RAPID SWITCHOVER TO CARBAMAZEPINE USING PHARMACOKINETIC PARAMETERS

Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increment s until the desired dose is reached, to avoid intolerable adverse effe ct (AE). In a pilot study, a protocol using single-dose kinetic studie s was developed to switch patients to CBZ through rapid-dose increment s and to manage concurrent rapid taper of the previous antiepileptic d rugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switch-over to CBZ could be done w ith minimal or no AE and without causing an increase in seizures (b) t o determine whether the maintenance-dose of CBZ predicted at the time of the single dose kinetic study can yield the desired concentration a t steady state (C-ss); and (c) to determine the degree to which the ca lculated maintenance dose of CBZ will need to be adjusted after the pr evious AED has been discontinued for a four-week period, Methods: Twen ty-five patients taking phenytoin (PHT) and/or phenobarbital (PB) and/ or primidone (PRM) underwent a rapid switchover to CBZ following a 10 mg/kg single-dose kinetic study (day 1) which allowed calculation of a maintenance dose necessary to yield a mean C-ss of 10.2 (+/-2.2) men, On day 2, patients received a CBZ dose equivalent to 10 mg/kg + 200 m g; thereafter, they underwent daily dose increments of 200 mg until th e calculated maintenance dose was reached. Dose increments were modifi ed in the case of AE. Concurrent tapering of the previous AED was star ted as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on d ay 1; PB was restarted before patients were to be discharged from the hospital if a PB serum concentration above 10 mg/l was identified at t hat time. Pharmacokinetic data and occurrence of AE were compared betw een the two groups at the time of the single-dose kinetic study, al th e completion of the switchover to CBZ and 4 weeks after discontinuatio n of the previous AED. Results: All patients completed the switchover to CBZ within a mean lime period of 6 days (+/-2), reaching a mean mai ntenance dose of 1,639 mg/day (+/-370) Which yielded a mean C-ss of 11 .3 (+/-3.2) mg/l. The maintenance dose had to be lowered by 20.4% (+/- 8.3) in 59% of patients within the four-week period following disconti nuation of at least one of the previous AEDs. None of the patients exp erienced an increase in seizure frequency relative to baseline, Fiftee n (60%) patients had no AE: five (20%) experienced AE of mild severity . AE rated as moderately severe (n = 4) or severe in = 1) occurred ill patients with a static encephalopathy: (p = 0.02. Fisher's exact test ) and among patients greater than or equal to 55 years (p = 0.017, Fis her's exact test). Conclusions: A rapid switch-over to CBZ from PHT, P B, or PRM can be carried out safely with no, or minimal, AE in young a dults, unless they suffer from static encephalopathy.