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Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update.
Ther Drug Monit 2018; 40(5):526-548TD

Abstract

BACKGROUND

Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, for example, pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug's prescribing indications, key pharmacokinetic characteristics, associated drug-drug pharmacokinetic interactions, and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total versus free concentrations in blood versus saliva) and sample collection and processing.

METHODS

The present review is based on published articles and searches in PubMed and Google Scholar, last searched in March 2018, in addition to references from relevant articles.

RESULTS

In total, 171 relevant references were identified and used to prepare this review.

CONCLUSIONS

TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide).

Authors+Show Affiliations

Epilepsy Society, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire. Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, Queen Square, London, United Kingdom.Epilepsy Society, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire.Epilepsy Society, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

29957667

Citation

Patsalos, Philip N., et al. "Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: a 2018 Update." Therapeutic Drug Monitoring, vol. 40, no. 5, 2018, pp. 526-548.
Patsalos PN, Spencer EP, Berry DJ. Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. Ther Drug Monit. 2018;40(5):526-548.
Patsalos, P. N., Spencer, E. P., & Berry, D. J. (2018). Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. Therapeutic Drug Monitoring, 40(5), pp. 526-548. doi:10.1097/FTD.0000000000000546.
Patsalos PN, Spencer EP, Berry DJ. Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: a 2018 Update. Ther Drug Monit. 2018;40(5):526-548. PubMed PMID: 29957667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. AU - Patsalos,Philip N, AU - Spencer,Edgar P, AU - Berry,Dave J, PY - 2018/6/30/pubmed PY - 2019/4/30/medline PY - 2018/6/30/entrez SP - 526 EP - 548 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 40 IS - 5 N2 - BACKGROUND: Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, for example, pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug's prescribing indications, key pharmacokinetic characteristics, associated drug-drug pharmacokinetic interactions, and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total versus free concentrations in blood versus saliva) and sample collection and processing. METHODS: The present review is based on published articles and searches in PubMed and Google Scholar, last searched in March 2018, in addition to references from relevant articles. RESULTS: In total, 171 relevant references were identified and used to prepare this review. CONCLUSIONS: TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide). SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/29957667/Therapeutic_Drug_Monitoring_of_Antiepileptic_Drugs_in_Epilepsy:_A_2018_Update_ L2 - http://Insights.ovid.com/pubmed?pmid=29957667 DB - PRIME DP - Unbound Medicine ER -