Enzymatic Induction and Tolerance in Transition to Oxcarbazepine in the STOPS Trial
Abstract number :
3.110
Submission category :
Year :
2001
Submission ID :
353
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
J.R. Gates, MD, Minnesota Epilepsy Group, PA, St Paul, MN; R.C. Sachdeo, MD, University of Medicine and Dentistry of New Jersey, Brunswick, NJ; S.M. Graham, PhD, Novartis Pharmaceuticals Corp, East Hanover, NJ; K. McCague, MA, Novartis Pharmaceuticals Cor
RATIONALE: Liver enzymatic induction facillitates tolerance of oxcarbazepine transition by a factor of 2-3 times for patients previously taking inducing agents such as phenytoin or carbamazepine. This result argues for a slower titration schedule for non-induced patients for transition from valproate, gabapentin, lamotrigine, or other non-inducing or minimally inducing AEDs or for initial therapy.
METHODS: The Safety and Therapeutic Effect of Oxcarbazepine in Patients with Partial Seizures Study (STOPS Trial) was designed as an open-label, single-arm, 16-week treatment utilizing 600-2400 mg/day of OXC. Patients were titrated off their current AED monotherapy from baseline (week 0) to week 4. At week 0 all patients were begun on OXC at 600 mg/day in 300 mg/bid dosing up to a maximum of 2400 mg/day. Patients were entered from 70 centers and were uncontrolled on current AED monotherapy with 2-40 seizures/month (137 patients, 55.9%) for the two months prior to study entry, or were unable to tolerate their current AED monotherapy treatment (105 patients, 42.9%).
RESULTS: 245 patients were enrolled, of whom 241 patients were exposed to OXC. 42 patients discontinued due to adverse events (AEs). Of the 109 transitioned from carbamazepine monotherapy, 12 (11.0%) discontinued due to AEs; 7/48 (14.6%) from phenytoin; 9/35 (25.7%) from valproate; 5/13 (38.5%) from gabapentin; 4/15 (26.7%)from lamotrigine; 2/14 (14.3%) from other AEDs; and 3/7 (42.9%) on no previous AEDs. The rate of discontinuation for AEs in the cohort of patients who were transitioned from the non-inducing AEDs valproate, gabapentin and lamotrigine (28.6%) was significantly different (p[lt]0.005) from that seen in the cohort of patients who transitioned from the inducing AEDs carbamazepine and phenytoin (12.1%).
CONCLUSIONS: Liver enzymatic induction facilitates tolerance of oxcarbazepine transition by a factor of 2-3 times for patients previously taking inducing agents, such as phenytoin or carbamazepine. This result argues for a slower titration schedule for non-induced patients for transition from valproate, gabapentin, lamotrigine or other non-inducing or minimally inducing AEDs or for initial therapy.
Support: Novartis