Lamotrigine

Renal Impairment Lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. In a small study comparing a single dose of immediate-release lamotrigine in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was approximately twice as long in the subjects with chronic renal failure [see Clinical Pharmacology ] .

Initial doses of lamotrigine extended-release should be based on patients’ AED regimens; reduced maintenance doses may be effective for patients with significant renal impairment. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. Because there is inadequate experience in this population, lamotrigine extended-release should be used with caution in these patients [see Dosage and Administration ] .

Hepatic Impairment Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study with immediate-release lamotrigine in 24 subjects with mild, moderate and severe liver impairment, the following general recommendations can be made [see Clinical Pharmacology ] . No dosage adjustment is needed in patients with mild liver impairment.

Initial, escalation and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response [see Dosage and Administration ] .