks 3 and 4. Then week 5 onwards to maintenance, increase dosage by 25 to 50 mg/day every 1 to 2 weeks. Usual maintenance dosage is 100 to 400 mg/day in one or two divided doses. For those taking valproate alone, maximum dosage is 200 mg/day.
Children ages 2 to 12: 0.15 mg/kg/day immediate-release P.O. (rounded down to nearest whole tablet) in one or two divided doses during weeks 1 and 2; then 0.3 mg/kg/day P.O. (rounded down to nearest whole tablet) in one or two divided doses during weeks 3 and 4. Then week 5 onwards to maintenance, increase every 1 to 2 weeks as 0.3 mg/kg/day (rounded down to nearest whole tablet) added to previously administered daily dose. Usual maintenance dosage is 1 to 5 mg/kg/day. Maximum dosage is 200 mg/day in one or two divided doses. For patients taking valproate alone, maintenance dosage is 1 to 3 mg/kg/day. May need to increase maintenance dose by as much as 50% in patients weighing less than 30 kg (66 lb), based on clinical response.
➣ Partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in patients receiving antiepileptic drugs (AEDs) other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate
Adults and children ages 12 and older: 25 mg immediate-release P.O. every day during weeks 1 and 2; then 50 mg daily during weeks 3 and 4. Increase by 50 mg/day every 1 to 2 weeks. Usual maintenance dosage is 225 to 375 mg/day in two divided doses.
Children ages 2 to 12: 0.3 mg/kg/day immediate-release P.O. in one or two divided doses (rounded down to nearest whole tablet) during weeks 1 and 2; then 0.6 mg/kg/day P.O. in two divided doses (rounded down to nearest whole tablet) during weeks 3 and 4. Then week 5 onwards to maintenance, increase every 1 to 2 weeks as 0.6 mg/kg/day (rounded down to nearest whole tablet) added to previously administered daily dose. Usual maintenance dosage is 4.5 to 7.5 mg/kg/day (maximum, 300 mg/day) in two divided doses. May need to increase maintenance dose by as much as 50% in patients weighing less than 30 kg, based on clinical response.
➣ Partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in patients receiving carbamazepine, phenytoin, phenobarbital, or primidone, but not receiving valproate
Adults and children ages 12 and older: 50 mg/day immediate-release P.O. during weeks 1 and 2; then 100 mg/day in two divided doses during weeks 3 and 4. Then week 5 onwards to maintenance, increase by 100 mg/day every 1 to 2 weeks. Usual maintenance dosage is 300 to 500 mg/day in two divided doses.
Children ages 2 to 12: 0.6 mg/kg/day immediate-release P.O. in two divided doses (rounded down to nearest whole tablet) during weeks 1 and 2; then 1.2 mg/kg/day in two divided doses (rounded down to nearest whole tablet) during weeks 3 and 4. Then week 5 onwards to maintenance, increase every 1 to 2 weeks as 1.2 mg/kg/day (rounded down to nearest whole tablet) added to previously administered daily dose. Usual maintenance dosage is 5 to 15 mg/kg/day (maximum, 400 mg/day) in two divided doses. May need to increase maintenance dose by as much as 50% in patients weighing less than 30 kg, based on clinical response.
➣ Adjunctive therapy for primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization in patients receiving valproate
Adults and children ages 13 and older: 25 mg P.O. (Lamictal XR) every other day during weeks 1 and 2; 25 mg daily during weeks 3 and 4; 50 mg daily week 5; 100 mg daily week 6; then 150 mg daily week 7. Usual maintenance dose starting week 8 and onward is 200 to 250 mg every day.
➣ Adjunctive therapy for primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization in patients not receiving carbamazepine, phenytoin, phenobarbital, primidone, or valproate
Adults and children ages 13 and older: 25 mg P.O. (Lamictal XR) daily during weeks 1 and 2; 50 mg daily during weeks 3 and 4; 100 mg daily week 5; 150 mg daily week 6; then 200 mg daily week 7. Usual maintenance dose starting week 8 and onward is 300 to 400 mg every day.
➣ Adjunctive therapy for primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization in patients receiving carbamazepine, phenytoin, phenobarbital, or primidone, but not receiving valproate
Adults and children ages 13 and older: 50 mg P.O. (Lamictal XR) daily during weeks 1 and 2; 100 mg daily during weeks 3 and 4; 200 mg daily week 5; 300 mg daily week 6; then 400 mg daily week 7. Usual maintenance dose starting week 8 and onward is 400 to 600 mg every day.
