Lamotrigine, Serum or Plasma

Lamotrigine is an antiepileptic drug (AED) of the phenyltriazine class that is chemically unrelated to existing AEDs. The precise mechanism of action is unknown although it has been postulated that lamotrigine inhibits voltage-sensitive sodium channels thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (eg, glutamate, aspartate). Lamotrigine is 55% bound to plasma proteins and is metabolized predominantly to an inactive 2-N-glucuronide conjugate. Peak plasma concentration occurs at 1.4 to 4.8 hours following oral administration.¹ The elimination half-life varies from 12 to 70 hours. The longer half-lives are observed in patients on concomitant valproic acid therapy. Accordingly, if lamotrigine is coadministered with valproic acid, the dose of lamotrigine must be reduced to less than half the normal dosage. The most common adverse reactions are associated with the use of lamotrigine in combination with other anticonvulsants, and include dizziness, diplopia, ataxia, blurred vision, nausea and vomiting, somnolence, headache, and rash. The anticonvulsants phenytoin, phenobarbital, primidone, and carbamazepine can reduce lamotrigine levels when coadministered.² Conversely, lamotrigine can reduce levels of levetiracetam when coadministered.³ In children, investigators⁴ have found large differences in lamotrigine plasma levels in patients with improvement in seizure frequency, but patients who were seizure-free had higher lamotrigine levels than other patients in the study.