Changed constitution without change in brand name--the risk of generics in epilepsy.

Purpose: Lamotrigine (LTG) is an anti epileptic medication (AEM) for which blood levels are helpful for optimal dosing. In late 2010, patients attending an epilepsy clinic were becoming toxic without obvious cause. This paper reports altered levels without change in regimen and provides unexpected findings.

Methods: Patients with elevated LTG blood levels were assessed to determine change in AEM regimen or generic substitution. Method of blood level determination was reviewed and the company (GlaxoSmithKline) contacted regarding change in source of medication.

Principal Results: The sample comprised 18 patients; mean age 40±16 years, mean daily LTG dose 493±218 mg. Mean serum LTG concentrations from August 2010 to February 2011 [91.8±17.7 μmolL(-1), range 69.9-133.7 μmolL(-1)] were significantly higher than those from January 2010 to July 2010 [50.3±9.1 μmolL(-1), range 32-60.1 μmolL(-1)), p<0.0001]. All patients received parent product (Lamictal(®)) and the method of LTG blood level determination was unchanged. GlaxoSmithKline confirmed that Lamictal(®) was sourced from a different site.

Conclusions: These results indicate that, even using a parent compound, AEM levels can fluctuate if the product source has changed, resulting in toxicity. It also highlights the value of determining AEM levels and the risks attached to generic substitution.

(Copyright © 2011 Elsevier B.V. All rights reserved.)