Abstracts

RATIONALE: Compliance with medication is directly related to the number of dosages that a patients must take. The delayed release (DR) form of VPA frequently requires 3 or 4 time a day dosing to maintain steady pharmacokinetics. A new extended release (ER) form of VPA was approved in the USA for migraine, but most likely will be of equal importance in epilepsy. We compared VPA levels in 53 patients on DR-VPA to levels following conversion to ER-VPA.
METHODS: Patients on a stable dose of DR-VPA were offered conversion to ER-VPA. If agreeable, a trough VPA level was performed while still on DR-VPA. Patients were then given instructions to convert to ER-VPA in an overnight fashion. The mg/day dosage of ER-VPA was unchanged in 22 patients, increased in 26 patients, and decreased in 5 patients. Once a day dosing was chosen in 9 patients and bid dosing in the other 42 patients. Repeat VPA levels were drawn after being on a stable dose of ER-VPA for at least 2 weeks. Changes in blood levels were evaluated, with each patient serving as their own control.
RESULTS: All patients tolerated the rapid converion to ER-VPA. Of patients converted to the same daily dose of VPA, 19 were on bid dosing and 3 received qD dosing. Patients on bid dosing showed an average VPA level change of only 0.9%. However more significant changes were seen in two patients switched from the sprinkle formulation of VPA and in one patient switched from bid DR-VPA. In the 3 patients changed to qD dosing, a more widespread variation in VPA levels was seen and the time of day that levels were drawn appeared to be significant.
Twenty-six patients had their daily VPA dosage increased. Five were converted to once a day dosing and 21 to bid dosing. Of those converted to bid dosing, the average increase in VPA dosage was 43.7% and the average change in VPA level was an increase of 27.48%. Again, those switched to qD dosing showed a wider variation in VPA levels, with the time of blood draw being important. Of the 5 patients that had a decrease in VPA dosage, doses were decreased from 6.7-20% and VPA levels showed changes ranging from -32.1 to +6.8%. Clinically, no patient had worsening of their seizures. Of 20 patients with tremor on DR-VPA, 5 reported significant improvement with ER-VPA. No new adverse event were reported.
CONCLUSIONS: Rapid conversion from DR-VPA to ER-VPA is well tolerated. If conversion is made to bid dosing, VPA blood levels show little variation, although one must be cautious if switching from bid dosing or sprinkle formulation. Conversion to once a day dosing requires more close follow-up of blood levels, and one must be careful to use blood levels drawn prior to dosing. Clinically, no worsening of seizure control was seen, and tremor improved in 25% of patients.
Support: Supported by an educational grant from Abbott Laboratories
Disclosure: Honoraria - Dr. McCabe is a member of the Abbott Laboratories Speaker[ssquote]s Program, as well as those of Glaxo-Smtih Kline, UCB Pharma, Ortho McNeil, Pfizer, Novartis, and Elan Pharmaceutical