Lamotrigine (Lamictal) probably acts on voltage-sensitive sodium channels and excitatory amino acid neurotransmitters. Two very important features of lamotrigine include its predilection to produce a significant rash, which could progress to Stevens-Johnson syndrome, and the effects of comedication. The half-life of lamotrigine is reduced by 50 percent when administered with enzyme inducers such as phenytoin, carbamazepine, and phenobarbital and doubled when used in conjunction with valproate. The combination with valproate has been associated with most of the adverse reactions. In children, it should be started very slowly and increased very gradually. It is indicated in the treatment of partial and generalized epilepsy, including absence, drop, and myoclonic seizures. When administered with enzyme inducers, the dose begins at 2 mg/kg/day and is increased over 6 to 8 weeks to a maximum of 15 mg/kg/day. When used with valproate (Depakote), it should be started at 0.2 mg/kg every other day, increased by 0.2 mg/kg/day to 1 mg/kg/day, and then, over the next 6 weeks, increased to a maximum of 5 mg/kg/day. When changes are made in reducing or introducing comedication, the lamotrigine dose will have to be modified in most instances. Given as monotherapy, the half-life is 25 to 30 h. It has minimal protein binding. Blood levels do not reflect toxic or therapeutic effects. There is no reported significant hepatic or hematologic side effect.
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