Rapid switchover to carbamazepine using pharmacokinetic parameters

Andres M Kanner, B. F D Bourgeois, Hisanori Hasegawa, Paul Hutson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increments until the desired close is reached, to avoid intolerable adverse effects (AE). In a pilot study, a protocol using single-dose kinetic studies was developed to switch patients to CBZ through rapid-dose increments and to manage concurrent rapid taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switchover to CBZ could be done with minimal or no AE and without causing an increase in seizures; (b) to determine whether the maintenance dose of CBZ predicted at the time of the single-dose kinetic study can yield the desired concentration at steady state (C(SS)); and (c) to determine the degree to which the calculated maintenance dose of CBZ will need to he adjusted after the previous AED has been discontinued for a four-week period. Methods: Twenty-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) mg/l. On day 2, patients received a CBZ dose equivalent to 10 mg/kg + 200 mg; thereafter, they underwent daily dose increments of 200 mg until the calculated maintenance dose was reached. Dose increments were modified in the case of AE. Concurrent tapering of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on day 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 that time. Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single-dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED. Results: All patients completed the switchover to CBZ within a mean time period of 6 days (±2), reaching a mean maintenance 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 discontinuation of at least one of the previous AEDs. None of the patients experienced an increase in seizure frequency relative to baseline. Fifteen (60%) patients had no AE; five (20%) experienced AE of mild severity. AE rated as moderately severe (n = 4) or severe (n = 1) occurred in patients with a static encephalopathy (p = 0.02, Fisher's exact test) and among patients ≤55 years (p = 0.017, Fisher's exact test). Conclusions: A rapid switch-over to CBZ from PHT, PB, or PRM can be carded out safely with no, or minimal, AE in young adults, unless they suffer from static encephalopathy.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalEpilepsia
Volume39
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

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Carbamazepine
Pharmacokinetics
Phenobarbital
Anticonvulsants
Primidone
Phenytoin
Brain Diseases
Seizures
Young Adult
Prospective Studies

Keywords

  • Carbamazepine
  • Pharmacodynamic cross-tolerance
  • Pharmacokinetic cross- tolerance
  • Rapid switchover

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Rapid switchover to carbamazepine using pharmacokinetic parameters. / Kanner, Andres M; Bourgeois, B. F D; Hasegawa, Hisanori; Hutson, Paul.

In: Epilepsia, Vol. 39, No. 2, 1998, p. 194-200.

Research output: Contribution to journalArticle

Kanner, Andres M ; Bourgeois, B. F D ; Hasegawa, Hisanori ; Hutson, Paul. / Rapid switchover to carbamazepine using pharmacokinetic parameters. In: Epilepsia. 1998 ; Vol. 39, No. 2. pp. 194-200.
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AU - Bourgeois, B. F D

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N2 - Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increments until the desired close is reached, to avoid intolerable adverse effects (AE). In a pilot study, a protocol using single-dose kinetic studies was developed to switch patients to CBZ through rapid-dose increments and to manage concurrent rapid taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switchover to CBZ could be done with minimal or no AE and without causing an increase in seizures; (b) to determine whether the maintenance dose of CBZ predicted at the time of the single-dose kinetic study can yield the desired concentration at steady state (C(SS)); and (c) to determine the degree to which the calculated maintenance dose of CBZ will need to he adjusted after the previous AED has been discontinued for a four-week period. Methods: Twenty-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) mg/l. On day 2, patients received a CBZ dose equivalent to 10 mg/kg + 200 mg; thereafter, they underwent daily dose increments of 200 mg until the calculated maintenance dose was reached. Dose increments were modified in the case of AE. Concurrent tapering of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on day 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 that time. Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single-dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED. Results: All patients completed the switchover to CBZ within a mean time period of 6 days (±2), reaching a mean maintenance 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 discontinuation of at least one of the previous AEDs. None of the patients experienced an increase in seizure frequency relative to baseline. Fifteen (60%) patients had no AE; five (20%) experienced AE of mild severity. AE rated as moderately severe (n = 4) or severe (n = 1) occurred in patients with a static encephalopathy (p = 0.02, Fisher's exact test) and among patients ≤55 years (p = 0.017, Fisher's exact test). Conclusions: A rapid switch-over to CBZ from PHT, PB, or PRM can be carded out safely with no, or minimal, AE in young adults, unless they suffer from static encephalopathy.

AB - Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increments until the desired close is reached, to avoid intolerable adverse effects (AE). In a pilot study, a protocol using single-dose kinetic studies was developed to switch patients to CBZ through rapid-dose increments and to manage concurrent rapid taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switchover to CBZ could be done with minimal or no AE and without causing an increase in seizures; (b) to determine whether the maintenance dose of CBZ predicted at the time of the single-dose kinetic study can yield the desired concentration at steady state (C(SS)); and (c) to determine the degree to which the calculated maintenance dose of CBZ will need to he adjusted after the previous AED has been discontinued for a four-week period. Methods: Twenty-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) mg/l. On day 2, patients received a CBZ dose equivalent to 10 mg/kg + 200 mg; thereafter, they underwent daily dose increments of 200 mg until the calculated maintenance dose was reached. Dose increments were modified in the case of AE. Concurrent tapering of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on day 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 that time. Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single-dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED. Results: All patients completed the switchover to CBZ within a mean time period of 6 days (±2), reaching a mean maintenance 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 discontinuation of at least one of the previous AEDs. None of the patients experienced an increase in seizure frequency relative to baseline. Fifteen (60%) patients had no AE; five (20%) experienced AE of mild severity. AE rated as moderately severe (n = 4) or severe (n = 1) occurred in patients with a static encephalopathy (p = 0.02, Fisher's exact test) and among patients ≤55 years (p = 0.017, Fisher's exact test). Conclusions: A rapid switch-over to CBZ from PHT, PB, or PRM can be carded out safely with no, or minimal, AE in young adults, unless they suffer from static encephalopathy.

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KW - Pharmacodynamic cross-tolerance

KW - Pharmacokinetic cross- tolerance

KW - Rapid switchover

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