Although lamictal was originally synthesized as a folate antagonist, it has very weak activity in that regard. Lamotrigine is a member of the phenyltriazine class and is believed to work by blockade of voltage sensitive sodium currents, slow binding of inactivated sodium channels, blockade of voltage activated calcium currents, inhibition of presynaptic N type calcium channels, and inhibition of glutamate and aspartate release. It inhibits the sodium channel in a manner that is different from other sodium channel inhibiting drugs such as phenytoin and carbamazepine.
Lamictal is approved as adjunctive therapy for patients 2 yr or older with partial seizures and for patients with Lennox Gastaut Syndrome. It can be used as monotherapy in patients being converted from carbamazepine, phenytoin, phenobarbital, primodine, or valproate monotherapy and is effective in a wide range of seizures, including partial, primary generalized tonic clonic, myoclonic, and absence. Lamotrigine is also indicated for the treatment of bipolar disorder. The reported ragne of effective concentrations is 2.5 -15mg/L
The pharmacokinetics of lamictal appear to be linear. It reaches peak concentrations in 1.4 to 4.8 hr and bioavailability is believed to be approximately 100%. Administration with food may reduce the maximum peak concentration but does not alter the total amount of drug absorbed. While the amount absorbed from the dispersible tablet given rectally is not the same as the amount following oral administration, there is adequate absorption to make this an alternative route of administration. Absorption also occurs when the compressed tablet is given rectally. The volume of distribution is 0.9 to 1.3 L/Kg, and the clearance averages 0.076 L/hr/kg. Lamotrigine is about 55 percent bound to plasma proteins and is metabolized predominately by glucuronidation catalyzed by UDPGT in the liver to inactive metabolites that are excreted renally.
Lamictal does not affect the metabolism of other drugs and does not affect the concentration of carbamazepine or its active 10, 11 di epoxide metabolite. Side effects may be increased in patients taking carbamazepine with lamotrigine is added, suggesting a potential pharmacodynamic interaction . Concurrent use of oral contraceptives in patients on lamotrigine has been reported to result in a decrease in lamotrigine concentrations and breakthrough seizures.
The most common side effects of lamotrigine are headache, nausea, vomiting, ataxia, somnolence, dizziness, sedation, blurred vision and diplopia. The incidence of CNS effects is increased in patients taking carbamazepine concurrently. The most troublesome side effects is skin rash, which generally occurs in the first 3-4 weeks of therapy. The initial rash is usually a generalized, erythematous, morbiliform rash that may progress to stevens johnson reaction or toxic epidermis necrolysis. It occurs more frequently in children than in adults and high starting doses rapid dosage titration and concurrent valproic acid therapy increase the incidence of rash. Therefore, the ode of lamotrigine should be started low and gradually titrated to the patients response. Doses up to 700 mg/day have been well tolerated. Patients who have been temporarily discontinued from lamotrigine in an epilepsy monitoring unit can be restarted with a single oral loading dose.