➣ Conversion to monotherapy for partial-onset seizures in patients receiving valproate
Adults and children ages 13 and older: 25 mg P.O. (Lamictal XR) every other day during weeks 1 and 2; 25 mg daily during weeks 3 and 4; 50 mg daily week 5; 100 mg daily week 6; then 150 mg daily week 7 while maintaining established valproate dose. Then maintain Lamictal XR at 150 mg daily while decreasing valproate dosage by decrements no greater than 500 mg/day/week and then maintain valproate for 1 week. Increase Lamictal XR to 200 mg/day and simultaneously decrease valproate to 250 mg/day and maintain for 1 week. Increase Lamictal XR to 250 or 300 mg/day and discontinue valproate.
➣ Conversion from adjunctive therapy of carbamazepine, phenytoin, phenobarbital, or primidone to monotherapy with Lamictal XR in patients with primary generalized tonic-clonic seizures and partial-onset seizures with or without secondary generalization
Adults and children ages 13 and older: After achieving a dosage of 500 mg/day P.O. of Lamictal XR, the concomitant enzyme-inducing antiepileptic drug (AED) should be withdrawn by 20% decrements each week over 4-week period. Two weeks after completion of withdrawal of the enzyme-inducing AED, the dosage of Lamictal XR may be decreased no faster than 100 mg/day each week to achieve the monotherapy maintenance dosage range of 250 to 300 mg/day.
➣ Conversion from adjunctive therapy with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate to monotherapy with Lamictal XR
Adults and children ages 13 and older: After achieving a dosage of 250 to 300 mg/day P.O. of Lamictal XR, the concomitant AED should be withdrawn by 20% decrements each week over 4-week period.
➣ Conversion to monotherapy for seizures in patients receiving carbamazepine, phenytoin, phenobarbital, primidone, or valproate as a single agent
Adults and children ages 16 and older: Usual maintenance dosage is 500 mg/day immediate-release P.O. in two divided doses.
➣ Conversion from carbamazepine, phenytoin, phenobarbital, or primidone to monotherapy with lamotrigine for seizures
Adults and children ages 16 and older: 50 mg/day immediate-release P.O. during weeks 1 and 2; then 100 mg/day in two divided doses during weeks 3 and 4. Then week 5 onwards to maintenance, increase by 100 mg/day every 1 to 2 weeks. Usual maintenance dosage is 300 to 500 mg/day in two divided doses. After achieving lamotrigine maintenance dosage of 500 mg/day P.O., withdraw concomitant AED by 20% decrements each week over 4-week period.
➣ Conversion from adjunctive therapy with valproate to monotherapy with lamotrigine for seizures
Adults and children ages 16 and older: Achieve lamotrigine dosage of 200 mg/day immediate-release P.O. and maintain previous stable valproate dosage. Maintain lamotrigine dosage of 200 mg/day and decrease valproate dosage to 500 mg/day by decrements no greater than 500 mg/day; maintain regimen for 1 week. Then increase lamotrigine dosage to 300 mg/day while simultaneously decreasing valproate to 250 mg/day; maintain regimen for 1 week. Then discontinue valproate completely and increase lamotrigine dosage by 100 mg/day every week to 500 mg/day.
➣ Maintenance treatment of bipolar I disorder to delay time to occurrence of mood episodes in patients treated with standard therapy for acute mood episodes
Adults: Target dosage is 200 mg immediate-release P.O. daily titrated over 7 weeks (or 100 mg daily in patients taking valproate, or 400 mg daily in patients not taking valproate who are receiving carbamazepine, rifampin, phenytoin, phenobarbital, or primidone). If other psychotropic drugs are withdrawn following stabilization, adjust lamotrigine dosage as indicated.
Dosage adjustment
• Moderate to severe hepatic dysfunction
• Renal impairment
• Heart disease
• Starting or stopping estrogen-containing oral hormonal contraceptives
• Concurrent use of valproate
Off-label uses
• Drug-resistant seizures
• Mood stabilization in rapid-cycling bipolar II disorder
Contraindications
• Hypersensitivity to drug or its components
Precautions
Use cautiously in:
• renal or hepatic impairment or other diseases or conditions that affect metabolism or elimination
• concurrent use of other anticonvulsants or estrogen-containing oral contraceptives
• history of allergy to or rash from other AEDs
• clinical worsening, emergence of new symptoms, and suicidal ideation or behaviors
• aseptic meningitis, multiorgan hypersensitivity reactions, blood dyscrasias, ophthalmologic effects
• pregnant or breastfeeding patients
• children younger than age 2; children younger than age 13 (extended-release form); children younger than age 18 with mood disorders (safety and efficacy not established).
Administration
• Give with or without food.
