Lamotrigine (Lamictal, Glaxo-Smith-Kline)
Lamotrigine was the third drug (after felbamate and gabapentin) in the wave of new antiepileptic medications introduced in the mid-1990's. In the United States, the drug has an indication for partial and secondarily generalized seizures. Nevertheless, lamotrigine is a true broad-spectrum anti-seizure medication and may have its most dramatic successes in treatment of generalized seizures.
The use of the medication has been limited by an approximately 5 - 15% incidence of rash. This is an unusual type of rash, dependent upon the rate lamotrigine is started: with more rash at faster initiation rates. If the patient is already on valproic acid, then the risk of rash is further increased. Rash typically begins as itchy or blotchy red regions on the face, arms or trunk.
The rash usually improves within three days of stopping lamotrigine (or sometimes even with reduction of dose), and resolves in 1-2 weeks. Rash on mucous membranes such as mouth, eyes or genital regions, or any blistering of skin, suggests a potentially more serious type of rash. The serious rash, called Stevens-Johnson syndrome or toxic epidermal necrosis, may require hospitalization, and rarely has been fatal. The slow titration mandated by the risk of rash makes it difficult to achieve therapeutic doses of lamotrigine in less than a month.
In clinical trials of lamotrigine, responder rates were similar to those of gabapentin, in the 20-30% range for add-on therapy in patients with uncontrolled seizures. As with gabapentin, few intractable patients became seizure free when lamotrigine was used as add-on therapy. Clinical experience has demonstrated higher responder rates in less severely affected patients, and in patients with generalized seizures.
Advantages of lamotrigine include its broad spectrum, its very good tolerance profile (with occasional problems of dizziness, ataxia, sleepiness, or GI upset, as well as a variety of other less common side effects, and the rash). Clinical studies were performed in the 300-500 mg per day range, but field use has gone to 800 mg, or even higher. Lamotrigine has the advantage of single daily dosing, but patients also taking phenytoin, carbamazepine, phenobarbital, topiramate, zonisamide, tiagabine, felbamate, or other inducers of liver metabolism, need to take lamotrigine twice a day. Serious adverse events other than rash are quite rare.
Be aware of the sound-alike drug, Lamisil, an over-the-counter anti-fungal medicine, sometimes mistakenly substituted for Lamictal!Summary Data for Lamotrigine
Pill sizes: 2, 5, 25 mg chewable-dispersible tablets.
Tablets, 6-sided "shields"¯
25 mg (white)
100 mg (orange)
150 mg (peach-tan)
200 mg (blue)
Liquid for oral: none.
Injectable: none.
Typical adult dose: In patients not on valproate, the manufacturer recommends starting with 50 mg/d divided into two dose for 2 weeks, then 100 mg/d divided into two doses for 2 weeks, then increase by 100 mg daily every two weeks. It is simpler and better tolerated to start with 25 mg per day for a week, and then increase each week by 25 mg daily (1 pill) on a twice a day schedule until at 100 mg (4 pills) twice a day. One can then switch to 100 mg pills, and increase to 100 mg in the am and 200 mg in the pm for a week, then 200 mg in the am and pm (400 mg/d). In patients on valproate, the above dosages can be cut in half and one aims for 150-250 mg/d in 1 or 2 doses.
Typical pediatric dose: If not on valproate start 0.6 mg/kg/d, increase over 1-2 months to 5-15 mg/kg/d in 1-2 divided doses. If on valproate, start at 0.15 mg/kg/d and increase over 2-3 months to 1-5 mg/kg/d.
Metabolism: liver, the N-glucuronidation pathway.
Half-life: about 24 hours in monotherapy; 12 hours in conjunction with Dilantin, Tegretol, phenobarbital, Trileptal; 72 hours with valproate
Serum levels: 2-20 mcg/L, not very useful.
Pregnancy: Category C - can cause birth defects in animals, unknown in humans.
Drugs that raise LTG levels: VPA, sertraline.
Drugs that lower LTG levels: Dilantin, phenobarbital, Mysoline, Tegretol, Trileptal, Zarontin
LTG does not raise or lower levels of other AEDs (though the reverse does occur).
LTG decreases effects of other drugs: VPA. Does not affect oral contraceptives.
Dangerous Side Effects
serious rash (Stevens-Johnson syndrome, toxic epidermal necrolysis); rare liver injury; production of myoclonic seizures with toxic doses.
Common Side Effects
Rash in 5 - 10 percent, especially early in use; dizziness, GI upset, somnolence.
Other Side Effects
Usually few, if no rash; may occasionally get headache or blurred vision.