Lacosamide therapeutic monitoring in patients with epilepsy: Effect of concomitant antiepileptic drugs

Manuela Contin, Fiorenzo Albani, Roberto Riva, Carmina Candela, Susan Mohamed, Agostino Baruzzi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

BACKGROUND:: Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy. METHODS:: Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection. RESULTS:: Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P <0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration. CONCLUSIONS:: Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30% higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.

Original languageEnglish
Pages (from-to)849-852
Number of pages4
JournalTherapeutic Drug Monitoring
Volume35
Issue number6
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Physiologic Monitoring
Anticonvulsants
Epilepsy
Therapeutics
etiracetam
Carbamazepine
Phenytoin
Phenobarbital
Pharmaceutical Preparations
lacosamide
Neuropharmacology
Weights and Measures
Drug Therapy
Partial Epilepsy
Drug Monitoring
Valproic Acid
Cytochrome P-450 Enzyme System
Randomized Controlled Trials
Pharmacokinetics
High Pressure Liquid Chromatography

Keywords

  • Antiepileptic drug pharmacokinetic interaction
  • Lacosamide
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Lacosamide therapeutic monitoring in patients with epilepsy : Effect of concomitant antiepileptic drugs. / Contin, Manuela; Albani, Fiorenzo; Riva, Roberto; Candela, Carmina; Mohamed, Susan; Baruzzi, Agostino.

In: Therapeutic Drug Monitoring, Vol. 35, No. 6, 12.2013, p. 849-852.

Research output: Contribution to journalArticle

Contin, Manuela ; Albani, Fiorenzo ; Riva, Roberto ; Candela, Carmina ; Mohamed, Susan ; Baruzzi, Agostino. / Lacosamide therapeutic monitoring in patients with epilepsy : Effect of concomitant antiepileptic drugs. In: Therapeutic Drug Monitoring. 2013 ; Vol. 35, No. 6. pp. 849-852.
@article{ce1f606e2b254b8ca6e2aea81b32cb68,
title = "Lacosamide therapeutic monitoring in patients with epilepsy: Effect of concomitant antiepileptic drugs",
abstract = "BACKGROUND:: Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy. METHODS:: Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection. RESULTS:: Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P <0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration. CONCLUSIONS:: Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30{\%} higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.",
keywords = "Antiepileptic drug pharmacokinetic interaction, Lacosamide, Therapeutic drug monitoring",
author = "Manuela Contin and Fiorenzo Albani and Roberto Riva and Carmina Candela and Susan Mohamed and Agostino Baruzzi",
year = "2013",
month = "12",
doi = "10.1097/FTD.0b013e318290eacc",
language = "English",
volume = "35",
pages = "849--852",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Lacosamide therapeutic monitoring in patients with epilepsy

T2 - Effect of concomitant antiepileptic drugs

AU - Contin, Manuela

AU - Albani, Fiorenzo

AU - Riva, Roberto

AU - Candela, Carmina

AU - Mohamed, Susan

AU - Baruzzi, Agostino

PY - 2013/12

Y1 - 2013/12

N2 - BACKGROUND:: Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy. METHODS:: Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection. RESULTS:: Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P <0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration. CONCLUSIONS:: Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30% higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.

AB - BACKGROUND:: Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentrations of LCM in a population of patients with epilepsy. METHODS:: Steady state plasma concentrations of LCM were assessed in a cohort of 75 consecutive patients with epilepsy referred to the Laboratory of Clinical Neuropharmacology for AED therapeutic monitoring over 16 months. Plasma LCM concentrations were measured by high-performance liquid chromatography with spectrophotometric detection. RESULTS:: Median morning trough plasma concentration-to-weight-adjusted dose ratio of LCM [(mg/L)/(mg/kg/d)] was significantly reduced (0.94 versus 1.35, P <0.001) in patients treated with LCM plus AED strong inducers of cytochrome P450 metabolism, namely, carbamazepine, phenobarbital, and phenytoin (group A, n = 33), compared with a pool of patients not comedicated with AED strong inducers, predominantly including oxcarbazepine, levetiracetam, lamotrigine, and valproic acid (group B, n = 42). The 2 groups were comparable for age, gender, weight, LCM daily dose, and dosing frequency. LCM plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 75 to 600 mg/d, although, at a given drug dose, a large interpatient variability was observed in matched, plasma drug concentration. CONCLUSIONS:: Our findings confirm, in a real-patient clinical setting, preliminary evidence from randomized, clinical trials showing that carbamazepine, phenobarbital, or phenytoin significantly reduces the overall systemic exposure to LCM. From a practical point of view, patients on concomitant AED strong inducers may require a 30% higher dose of LCM compared with patients not receiving strongly inducing AED cotherapy, to achieve the same plasma drug concentration.

KW - Antiepileptic drug pharmacokinetic interaction

KW - Lacosamide

KW - Therapeutic drug monitoring

UR - http://www.scopus.com/inward/record.url?scp=84889238111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84889238111&partnerID=8YFLogxK

U2 - 10.1097/FTD.0b013e318290eacc

DO - 10.1097/FTD.0b013e318290eacc

M3 - Article

C2 - 23942540

AN - SCOPUS:84889238111

VL - 35

SP - 849

EP - 852

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 6

ER -