CONVERSION TO LAMOTRIGINE MONOTHERAPY FROM VALPROATE IN PATIENTS WITH EPILEPSY: A PRELIMINARY ANALYSIS
Abstract number :
1.275
Submission category :
Year :
2003
Submission ID :
1172
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Mark Sale, Alain Vuong, Sheri Hoyler, John A. Messenheimer, Anne E. Hammer Pharmacokinetic Modeling and Simulation, GlaxoSmithKline, Research Triangle Park, NC; Epilepsy Clinical Development and Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC
Lamotrigine (LTG) and valproate (VPA) treat a broad range of seizures. Some patients are converted from VPA to LTG for efficacy or tolerability reasons. This conversion is complicated by the inhibitory effect of VPA on the metabolism of LTG. This open-label study assessed serum concentrations in patients following a dosing conversion algorithm derived from pharmacokinetic modeling. The study provides guidelines to enable maintenance of stable LTG concentrations during conversion from VPA to LTG monotherapy in patients with epilepsy.
All patients ([gt] 16 years, receiving VPA monotherapy and candidates for conversion to LTG due to poor seizure control or intolerable side effects) received LTG (LAMICTAL[reg]) with a total study duration of up to 19 weeks. Study phases consisted of Screening ([le]1 week), LTG Escalation (8 weeks), VPA Withdrawal (0-6 weeks based upon initial VPA dose) and LTG Monotherapy (4 weeks). Dose conversion was conducted in 4 steps: 1) escalate LTG to 200 mg/day according to package insert for add-on to VPA, 2) once at 200mg/day LTG, gradually decrease VPA to 500 mg/day by up to 500 mg/week dose decrements, and hold stable for one week, 3) decrease VPA to 250 mg/day and increase LTG to 300 mg/day holding stable for one week, 4) discontinue VPA, and make weekly adjustments in LTG based on clinical response. LTG and VPA trough serum concentrations were collected 3 times during escalation of LTG and weekly thereafter.
77 patients enrolled, mean age=34 years, female=60%, seizures: partial=72% and generalized=55% with some patients having both. Of the 77 patients, 29 prematurely discontinued. Overall compliance was excellent (over 90%) for most patients completing the study. Mean weekly trough serum concentrations from evaluable patients are summarized in Table 1: [table1]
The data show that serum LTG concentrations were held relatively stable while converting from VPA to LTG monotherapy using the specified 4-step dosing algorithm.
[Supported by: GlaxoSmithKline Research and Development]