lamotrigine
Lamictal

Available forms
Available by prescription only
Tablets: 25 mg, 100 mg, 150 mg, 200 mg
Tablets (chewable): 2 mg, 5 mg, 25 mg

Indications and dosages
 Adjunct therapy for partial seizures caused by epilepsy and Lennox-Gastaut syndrome. Adults and children age 16 and older (12 and older for Lennox-Gastaut syndrome): 50 mg P.O. daily for 2 weeks, followed by 100 mg daily in two divided doses for 2 weeks. Thereafter, usual maintenance dosage is 300 to 500 mg P.O. daily given in two divided doses. For patients also taking valproic acid, give 25 mg P.O. every other day for 2 weeks, followed by 25 mg P.O. daily for 2 weeks. Thereafter, increase 25 to 50 mg q 1 to 2 weeks. Effective maintenance dosage is 100 to 400 mg daily in one or two divided doses.
 Adjunct treatment of Lennox-Gastaut syndrome in patients receiving hepatic-enzyme-inducing anticonvulsants without concomitant valproic acid therapy. Children ages 2 to 12: 0.6 mg/kg P.O. daily (rounded down to the nearest 5 mg) in two divided doses for 2 weeks. During subsequent 2 weeks, 1.2 mg/kg (rounded down to the nearest 5 mg) daily in two divided doses. Then, increase q 1 to 2 weeks by 1.2 mg/kg (rounded down to the nearest 5 mg) until effective daily dose of about 5 to 15 mg/kg (maximum of 400 mg daily in two divided doses) is reached.
 Adjunct treatment of Lennox-Gastaut syndrome in patients receiving hepatic-enzyme-inducing anticonvulsants with concomitant valproic acid therapy. Children ages 2 to 12: 0.15 mg/kg P.O. daily (rounded down to the nearest 5 mg) in one or two divided doses for 2 weeks. If the initial calculated daily dose of lamotrigine is 2.5 to 5 mg, then a 5-mg dose should be administered on alternate days for the first 2 weeks. During subsequent 2 weeks, 0.3 mg/kg (rounded down to the nearest 5 mg) daily in one or two divided doses. Then, increase q 1 to 2 weeks by 0.3 mg/kg (rounded down to the nearest 5 mg) until effective daily dose of about 1 to 5 mg/kg (maximum of 200 mg daily in one or two divided doses) is reached.

Pharmacodynamics
Anticonvulsant action: Unknown. Possibly related to inhibition of release of glutamate and aspartate in the brain. This may occur by acting on voltage-sensitive sodium channels.

Pharmacokinetics
Absorption: Rapidly and completely absorbed from the GI tract with negligible first-pass metabolism. Absolute bioavailability is 98%.
Distribution: About 55% is bound to plasma proteins, primarily albumin.
Metabolism: Metabolized predominantly by glucuronic acid conjugation; the major metabolite is an inactive 2-N-glucuronide conjugate.
Excretion: Excreted primarily in urine with only a small portion excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal, hepatic, or cardiac function.

Interactions
Drug-drug. Carbamazepine, phenobarbital, phenytoin, primidone: Decreases lamotrigine steady state levels. Monitor patient carefully.
Folate inhibitors such as co-trimoxazole, methotrexate: May cause additive effect because lamotrigine inhibits dihydrofolate reductase, an enzyme involved in the synthesis of folic acid. Monitor patient closely.
Valproic acid: Decreases lamotrigine clearance, which increases steady state levels of drug. Monitor patient closely for toxicity.
Drug-lifestyle. Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: dizziness, headache, ataxia, somnolence, malaise, incoordination, insomnia, tremor, depression, anxiety, seizures, irritability, speech disorder, decreased memory, concentration disturbance, sleep disorder, emotional lability, vertigo, mind racing, fever, suicide attempts.
CV: palpitations, peripheral edema, hot flashes.
EENT: rhinitis, pharyngitis, diplopia, blurred vision, vision abnormality, nystagmus, epistaxis.
GI: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, constipation, anorexia, dry mouth, rectal hemorrhage, peptic ulcer.
GU: dysmenorrhea, vaginitis, amenorrhea.
Metabolic: weight loss.
Musculoskeletal: dysarthria, muscle spasm, neck pain.
Respiratory: cough, dyspnea, bronchitis.
Skin: Stevens-Johnson syndrome, rash, pruritus, alopecia, acne, epidermal neurolyisis, photosensitivity, contact dermatitis, dry skin, sweating.
Other: tooth disorder, flu syndrome, infection, chills.

Effects on lab test results
None reported.

Overdose and treatment
Limited information available.
 Following a suspected overdose, treatment should be supportive. Induce emesis or perform gastric lavage, if needed. It isn’t known whether hemodialysis is effective.

Special considerations
• Drug may be given without regard to meals. Chewable tablets may be swallowed whole, chewed and swallowed with a small amount of water or diluted fruit juice, or dispersed in about 5 ml of liquid for about 1 minute and consumed immediately.
• Don’t stop drug abruptly because of increased risk of seizures. Instead, taper drug over at least 2 weeks.
• Stop drug immediately if drug-induced rash appears.
• If lamotrigine is added to a multidrug regimen that includes valproate, reduce dose of lamotrigine and use a lower maintenance dosage in patients with severe renal impairment.
 ALERT Don’t confuse Lamictal with Lamisil.
Breast-feeding patients
• Use in breast-feeding women isn’t recommended.
Pediatric patients
• Limit use in children ages 2 to 12; drug must be carefully administered following the detailed guidelines provided with it. The risk of severe, potentially life-threatening rash in children is much higher than that in adults.
Geriatric patients
• Safety and efficacy in patients older than age 65 haven’t been established.

Patient education
• Inform patient that rash may occur, especially during first 6 weeks of therapy and in children. Combination therapy of valproic acid and lamotrigine is likely to precipitate a serious rash. Although it may resolve with continued therapy, tell patient to report rash immediately in case drug needs to be discontinued.
• Warn patient not to perform potentially hazardous activities until CNS effects are known.
• Advise patient to take protective measures against photosensitivity reactions until tolerance is known.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use