Pharmacokinetics, toxicology and safety of lamotrigine in epilepsy

Optimisation of pharmacotherapy for epilepsy requires consideration of the impact of drug metabolism and toxicology on the therapeutic profiles and clinical use of antiepileptic drugs (AEDs). This review discusses the pharmacokinetics and toxicology of the AED lamotrigine, and considers the implications of these data for optimising its use in the management of epilepsy. Lamotrigine has good absorption, minimal plasma protein binding and linear pharmacokinetics. Partly because of these properties, frequent dosing adjustments are generally unnecessary, and therapeutic monitoring is not required under most circumstances. Lamotrigine is not associated with clinically significant neurological, cognitive, metabolic, hepatic or reproductive endocrine toxicity. Like other AEDs, including carbamazepine and phenytoin, lamotrigine has been associated with serious rash. With some exceptions, lamotrigine has relatively few clinically relevant drug interactions, a characteristic important in reducing safety risks, especially among patients who require polytherapy. The clinical impact of pharmacokinetic interactions between lamotrigine and enzyme-inducing AEDs or valproate can be minimised by adhering to recommended dose-escalation schedules with demonstrated reliability in clinical trials and clinical practice. Likewise, adhering to recommended dosing guidelines can minimise the risk of lamotrigine-associated rash. The pharmacokinetic, toxicology and safety profiles of lamotrigine make the drug suitable for use across a spectrum of patients with epilepsy.