CONVERSION FROM VALPROATE MONOTHERAPY TO LAMOTRIGINE MONOTHERAPY: A CLINICAL AND PHARMACOKINETIC STUDY
Abstract number :
1.294
Submission category :
Year :
2002
Submission ID :
3490
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Adriana Serje, Harold H. Morris, Collin Covinga, Kim Merner. Neurology, The Cleveland Clinic Foundation, Cleveland, OH
RATIONALE: Valproate (VPA) has a significant inhibitory effect on lamotrigine (LTG) clearance. Clinically, this becomes problematic when patients are being converted from VPA to LTG as the concentration of LTG decreases with the discontinuation of VPA. During this time patients are at risk for increased seizures and side effects.This report reflects our experience using a standard protocol.
At the end of this presentation the participants should be able to discuss a method for switching patients from VPA to LTG.
METHODS: A retrospective chart review approved by our Institutional Review Board was conducted of patients who were switched between 1997 and 2001 from VPA monotherapy to LTG monotherapy using a predefined method.
LTG was started at 25 mg every other day with gradual increases to a dose of 200 mg/day (or LTG [gt] 5mg/L), then VPA was gradually tapered to 250 mg/day and removed 1 week later.
The day after the last VPA dose, the dose of LTG was doubled.
Medical records were evaluated for changes in seizure frequency and the presence of side effects. LTG plasma concentrations were collected before VPA removal and at steady state on LTG monotherapy .
RESULTS: 11 adult patients with generalized epilepsy were included in this study. All were receiving VPA monotherapy before conversion. The median dose of VPA before conversion was 1000 mg/day (750 to 4500 mg/day). Immediately before conversion the median LTG dose was 200 mg/day (150-600 mg/day). The median LTG dose after transition was 400 mg/day (200 to 600 mg/day). Median LTG concentration before and after switch to LTG monotherapy were 7.9 mg/L (3-12.4 mg/L) and 8.4 mg/L (3.9-25 mg/L), respectively. No patient had seizures during or immediately following the transition period. Two patients experienced nausea, vomiting and dizziness during the conversion.
CONCLUSIONS: Overall, the conversion to LTG monotherapy was well tolerated. LTG plasma concentrations were comparable before and after transition to monotherapy and none of the patients experienced seizures during the conversion period.
This pilot study suggests our titration method may be used safely in clinical practice.