• Don't crush or break regular tablets; make sure patient swallows them whole.
• Crush chewable tablets or mix in diluted fruit juice if patient can't chew them.
• Know that patients may be converted directly from immediate-release form to extended-release form, with the initial extended-release dose matching the total daily immediate-release dose.
• Be aware that effectiveness of drug in treating acute mood episodes hasn't been established.
See Be aware that abrupt drug withdrawal may induce seizures. If drug must be discontinued, decrease dosage by 50% per week over at least 2 weeks.
See Don't confuse Lamictal with other drugs having sound-alike names (such as Lamisil, Lomotil, and Ludiomil).
Adverse reactions
CNS: dizziness, vertigo, headache, drowsiness, ataxia, incoordination, insomnia, sleep disorders, tremor, depression, anxiety, irritability, impaired memory, poor concentration, emotional lability, racing thoughts, dysarthria, malaise, asthenia, somnolence, amnesia, hypoesthesia, decreased or increased reflexes, fatigue, migraine, dream abnormality, suicidal ideation, seizures, aseptic meningitis
CV: palpitations, hemorrhage
EENT: diplopia, nystagmus, blurred vision, possible long-term ophthalmologic effects, ear disorder, rhinitis, epistaxis, sinusitis, pharyngitis
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, dry mouth, anorexia, peptic ulcer, flatulence, rectal hemorrhage
GU: dysmenorrhea, amenorrhea, vaginitis, increased libido, urinary tract infection, urinary frequency, penis disorder
Hematologic: blood dyscrasias (such as neutropenia, thrombocytopenia, pancytopenia)
Musculoskeletal: muscle spasm, neck pain, back pain, arthralgia, myalgia
Respiratory: cough, dyspnea, bronchitis, bronchospasm
Skin: pruritus, contact dermatitis, dry skin, sweating, photosensitivity, eczema, alopecia, rash, urticaria, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome
Other: infection, pain, weight changes, chest pain, accidental injury, lymphadenopathy, flulike syndrome, fever, tooth disorder, edema, peripheral edema, facial edema, hypersensitivity reactions (rare) including anaphylaxis; multiorgan hypersensitivity reactions
Interactions
Drug-drug. Carbamazepine, phenobarbital, phenytoin, primidone: decreased lamotrigine steady-state level
Estrogen-containing oral contraceptives, rifampin: increased lamotrigine clearance
Folate inhibitors (such as methotrexate, co-trimoxazole): additive effects of lamotrigine
Topiramate: increased topiramate concentrations
Valproate: decreased lamotrigine clearance, increased steady-state level
Drug-diagnostic tests. All blood cells: decreased levels
Liver function tests: abnormal
Drug-behaviors. Sun exposure: photosensitivity
Patient monitoring
• Monitor renal and hepatic function.
See Watch for signs and symptoms of hypersensitivity reaction (Stevens-Johnson syndrome or anaphylaxis) and potentially fatal or life-threatening multiorgan hypersensitivity reactions (early signs may include rash, fever, and lymphadenopathy); discontinue drug if alternative etiology for this reaction isn't found.
See Monitor patient with bipolar disorder closely for clinical worsening and suicidality.
• Monitor vital signs regularly.
• Monitor CNS status carefully, noting adverse reactions and changes in seizure pattern.
• Monitor patient for signs and symptoms of anemia, unexpected infection, or bleeding.
• Be aware that because drug binds to melanin, it could accumulate over time in the eye and other melanin-containing tissues.
• Monitor lamotrigine blood levels, especially during dosage adjustments.
Patient teaching
• Tell patient or caregiver that drug may be taken with or without food.
• Instruct patient or caregiver that immediate- and extended-release tablets must be swallowed whole without crushing or breaking.
• Instruct patient or caregiver that orally disintegrating tablets should be placed on the tongue and moved around in the mouth; the tablets will disintegrate rapidly. Then they can be swallowed with or without water, and can be taken with or without food.
• Instruct patient or caregiver to crush chewable tablets or mix them in diluted fruit juice if patient can't chew them. Tell patient to add dispersed tablets to approximately 1 teaspoon of liquid in glass or spoon, mix solution when tablets are completely dispersed, and then take entire amount immediately.
• Inform patient or caregiver not to stop drug abruptly and that dosage is adjusted slowly, as indicated.
See Advise patient or caregiver to stop drug and notify prescriber immediately at first sign of rash or enlarged lymph nodes.
• Instruct patient or caregiver to immediately report unexpected infection, unusual fatigue, bleeding, headache, fever, nausea, vomiting, or nuchal rigidity.
• Tell patient or caregiver to report vision changes.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.