LONG-TERM SAFETY OF CARBAMAZEPINE EXTENDED-RELEASE CAPSULES TWICE DAILY IN THE TREATMENT OF SEIZURE DISORDERS
Abstract number :
2.213
Submission category :
Year :
2002
Submission ID :
3428
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Vijay M. Thadani, William R. Garnett, R. Edward Hogan, The Carbatrol Study Group. Section of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Epilepsy Offices, St Louis University, St Louis, MO; Pharmacy and Pharmaceutics, Medical College of Vi
RATIONALE: The objective of this study was to evaluate the long-term safety of carbamazepine extended-release capsules (CBZ-ERC; Carbatrol) in patients with seizure disorders. Carbamazepine (CBZ) is established as effective first-line therapy for patients with seizure disorders. Extended-release formulations allow twice-daily dosing which improves adherence. CBZ-ERC consist of 3 types of beads: uncoated immediate-release, polymer-coated extended-release, and pH-sensitive coated enteric-release to provide decreased fluctuations of CBZ throughout the 12-hour dosing interval. A previous, 6-month study demonstrated that switching patients from multiple daily-dose CBZ to twice-daily CBZ-ERC was safe and effective (Neurology 1998 51:1727-1729).
METHODS: 118 pts with seizure disorders enrolled in a 36-month, open-label evaluation of twice-daily CBZ-ERC at an initial daily dose equivalent to the daily dose prior to entry. CBZ-ERC dose could be changed if clinically necessary up to 1600 mg/day. Up to two other AEDs could be maintained at a stable dose. Patients kept a seizure diary, reported adverse events (AEs) and returned to the clinic every 6 months for evaluations.
RESULTS: Of 118 patients enrolled, 81 (68.6%) either completed 36 months of participation or were still participating when the study was phased out following commercial availability of CBZ-ERC. Of the 37 patients discontinued from the study, 9 met seizure-escape criteria, but seizures were well controlled in the remainder. Overall seizure frequency was stable throughout. At baseline, 6-month, and 12-month time points, mean highest 2-day generalized tonic clonic (GTC) seizure frequencies were 0.2, 0.1, and 0.1, respectively, while mean highest 2-day non-GTC seizure frequencies were 1.2, 1.3, and 1.4, respectively. Drug related AEs, reported by more than 1% of patients, were typical of CBZ and are listed below. Only 3 patients discontinued due to AEs, and all were deemed unrelated to study drug by the investigator. Quality-of-life measures showed no improvement beyond that attained in the previous 6-month study.
CONCLUSIONS: CBZ-ERC is well tolerated and can be used safely and effectively for long-term treatment of seizure disorders.[table1]
[Supported by: Shire US Inc.]; (Disclosure: Grant - WR Garnett, Shire, Consulting - VM Thadani, Shire, Honoraria - VM Thadani, Shire; RE Hogan, Shire; WR Garnett, Shire)